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Lateral ventricle size, smooth pursuit eye tracking and neuropsychological test performance in chronic… Shepard Tallman, Karen 1986

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LATERAL VENTRICLE SIZE, SMOOTH PURSUIT EYE TRACKING AND NEUROPSYCHOLOGICAL TEST PERFORMANCE IN CHRONIC SCHIZOPHRENIA By Karen Shepard Tallman B . S c , U n i v e r s i t y o f B r i t i s h Columbia, 1976 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF ARTS i n THE FACULTY OF GRADUATE STUDIES (Department of Psychology) We accept t h i s t h e s i s as conforming t o the r e q u i r e d standard THE UNIVERSITY OF August © Karen Shepard BRITISH COLUMBIA 1986 Tallman, 1986 In p r e s e n t i n g t h i s t h e s i s i n p a r t i a l f u l f i l m e n t o f the requirements f o r an advanced degree a t the U n i v e r s i t y o f B r i t i s h Columbia, I agree t h a t the L i b r a r y s h a l l make i t f r e e l y a v a i l a b l e f o r r e f e r e n c e and study. I f u r t h e r agree t h a t p e r m i s s i o n f o r e x t e n s i v e copying o f t h i s t h e s i s f o r s c h o l a r l y purposes may be granted by the head o f my department o r by h i s or her r e p r e s e n t a t i v e s . I t i s understood t h a t copying or p u b l i c a t i o n o f t h i s t h e s i s f o r f i n a n c i a l g a i n s h a l l not be allowed without my w r i t t e n p e r m i s s i o n . Department o f The U n i v e r s i t y of B r i t i s h Columbia 1956 Main Mall Vancouver, Canada V6T 1Y3 Date DA 1 IK<Q -6 n/flin ABSTRACT The r e l a t i o n s h i p s between l a t e r a l v e n t r i c l e s i z e , smooth p u r s u i t eye t r a c k i n g , and n e u r o p s y c h o l o g i c a l t e s t p e r f o r m a n c e were i n v e s t i g a t e d u s i n g a sample o f 30 c h r o n i c s c h i z o p h r e n i c i n p a t i e n t s . There were no s i g n i f i c a n t c o r r e l a t i o n s between any o f t h e m e a s u r e s . Compared t o a c o n t r o l g r o u p o f normal v o l u n t e e r s , the s c h i z o p h r e n i c p a t i e n t s showed abnormally poor eye t r a c k i n g a c c u r a c y b u t d i d n o t show l a t e r a l v e n t r i c u l a r e n l a r g e m e n t . Compared t o a g r o u p o f a g e m a t c h e d n o n -s c h i z o p h r e n i c p s y c h i a t r i c p a t i e n t s , the s c h i z o p h r e n i c p a t i e n t s were impaired on s i x out of ten n e u r o p s y c h o l o g i c a l t e s t s . As t h e r e was no e v i d e n c e o f l a t e r a l v e n t r i c l e enlargement, i t i s c l e a r t h a t e y e t r a c k i n g i m p a i r m e n t a n d d e f i c i t s o n n e u r o p s y c h o l o g i c a l t e s t s may o c c u r i n d e p e n d e n t l y o f en l a r g e d l a t e r a l v e n t r i c l e s . The absence o f r e l a t i o n s h i p s b e t w e e n impairments on the n e u r o p s y c h o l o g i c a l t e s t s and poor eye t r a c k i n g i s not thought to be the r e s u l t of r e s t r i c t e d performance ranges f o r any o f t h e measures. The most parsimonious c o n c l u s i o n i s t h a t t h e r e i s no r e l a t i o n s h i p between eye t r a c k i n g and t h e v a r i e t y of n e u r o p s y c h o l o g i c a l f u n c t i o n s assessed i n t h i s study. However, an a l t e r n a t i v e p o s s i b i l i t y i s t h a t the study sample was t o o h o m o g e n e o u s l y i m p a i r e d , and a r e l a t i o n s h i p between eye t r a c k i n g impairment and n e u r o p s y c h o l o g i c a l d e f i c i t s might emerge i n a more d i v e r s e s a m p l e r e p r e s e n t a t i v e o f t h e range o f i n d i v i d u a l s c u r r e n t l y diagnosed as s c h i z o p h r e n i c . i i TABLE OF CONTENTS PAGE ABSTRACT i i TABLE OF CONTENTS i i i LIST OF TABLES v i LIST OF FIGURES v i i ACKNOWLEDGEMENTS 8 INTRODUCTION . . . . 1 RELEVANT LITERATURE 2 Smooth P u r s u i t Eye T r a c k i n g 2 D e f i n i t i o n 2 P r e v a l e n c e o f S P E M D y s f u n c t i o n i n S c h i z o p h r e n i a 5 S i g n i f i c a n c e O f SPEM D y s f u n c t i o n i n S c h i z o p h r e n i a 6 Summary-SPEM 8 CT Scan F i n d i n g s 9 D e f i n i t i o n 9 P r e v a l e n c e o f L a t e r a l V e n t r i c u l a r Enlargement (LVE) 12 S i g n i f i c a n c e o f L a t e r a l V e n t r i c u l a r Enlargement i n S c h i z o p h r e n i a 14 A r t i f a c t or c o i n c i d e n c e ? 14 C l i n i c a l c o r r e l a t e s o f LVE 16 C o g n i t i v e / n e u r o p s y c h o l o g i c a l f u n c t i o n and CT scan a b n o r m a l i t i e s 18 Summary o f CT Scan F i n d i n g s i n S c h i z o p h r e n i a . 26 N e u r o p s y c h o l o g i c a l and C o g n i t i v e F u n c t i o n i n g i n S c h i z o p h r e n i a 28 D e f i n i t i o n and D e s c r i p t i o n . 28 N e u r o p s y c h o l o g i c a l t e s t s a n d d i f f e r e n t i a l d i a g n o s e s o f " f u n c t i o n a l " v s . " o r g a n i c " c o n d i t i o n s 29 Summary o f c l a s s i f i c a t i o n s t u d i e s . . . . 32 S e l e c t e d ' d e s c r i p t i v e ' s t u d i e s o f n e u r o p s y c h o l o g i c a l i m p a i r m e n t i n s c h i z o p h r e n i a 3 4 Summary o f d e s c r i p t i v e s t u d i e s 42 i i i TABLE OF CONTENTS (Continued) C o n c l u d i n g comments on d e f i n i t i o n and d e s c r i p t i o n o f n e u r o p s y c h o l o g i c a l and c o g n i t i v e f u n c t i o n i n g i n s c h i z o p h r e n i a 45 P r e v a l e n c e o f N e u r o p s y c h o l o g i c a l Impairment . 46 M e d i c a t i o n and n e u r o p s y c h o l o g i c a l performance 48 S u b j e c t c h a r a c t e r i s t i c s ; e f f e c t o f age, e d u c a t i o n a n d e t h n i c i t y o n n e u r o p s y c h o l o g i c a l performance . . . 50 S i g n i f i c a n c e on N e u r o p s y c h o l o g i c a l D e f i c i t s i n S c h i z o p h r e n i a 51 Summary o f N e u r o p s y c h o l o g i c a l F i n d i n g s i n S c h i z o p h r e n i a 52 Summary o f R e l a t i o n s h i p s Among Measures o f Smooth P u r s u i t E y e M o v ements ( S P E M ) , L a t e r a l V e n t r i c l e E n l a r g e m e n t ( L V E ) , a n d N e u r o p s y c h o l o g i c a l T e s t Performance (NTP) i n S c h i z o p h r e n i a 55 SPEM and LVE 56 SPEM and NTP 57 LVE and NTP 57 SPEM, LVE and NTP 60 C o n c l u s i o n s From L i t e r a t u r e Review 6 3 RESEARCH OBJECTIVES 67 Hypotheses 6 8 Group D i f f e r e n c e s 68 C o r r e l a t i o n s Among VBR, Smooth P u r s u i t Eye T r a c k i n g , a n d N e u r o p s y c h o l o g i c a l Performance 6 8 C o r r e l a t i o n s W i t h i n B a t t e r y . . 70 METHOD 71 S u b j e c t s 71 C h r o n i c s c h i z o p h r e n i c p a t i e n t s 71 Normal C o n t r o l Group 82 P s y c h i a t r i c C o n t r o l Group 82 Measures 8 3 Smooth p u r s u i t eye movement r e c o r d i n g . . 8 3 L a t e r a l v e n t r i c l e s i z e s 84 Measurement o f VBR v e n t r i c l e s i z e . . . . 85 N e u r o p s y c h o l o g i c a l assessment 85 S c o r i n g n e u r o p s y c h o l o g i c a l t e s t s . . . . 86 Procedure 87 i v TABLE OF CONTENTS (Continued) RESULTS . 89 R e l i a b i l i t y o f VBR measure 90 R e l a t i o n s h i p s B e t w e e n D u r a t i o n o f H o s p i t a l i z a t i o n , Age and Substance Abuse and the P r i n c i p a l Measures 91 Group D i f f e r e n c e s 9 3 R e l a t i o n s h i p s Among VBR, LRMS D e v i a t i o n i n Eye T r a c k i n g and N e u r o p s y c h o l o g i c a l T e s t Performance 101 VBR and eye t r a c k i n g 101 VBR a n d N e u r o p s y c h o l o g i c a l T e s t Performance 101 Eye T r a c k i n g and N e u r o p s y c h o l o g i c a l T e s t Performance . . . 103 C o r r e l a t i o n s w i t h i n t h e N e u r o p s y c h o l o g i c a l T e s t B a t t e r y 10 3 Summary o f R e s u l t s 10 6 DISCUSSION 108 Group D i f f e r e n c e s 108 R e l a t i o n s h i p s Among VBR, LRMS D e v i a t i o n i n Eye T r a c k i n g and N e u r o p s y c h o l o g i c a l T e s t Performance 114 VBR and eye t r a c k i n g 115 VBR a n d N e u r o p s y c h o l o g i c a l T e s t Performance 117 Eye T r a c k i n g and N e u r o p s y c h o l o g i c a l T e s t Performance 120 Su b j e c t v a r i a b l e s 121 C o r r e l a t i o n s w i t h i n t h e N e u r o p s y c h o l o g i c a l T e s t B a t t e r y 122 S t a t i s t i c a l Issues 125 C o n c l u s i o n 126 REFERENCES 129 APPENDIX A: TESTING THE IDENTITY MATRIX HYPOTHESIS . . . . 138 APPENDIX B l : CONSENT TO BE INTERVIEWED 139 APPENDIX B2: CONSENT TO BE TESTED 140 V LIST OF TABLES PAGE Table 1 Age o f P a r t i c i p a n t s 75 Table 2 E d u c a t i o n a l Attainment o f P a r t i c i p a n t s 76 Tab l e 3 Number o f P s y c h i a t r i c H o s p i t a l i z a t i o n s f o r C h r o n i c S c h i z o p h r e n i c P a t i e n t s 77 Ta b l e 4 A c c u m u l a t e d D u r a t i o n o f I n s t i t u t i o n a l i z a t i o n f o r Ch r o n i c S c h i z o p h r e n i c P a t i e n t s 7 8 T a b l e 5 D S M - I I I S u b t y p e s o f S c h i z o p h r e n i a i n C h r o n i c S c h i z o p h r e n i c Sample 7 9 T a b l e 6 Means, Standard D e v i a t i o n s , and t - t e s t Values f o r VBR, LRMS D e v i a t i o n i n Eye T r a c k i n g and WAIS-R F u l l S c a l e IQ f o r S c h i z o p h r e n i c P a t i e n t s w i t h H i s t o r i e s o f A l c o h o l and/or I l l i c i t Drug Abuse ( n = l l ) compared w i t h S c h i z o p h r e n i c P a t i e n t s w i t h L i t t l e o r No Use o f I l l i c i t Drugs o r A l c o h o l (n=10) 94 Ta b l e 7 Means, Standard D e v i a t i o n s , and t- V a l u e s f o r VBR and Eye T r a c k i n g A c c u r a c y f o r S c h i z o p h r e n i c P a t i e n t s and Normal C o n t r o l s 95 Tab l e 8 Means, S t a n d a r d D e v i a t i o n s , and Ranges (where a v a i l a b l e ) f o r N e u r o p s y c h o l o g i c a l T e s t s f o r S c h i z o p h r e n i c P a t i e n t s and Normal C o n t r o l s . . . . 97 Tab l e 9 T - t e s t s B e t w e e n S c h i z o p h r e n i c p a t i e n t s and P s y c h i a t r i c C o n t r o l s f o r t h e N e u r o p s y c h o l o g i c a l T e s t s 98 Tab l e 10 C o r r e l a t i o n s Bewteen VBR, LRMS T r a c k i n g E r r o r , D u r a t i o n o f H o s p i t a l i z a t i o n and the Ne u r o p s y c h o -l o g i c a l T e s t s f o r the Ch r o n i c S c h i z o p h r e n i c Sample (n=30) 102 Tab l e 11 C o r r e l a t i o n M a t r i x o f N e u r o p s y c h o l o g i c a l T e s t s f o r S c h i z o p h r e n i c Sample (n=30) . . 104 v i LIST OF FIGURES PAGE F i g u r e 1 D i s t r i b u t i o n o f V e n t r i c l e B r a i n R a t i o s f o r S c h i z o -p h r e n i c P a t i e n t s and V o l u n t e e r C o n t r o l s . . . . . . 99 F i g u r e 2 D i s t r i b u t i o n o f LRMS eye t r a c k i n g accuracy s c o r e s f o r S c h i z o p h r e n i c P a t i e n t s and V o l u n t e e r C o n t r o l s 100 v i i ACKNOWLEDGEMENTS The r e s e a r c h r e p o r t e d i n t h i s t h e s i s r e p r e s e n t s the effort's o f many i n d i v i d u a l s . Each member o f my t h e s i s committee p r o v i d e d generous guidance and support. Dr. D i m i t r i P a p a g o r g i s k i n d l y took over chairmanship o f the committee i n Dr. Iacono's absence and p r o v i d e d v a l u a b l e a s s i s t a n c e i n the p r e p a r a t i o n o f the t e x t o f t h i s t h e s i s . Dr. D a v i d C r o c k e t t ' s o n g o i n g g u i d a n c e , and g e n e r o s i t y w i t h h i s t i m e and e x p e r t i s e , i s g r a t e f u l l y a c k n o w l e d g e d . Dr. W i l l i a m I a c o n o , my p r i n c i p a l a d v i s o r , has p l a y e d a c r i t i c a l r o l e i n a l l s t a g e s o f t h i s p r o j e c t and throughout my graduate t r a i n i n g . I f e e l tremendously f o r t u n a t e to have had the o p p o r t u n i t y t o work w i t h Dr. Iacono and wish to e x p r e s s s p e c i a l t h a n k s f o r h i s u n f l a g g i n g s u p p o r t i n t h i s r e s e a r c h . The p r e s e n t r e s e a r c h would have been i m p o s s i b l e without the c o o p e r a t i o n and g e n e r o s i t y o f s e v e r a l i n d i v i d u a l s a t R i v e r v i e w H o s p i t a l . I would l i k e e s p e c i a l l y t o thank Dr. J . Higgenbottom, Dr. B. Ledwidge and Mr. K. Judd f o r t h e i r h e l p i n t h i s p r o j e c t . F i n a l l y , I w i s h t o acknowledge t h r e e s t a r s who played a major r o l e i n my l i f e throughout the l o n g days and l o n g e r n i g h t s t h a t went i n t o t h i s r e s e a r c h . Shine on B r i a n , J e s s , and Kora. v i i i INTRODUCTION Over the p a s t decade many r e s e a r c h e r s have turned t h e i r a t t e n t i o n t o d e s c r i b i n g p h y s i o l o g i c a l and n e u r o a n a t o m i c a l anomalies which may occur i n s c h i z o p h r e n i c p a t i e n t s . Viewing s c h i z o p h r e n i a as a b i o l o g i c a l l y based d i s o r d e r has much c r e d i b i l i t y i n l i g h t o f the c l e a r evidence t h a t many s c h i z o -p h r e n i c s b e n e f i t from dopamine a n t a g o n i s t i c drugs and repeated demonstrations t h a t t h e r e may be a h e r i t a b l e l i a b i l i t y or pre -d i s p o s i t i o n t o s c h i z o p h r e n i a . P r o g r e s s i n g beyond t h e s e o b s e r v a t i o n s t o the l e v e l o f d e s c r i b i n g s y s t e m a t i c r e l a t i o n -s h i p s among c r i t i c a l b i o l o g i c a l v a r i a b l e s has proven t o be a very demanding c h a l l e n g e f o r r e s e a r c h e r s . The p r e s e n t study i s an i n v e s t i g a t i o n o f t h r e e b i o l o g i c a l m e a s ures, e a c h o f w h i c h has been a s s o c i a t e d w i t h s c h i z o -p h r e n i a . The p u r p o s e o f t h e r e s e a r c h i s t o d e s c r i b e the r e l a t i o n s h i p between smooth p u r s u i t eye t r a c k i n g , n e u r o -p s y c h o l o g i c a l t e s t performance, and computed tomography (CT) scan measures o f l a t e r a l v e n t r i c l e s i z e . A lthough t h e r e are f a i r l y e x t e n s i v e l i t e r a t u r e s on each measure i n i s o l a t i o n and on v e n t r i c l e s i z e and c o g n i t i v e f u n c t i o n i n g i n combination, t o d a t e t h e r e i s o n l y one p u b l i s h e d s t u d y w h i c h has s i m u l -t a n e o u s l y i n v e s t i g a t e d a l l t h r e e v a r i a b l e s i n the same sample of s u b j e c t s ( B a r t f a i , Levander, Nyback, Berggren & S c h a l l i n g , 1985). I 2 RELEVANT LITERATURE The f o l l o w i n g review o f the r e s e a r c h l i t e r a t u r e r e l e v a n t t o t h i s study w i l l be o r g a n i z e d i n t o f i v e s e c t i o n s . The f i r s t t h r e e s e c t i o n s w i l l be devoted t o reviews o f the l i t e r a t u r e on smooth p u r s u i t eye t r a c k i n g , CT s c a n f i n d i n g s o f l a t e r a l v e n t r i c u l a r enlargement, and n e u r o p s y c h o l o g i c a l and c o g n i t i v e f u n c t i o n i n g i n s c h i z o p h r e n i a . The s e c t i o n s on these t h r e e measures w i l l be s u b d i v i d e d t o d i s c u s s i ) o p e r a t i o n a l d e f i n i -t i o n s o f d e v i a n t attainment, i i ) the p r e v a l e n c e o f d e v i a t i o n s i n s c h i z o p h r e n i c samples, i i i ) the s i g n i f i c a n c e o f abnormal a t t a i n m e n t on the measure i n q u e s t i o n , and i v ) a summary o f f i n d i n g s and m e t h o d o l o g i c a l i s s u e s . The f o u r t h major s e c t i o n o f t h e l i t e r a t u r e r e v i e w w i l l summarize r e s e a r c h which has i n v e s t i g a t e d r e l a t i o n s h i p s among t h e v a r i a b l e s . The f i f t h s e c t i o n c o n s i s t s o f g e n e r a l c o n c l u s i o n s and a r a t i o n a l e f o r the c u r r e n t r e s e a r c h p r o j e c t based on the e x i s t i n g l i t e r a t u r e . Smooth P u r s u i t Eye T r a c k i n g D e f i n i t i o n S m ooth p u r s u i t e y e movements (SPEM) a r e c o n j u g a t e f o l l o w i n g movements u t i l i z e d i n t r a c k i n g t a r g e t s i n continuous motion a t v e l o c i t i e s up t o 40 degrees/second ( L i p t o n , Levy, & Holzman, & L e v i n , 1983; Yee, 1983). They are b e l i e v e d t o be more or l e s s n o n v o l u n t a r y i n t h e p r e s e n c e o f slow moving t a r g e t s and t o s e r v e t h e f u n c t i o n o f m a i n t a i n i n g a s t a b l e 3 image on the r e t i n a . B e g i n n i n g w i t h r e p o r t s by Holzman and a s s o c i a t e s (Holzman, P r o c t o r , Y a s i l l o , M e l t z e r , & Hurt, 1974; Holzman, P r o c t o r , & Hughes, 1973) on t h e i r i n v e s t i g a t i o n o f f i n d i n g s t h a t o r i g i n a t e d i n the work o f D i e f e n d o r f and Dodge i n 1908 and Couch and Fox i n 1934, numerous s t u d i e s have found d i s r u p t e d p u r s u i t eye movements i n p s y c h i a t r i c p a t i e n t s and t h e i r r e l a t i v e s . A s t a n d a r d p r o t o c o l f o r m e a s u r i n g smooth p u r s u i t eye movements i n v o l v e s p l a c i n g t h e s u b j e c t about 30 cm from a s c r e e n on w h i c h a s m a l l dot or a c u r s o r i s d r i v e n back and f o r t h a t v e l o c i t i e s up t o 30-40 d e g r e e s p e r s e c o n d . The movements o f t h e eye may be r e c o r d e d w i t h a v a r i e t y o f t e c h n i q u e s a l t h o u g h e l e c t r o o c u l o g r a p h y (EOG) and i n f r a r e d r e f l e c t o m e t r y (IR) are probably the most common. Both t a r g e t p o s i t i o n and eye p o s i t i o n a r e r e c o r d e d on a p o l y g r a p h f o r v i s u a l i n s p e c t i o n and may a l s o be s t o r e d i n some form which all o w s q u a n t i t a t i v e a n a l y s i s by computer. Methods o f s c o r i n g t r a c k i n g p e r f o r m a n c e h a v e d i f f e r e d c o n s i d e r a b l y a c r o s s s t u d i e s . T r a c k i n g performance can be q u a l i t a t i v e l y e v a l u a t e d by e x a m i n i n g p o l y g r a p h r e c o r d s and n o t i n g the o c c u r r e n c e o f obvious d e v i a t i o n s i n the eye movement channel r e l a t i v e to the t a r g e t c h a n n e l , or i t may be compared to r e c o r d s o f normal s u b j e c t s . More s o p h i s t i c a t e d and r e l i a b l e s c o r i n g methods i n v o l v e q u a n t i f y i n g the t r a c k i n g performance, o f t e n through s p e c i a l l y designed computer programs t h a t sample the t r a c k i n g r e c o r d and compare i t to t a r g e t p o s i t i o n . 4 Each s c o r i n g method c o n s t i t u t e s an- o p e r a t i o n a l d e f i n i t i o n o f the p u r s u i t d e f i c i t . D i f f e r e n t measurement te c h n i q u e s have f o c u s e d on q u a l i t a t i v e l y d i f f e r e n t a spects o f eye t r a c k i n g performance (Iacono & Koenig, 1983). At p r e s e n t t h e r e does not appear t o be a c o n s e n s u a l l y agreed-upon d e f i n i t i o n o f the p r e c i s e n a t u r e o f the abnormal p u r s u i t p a t t e r n . I a c o n o and Koenig (1983) d e s c r i b e two aspects o f the smooth p u r s u i t eye t r a c k i n g p e r f o r m a n c e o f s c h i z o p h r e n i c p a t i e n t s w h i c h t h e y f o u n d d i f f e r e d q u a l i t a t i v e l y from t h a t o f a f f e c t i v e - d i s o r d e r p a t i e n t s and n o rmal i n d i v i d u a l s . They f o u n d t h a t s c h i z o -p h r e n i c p a t i e n t s t r a c k e d w i t h s i g n i f i c a n t l y more "phase-lag" ( d e f i n e d as the average number o f degrees o f v i s u a l a r c t h e eyes l a g behind the t a r g e t ) and produced s a c c a d i c e r r o r s o f s m a l l e r amplitude than those seen i n o t h e r s u b j e c t s . L e v i n , Jones, S t a r k , M e r r i n , and Holzman (19 82) r e p o r t e d f i n d i n g s on a group o f s i x s c h i z o p h r e n i c p a t i e n t s u s i n g s o p h i s t i c a t e d i n f r a r e d r e c o r d i n g i n s t r u m e n t a t i o n they b e l i e v e t o be c o n s i -d e r a b l y more p r e c i s e than the measurement te c h n i q u e s used i n t h e o t h e r eye movement s t u d i e s . They d e s c r i b e two types o f eye movement i r r e g u l a r i t i e s they b e l i e v e to be the u n d e r l y i n g f a c t o r s i n d i s r u p t e d smooth p u r s u i t eye movements i n s c h i z o -p h r e n i a . They s u g g e s t t h a t i m p a i r e d SPEM i s a r e s u l t o f e i t h e r / b o t h " s a c c a d i c i n t r u s i o n s " ( d e f i n e d as p a i r s o f s m a l l amplitude saccades, 0.5° to 2.5° i n o p p o s i t e d i r e c t i o n s t o each ot h e r and o c c u r r i n g at a r a t e o f 1 to 3 per second) and " s a c c a d i c smooth p u r s u i t " t r a c k i n g ( d e f i n e d as p u r s u i t 5 t r a c k i n g accomplished by s m a l l s a c c a d i c steps o f about 1° i n am p l i t u d e ) . Prevalence of SPEM Dysfunction i n Schizophrenia Recent reviews suggest t h a t 50% to 80% o f s c h i z o p h r e n i c s show i m p a i r e d smooth p u r s u i t eye movement (Holzman, 1983; Latham, Holzman, Manschrech, & T o l e , 1981; Spohn, 1983). The f i n d i n g s o f the e a r l y Holzman s t u d i e s (Holzman e t a l . , 1974) have e s s e n t i a l l y stood the t e s t o f time and been r e p l i c a t e d by Holzman and h i s group, and c o n f i r m e d by o t h e r s ( C e g a l i s & Sweeney, 1979; L e v i n , L i p t o n , & Holzman, 1981; L i p t o n , L e v i n , & Holzman, 1980; M i a l e t & P i c h o t , 1981). In the Holzman e t a l . (1974) study d e v i a n t eye t r a c k i n g was f o u n d i n 52% o f r e c e n t l y h o s p i t a l i z e d s c h i z o p h r e n i c p a t i e n t s (n=46); 85% o f c h r o n i c s c h i z o p h r e n i c p a t i e n t s ( n = 2 9 ) ; 2 2 % o f m a n i c d e p r e s s i v e s (n=9); 21% o f non - p s y c h o t i c p s y c h i a t r i c p a t i e n t s (n=19); 45% o f f i r s t d e g r e e r e l a t i v e s o f s c h i z o p h r e n i c p a t i e n t s (n=34); 11% o f f i r s t d e g r e e r e l a t i v e s o f o t h e r p s y c h i a t r i c p a t i e n t s (n=19); and i n 8% o f n o r m a l c o n t r o l s (n=72). I a c o n o , Tuason, and Johnson (1981) found t h a t the performance o f r e m i t t e d s c h i z o p h r e n i c s was s i m i l a r t o t h a t found i n h o s p i t a l i z e d p a t i e n t s i n d i c a t i n g the SPEM d y s f u n c t i o n i s not simply a s t a t e v a r i a b l e o c c u r r i n g d u r i n g a p s y c h o t i c episode. I t i s f r e q u e n t l y acknowledged t h a t SPEM d y s f u n c t i o n i s not s p e c i f i c t o s c h i z o p h r e n i a and occurs i n s e v e r a l n e u r o l o g i c 6 d i s o r d e r s ( L e i g h , Newman, F o l s t e i n , L a s k e r , & J e n s e n , 198 3 ; Spohn, 1983; Yee, 1983) and i s p r e s e n t i n o t h e r p s y c h i a t r i c groups such as manic-depressives ( L e v i n , L i p t o n , Rothenberg & L i p t o n , 1981; L i p t o n e t a l . , 1980). D e s p i t e t h e l a c k o f s p e c i f i c i t y , SPEM d y s f u n c t i o n seems t o be more c h a r a c t e r i s t i c o f s c h i z o p h r e n i a t h a n o t h e r p s y c h o t i c groups and a l s o more p r e v a l e n t i n p s y c h o t i c d i s o r d e r s t h a n i n n o n p s y c h o t i c and normal groups. I t a l s o appears t h a t p r e v a l e n c e o f d i s r u p t e d p u r s u i t v a r i e s somewhat w i t h the c l i n i c a l c h a r a c t e r i s t i c s o f t h e p o p u l a t i o n ; a h i g h e r p r e v a l e n c e o f t r a c k i n g d e f i c i t has been noted i n c h r o n i c p a t i e n t s ( L i p t o n e t a l . , 1983). S i g n i f i c a n c e Of SPEM Dysfunction i n Schizophrenia The t w i n s t u d i e s and f a m i l y s t u d i e s o f H o l z m a n and c o l l e a g u e s and t h e t w i n s t u d i e s o f Iacono and Lykken le n d c o n s i d e r a b l e weight t o the p r o p o s i t i o n t h a t d e v i a n t p u r s u i t t r a c k i n g may s e r v e as a g e n e t i c marker f o r s c h i z o p h r e n i a . While t h i s p a r t i c u l a r aspect o f the SPEM l i t e r a t u r e w i l l not be f u r t h e r p u r s u e d a t t h i s t i m e i t should be noted t h a t a c o n s i d e r a b l e p r o p o r t i o n o f eye movement r e s e a r c h i n s c h i z o -p h r e n i a has been concerned w i t h g e n e t i c hypotheses. Abnormal SPEM have been r e p o r t e d i n Par k i n s o n ' s d i s e a s e ( L e i g h e t a l . , 1983) and i n Alzheimer.'s-type dementia (Hutton, Nagel, & Loewenson, 1984; Jones, F r i e d l a n d , K o s s , S t a r k , & Thompkins-Ober, 1983). Corvera, T o r r e s - C o u r t n e y , and Lopez-Rios (1973) r e p o r t e d t h a t 73% o f a l a r g e group (n=325) o f 7 p a t i e n t s w i t h a v a r i e t y o f n e u r o l o g i c a l d i s o r d e r s showed smooth p u r s u i t a b n o r m a l i t i e s . As SPEM d i s r u p t i o n s are o f t e n found t o be a s s o c i a t e d w i t h d i f f u s e n e u r o l o g i c a l d i s o r d e r s i t seems p o s s i b l e t h a t v e n t r i c u l a r e n l a r g e m e n t and p o o r eye t r a c k i n g p e r f o r m a n c e m i g h t be a s s o c i a t e d i n s c h i z o p h r e n i c p a t i e n t s . On t h e o t h e r hand, L e v i n e t a l . (1981a) have h y p o t h e s i z e d t h a t the t r a c k i n g i m p a i r m e n t o f s c h i z o p h r e n i c p a t i e n t s i s the r e s u l t o f a l o c a l i z e d neuropathology i n the f r o n t a l l o b e s . They s u g g e s t t h a t d i s o r d e r o f a ' s a c c a d i c i n h i b i t i o n system' l o c a t e d i n the f r o n t a l eye f i e l d s may be the l o c u s o f the smooth p u r s u i t t r a c k i n g impairment. To d a t e , two s t u d i e s have i n v e s t i g a t e d the a s s o c i a t i o n between SPEM and l a t e r a l v e n t r i c l e s i z e i n s c h i z o p h r e n i c p a t i e n t s . Weinberger and Wyatt (1982) r e p o r t some p r e l i m i n a r y r e s u l t s o f a comparison o f t r a c k i n g p r o f i c i e n c y between 20 s c h i z o p h r e n i c p a t i e n t s w i t h normal v e n t r i c l e s and 14 p a t i e n t s w i t h e n l a r g e d v e n t r i c l e s . S i x t y f o u r p e r c e n t (9/14) o f t h e p a t i e n t s w i t h l a r g e v e n t r i c l e s showed i m p a i r e d t r a c k i n g compared w i t h 30% (6/20) o f t h e p a t i e n t s w i t h n o r m a l ven-t r i c l e s . B a r t f a i e t a l . (1985) r a t e d eye t r a c k i n g performance o f 17 s c h i z o p h r e n i c s on a 5 p o i n t s c a l e . On t h e b a s i s o f t h e i r r a t i n g system they r e p o r t t h a t 83% o f t h e i r sample were i m p a i r e d on t h e eye t r a c k i n g t a s k . V e n t r i c l e s i z e was a s s e s s e d by a l i n e a r measure o f t h e f r o n t a l h o r n s o f the l a t e r a l v e n t r i c l e s . B a r t f a i e t a l . r e p o r t t h a t few p a t i a n t s 8 had abnormal v e n t r i c l e s . No s i g n i f i c a n t r e l a t i o n s h i p was found between v e n t r i c l e s i z e and eye t r a c k i n g . Summary-SPEM Smooth p u r s u i t t r a c k i n g has been found t o be abnormal i n 50% t o 80% o f s c h i z o p h r e n i c s and about 45% o f t h e i r f i r s t d e g r e e r e l a t i v e s . I m p o r t a n t f e a t u r e s o f t h e i m p a i r m e n t i n c l u d e t h e f o l l o w i n g : 1) i t a p p e a r s t o be r e l a t i v e l y independent o f v o l u n t a r y a t t e n t i o n and i s not simply a r e s u l t o f low m o t i v a t i o n ; 2) i t seems to be a t r a i t which i s s t a b l e over time and independent o f the p a t i e n t s ' c l i n i c a l s t a t u s ; 3) i t does not appear t o be caused or a f f e c t e d by a n t i p s y c h o t i c m e d i c a t i o n ; 4) w h i l e not s p e c i f i c t o s c h i z o p h r e n i a i t appears more s t r o n g l y a s s o c i a t e d w i t h t h a t d i a g n o s t i c group than any ot h e r p s y c h i a t r i c d i s o r d e r s ; 5) i t has a low base r a t e i n the normal p o p u l a t i o n (about 8%); 6) i t shows a h i g h d e g r e e o f h e r i t a b i l i t y both i n normal i d e n t i c a l twins and i n monozygotic t w i n s d i s c o r d a n t f o r s c h i z o p h r e n i a ; 7) s i m i l a r t y p e s o f impairment are seen i n some n e u r o l o g i c a l d i s o r d e r s w i t h known s i t e s o f pathology, which may p r o v i d e some n e u r o a n a t o m i c a l i n f o r m a t i o n u s e f u l t o u n d e r s t a n d i n g s c h i z o p h r e n i a . In a d d i t i o n , t h e r e i s growing u n d e r s t a n d i n g and consensus on the m e t h o d o l o g i c a l i s s u e s i n v o l v e d i n measurement and s c o r i n g o f eye movement r e c o r d s . In a l l l i k e l i h o o d t h i s w i l l l e a d to a more p r e c i s e u n d e r s t a n d i n g o f what i s d e v i a n t i n d e v i a n t eye t r a c k i n g . 9 CT Scan Findings D e f i n i t i o n The s e a r c h f o r s t r u c t u r a l a b n o r m a l i t i e s i n the b r a i n s o f s c h i z o p h r e n i c s began s h o r t l y a f t e r K r a e p e l i n d e s c r i b e d t h e syndrome o f dementia praecox. Post-mortem s t u d i e s c a r r i e d out from the 1920s i n t o the 1950s y i e l d e d some p o s i t i v e f i n d i n g s , p a r t i c u l a r l y decreased c o r t i c a l c e l l and nerve f i b r e d e n s i t y . However, thes e d e f i c i t s were soon r e c o g n i z e d as n o n s p e c i f i c to s c h i z o p h r e n i a t h e r e b y d i s c o u r a g i n g f u r t h e r e f f o r t i n t h i s d i r e c t i o n (Seidman, 1983). CT scan s t u d i e s w i t h s c h i z o p h r e n i c p a t i e n t s are a f a i r l y new a d d i t i o n t o the l i t e r a t u r e h a v ing f i r s t appeared i n 1976 ( J o h n s t o n e , Crow, F r i t h , Husband, & K r e e l , 1976). S e v e r a l a s p e c t s o f b r a i n s t r u c t u r e have been i n v e s t i g a t e d w i t h the CT s c a n i n c l u d i n g l a t e r a l v e n t r i c l e s i z e , t h i r d v e n t r i c l e s i z e , p r o m i n e n c e o f c o r t i c a l s u l c i , c e r e b e l l a r a t r o p h y , and h e m i s p h e r i c asymmetry. The measure most f r e q u e n t l y u t i l i z e d t o date i s l a t e r a l v e n t r i c l e s i z e , o f t e n expressed as a r a t i o o f v e n t r i c l e area to t o t a l b r a i n area (termed v e n t r i c l e b r a i n r a t i o or VBR) on the s c a n s e c t i o n w h i c h shows t h e l a t e r a l v e n t r i c l e s a t t h e i r l a r g e s t . There i s i n c r e a s e d i n t e r e s t i n r e c e n t s t u d i e s i n s u l c a l prominence as a measure o f c o r t i c a l a t r o p h y . U n f o r t u n a t e l y t h i s a s p e c t o f b r a i n s t r u c t u r e i s d i f f i c u l t t o a s s e s s from CT s c a n s and i s c o n s i d e r e d by 10 r a d i o l o g y e x p e r t s t o p r e s e n t more complex measurement problems than v e n t r i c u l a r measures ( B i r d , 1982). L a t e r a l v e n t r i c u l a r enlargement (LVE) i s c o n s i d e r e d t o be an index o f n o n - s p e c i f i c a l t e r a t i o n s i n gross b r a i n s t r u c t u r e . Weinberger and Wyatt (1982) s t a t e " i t i s a b i o l o g i c a l marker o f a p a s t o r p r e s e n t b r a i n d i s o r d e r , u s u a l l y one i n v o l v i n g e i t h e r d e g e n e r a t i o n o f b r a i n t i s s u e o r o b s t r u c t i o n t o c e r e b r o s p i n a l f l u i d c i r c u l a t i o n " (p.506). V e n t r i c u l a r enlargement a s s o c i a t e d w i t h d i s o r d e r s such as d e m e n t i a i s o f t e n q u i t e o b v i o u s on a CT s c a n ( e . g . , VBRs ra n g i n g from 16 t o 30 i n demented p a t i e n t s compared w i t h a mean VBR o f 4 i n c o n t r o l s u b j e c t s ) . W e i n b e r g e r , T o r r e y , Neophytides, and Wyatt (1979a) p o i n t o u t t h a t t h i s s o r t o f d r a m a t i c s t r u c t u r a l change i s n o t t h e s o r t o f v e n t r i c u l a r e n l a r g e m e n t s e e n i n s c h i z o p h r e n i c p a t i e n t s : " V e n t r i c u l a r enlargement seen i n s c h i z o p h r e n i c p a t i e n t s i s modest and may be e a s i l y o v e r l o o k e d . In f a c t , mean v e n t r i c u l a r s i z e f o r these p a t i e n t s f a l l s w i t h i n the normal range f o r i n d i v i d u a l s a pproximately 70 years o l d " (p.738). D e f i n i n g abnormal LVE i n s c h i z o p h r e n i c p o p u l a t i o n s has proved d i f f i c u l t . L a b o r a t o r i e s d i f f e r i n the type o f scanner used, scanning procedures, s c o r i n g methods, c u t o f f s c o r e used t o d e f i n e a b n o r m a l i t y , and c o m p o s i t i o n o f p a t i e n t and comparison groups (Andreasen, Smith, Jacoby, Dennert, & Olson, 1982; J e r n i g a n , Z a t z , Moses, & Berger, 1982a; Maser & K e i t h , 1983). R e c e n t l y t h e r e i s e v i d e n c e o f e f f o r t by t h e major 11 p s y c h i a t r i c CT l a b o r a t o r i e s t o s t a n d a r d i z e procedures as much as p o s s i b l e (Maser & K e i t h , 1983). S t u d i e s by Penn, B e l a n g e r , and Y a s n o f f (1977) and by J e r n i g a n e t a l . (1982a) have demonstrated t h a t measures o f VBR u s i n g p l a n i m e t r y o r computer d e r i v e d a r e a on a s i n g l e c u t t h r o u g h t h e body o f t h e l a t e r a l v e n t r i c l e s p r o v i d e s an e s t i m a t e o f v e n t r i c u l a r s i z e which c o r r e l a t e s h i g h l y w i t h more s o p h i s t i c a t e d computer d e r i v e d t o t a l volume e s t i m a t e s . While VBR o b t a i n e d by p l a n i m e t r y or computer appears t o be a v a l i d measure o f v e n t r i c u l a r volume and has been demonstrated t o have h i g h i n t e r - r a t e r r e l i a b i l i t y w i t h i n l a b o r a t o r i e s , t h e r e are d i f f e r e n c e s between r e s e a r c h groups, which make i t unwise t o compare raw v a l u e s . ( J e r n i g a n e t a l . 1982a) U n t i l o b j e c t i v e s t a n d a r d i z e d s c o r i n g procedures are a v a i l a b l e f o r u t i l i z a t i o n by groups w i s h i n g t o compare f i n d i n g s , a s h o r t t e r m s o l u t i o n i s c o l l e c t i o n o f c o n t r o l group data by each l a b o r a t o r y a g a i n s t which they can compare the data from t h e i r c l i n i c a l p o p u l a t i o n s . Weinberger and c o l l a b o r a t o r s i n the N a t i o n a l I n s t i t u t e o f M e n t a l H e a l t h (NIMH) CT s c a n g r o u p h a v e p r o v i d e d two o p e r a t i o n a l d e f i n i t i o n s o f LVE; 1) a VBR i n excess o f 2 SD above a c o n t r o l group mean, and 2) VBR g r e a t e r than 10. While the f i r s t d e f i n i t i o n takes account o f d i f f e r e n t p r a c t i c e s i n d i f f e r e n t l a b o r a t o r i e s , the second d e f i n i t i o n i s based on the f i n d i n g s o f Synek and Reuben (1976) and o t h e r s t h a t VBRs i n excess o f 10 occur i n l e s s than 5% o f the normal p o p u l a t i o n . 12 Both t h e s e d e f i n i t i o n s are w i d e l y used, but Andreasen e t a l . ( 1 9 8 2 b ) h a v e commented t h a t t h e y may be t o o s t r i n g e n t , p a r t i c u l a r l y i n p r e l i m i n a r y s t a g e s o f CT r e s e a r c h i n s c h i z o p h r e n i a . • Prevalence of L a t e r a l V e n t r i c u l a r Enlargement (LVE) Johnstone e t a l . (1976) and W e i n b e r g e r e t a l . ( 1979a) were t h e f i r s t r e s e a r c h groups to undertake c o n t r o l l e d CT scan studies' w i t h s c h i z o p h r e n i c p a t i e n t s . The J o h n s t o n e e t a l . sample c o n s i s t e d o f 17 male c h r o n i c p a t i e n t s (mean age 58y) and the Weinberger e t a l . sample c o n t a i n e d 65 p a t i e n t s a l l under the age o f 50; both s t u d i e s found approx. 50% o f the s c h i z o p h r e n i c p a t i e n t s evidenced e n l a r g e d l a t e r a l v e n t r i c l e s r e l a t i v e t o c o n t r o l s . Reveley (1985) l i s t s 26 s t u d i e s con-d u c t e d between 1976 and 1985 w h i c h have r e p o r t e d l a t e r a l v e n t r i c u l a r enlargement i n samples o f s c h i z o p h r e n i c p a t i e n t s . Many o f the s t u d i e s c i t e d by Reveley d i d not i n c l u d e n o r m a l c o n t r o l g r o u p s s c a n n e d on t h e same e q u i p m e n t as t h e s c h i z o p h r e n i c p a t i e n t s and many i n v e s t i g a t o r s a s s e s s e d v e n t r i c u l a r enlargement by methods other than VBR. Boronow, P i c k a r , Ninan, Roy e t a l . (1985) r e v i e w e d 11 s t u d i e s w h i c h i n c l u d e d a normal c o n t r o l group and r e p o r t e d v e n t r i c l e s i z e i n terms o f VBR. N i n e o f t h e s e s t u d i e s r e p o r t e d s i g n i f i c a n t l y l a r g e r mean VBRs i n t h e i r s c h i z o p h r e n i c samples — r a n g i n g from 35% t o 207% — g r e a t e r than the mean VBRs f o r t h e c o n t r o l g r o u p s . The a v e r a g e p e r c e n t a g e o f 13 p a t i e n t s w i t h a VBR g r e a t e r than 2 SDs above the c o n t r o l group mean was 3 8% ( r a n g e 6% to 90%). Recent c o n t r o l l e d s t u d i e s have found p r e v a l e n c e r a t e s o f s i g n i f i c a n t l a t e r a l v e n t r i c u l a r e n l a r g e m e n t r a n g i n g from 15% ( W i l l i a m s , Reveley, Kolakowska, A r l e n , & Mandelbrote, 1985) t o 7% (Boronow e t a l . , 1985). In a d d i t i o n t o marked v a r i a b i l i t y i n p r e v a l e n c e r a t e s f o r s t u d i e s w i t h p o s i t i v e f i n d i n g s t h e r e a r e a l s o p u b l i s h e d s t u d i e s which f a i l e d t o f i n d v e n t r i c u l a r enlargement (Benes, Pearson, Jones, LeMay, Cohen, & L i p i n s k i , 1982; Gluck, Radu, Mundt, & Gerhardt, 1980; J e r n i g a n e t a l . , 1982; Largen, Smith, C a l d e r o n , Baumgartner, S c h o o l a r , & Ravichandran, 19 84; Shima, Kanba, Masuda, Tsukumo, K i t a m u r a & A s a i , 1985; T r i m b l e , & K i n g s l e y , 1978). I n a p a p e r p u b l i s h e d s h o r t l y a f t e r an NIMH sponsored workshop on the CT scan i n P s y c h i a t r y (see Maser & K e i t h 1983, f o r r e v i e w ) , L u c h i n s (1982) d i s c u s s e s some sample charac-t e r i s t i c s which might account f o r the r e p o r t e d d i s p a r i t i e s . C omparing r e s e a r c h samples w i t h r e s p e c t t o locked-ward vs. open-ward t r e a t m e n t , r e s p o n s e t o n e u r o l e p t i c m e d i c a t i o n , n e u r o p s y c h o l o g i c a l s t a t u s , l e v e l s o f s o c i a l , o c c u p a t i o n a l and s e l f - c a r e f u n c t i o n i n g , and c h r o n i c i t y s u g g e s t t h a t samples c o m p r i s e d o f s u b j e c t s r e l a t i v e l y more i m p a i r e d on t h e s e dimensions are the samples most l i k e l y t o evidence a g r e a t e r p r e v a l e n c e o f v e n t r i c u l a r e n l a r g e m e n t . A r e c e n t paper by Smith & Iacono (1986) suggests t h a t the s e l e c t i o n and composi-t i o n o f c o n t r o l groups may be t h e c r i t i c a l f a c t o r i n d i f -f e r e n c e s between s t u d i e s i n p r e v a l e n c e o f LVE. In l i g h t o f t h e many m e t h o d o l o g i c a l f a c t o r s and s u b j e c t v a r i a b l e s which c o l l e c t i v e l y a f f e c t e s t i m a t e s o f the p r e v a l e n c e o f v e n t r i c u l a r enlargement, i t i s apparent t h a t a c l e a r u n d e r s t a n d i n g o f t h i s parameter w i l l r e q u i r e the f u r t h e r a c c u m u l a t i o n o f e v i d e n c e f r o m a w i d e v a r i e t y o f p a t i e n t samples and measurement t e c h n i q u e s . S i g n i f i c a n c e o f L a t e r a l V e n t r i c u l a r E n l a r g e m e n t i n  S c h i z o p h r e n i a The b r a i n s t r u c t u r e a b n o r m a l i t i e s observed i n CT scan i n v e s t i g a t i o n s w i t h p a t i e n t s are d e s c r i b e d by Weinberger and Wyatt (1982) as both s u b t l e and n o n s p e c i f i c . While s e v e r a l i n v e s t i g a t o r s r e p o r t t h a t a p r o p o r t i o n o f s c h i z o p h r e n i c s e vidence d e v i a n t l y l a r g e l a t e r a l v e n t r i c l e s , the s i g n i f i c a n c e o f LVE remains u n c l e a r . A r t i f a c t o r c o i n c i d e n c e ? Research which addresses the p o s s i b i l i t y t h a t LVE i s an a r t i f a c t , t o date, i s q u i t e c o n s i s -t e n t i n f i n d i n g t h a t LVE i n s c h i z o p h r e n i c p a t i e n t s cannot be accounted f o r simply on the b a s i s o f m e d i c a t i o n o r i n s t i t u -t i o n a l i z a t i o n h i s t o r y . LVE occurs i n p a t i e n t s who have never been medicated and/or have l i t t l e or no h i s t o r y o f i n s t i t u -t i o n a l i z a t i o n . S t u d i e s a l s o i n d i c a t e t h a t t h e r e i s no s i g n i f i c a n t c o r r e l a t i o n a l t r e n d i n c r o s s s e c t i o n a l samples between LVE and d u r a t i o n o f m e d i c a t i o n or i n s t i t u t i o n a l i z a t i o n per se, although t h i s p o s s i b i l i t y cannot be r u l e d out without 15 l o n g i t u d i n a l data (Johnstone, e t a l 1976 ; N a s r a l l a h , 1982; O wens, J o h n s t o n e , Crow, F r i t h , J a g o e & K r e e l , 1985; Weinberger, De L i s i , Purman, Targom & Wyatt, 1982). There i s c o n s i d e r a b l e and c o n v i n c i n g evidence t h a t LVE i s not simply an age dependent anomaly s i n c e i t has been found to o c c u r i n young s c h i z o p h r e n i f o r m p a t i e n t s ( S c h u l z , K o l l e r , et a l . , 1983; Weinberger e t a l . , 1982) and i n a number o f samples of young c h r o n i c p a t i e n t s (Golden, Moses, Zal a z o w s k i , e t a l . , 1980; K l i n g , K u r t z , T a c h i k i & Orzeck 1982/83; W e i n b e r g e r e t a l . , 1982). A d d r e s s i n g the p o s s i b i l i t y t h a t LVE i n s c h i z o p h r e n i a may be a c o i n c i d e n t a l o c c u r r e n c e i s made d i f f i c u l t by the l a c k o f independent l a r g e s c a l e e p i d e m i o l o g i c a l s t u d i e s o f v e n t r i c u l a r s i z e (Maser & K e i t h , 1983). However, t h e r e a r e numerous s m a l l e r s c a l e s t u d i e s i n many r e s e a r c h areas which are thought to p r o v i d e f a i r l y r e l i a b l e and v a l i d e s t i m a t e s o f t h e base r a t e o f LVE i n t h e g e n e r a l p o p u l a t i o n . Based a review of t h e s e s t u d i e s ; a) Weinberger, Wagner & Wyatt (1983) conclude t h a t VBR v a l u e s f o r normal c o n t r o l s are remarkably c o n s i s t e n t and a VBR o f 10 probably o c c u r s i n l e s s t h a t 5% o f n o r m a l i n d i v i d u a l s u n d e r 40 y e a r s o f age (Weinberger e t a l . , 1983 l i s t the mean VBRs f o r the c o n t r o l groups f o r 9 s t u d i e s , t o t a l c o n t r o l s u b j e c t n=329, x mean age = 29.8 + 8.7 y e a r s , x mean VBR = 3.9 + 0.8); b) Z a t z , J e r n i g a n & Ahumanda (1981) suggest t h a t t h e r e i n g e n e r a l v e n t r i c u l a r volume r e m a i n s c o n s t a n t 16 u n t i l age 60, s u g g e s t i n g t h a t spontaneously o c c u r r i n g marked changes i n v e n t r i c u l a r s i z e b e f o r e the 7th decade are u n u s u a l . I n summary, t h e c o n c l u s i o n t h a t LVE i s n o t a s i m p l e a r t i f a c t o f age, m e d i c a t i o n , and i n s t i t u t i o n a l i z a t i o n i s w e l l supported and w i d e l y accepted. C l i n i c a l c o r r e l a t e s o f LVE. C o n s i d e r a b l e r e s e a r c h has been concerned w i t h the i n v e s t i g a t i o n o f f a c t o r s which might prove t o be d e t e r m i n i n g c l i n i c a l / b e h a v i o r a l c o r r e l a t e s o f LVE. The work o f Crow, J o h n s t o n e and c o l l a b o r a t o r s p r o v i d e d a framework f o r the f i r s t s e r i e s o f such s t u d i e s . Crow (1982) and Crow, Cr o s s , Johnstone, and Owen (1982) proposed t h a t the d i s o r d e r c u r r e n t l y c a l l e d s c h i z o p h r e n i a might a c t u a l l y c o n s i s t o f two o v e r l a p p i n g syndromes w h i c h d i f f e r c o n s i d e r a b l y i n p r e s e n t i n g symptoms, c o u r s e , r e s p o n s e t o t r e a t m e n t , and p a t h o l o g i c a l p r o c e s s . Crow (1982) d e f i n e d a Type I syndrome as b e i n g c h a r a c t e r i z e d by p o s i t i v e symptoms ( d e l u s i o n s , h a l l u c i n a t i o n s , thought d i s o r d e r ) , acute s c h i z o p h r e n i a , good response to n e u r o l e p t i c drugs, r e v e r s i b l e outcome, and absence o f i n t e l l e c t u a l impairment. He p o s t u l a t e d t h a t the u n d e r l y i n g p a t h o l o g i c a l p r o c e s s might be i n c r e a s e d dopamine r e c e p t o r s . In c o n t r a s t , a Type I I syndrome was c h a r a c t e r i z e d by n e g a t i v e symptoms ( f l a t t e n i n g o f a f f e c t , p overty o f speech, l o s s of d r i v e ) , c h r o n i c s c h i z o p h r e n i a , poor response t o n e u r o l e p t i c s , i r r e v e r s i b l e outcome, and sometimes, i n t e l l e c t u a l impairment. The p o s t u l a t e d p a t h o l o g i c a l process i n Type I I s c h i z o p h r e n i a was h y p o t h e s i z e d t o be c e l l l o s s and s t r u c t u r a l changes i n the b r a i n . There a r e s e v e r a l s t u d i e s w h i c h have i n v e s t i g a t e d t h e s e and a s s o c i a t e d v a r i a b l e s u s i n g LVE as an independent v a r i a b l e . Andreasen, Olsen, Dennert, and Smith (1982a) found l a r g e v e n t r i c l e p a t i e n t had a p r e p o n d e r a n c e o f n e g a t i v e symptoms w h i l e s m a l l v e n t r i c l e p a t e n t s were c h a r a c t e r i z e d by p o s i t i v e symptoms. Weinberger, Cannon-Spoor, P o t k i n and Wyatt (1980) r e p o r t e d an a s s o c i a t i o n between CT scan a b n o r m a l i t i e s and premorbid r a t i n g s . Two s t u d i e s found v e n t r i c u l a r e n l a r g e -ment t o be a s s o c i a t e d w i t h p o o r r e s p o n s e t o n e u r o l e p t i c m e d i c a t i o n ( L u c h i n s , L e v i n e , & M e l t z e r , 1984; Weinberger, Bigelow, Kleinman, e t a l . , 19 80). D e s p i t e t h e s e r a t h e r p r o m i s i n g f i n d i n g s most r e s e a r c h w h i c h has f o l l o w e d t h e s e o r i g i n a l r e p o r t s has f a i l e d t o r e p l i c a t e t h e i r f i n d i n g s . Owen e t a l . (1985) found few c o r r e l a t e s o f v e n t r i c u l a r e n l a r g e m e n t i n a sample o f 112 i n s t i t u t i o n a l i z e d c h r o n i c s c h i z o p h r e n i c p a t i e n t s . P a t i e n t s w i t h n e g a t i v e symptoms, i n t e l l e c t u a l impairment, and poor drug-response d i d not have l a r g e r v e n t r i c l e s t h a n a matched group o f p a t i e n t s without these f e a t u r e s . W i l l i a m s e t a l . (1985) were unable t o f i n d an a s s o c i a t i o n between VBR and symptom t y p e ( i . e . p o s i t i v e / n e g a t i v e ) , response t o n e u r o l e p t i c s , d u r a t i o n o f i l l n e s s , o r c o g n i t i v e impairment i n . a sample o f s c h i z o p h r e n i c p a t i e n t s . However, t h i s r e s e a r c h group d i d f i n d t h a t s i g n i f i c a n t v e n t r i c u l a r e n l a r g e m e n t was most common i n t h e c h r o n i c p a t i e n t s i n t h e i r s a m p l e d e s p i t e t h e l a c k o f o v e r a l l 18 c o r r e l a t i o n between d u r a t i o n o f i l l n e s s and v e n t r i c u l a r e n l a r g e m e n t . A r e c e n t s t u d y by Boronow e t a l . (1985) i n v e s t i g a t e d the a s s o c i a t i o n between d r u g r e s p o n s e , a wide v a r i e t y o f c l i n i c a l f e a t u r e s , and b r a i n morphology i n a sample o f 30 s c h i z o p h r e n i c and s c h i z o - a f f e c t i v e p a t i e n t s . They were u n a b l e t o f i n d any s i g n i f i c a n t c o r r e l a t i o n s between c l i n i c a l v a r i a b l e s or drug response and v e n t r i c l e s i z e . In summary, i t appears t h a t the e a r l y hope t h a t v e n t r i -c u l a r enlargement might s e r v e as a b i o l o g i c a l marker f o r a subtype o f s c h i z o p h r e n i a c h a r a c t e r i z e d by a c l i n i c a l syndrome o f n e g a t i v e , symptoms, po o r r e s p o n s e t o m e d i c a t i o n , and s p e c i f i c t o poor outcome has not been supported by the most r e c e n t r e s e a r c h f i n d i n g s . C o g n i t i v e / n e u r o p s y c h o l o g i c a l f u n c t i o n and CT scan abnor- m a l i t i e s . In a d d i t i o n t o c l i n i c a l c o r r e l a t e s o f LVE, many r e -s e a r c h e r s have i n v e s t i g a t e d t h e p o s s i b i l i t y t h a t the b r a i n s t r u c t u r e a b n o r m a l i t i e s seen on CT scans o f s c h i z o p h r e n i c s may be a s s o c i a t e d w i t h i n t e l l e c t u a l and n e u r o p s y c h o l o g i c a l i m p a i r -ment. The tendency towards i n c r e a s i n g l y n e g a t i v e f i n d i n g s a c r o s s t i m e n o t e d i n t h e p r e v i o u s s e c t i o n on c l i n i c a l c o r -r e l a t e s o f v e n t r i c u l a r e n l a r g e m e n t a l s o a p p l i e s t o t h e a s s o c i a t i o n between c o g n i t i v e f u n c t i o n i n g and l a t e r a l ven-t r i c u l a r enlargement. Nonetheless CT scan a b n o r m a l i t i e s i n v e n t r i c l e and s u l c a l s i z e and c o g n i t i v e / n e u r o p s y c h o l o g i c a l d e f i c i t s have f r e q u e n t l y been r e p o r t e d to co-occur i n s c h i z o -p h r e n i c p a t i e n t s . Masser and K e i t h (1983) i n t h e i r r e p o r t on 19 the NIMH CT scan workshop c i t e Weinberger as s t a t i n g t h a t he "knew o f no p u b l i s h e d s t u d y showing LVE w i t h o u t c o g n i t i v e impairment" (p.275). While t h e r e are good grounds t o d i s a g r e e w i t h t h i s as an e n t i r e l y f a c t u a l s t a t e m e n t -- i n d e e d Weinberger e t a l . (1979) f a i l e d t o f i n d a r e l a t i o n s h i p between VBR and IQ s c o r e s — i t does appear t h a t c o g n i t i v e impairment f r e q u e n t l y occurs i n samples of p a t i e n t s who a l s o show CT scan a b n o r m a l i t i e s . B e f o r e p r e s e n t i n g t h e r e s e a r c h f i n d i n g s , two m e a s u r e m e n t / d e f i n i t i o n i s s u e s a r e worthy o f m e n t i o n . The f i r s t r e l a t e s t o the v a r i a b i l i t y i n both measures and d e f i -n i t i o n o f " c o g n i t i v e f u n c t i o n . " While t h e r e i s u n d o u b t e d l y o v e r l a p between the c o g n i t i v e f u n c t i o n s assessed on a mental s t a t u s examination, a standard IQ t e s t , and n e u r o p s y c h o l o g i c a l t e s t s , t h e r e i s c o n s i d e r a b l e r e s e a r c h t o i n d i c a t e t h a t these t e s t s a re not i n t e r c h a n g e a b l e measures o f the same f u n c t i o n s . I n c o n s i s t e n t f i n d i n g s and l o s s o f u s e f u l i n f o r m a t i o n may r e s u l t from t r e a t i n g t h e s e d i f f e r e n t measures as i n t e r -changeable i n d i c a n t s o f " c o g n i t i v e " f u n c t i o n . A second m e a s u r e m e n t / d e f i n i t i o n problem i n v o l v e s the use o f CT measures o f e i t h e r / b o t h v e n t r i c u l a r enlargement and s u l c a l prominence i n r e l a t i o n t o c o g n i t i v e f u n c t i o n . As w i l l be seen i n the s t u d i e s t o f o l l o w , both measures o f s t r u c t u r a l a b n o r m a l i t y have been found t o be a s s o c i a t e d w i t h i m p a i r e d c o g n i t i v e f u n c t i o n . U n f o r t u n a t e l y t h e i r r e l a t i o n t o each oth e r i s p o o r l y understood and s e v e r a l s t u d i e s have f a i l e d to 20 f i n d a s y s t e m a t i c r e l a t i o n s h i p between l a t e r a l v e n t r i c l e s i z e and s u l c a l p r o m i n e n c e ( e . g . N a s r a l l a h , Kuperman, Hamara & M c C a l l e y - W h i t t e r s , 1983a; P a n d u r a n g i , Dewan, Lee, e t a l . , 1984; Weinberger e t a l . 1979b). On the o t h e r hand K l i n g e t a l . (1982/83) and R i e d e r e t a l . (1983) d i d f i n d s i g n i f i c a n t c o v a r i a t i o n between LVE and s u l c a l prominence. Weinberger, T o r r e y , N e o p h y t i d e s , & Wyatt (1979a) have s u g g e s t e d t h a t t h e two a b n o r m a l i t i e s may be i n d e p e n d e n t p a t h o l o g i c a l p r o c e s s e s . N a s r a l l a h , K u p e r m a n , J a c o b y , M c C a l l e y - W h i t t e r s , & Hamara (1983b) have suggested t h a t the c l i n i c a l c o r r e l a t e s o f LVE and s u l c a l widening may d i f f e r , and t h a t s u l c a l w i d e n i n g may be more s t r o n g l y a s s o c i a t e d w i t h i n t e l l e c t u a l i m p a i r m e n t t h a n i s LVE. U n f o r t u n a t e l y t h e c o r t i c a l s u l c i a r e n o t p a r t i c u l a r l y w e l l - v i s u a l i z e d by CT procedures, compromising the v a l i d i t y o f t h i s i n d e x . Some s t u d i e s (eg. D o n n e l l y , W e i n b e r g e r , Waldman, & Wyatt, 1980; W e i n b e r g e r , T o r r e y , N e o p h y t i d e s , & Wyatt, 1979b) d e f i n e s t r u c t u r a l a b n o r m a l i t y as a s i g n i f i c a n t d i f f e r e n c e from the c o n t r o l group on any o f a number o f CT measures, i n c l u d i n g LVE and s u l c a l prominence, and f a i l t o a n a l y s e r e l a t i o n s h i p s w i t h dependent v a r i a b l e s s e p a r a t e l y f o r t h e d i f f e r e n t forms o f s t r u c t u r a l a b n o r m a l i t y . T h i s i s s u e may be found t r i v i a l i n the l o n g run; however, i t i s r e c e i v i n g c o n s i d e r a b l e a t t e n t i o n i n t h e l i t e r a t u r e on i n t e l l e c t u a l changes i n a g i n g and d e m e n t i a as a s s o c i a t e d w i t h c o r t i c a l a t r o p h y ( s u l c a l e n l a r g e m e n t ) and v e n t r i c l e e n l a r g e m e n t . I n t h i s a r e a 21 i n v e s t i g a t o r s are a l s o f i n d i n g t h a t the two measures seem t o have d i f f e r e n t c l i n i c a l c o r r e l a t e s ( B i r d , 1982; Kaszniak, Garron, Fox, Bergen, & Huckman, 1979). The o r i g i n a l CT scan study c a r r i e d out by Johnstone e t a l . (1976) i n c o r p o r a t e d measures o f c o g n i t i v e f u n c t i o n i n g s i m i l a r t o a mental s t a t u s exam (the Withers and Hi n t o n t e s t b a t t e r y ) and foun d a c o r r e l a t i o n o f -0.70 (n=14) between v e n t r i c l e s i z e and c o g n i t i v e f u n c t i o n . In the second CT study W e i n b e r g e r e t a l . (1979a) c o m p l e t e d WAIS t e s t i n g w i t h 19 i n d i v i d u a l s i n t h e i r sample o f 7 3 mixed p s y c h i a t r i c p a t i e n t s (WAIS s c o r e s a v a i l a b l e f o r 14 c h r o n i c s c h i z o p h r e n i c p a t i e n t s and 5 "other" p s y c h i a t r i c p a t i e n t s ) . They found the s c h i z o -p h r e n i c p a t i e n t s performed s i g n i f i c a n t l y worse than the oth e r p s y c h i a t r i c p a t i e n t s on a l l s u b t e s t and IQ measures, but found no s i g n i f i c a n t r e l a t i o n s h i p between v e n t r i c l e s i z e and any WAIS s c o r e s i n t h e c h r o n i c s c h i z o p h r e n i c g r o u p . S i m i l a r f i n d i n g s are r e p o r t e d by K l i n g e t a l . (1982/1983) who ad-m i n i s t e r e d a compete "Mental S t a t u s i n Neurology" examination and found t h a t w h i l e s c h i z o p h r e n i c p a t i e n t s s c o r e d lower than would be expected i n a normal p o p u l a t i o n t h e r e was no asso-c i a t i o n between mental s t a t u s s c o r e s and VBR. D o n n e l l e y e t a l . (1980) a d m i n i s t e r e d the H a l s t e a d - R e i t a n B a t t e r y (HRB) and the WAIS t o 15 young c h r o n i c s c h i z o p h r e n i c p a t i e n t s on whom CT s c a n measures o f LVE, w i d t h o f i n t e r h e m i s p h e r i c f i s s u r e s , width o f S y l v i a n f i s s u r e s , and w i d t h o f c o r t i c a l s u l c i were a v a i l a b l e . T e s t s c o r e s on the HRB were combined i n a s t a n d a r d i z e d f a s h i o n to form the Average Impairment R a t i n g (AIR) ( R u s s e l l , Neuringer, & G o l d s t e i n , 1970). In the group o f 15 p a t i e n t s , 8 had a b n o r m a l s c a n s and 7 showed no a b n o r m a l i t y — where CT abn o r m a l i t y was d e f i n e d as enlargement t h a t exceeded the c o n t r o l range f o r any o f the f o u r measures o f b r a i n s t r u c t u r e l i s t e d above. U t i l i z i n g a c u t t i n g s c o r e on the AIR (5 p o i n t s c a l e ) o f 1.55 (which f a l l s between "average" p e r f o r m a n c e a n d " m i l d l y i m p a i r e d " p e r f o r m a n c e ) t h e i n v e s t i g a t o r s were a b l e t o p r e d i c t CT s t a t u s w i t h an o v e r a l l h i t r a t e o f 80% ( 1 2 / 1 5 ) . T h e y a l s o f o u n d s i g n i f i c a n t d i f f e r e n c e s between the normal and abnormal CT scan groups on e i g h t o f t h e e l e v e n s u b t e s t s o f t h e WAIS (Compr e h e n s i o n , A r i t h m e t i c , S i m i l a r i t i e s , D i g i t Span, B l o c k D e s i g n , P i c t u r e A r r a n g e m e n t and O b j e c t A s s e m b l y ) , and on a l l t h r e e IQ components. I t i s u n f o r t u n a t e t h a t they f a i l e d t o s p e c i f y the r a t e s o f a b n o r m a l i t y f o r each o f the f o u r measures o f b r a i n s t r u c t u r e . A s e r i e s o f t h r e e s t u d i e s by C . J . G o l d e n and c o l l a -b o r a t o r s show i m p r e s s i v e c l a s s i f i c a t i o n h i t r a t e s and c o r -r e l a t i o n s between p e r f o r m a n c e on the L u r i a Nebraska Neuro-p s y c h o l o g i c a l B a t t e r y (LNNB) and VBR. Golden e t a l . (1980a) assessed a group o f c h r o n i c s c h i z o p h r e n i a p a t i e n t s (mean age 32.3) w i t h the LNNB. H a l f o f the s u b j e c t s had been r e f e r r e d because o f suspected b r a i n damage. The VBR w i t h i n the e n t i r e group ranged from 1 to 24 (mean 12.0 + 5 ) . These r a t i o s are c o n s i d e r a b l y h i g h e r t h a n seen i n o t h e r CT s t u d i e s and a r e b e l i e v e d t o r e f l e c t a s y s t e m a t i c d i f f e r e n c e i n s c o r i n g p r o c e d u r e s between t h e N e b r a s k a group and o t h e r CT l a b s (Weinberger, Wagner, & Wyatt, 1983). U n f o r t u n a t e l y , Golden e t a l . (1980a) d i d n o t have a c o n t r o l group f o r t h i s s t u d y , making c o m p a r i s o n o f t h e i r VBR s c o r e s w i t h o t h e r samples unwise. They d i d , however, s t a t e t h a t u s i n g a VBR c u t o f f o f >10 as a d e f i n i t i o n o f abnormality - 60% o f t h e i r sample would be c l a s s i f i e d as b r a i n damaged. A m u l t i p l e r e g r e s s i o n u s i n g the e i g h t LNNB s c a l e s which had s i g n i f i c a n t c o r r e l a t i o n s w i t h VBR ( t a c t i l e , e x p r e s s i v e , r e a d i n g , w r i t i n g , a r i t h m e t i c , pathognomic, l e f t hemisphere, and r i g h t h e m i s p h e r e ) gave a m u l t i p l e c o r r e l a t i o n o f 0.72. G o l d e n e t a l . ( 1 9 8 0 a ) i n v e s t i g a t e d t h e a c c u r a c y o f a s e t o f i n t e r p r e t i v e r u l e s a p p l i e d t o LNNB f o r de t e r m i n i n g the presence o f LVE and s u l c a l enlargement. Of 42 p a t i e n t s assessed, 26 were d i a g n o s e d as normal and 16 as abnormal by the LNNB; 20 were r a t e d as having e n l a r g e d v e n t r i c l e s and 22 as h a v i n g n o r m a l v e n t r i c l e s ; 16 were r a t e d as showing s u l c a l prominence and 26 having normal s u l c i . The o v e r a l l h i t r a t e f o r p r e d i c t i o n o f LVE from LNNB performance was 81%. O v e r a l l agreement f o r s u l c a l prominence was 90%. Golden, Maclnnes, A r i a l , R u e d r i c h , Chu, Coffman, G r a b e r , and B l o c k (1982) a p p l i e d t h e r u l e s d e r i v e d i n the Golden e t a l . (1980b) study t o a c r o s s - v a l i d a t i o n sample o f 43 c h r o n i c s c h i z o p h r e n i c s . Using the r u l e s t o p r e d i c t LVE they a c h i e v e an o v e r a l l h i t r a t e o f 77% w i t h no f a l s e n e g a t i v e s and ten f a l s e p o s i t i v e s . The m u l t i p l e c o r r e l a t i o n between the 14 LNNB s c a l e s and VBR was 0.76, very s i m i l a r t o t h a t o b t a i n e d i n t h e G o l d e n e t a l . (1980a) s t u d y . D i f f e r e n c e s between the Golden e t a l . (1980a) and the Golden e t a l . (1982b) s t u d i e s are found i n -the s p e c i f i c s c a l e s which c o r r e l a t e w i t h VBR and the magnitude o f the c o r r e l a t i o n s . F i v e o f the 14 LNNB s c a l e s were s i g n i f i c a n t l y c o r r e l a t e d w i t h VBR i n both s t u d i e s , w h i l e n o n - o v e r l a p p i n g s e t s o f t h r e e s c a l e s were s i g n i f i c a n t i n one study but not the o t h e r . The VBR - LNNB c o r r e l a t i o n s r e p o r t e d by Golden's group a r e i m p r e s s i v e l y h i g h . W h i l e t h e 1980 s t u d y had s a m p l e c h a r a c t e r i s t i c s w h i c h m i g h t be e x p e c t e d t o boost the c o r -r e l a t i o n , ( h a l f t h e s u b j e c t s had been r e f e r r e d f o r n e u r o -p s y c h o l o g i c a l assessment w h i l e the o t h e r h a l f were b e l i e v e d to be f r e e o f b r a i n d y s f u n c t i o n ) the 1982 study was not flawed by t h i s s o r t o f sampling procedure and was n o n e t h e l e s s a b l e to r e p l i c a t e the h i g h degree o f a s s o c i a t i o n found i n the e a r l i e r study. R e c e n t a d d i t i o n s t o t h e l i t e r a t u r e f a i l e d t o f i n d e n l a r g e d v e n t r i c l e s t o be p r e d i c t i v e o f i m p a i r e d n e u r o -p s y c h o l o g i c a l performance. W i l l i a m s e t a l . (1985) s t u d i e d a group o f 40 s c h i z o p h r e n i c and s c h i z o - a f f e c t i v e p a t i e n t s . The mean VBR o f the p a t i e n t sample was s i g n i f i c a n t l y g r e a t e r than t h a t o f t h e c o n t r o l g r o u p and 15% o f t h e p a t i e n t s had v e n t r i c l e s more than 2 s.d. above the c o n t r o l group mean. Of 36 p a t i e n t s g i v e n a c o g n i t i v e a s s e s s m e n t , 13 (36%) were c l a s s i f i e d as i m p a i r e d . C o g n i t i v e i m p a i r m e n t was n o t a s s o c i a t e d w i t h v e n t r i c u l a r e n l a r g e m e n t i n t h e s e p a t i e n t s . Owens e t a l . (1985) r e p o r t f i n d i n g s o b t a i n e d from a study c o n d u c t e d w i t h a sample o f 112 i n s t i t u t i o n a l i z e d c h r o n i c s c h i z o p h r e n i c p a t i e n t s and 5 comparison groups c o n s i s t i n g o f 18 o u t - p a t i e n t s c h i z o p h r e n i c s , 8 f i r s t - e p i s o d e s c h i z o p h r e n i c s , 33 p a t i e n t s w i t h b i p o l a r d i s o r d e r , and 19 n e u r o t i c o u t p a t i e n t s . Among t h e s i x d i a g n o s t i c g r o u p s t h e o n l y s i g n i f i c a n t group d i f f e r e n c e s i n VBRs were between the c h r o n i c s c h i z o p h r e n i c i n p a t i e n t s and the n e u r o t i c o u t p a t i e n t s . W i t h i n t h e i n p a t i e n t s c h i z o p h r e n i c sample, v e n t r i c u l a r s i z e and c o g n i t i v e f u n c t i o n were not l i n e a r l y r e l a t e d . However, Owen e t a l . f o u n d a s i g n i f i c a n t c u r v i l i n e a r r e l a t i o n s h i p between v e n t r i c u l a r s i z e and s c o r e s on t h e i r measure o f c o g n i t i v e f u n c t i o n ( t h e W i t h e r s and Hinton) . There was an excess o f p a t i e n t s w i t h impaired c o g n i t i v e f u n c t i o n at both extremes o f v e n t r i c l e s i z e . DeMeyer, Gilmore, DeMeyer, Hendrie, Edwards, and Franco (1984) r e p o r t s i g n i f i c a n t c o r r e l a t i o n s between VBR and a v e r y e x t e n s i v e b a t t e r y o f n e u r o p s y c h o l o g i c a l t e s t s (a f u l l Ha 1 s t e a d - R e i t a n B a t t e r y , L u r i a - N e b r a s k a N e u r o p s y c h o l o g i c a l B a t t e r y , and Weschler A d u l t I n t e l l i g e n c e S c a l e ) s u c h t h a t i n d i v i d u a l s w i t h l a r g e r VBRs p e r f o r m e d s i g n i f i c a n t l y b e t t e r than i n d i v i d u a l s w i t h s m a l l v e n t r i c l e s . The s u b j e c t s i n t h i s study were o f mixed p s y c h i a t r i c d i a g n o s i s and as such the r e s u l t s are not d i r e c t l y comparable t o s t u d i e s o f p u r e l y s c h i z o p h r e n i c p a t i e n t s . 26 Summary of CT Scan Findings i n Schizophrenia Many aspects o f CT scan i n v e s t i g a t i o n s w i t h s c h i z o p h r e n i c samples have been d i s c u s s e d i n t h i s review and may be b r i e f l y summarized by t h e f o l l o w i n g : 1) S e v e r a l a s p e c t s o f b r a i n s t r u c t u r e a re assessed by CT scan. In s c h i z o p h r e n i a the two most f r e q u e n t l y i n v e s t i g a t e d v a r i a b l e s are l a t e r a l v e n t r i c u l a r e n l a r g e m e n t (LVE) and s u l c a l widening or prominence. 2) A commonly used index o f v e n t r i c l e s i z e i s the v e n t r i c l e b r a i n r a t i o (VBR) d e r i v e d from area measures o f the v e n t r i c l e s and the i n n e r t a b l e o f t h e s k u l l on t h e CT s l i c e showing t h e l a t e r a l v e n t r i c l e s at t h e i r l a r g e s t . 3) V e n t r i c u l a r e n l a r g e -ment i s u s u a l l y d e f i n e d as e i t h e r a VBR g r e a t e r t h a n two s t a n d a r d d e v i a t i o n s above a c o n t r o l group mean, or i n some cases, a VBR>10. 4) LVE i s s u b t l e i n s c h i z o p h r e n i c samples a n d o f t e n w o u l d n o t be c l a s s i f i e d a s a b n o r m a l by n e u r o r a d i o l o g i s t s although i t i s b e l i e v e d t h a t a VBR o f 10 occurs i n l e s s than 5% o f a normal p o p u l a t i o n . 5) Pr e v a l e n c e r a t e s vary w i d e l y a c r o s s s t u d i e s (0% t o 60% range). I t has been s u g g e s t e d t h a t r e p r e s e n t a t i v e samples o f s c h i z o p h r e n i c p a t i e n t s may evidence a p r e v a l e n c e r a t e o f 20%. 6) LVE i s not s p e c i f i c t o s c h i z o p h r e n i c p a t i e n t s but i s f o u n d i n o t h e r p s y c h i a t r i c p o p u l a t i o n s , p a r t i c u l a r l y manic d e p r e s s i v e s . 7) LVE i s fou n d i n young and o l d p a t i e n t s , c h r o n i c and f i r s t e p i s o d e , t h o s e w i t h l o n g h i s t o r i e s o f d r u g and s o m a t i c treatments and h o s p i t a l i z a t i o n , and those w i t h no h i s t o r y o f such i n t e r v e n t i o n s . I t i s t h e r e f o r e n o t b e l i e v e d t o be a simple a r t i f a c t o f age, m e d i c a t i o n , or i n s t i t u t i o n a l i z a t i o n . However, t h e r e i s r e a s o n t o e x p e c t t h a t LVE may be more p r e v a l e n t i n more s e r i o u s l y - i l l p a t i e n t s t han i n t h o s e w i t h m i l d e r forms o f t h e d i s o r d e r . 8) LVE and o t h e r s t r u c t u r a l a b n o r m a l i t i e s are among the d e s c r i p t o r s o f the syndrome Crow c a l l s Type I I S c h i z o p h r e n i a . A l o n g w i t h s t r u c t u r a l b r a i n a b n o r m a l i t i e s , Type I I syndrome i s p o s t u l a t e d t o i n c l u d e n e g a t i v e symptoms, c h r o n i c i r r e v e r s i b l e c ourse, i n t e l l e c t u a l i m p a i r m e n t , and p o o r r e s p o n s e t o n e u r o l e p t i c m e d i c a t i o n . While data are e q u i v o c a l w i t h r e s p e c t t o c l e a r c o v a r i a t i o n o f t h i s c l u s t e r o f v a r i a b l e s , the Type I / Type I I c o n s t r u c t has generated a c o n s i d e r a b l e body o f b i o p s y c h i a t r i c r e s e a r c h . 9) S e v e r a l s t u d i e s have i n v e s t i g a t e d the a s s o c i a t i o n o f s t r u c -t u r a l a b n o r m a l i t i e s and n e u r o p s y c h o l o g i c a l / c o g n i t i v e impairment and s e v e r a l have demonstrated q u i t e h i g h l e v e l s o f a s s o c i a t i o n , a l t h o u g h t h e r e are i n c o n s i s t e n t and c o n t r a d i c t o r y f i n d i n g s . 10) Some i n v e s t i g a t o r s s u g g e s t t h a t c o r t i c a l atrophy as indexed by s u l c a l widening may occur independently o f v e n t r i c u l a r enlargement and may have d i f f e r e n t c l i n i c a l c o r r e l a t e s . U n f o r t u n a t e l y s u l c a l widening i s more d i f f i c u l t t o a s s e s s t h a n i s LVE. 11) S p e c u l a t i o n s based on r e c e n t r e s e a r c h suggest the p o s s i b i l i t y t h a t t h e r e are at l e a s t two n e u r o a n a t o n i c a l l y d i s t i n c t groups o f c h r o n i c s c h i z o p h r e n i c s who evidence marked c o g n i t i v e impairment. Owens et a l . (1985) found c o g n i t i v e impairment was o v e r - r e p r e s e n t e d i n p o r t i o n s o f t h e i r sample which had both the l a r g e s t and s m a l l e s t ( g r e a t e r 28 than 1 s.d. s m a l l e r than c o n t r o l group) v e n t r i c l e s . DeMeyer e t a l . found t h a t s m a l l e r v e n t r i c l e s were a s s o c i a t e d w i t h more marked c o g n i t i v e impairment than l a r g e ones. Neuropsychological and Cognitive Functioning i n Schizophrenia  D e f i n i t i o n and Description N e u r o p s y c h o l o g i c a l s t a t u s i s i n f e r r e d from t e s t p e r f o r -mance on t a s k s designed, or b e l i e v e d t o measure the b e h a v i o r a l e x p r e s s i o n o f b r a i n f u n c t i o n . As Lezak (1981) d e s c r i b e s i t "The d i s t i n g u i s h i n g c h a r a c t e r i s t i c o f n e u r o p s y -c h o l o g i c a l a s s e s s m e n t i s i t s e m p h a s i s on t h e i d e n t i f i c a t i o n and measurement o f p s y c h o l o g i c a l d e f i c i t s , f o r i t i s p r i m a r i l y i n d e f i c i e n c i e s o f i n t e l l e c t , e m o t i o n a l i t y and c o n t r o l t h a t b r a i n damage i s manifested b e h a v i o r a l l y " (p.85). Thus, many n e u r o p s y c h o l o g i c a l i n s t r u m e n t s were d e s i g n e d by q u a n t i f y i n g d i f f e r e n c e s i n p e r f o r m a n c e between i n d i v i d u a l s w i t h known o r g a n i c syndromes and n o r m a l c o n t r o l s , t h e r e b y p r o v i d i n g measures o f a " d e f i c i t " presumed t o be caused by b r a i n damage. The m a j o r i t y o f n e u r o p s y c h o l o g i c a l r e s e a r c h s t u d i e s w i t h p s y c h i a t r i c p o p u l a t i o n s has been d e s i g n e d t o a s s e s s t h e u t i l i t y o f n e u r o p s y c h o l o g i c a l t e s t s i n d i s c r i m i n a t i n g between p a t i e n t s w i t h ' f u n c t i o n a l ' and ' o r g a n i c ' d i a g n o s e s . W h i l e some i n v e s t i g a t o r s u t i l i z e f u l l n e u r o p s y c h o l o g i c a l b a t t e r i e s i n c l u d i n g i n t e l l i g e n c e t e s t s , the g r e a t m a j o r i t y o f s t u d i e s have used o n l y the popular s c r e e n i n g t e s t s (e.g. Memory-for-D e s i g n s - T e s t , the Benton V i s u a l R e t e n t i o n T e s t (BVRT) , t h e 29 T r a i l Making T e s t , and the Bender G e s t a l t T e s t ) . O f t e n o n l y one o f t h e s e i n s t r u m e n t s i s used f o r data c o l l e c t i o n i n a g i v e n study (Heaton & Crowley, 1981). Malec (1978) reviewed 31 c l a s s i f i c a t i o n a t t e m p t s u s i n g b o t h s i n g l e n e u r o p s y c h o l o g i c a l t e s t s and/or the H a l s t e a d - R e i t a n B a t t e r y (HRB), and found t h a t i n g e n e r a l the HRB f a i l e d t o demonstrate g r e a t e r d i s c r i m i n a t o r y power t h a n many o f t h e l e s s t i m e -consuming s i n g l e measures i n d i f f e r e n t i a t i n g ' f u n c t i o n a l ' and 'organic' p a t i e n t s . N e u r o p s y c h o l o g i c a l t e s t s and d i f f e r e n t i a l diagnoses o f  " f u n c t i o n a l " v s . " o r g a n i c " c o n d i t i o n s . An e x t e n s i v e review by Heaton, Baade, and Johnson (197 8) and a subsequent update by Heaton and Crowley (1981) review 118 c l a s s i f i c a t i o n attempts p u b l i s h e d between 1960-1978. N i n e t y - n i n e o f t h e s t u d i e s u t i l i z e d g r o u p c o m p a r i s o n s between o r g a n i c and p s y c h i a t r i c p a t i e n t s , and e l e v e n compared p s y c h i a t r i c p a t i e n t s t o standard s c o r e s f o r impairment. They noted t h a t 90% o f the s t u d i e s had 3 or more m e t h o d o l o g i c a l f l a w s , p a r t i c u l a r l y i n the areas o f s a m p l e s e l e c t i o n and d e s c r i p t i o n . However, d e s p i t e t h e weakness o f i n d i v i d u a l s t u d i e s , Heaton e t a l . (1978, 1981) p r o v i d e d c u m u l a t i v e e s t i m a t e s o f median p e r c e n t c o r r e c t c l a s s i f i c a t i o n . T h ese e s t i m a t e s i n d i c a t e d t h a t n e u r o -p s y c h o l o g i c a l t e s t s were r e l a t i v e l y s u c c e s s f u l i n d i s c r i m i n a -t i n g f u n c t i o n a l from o r g a n i c p a t i e n t s except when t h e f u n c -t i o n a l sample was composed o f c h r o n i c / p r o c e s s s c h i z o p h r e n i c s . 30 The m e d i a n p e r c e n t f o r c o r r e c t c l a s s i f i c a t i o n o f f u n c t i o n a l v s . o r g a n i c was 75% (84 r e p o r t s ) u t i l i z i n g p s y c h i a t r i c s a m p l e s r a n g i n g f r o m n o n - p s y c h o t i c m e n t a l d i s o r d e r s t o mixed s c h i z o p h r e n i c d i s o r d e r s . T h i s i s the same median h i t r a t e r e p o r t e d by Spreen and Benton i n 1965 f o r 36 c l a s s i f i c a t i o n a t t e m p t s t h e y made i n v o l v i n g o r g a n i c s and normal c o n t r o l s (Heaton & Crowley, 1981). However the median h i t r a t e f o r 34 a t t e m p t s t o d i s c r i m i n a t e c h r o n i c / p r o c e s s s c h i z o p h r e n i c p a t i e n t s f r o m o r g a n i c p a t i e n t s was 54%, e s s e n t i a l l y chance l e v e l p r e d i c t i o n . E x c e p t i o n s t o t h e s e r a t h e r d i s m a l c l a s s i f i c a t i o n r a t e s encountered w i t h c h r o n i c s c h i z o p h r e n i c s a r e t h e s t u d i e s o f Golden and c o l l a b o r a t o r s w i t h the HRB (Golden, 1977) and the LNNB (Moses & Golden, 1980; P u r i s c h , Golden, & Hammeke, 1978). In t h e s e s t u d i e s approximately 90% c o r r e c t c l a s s i f i c a t i o n was a c h i e v e d . However d i s c u s s i o n o f these f i n d i n g s by Golden et a l . (1980b) and Moses, C a r d e l l i n o and Thompson (1983) i n d i c a t e t h a t t h e r e may be some q u e s t i o n as t o t h e v a l i d i t y o f t h e c o n c l u s i o n s r e p o r t e d i n these s t u d i e s . Golden e t a l . (19 82b) s t a t e " I t appears p o s s i b l e t h a t p r e v i o u s s t u d i e s comparing s c h i z o p h r e n i c s w i t h b r a i n - i n j u r e d g roups d i d n o t n e c e s s a r i l y measure what t h e y t h o u g h t t h e y were measuring. For example, P u r i s c h , Golden and Hammeke (1978) found d i f f e r e n c e s between the s c h i z o p h r e n i c and n e u r o l o g i c a l g r o u p s . T h i s s t u d y e s t a b l i s h e d t h a t n e u r o l o g i c a l and s c h i z o p h r e n i c p a t i e n t s performed d i f f e r e n t l y on the Luria-Nebraska B a t t e r y , n o t t h a t t h e s c h i z o p h r e n i c s were normal, as con-c l u d e d " , (p.84) 31 O v e r a l l t h e weight o f the evidence i n d i c a t e s t h a t when c h r o n i c s c h i z o p h r e n i c p a t i e n t s a r e e x c l u d e d , n e u r o p s y c h o l o g i c a l t e s t s a r e u s e f u l i n d i s c r i m i n a t i n g e m o t i o n a l l y / p s y c h o l o g i c a l l y d i s t u r b e d p s y c h i a t r i c p a t i e n t s from i n d i v i d u a l s w i t h known o r g a n i c b r a i n d y s f u n c t i o n (Heaton & C r o w l e y , 1981). As M a l e c (1978) p o i n t e d o u t , t h e s e p r e d i c t i o n s can be no more v a l i d than the d i a g n o s t i c c r i t e r i a they p r e d i c t , hence 75% may be a c e i l i n g imposed by the then c u r r e n t n e u r o d i a g n o s t i c t e c h n i q u e s . Heaton e t a l . (1978) d i s c u s s t h e p o o r p e r f o r m a n c e on n e u r o p s y c h o l o g i c a l t e s t s o f c h r o n i c s c h i z o p h r e n i c samples w i t h regard to the p o p u l a r e x p l a n a t i o n o f t h i s group's g e n e r a l i z e d d e f i c i t s * . I t was commonly h e l d t h a t p o o r p e r f o r m a n c e by c h r o n i c s on a l l manner o f t e s t s was ' f u n c t i o n a l ' and a t t r i -b u t a b l e t o m o t i v a t i o n a l d e f i c i e n c i e s - o f t e n s e e n as an outcome o f l o n g term i n s t i t u t i o n a l i z a t i o n - and t h o u g h t d i s o r d e r . While not a b l e t o r u l e out t h i s p o s s i b i l i t y , Heaton e t a l . (1978) q u e s t i o n i t as an adequate e x p l a n a t i o n . They suggest t h a t " f u n c t i o n a l problems" are not c o n f i n e d t o c h r o n i c s c h i z o p h r e n i c p a t i e n t s nor do a l l i n d i v i d u a l s w i t h t h o u g h t d i s o r d e r and m o t i v a t i o n a l d e f i c i e n c i e s perform i n the impaired range on n e u r o p s y c h o l o g i c a l t e s t s . They d i s c u s s the p o s s i b i -l i t y t h a t m e d i c a t i o n may a f f e c t t e s t performance, an i s s u e which w i l l be addressed at a l a t e r p o i n t i n t h i s review. The a l t e r n a t i v e e x p l a n a t i o n which i s most c o m p e l l i n g f o r Heaton e t a l . (1978) i s t h a t "groups o f c h r o n i c or p r o c e s s s c h i z o -p h r e n i c s may l o o k o r g a n i c on n e u r o p s y c h o l o g i c a l t e s t s because a s i g n i f i c a n t p r o p o r t i o n o f s u c h p a t i e n t s a r e o r g a n i c " (p.141)• The H e a t o n e t a l . (1978) r e v i e w s i g n a l e d a s h i f t i n d i r e c t i o n f o r n e u r o p s y c h o l o g i c a l r e s e a r c h i n s c h i z o p h r e n i a . Golden e t a l . (1982) a r t i c u l a t e the change i n p e r s p e c t i v e as f o l l o w s "The CT s c a n r e s e a r c h - as w e l l as the data from many o f the s t u d i e s reviewed by Heaton e t a l . (1978) . . . s u g g e s t t h a t t h e r e a r e a t l e a s t s e v e r a l sub-groups o f s c h i z o p h r e n i a , some o f w h i c h show b r a i n d y s f u n c t i o n . T h i s c o n c l u s i o n c l e a r l y n e c e s s i t a t e s the a d o p t i o n o f a new r e s e a r c h s t r a t e g y i n n e u r o -p s y c h o l o g i c a l r e s e a r c h w i t h s c h i z o p h r e n i a . Rather than compare s c h i z o p h r e n i c s t o n e u r o l o g i c a l p a t i -e n t s , o u r f o c u s s h o u l d be on i d e n t i f y i n g t h o s e s c h i z o p h r e n i c s w i t h b r a i n damage and e v e n t u a l l y d i s c o v e r i n g how s u c h p a t i e n t s d i f f e r i n age o f onset, response to treatment, symptoms, l i k e l i h o o d o f e n d i n g up i n c h r o n i c i n s t i t u t i o n s o r j a i l or s i m i l a r s e t t i n g s and o t h e r such f a c t o r s important i n u n d e r s t a n d i n g these subgroups" (p.89) Summary o f c l a s s i f i c a t i o n s t u d i e s . W i t h r e g a r d t o a d e f i n i t i o n o f the form o f n e u r o p s y c h o l o g i c a l impairment to be e x p e c t e d i n c h r o n i c s c h i z o p h r e n i c p a t i e n t s , the m a j o r i t y o f c l a s s i f i c a t i o n s t u d i e s are not, i n t h e m s e l v e s , v e r y u s e f u l . C l a s s i f i c a t i o n s t u d i e s i n which t e s t s are u t i l i z e d t o d i c h o t o -mize between ' b r a i n damaged' vs. 'non b r a i n damaged' do n o t p r o v i d e a g r e a t d e a l o f i n f o r m a t i o n r e l e v a n t t o d e f i n i n g the n a t u r e or e x t e n t o f the d e f i c i t s e x h i b i t e d by s c h i z o p h r e n i c p a t i e n t s . 33 The u s e f u l n e s s o f comparison group s t u d i e s o f the s o r t d i s c u s s e d above has been q u e s t i o n e d by many i n v e s t i g a t o r s (Golden e t a l . , 1981; Heaton e t a l . , 1978; Satz and F l e t c h e r , 1981). With the growing b e l i e f t h a t a s i z a b l e p r o p o r t i o n o f c h r o n i c s c h i z o p h r e n i c p a t i e n t s are n e u r o l o g i c a l l y impaired, d i f f i c u l t y d i s c r i m i n a t i n g them from p a t i e n t s w i t h known o r g a n i c d y s f u n c t i o n s no l o n g e r d i s t u r b s n e u r o p s y c h o l o g i s t s . The c l a s s i f i c a t i o n s t u d i e s were o f t e n c a r r i e d o u t w i t h t h e e x p r e s s aim o f s e p a r a t i n g s c h i z o p h r e n i c s from o r g a n i c s . In overview, t h e i r r e l a t i v e l y c o n s i s t e n t f a i l u r e t o do so p r o v i d e s us w i t h a few i m p o r t a n t p i e c e s o f d e s c r i p t i v e i n f o r m a t i o n ; a) c h r o n i c s c h i z o p h r e n i c p a t i e n t s do p o o r l y on a wide r a n g e o f t e s t s r e q u i r i n g p e r f o r m a n c e i n a v a r i e t y o f m o d a l i t i e s ; b) s c h i z o p h r e n i c p a t i e n t s e x h i b i t d e f i c i t s on a r a nge o f t e s t s which are b e l i e v e d to assess the f u n c t i o n o f v a r i o u s b r a i n r e g i o n s and do not appear to show c l e a r f o c a l i m p a i r m e n t ; i n s t e a d t h e o v e r a l l p i c t u r e i s one o f d i f f u s e i m p a i r m e n t ; c) many s c h i z o p h r e n i c s a m p l e s c a n n o t be s t a t i s t i c a l l y d i f f e r e n t i a t e d from samples o f d i f f u s e l y b r a i n damaged p a t i e n t s (Seidman, 1983). These c o n c l u s i o n s suggest, as does Seidman (1983), t h a t the form o f n e u r o p s y c h o l o g i c a l impairment evidenced by c h r o n i c s c h i z o p h r e n i c p a t i e n t s " a p p e a r s t o be m i l d to moderate i n s e v e r i t y and more l i k e l y t o be d i f f u s e o r b i l a t e r a l t h a n f o c a l " (p.212) 34 S e l e c t e d ' d e s c r i p t i v e ' s t u d i e s o f n e u r o p s y c h o l o g i c a l  impairment i n s c h i z o p h r e n i a . As s t a t e d above, the c l a s s i f i -c a t i o n s t u d i e s designed to v a l i d a t e n e u r o p s y c h o l o g i c a l t e s t s f o r d i f f e r e n t i a l diagnoses were g e n e r a l l y conducted w i t h t h e i n t e n t i o n o f demonstrating t h a t the t e s t s were d i f f e r e n t i a l l y s e n s i t i v e t o b r a i n damage. Because o f the commonly h e l d a-p r i o r i a s s u m p t i o n t h a t s c h i z o p h r e n i c s were ' f u n c t i o n a l * and n o t ' o r g a n i c * , i n v e s t i g a t i o n and d e s c r i p t i o n o f " a c t u a l " n e u r o p s y c h o l o g i c a l i m p a i r m e n t i n t h i s g r o u p c o n s t i t u t e d a c o n t r a d i c t i o n i n terms and was not e x t e n s i v e l y pursued. Over t h e p a s t 6 t o 8 y e a r s t h e r e has been a r e - a p p r a i s a l o f the n e u r o p s y c h o l o g i c a l f i n d i n g s i n s c h i z o p h r e n i a c o n c u r r e n t w i t h a g e n e r a l r e - a p p r a i s a l o f t h e c o n c e p t o f s c h i z o p h r e n i a as a u n i t a r y d i s o r d e r . I t i s now w i d e l y b e l i e v e d t h a t a subgroup o f s c h i z o p h r e n i a p a t i e n t s s u f f e r from a n e u r o p a t h o l o g i c a l d i s o r d e r . Given t h i s assumption; p o s i t i v e n e u r o p s y c h o l o g i c a l f i n d i n g s i n s c h i z o p h r e n i c i n d i v i d u a l s are no l o n g e r neces-s a r i l y seen as a weakness i n t e s t s e n s i t i v i t y t o f u n c t i o n a l v s . o r g a n i c c o n d i t i o n s but r a t h e r as a p o t e n t i a l l y v a l i d r e f l e c t i o n o f b r a i n d y s f u n c t i o n . Chelune, Heaton, Lehman, and Robinson (1979) c a r r i e d out an i n t e r e s t i n g s t u d y d e s i g n e d t o examine t h e d i a g n o s t i c u t i l i t y o f both mean l e v e l and p a t t e r n o f n e u r o p s y c h o l o g i c a l t e s t p e r f o r m a n c e i n d i s c r i m i n a t i n g a s c h i z o p h r e n i c g roup, n=24, from two g r o u p s o f d i f f u s e l y b r a i n damaged p a t i e n t s ('acute b r a i n damage, n=24, and c h r o n i c b r a i n damage, n=24). 35 The s c h i z o p h r e n i c group was d i a g n o s e d based on S p i t z e r and E n d i c o t t ' s 1968 P s y c h i a t r i c S t a t u s Schedule. A l l s u b j e c t s were v o l u n t a r y s h o r t s t a y i n p a t i e n t s . The WAIS and f u l l HRB were g i v e n t o the s c h i z o p h r e n i c g r o u p , b o t h n e u r o l o g i c a l g r o u p s , and a 150 member n o r m a l c o n t r o l sample used t o produce a normative p r o f i l e f o r p a t t e r n and l e v e l a n a l y s i s . On the WAIS, the s c h i z o p h r e n i c group per-formed s i g n i f i c a n t l y b e t t e r than the acute b r a i n damage sample but not d i f f e r e n t l y f rom t h e c h r o n i c b r a i n damage sample'. Acute and c h r o n i c b r a i n damage groups d i d not d i f f e r . On the HRB t e s t s the acute and c h r o n i c b r a i n damage p a t i e n t s d i d not d i f f e r s i g n i f i c a n t l y from e a c h o t h e r but d i d s i g n i f i c a n t l y worse t h a n t h e s c h i z o p h r e n i c g r o u p . T h e s e i n v e s t i g a t o r s f a i l e d t o f i n d d i f f e r e n c e s i n p a t t e r n o f performance between the b r a i n d i s o r d e r and s c h i z o p h r e n i c groups. U n f o r t u n a t e l y , Chelune e t a l . (197 9) p r e s e n t the WAIS and HRB s c o r e s o n l y i n t h e form o f T - s c o r e s w i t h means and standard d e v i a t i o n d e r i v e d from t h e i r c o n t r o l sample hence, i t i s not p o s s i b l e t o compare t h e i r samples w i t h those o f other s t u d i e s . However, the study i s w e l l - d e s i g n e d t o assess the i s s u e o f whether p a t t e r n s o f n e u r o p s y c h o l o g i c a l p e r f o r m a n c e d i f f e r b e t w e e n s c h i z o p h r e n i c p a t i e n t s and b r a i n damaged i n d i v i d u a l s . T h i s i s s u e has been c o n s i d e r e d i n e a r l i e r r e s e a r c h ( s e e Heaton & Crowle y , 1981, f o r d i s c u s s i o n ) w i t h l e s s adequate methodology, and w i t h mixed r e s u l t s . I t has b e e n o f i n t e r e s t b e c a u s e o f t h e f r e q u e n t f a i l u r e o f 36 n e u r o p s y c h o l o g i c a l t e s t s i n demonstrating d i f f e r e n c e s between d i f f u s e l y b r a i n d i s o r d e r e d p a t i e n t s and s c h i z o p h r e n i c groups i n l e v e l o f performance. A c c o r d i n g to Chelune e t a l . (1979), the use of* 150 age and education-matched c o n t r o l s u b j e c t s f o r d e r i v a t i o n o f an " i d e a l " n o r m a t i v e t e s t p r o f i l e a l l o w s f o r more v a l i d p a t t e r n a n a l y s i s o f t e s t responses i n the p a t i e n t samples than would be o b t a i n e d by use o f g e n e r a l p o p u l a t i o n norms ( w h i c h do n o t c o n t r o l p a t t e r n and l e v e l d i f f e r e n c e s found t o vary w i t h age and e d u c a t i o n ) . I n l i g h t o f t h e i r e f f o r t s a t m e t h o d o l o g i c a l adequacy i n p a t t e r n a n a l y s i s , the f i n d i n g o f a h i g h degree o f p r o f i l e s i m i l a r i t y between t h e d i f f u s e b r a i n d a m a g e d a n d s c h i z o p h r e n i c s a m p l e s i s i n t e r e s t i n g . A p a i r o f s t u d i e s by T a y l o r , R e d f i e l d , and Abrams (1981), and T a y l o r and Abrams (1984) p r o v i d e i n t e r e s t i n g d a t a on n e u r o p s y c h o l o g i c a l and c o g n i t i v e impairment i n s c h i z o p h r e n i c p a t i e n t s , and a d i s c u s s i o n o f hypotheses r e l a t e d to l a t e r a l i -z a t i o n o f impairment vs. d i f f u s e or b i l a t e r a l impairment. T a y l o r e t a l . (1981) used a b a t t e r y o f p s y c h o l o g i c a l t e s t s which they r e f e r t o as "Smith's n e u r o p s y c h o l o g i c a l t e s t b a t t e r y " comprised o f the WAIS, Peabody P i c t u r e V o c a b u l a r y T e s t ( P P V T ) , B e n t o n ' s S e n t e n c e R e p e t i t i o n T e s t , Purdue Pegboard T e s t , S i n g l e and D o uble S i m u l t a n e o u s S t i m u l a t i o n T e s t , Hooper O r g a n i z a t i o n T e s t , Raven's P r o g r e s s i v e M a t r i c e s , and Benton V i s u a l R e t e n t i o n T e s t (BVRT). The s u b j e c t s i n t h i s study c o n s i s t e d o f 52 p a t i e n t s w i t h a f f e c t i v e d i s o r d e r s (both mania and endogenous de p r e s s i o n ) , 17 s c h i z o p h r e n i c p a t i e n t s and 8 p a t i e n t s w i t h "coarse" b r a i n d i s e a s e (CBD). "Dominant hemisphere f u n c t i o n " was a s s e s s e d from p e r f o r m a n c e on WAIS V e r b a l IQ, PPVT, S e n t e n c e R e p e t i t i o n , r i g h t hand Peg Board s p e e d , and r i g h t - s i d e d e r r o r s on t h e D o u b l e S i m u l t a n e o u s S t i m u l a t i o n T e s t . "Nondominant hemisphere f u n c t i o n i n g " was measured by p e r f o r m a n c e on WAIS p e r f o r m a n c e IQ, H o o p e r , Raven's M a t r i c e s , BVRT, l e f t - h a n d e d Peg Board speed, and l e f t -s i d e d e r r o r s on the Double Simultaneous S t i m u l a t i o n T e s t . i n ord e r t o compare d i a g n o s t i c groups w h i l e c o n t r o l l i n g f o r the e f f e c t s o f age, sex, handedness, e d u c a t i o n l e v e l , and d r u g treatment, m u l t i p l e r e g r e s s i o n analyses were done w i t h these 5 v a r i a b l e s c o v a r i e d out o f the n e u r o p s y c h o l o g i c a l t e s t s c o r e s b e f o r e d i a g n o s i s was entered i n t o the e q u a t i o n . In the h i e r a r c h i c a l r e g r e s s i o n o f "dominant h e m i s p h e r e f u n c t i o n " , sex, age, handedness, and drug treatment were not fou n d t o be s i g n i f i c a n t l y r e l a t e d t o p e r f o r m a n c e , w h i l e e d u c a t i o n was. A f t e r a c c o u n t i n g f o r the v a r i a n c e due to these f i v e v a r i a b l e s , d i a g n o s i s was s t i l l s i g n i f i c a n t l y r e l a t e d t o t e s t performance and the f o l l o w i n g p a i r - w i s e group d i f f e r e n c e s and s i m i l a r i t i e s were found: s c h i z o p h r e n i c s u b j e c t s were more impaired than manic or d e p r e s s i v e s u b j e c t s , but not d i f f e r e n t from i n d i v i d u a l s w i t h CBD; the a f f e c t i v e d i s o r d e r groups d i d not d i f f e r from each o t h e r , but d i d s i g n i f i c a n t l y b e t t e r than the CBD sample. 38 I n t h e r e g r e s s i o n a n a l y s i s o f "nondominant hemisphere f u n c t i o n " i t was f o u n d t h a t age, e d u c a t i o n l e v e l , d r u g t r e a t m e n t and d i a g n o s i s were a l l s i g n i f i c a n t l y r e l a t e d to performance. E d u c a t i o n l e v e l and i n c r e a s i n g age were i n -v e r s e l y r e l a t e d t o n e u r o p s y c h o l o g i c a l p e r f o r m a n c e , serum l i t h i u m l e v e l was a s s o c i a t e d w i t h l e s s i m p a i r m e n t , whereas n e u r o l e p t i c exposure was a s s o c i a t e d w i t h g r e a t e r impairment. A f t e r a c c o u n t i n g f o r v a r i a n c e due t o those v a r i a b l e s T a y l o r e t a l . found t h a t s c h i z o p h r e n i c p a t i e n t s d i d not d i f f e r from the manic or depressed groups or from the CBD sample. The manics and d e p r e s s i v e s were n o t d i f f e r e n t from each ot h e r but d i d perform s i g n i f i c a n t l y b e t t e r than CBD s u b j e c t s . I n t e r e s t i n g l y i n stepwise d i s c r i m i n e n t f u n c t i o n a n a l y s i s u s i n g both dominant and nondominant h e m i s p h e r e t e s t s , t h e v a r i a b l e s w h i c h s i g n i f i c a n t l y d i s c r i m i n a t e d between groups were the WAIS In f o r m a t i o n , Comprehension, and O b j e c t Assembly s u b t e s t s and the Hooper V i s u a l O r g a n i z a t i o n T e s t . Using these v a r i a b l e s T a y l o r e t a l . obtained an o v e r a l l h i t r a t e o f 84% ( t h e y comment t h a t t h e d i s c r i m i n a t o r y power o f these f o u r t a s k s i s p r o b a b l y s t a t i s t i c a l l y i n f l a t e d ! ) . In summary, the a u t h o r s r e p o r t t h a t t h e o u t c o m e o f t h e a n a l y s e s shows d i f f e r e n t p a t t e r n s of hemispheric d y s f u n c t i o n among p a t i e n t groups. The s c h i z o p h r e n i c sample showed b i l a t e r a l d y s f u n c t i o n and p e r f o r m e d l e s s w e l l t h a n manics on dominant b u t n o t nondominant h e m i s p h e r i c t a s k s . A f f e c t i v e d i s o r d e r p a t i e n t s were impaired on t a s k s o f nondominant hemisphere f u n c t i o n . 39 I n a n o t h e r s t u d y , T a y l o r and Abrams (1984) compared c o g n i t i v e f u n c t i o n i n g o f 62 s c h i z o p h r e n i c s u b j e c t s and 42 n o r m a l s , u s i n g a v a r i e t y o f ' n e u r o p s y c h o l o g i c a l t a s k s ' t h a t i n c l u d e d assessment o f s o f t n e u r o l o g i c a l s i g n s , an a p h a s i a s c r e e n i n g t e s t , t a c h i s t o s c o p e s t i m u l a t i o n , a u d i t o r y t h r e s h o l d d e t e r m i n a t i o n s , and i t e m s f r o m t h e M i n i - M e n t a l S t a t e , H a l s t e a d - R e i t a n , and L u r i a - N e b r a s k a b a t t e r i e s . E a c h p a r t i c i p a n t ' s p r o t o c o l was r a t e d b l i n d l y f o r i m p a i r m e n t o f each hem i s p h e r i c r e g i o n , f o r l a t e r a l i t y o f impairment, and f o r g l o b a l impairment on 5-point s c a l e s . U s i n g s t a t i s t i c a l procedures s i m i l a r t o those d e s c r i b e d i n the T a y l o r e t a l . (1981) study, t o c o n t r o l f o r v a r i a n c e a t t r i b u t a b l e t o age, sex, handedness, and drug a d m i n i s t r a t i o n , t h e i n v e s t i g a t o r s f o u n d t h a t t h r e e q u a r t e r s o f t h e i r s c h i z o p h r e n i c s u b j e c t s showed marked t o severe ' c o g n i t i v e ' impairment, w h i l e none o f t h e i r c o n t r o l s d i d . They s t a t e t h a t t h e i r s c h i z o p h r e n i c s u b j e c t s e x h i b i t e d b i l a t e r a l d i f f u s e c o g n i t i v e impairment which was more pronounced i n the f r o n t o -t e m p o r a l r e g i o n s . In d i s c u s s i n g t h i s s t u d y , t h e a u t h o r s a d d r e s s c o n f l i c t s i n t h e l i t e r a t u r e w i t h r e s p e c t t o t h e h y p o t h e s i s t h a t s c h i z o p h r e n i a i s e x c l u s i v e l y a l e f t - h e m i s p h e r e d i s o r d e r . They s u g g e s t t h a t even t h e s t u d i e s w h i c h were o r i g i n a l l y c i t e d as evidence f o r l e f t hemisphere d y s f u n c t i o n i n s c h i z o p h r e n i a (e.g. F l o r - H e n r y ' s 1969 s t u d i e s ) a c t u a l l y show o n l y a c o r r e l a t i o n b e t w e e n b i l a t e r a l f o c i and s c h i z o p h r e n i c symptoms. They conclude t h a t t h e i r own d a t a , 40 and those from s t u d i e s u s i n g a v a r i e t y o f t e s t s t r a t e g i e s , can be m o s t p a r s i m o n i o u s l y i n t e r p r e t e d t o r e f l e c t b i l a t e r a l d i f f u s e c o g n i t i v e impairment i n s c h i z o p h r e n i a . However, they add t h a t t h e i r s t u d i e s and those by o t h e r i n v e s t i g a t o r s o f t e n f i n d t h a t the impairment i s most pronounced i n t h e dominant f r o n t o - t e m p o r a l r e g i o n s . They make the f o l l o w i n g i n t e r e s t i n g s p e c u l a t i o n , " T h i s p a t t e r n o f b i l a t e r a l c o r t i c a l d y s f u n c t i o n w i t h dominant f r o n t o - t e m p o r a l a c c e n t u a t i o n i n s c h i z o p h r e n i a may r e f l e c t s e l e c t i o n f o r s p e c i f i c p s y c h o p a t h o l o g i c a l f e a t u r e s . S t u d i e s u s i n g d i a g n o s t i c c r i t e r i a f o r s c h i z o p h r e n i a t h a t r e l y h e a v i l y on the presence o f formal thought d i s o r d e r , t h e f i r s t - r a n k symptoms o f S c h neider, and emotional b l u n t i n g and then f i n d t h e p a t t e r n o f d y s f u n c t i o n n o t e d above r a i s e t h e p o s s i b i l i t y t h a t t h e s e phenomena a r e a s s o c i a t e d w i t h d o m i n a n t -hemisphere ( p a r t i c u l a r l y f r o n t o - t e m p o r a l ) d y s f u n c t i o n . The c o g n i t i v e p a t t e r n t h a t we and o t h e r s have o b s e r v e d i n s c h i z o -p h r e n i c s may thus r e f l e c t t h e c h o i c e o f d i a g n o s t i c c r i t e r i a , and one m i g h t l o g i c a l l y p r e d i c t t h a t p a t i e n t s w i t h f o r m a l t h o u g h t d i s o r d e r , f i r s t - r a n k symptoms, and e m o t i o n a l b l u n t i n g s h o u l d d e m o n s t r a t e d o m i n a n t f r o n t o - t e m p o r a l impairment." (p. 200) They conclude t h e i r r e p o r t w i t h the f o l l o w i n g , ". . . l a t e r a l i z e d dominant f r o n t o - t e m p o r a l d y s f u n c t i o n may g i v e t h e s c h i z o p h r e n i c syndrome i t s c h a r a c t e r i s t i c stamp, but the d i f f u s e b i l a t e r a l i m p a i r m e n t may u l t i -mately l e a d n o s o l o g i s t s to r e t u r n s c h i z o -p h r e n i a to i t s o r i g i n a l c l a s s i f i c a t i o n as a dementia." (p. 200) F i n a l l y , a study by Kolb and Whishaw (1983) shows some i n t e r e s t i n g p a r a l l e l s t o and d i f f e r e n c e s from the T a y l o r e t a l s t u d i e s (1981, 1984). Kolb and Whishaw u t i l i z e d an e x t e n s i v e b a t t e r y o f p s y c h o l o g i c a l t e s t s t o assess g e n e r a l i n t e l l i g e n c e and l e f t and r i g h t f r o n t a l , t e m p o r a l , and p a r i e t a l l o b e f u n c t i o n i n 30 c a r e f u l l y d i a g n o s e d DSM-III s c h i z o p h r e n i c p a t i e n t s and 30 age-matched c o n t r o l s . The t e s t s used i n t h i s study have been v a l i d a t e d on p a t i e n t s w i t h s t a t i c a t r o p h i c l e s i o n s from the Montreal N e u r o l o g i c a l H o s p i t a l . They found t h a t r e l a t i v e t o the c o n t r o l g r o u p , s c h i z o p h r e n i c s u b j e c t s showed marked impairment on t e s t s s e n s i t i v e to r i g h t and l e f t temporal l o b e f u n c t i o n i n g (e.g. on t e s t s o f V e r b a l and non V e r b a l memory such as r e c a l l o f Weschler s t o r i e s and f i g u r e s ) , on t e s t s s e n s i t i v e t o r i g h t and l e f t f r o n t a l l o b e f u n c t i o n i n g (eg. C h i c a g o Word Flue n c y , Gotman Design F l u e n c y , Wisconsin Card S o r t i n g T e s t ) . In c o n t r a s t to poor performance on t e s t s o f t e m p o r a l and f r o n t a l l o b e f u n c t i o n , t h e s c h i z o p h r e n i c p a t i e n t s performed w i t h i n normal l i m i t s on t e s t s s e n s i t i v e to p a r i e t a l l o b e f u n c t i o n (eg. Rey Complex F i g u r e s , C o r s i Block S p a n , D i g i t s F o r w a r d a n d B a c k w a r d , R i g h t - L e f t D i f f e r e n t i a t i o n ) . The s c h i z o p h r e n i c sample had a mean F u l l -S c a l e WAIS IQ 15 p o i n t s lower than the c o n t r o l group, t h e i r Performance IQ was 19 p o i n t s lower than the c o n t r o l group, and t h e i r v e r b a l IQ 6 p o i n t s lower. The authors conclude t h a t the data suggest t h a t s c h i z o -p h r e n i a i s accompanied by a s e l e c t i v e b i l a t e r a l d y s f u n c t i o n of the f r o n t a l and temporal l o b e s i n the presence o f r e l a t i v e l y n o r m a l f u n c t i o n i n g o f t h e p a r i e t a l l o b e s . They d i s c u s s an a l t e r n a t i v e p o s s i b i l i t y , s u g g e s t i n g t h a t i f p a r i e t a l l o b e t e s t s are l e s s s e n s i t i v e t o d i f f u s e d i s o r d e r s than the oth e r t e s t s used, then r a t h e r t h a n h a v i n g a s p e c i f i c d e f i c i t o f f r o n t a l and temporal l o b e f u n c t i o n i n g , s c h i z o p h r e n i c s might be b e t t e r d e s c r i b e d as e x h i b i t i n g d i f f u s e impairment. They argue a g a i n s t t h i s i n t e r p r e t a t i o n on grounds t h a t : a) t e s t s such as d i g i t span and R i g h t / L e f t D i f f e r e n t i a t i o n have been shown to be very s e n s i t i v e t o d i f f u s e l e f t hemisphere ab n o r m a l i t y ; b) gl u c o s e metabolism and c e r e b r a l blood flow s t u d i e s i n d i c a t e abnormal f u n c t i o n i n f r o n t a l l o b e s o f s c h i z o p h r e n i c i n d i v i -d u a l s ; c) and a b s e n c e o f r e p o r t e d e v i d e n c e o f s t r u c t u r a l a b n o r m a l i t y w i t h i n the p a r i e t a l c o r t e x o f s c h i z o p h r e n i c s . Summary of d e s c r i p t i v e s t u d i e s . Chelune e t a l . (1979) found t h a t t h e i r s c h i z o p h r e n i c sample performed a t a s i g n i f i -c a n t l y h i g h e r l e v e l on the HRB than both the acute and c h r o n i c d i f f u s e l y b r a i n damaged p a t i e n t s . On the WAIS s c h i z o p h r e n i c p a t i e n t s d i d n o t d i f f e r from c h r o n i c b r a i n damaged p a t i e n t s but d i d b e t t e r than acute b r a i n damaged p a t i e n t s . When l e v e l o f p e r f o r m a n c e s d i f f e r e n c e s were removed, p r o f i l e s o f t e s t s performance were very s i m i l a r among the groups. On the b a s i s o f t h e i r d a t a t h e a u t h o r s c o n c l u d e t h a t when c a r e f u l l y screened groups o f n o n i n s t i t u t i o n a l i z e d s c h i z o p h r e n i c s and b r a i n damaged i n d i v i d u a l s are compared, d i f f e r e n c e s i n mean l e v e l o f performance w i l l be found, but s c h i z o p h r e n i c s u b j e c t s 43 would be expected to show a p a t t e r n o f t e s t b a t t e r y s c o r e s on the HRB t h a t i s i n d i s t i n g u i s h a b l e from t h a t o f d i f f u s e l y b r a i n damaged p a t i e n t s . T a y l o r e t a l . (1981 , 1983 ) f o u n d g l o b a l d e f i c i t s i n d i c a t i v e o f d i f f u s e i m p a i r m e n t i n t h e i r two samples o f s c h i z o p h r e n i c p a t i e n t s . T a y l o r e t a l . (1981) were unable to d i s t i n g u i s h s c h i z o p h r e n i c p a t i e n t s from i n d i v i d u a l s w i t h c o a r s e b r a i n damage on t e s t s intended t o assess dominant and nondominant h e m i s p h e r e f u n c t i o n . I n a d d i t i o n t o g l o b a l impairment, T a y l o r and Abrams (1984) found an a c c e n t u a t i o n o f d e f i c i t p e r f o r m a n c e on t e s t s i n t e n d e d t o measure dominant f r o n t a l l o b e f u n c t i o n i n t h e i r s c h i z o p h r e n i c sample. Kolb and Whishaw (1983) fou n d marked p e r f o r m a n c e d e f i c i t s on t e s t s s e n s i t i v e t o f r o n t a l and temporal l o b e f u n c t i o n , w i t h normal performance on t e s t s s e n s i t i v e t o p a r i e t a l l o b e l e s i o n s . Thus the l i t e r a t u r e reviewed p r e s e n t s some c o n s i s t e n c i e s and a few a p p a r e n t l y c o n t r a d i c t o r y f i n d i n g s . R e s u l t s such as those r e p o r t e d by Chelune e t a l . (1979) might be expected i n l i g h t o f a) the 'subgroup h y p o t h e s i s ' , under which we would e x p e c t o n l y a c e r t a i n p r o p o r t i o n , probably c o n s i d e r a b l e l e s s than one h a l f o f a r e p r e s e n t a t i v e sample o f s c h i z o p h r e n i c s , to be members o f a s u b g r o u p w i t h i d e n t i f i a b l e n e u r o l o g i c d y s f u n c t i o n , a n d b) t h e f i n d i n g s o f t h e n u m e r o u s c l a s s i f i c a t i o n s t u d i e s w h i c h i n d i c a t e t h a t ' c h r o n i c i t y ' or s e v e r i t y o f i l l n e s s i s a s i g n i f i c a n t f a c t o r i n d e t e r m i n i n g the l i k e l i h o o d t h a t a n e u r o p s y c h o l o g i c a l d e f i c i t w i l l be found. 44 The C h e l u n e e t a l . (1979) s c h i z o p h r e n i c s a m p l e were a) " r i g o r o u s l y s c r e e n e d " t o r u l e o u t n e u r o l o g i c d i s e a s e , b) v o l u n t a r y p a t i e n t s i n a s h o r t s t a y treatment f a c i l i t y and c) were diagnosed by DSM-II c r i t e r i a , p o t e n t i a l l y c o n t r i b u t i n g to a more heterogeneous sample t h a n i n o t h e r s t u d i e s . G i v e n t h e s e sample c h a r a c t e r i s t i c s t h i s study may resemble those r e p o r t e d by H eaton e t a l . (1978) u n d e r t h e h e a d i n g s o f c l a s s i f i c a t i o n s t u d i e s w i t h "acute or r e a c t i v e s c h i z o p h r e n i a " . The median h i t r a t e s f o r d i s t i n g u i s h i n g between p s y c h i a t r i c and o r g a n i c groups f o r s t u d i e s u s i n g these p o p u l a t i o n s were 77% and 69% r e s p e c t i v e l y . The T a y l o r e t a l . (1981) a n d . T a y l o r and Abrams (1984) s t u d i e s are c o n s i s t e n t i n demonstrating a h i g h p r e v a l e n c e o f g l o b a l impairment i n n e u r o p s y c h o l o g i c a l f u n c t i o n i n g . The Kolb and Whishaw (1983) study r e p o r t s marked impairment on f r o n t a l -and t e m p o r a l l o b e - s e n s i t i v e t e s t s which i s c o n s i s t e n t w i t h T a y l o r and Abrams (1984); however these s t u d i e s d i f f e r i n t h a t T a y l o r and Abrams a l s o r e p o r t impaired performance on p a r i e t a l l o b e t e s t s . T hese i n v e s t i g a t o r s u s ed d i f f e r e n t t e s t s t o a s s e s s p a r i e t a l f u n c t i o n and u n f o r t u n a t e l y T a y l o r and Abrams (1984) do n o t s p e c i f y w h i c h t a s k s i n t h e i r b a t t e r y were c o n s i d e r e d p a r i e t a l l o b e t e s t s . In any case, a l t h o u g h these s t u d i e s do not show c o n s e n s u s on t h e i s s u e o f d i f f u s e v s . l o c a l i z e d d y s f u n c t i o n , the T a y l o r e t a l . (1981), T a y l o r and Abrams (1 9 8 4 ) , and K o l b and Whishaw (1983) s t u d i e s a r e 45 concordant w i t h r e s p e c t t o o b s e r v i n g b i l a t e r a l d e f i c i t s on t e s t s b e l i e v e d s e n s i t i v e t o temporal and f r o n t a l f u n c t i o n . C o n c l u d i n g comments on d e f i n i t i o n and d e s c r i p t i o n o f  n e u r o p s y c h o l o g i c a l and c o g n i t i v e f u n c t i o n i n g i n s c h i z o p h r e n i a . As one proceeds through the t o p i c s d i s c u s s e d i n t h i s r e v i e w ( i . e . eye t r a c k i n g d e f i c i t s , CT scan a b n o r m a l i t i e s and f i n a l l y n e u r o p s y c h o l o g i c a l and c o g n i t i v e d y s f u n c t i o n ) t h e r e appears to be an e x p o n e n t i a l i n c r e a s e i n the number o f ways a b n o r m a l i t i e s might be and have been d e f i n e d . The terms 'n e u r o p s y c h o l o g i -c a l ' and/or ' c o g n i t i v e ' f u n c t i o n - a l s o impairment, d e f i c i t , and d y s f u n c t i o n - have a wide v a r i e t y o f s p e c i f i c and g e n e r a l r e f e r e n t s . For the purposes o f t h i s review, l i t t l e would be gained from what would n e c e s s a r i l y be an inadequate attempt to enumerate the many d i f f e r e n t senses i n which these terms might a p p l y ( o r be i n a p p r o p r i a t e ) i n s c h i z o p h r e n i a . E v e n t h e p o t e n t i a l l y i m p o r t a n t d i s t i n c t i o n b e t w e e n m e a s u r e s o f ' i n t e l l i g e n c e ' as d i s t i n c t from ' n e u r o p s y c h o l o g i c a l f u n c t i o n ' w i l l n o t be a t t e m p t e d . F o r p r e s e n t p u r p o s e s i t w i l l be a s s e r t e d t h a t n e u r o p s y c h o l o g i c a l f u n c t i o n may be o p e r a t i o n a l l y d e f i n e d as s c o r e s on a v a r i e t y o f t e s t s , i n c l u d i n g i n t e l l i g e n c e t e s t s , c o n v e n t i o n a l l y t h o u g h t o f a s n e u r o p s y c h o l o g i c a l measures. I t i s a p p a r e n t from t h e l i t e r a t u r e reviewed t h a t some s c h i z o p h r e n i c s , and p a r t i c u l a r l y c h r o n i c s c h i z o p h r e n i c p a t i e n t s , perform i n a manner s t a t i s t i c a l l y i n d i s t i n g u i s h a b l e from b r a i n damaged comparison groups. D e f i c i t s are found i n 46 such a wide v a r i e t y o f t e s t s t h a t many i n v e s t i g a t o r s conclude t h e r e i s a subgroup o f s c h i z o p h r e n i c p a t i e n t s who are g l o b a l l y impaired and who probably s u f f e r from a d i f f u s e b r a i n d i s -o r d e r . D e s p i t e repeated f i n d i n g s o f t h i s s o r t , t h e r e are a s u f f i c i e n t number o f i n c o n s i s t e n c i e s and o u t r i g h t c o n t r a d i c -t i o n s i n t h e l i t e r a t u r e t o p r e c l u d e s p e c i f y i n g any s e t o f t e s t s , or any measurement paradigm, as the most a p p r o p r i a t e or s e n s i t i v e measure o f 'the s c h i z o p h r e n i c d e f i c i t ' , i f indeed such a t h i n g e x i s t s . Prevalence of Neuropsychological Impairment I n f o r m a t i o n on t h i s p a r a m e t e r i s r a t h e r s c a r c e , and n e c e s s a r i l y confounded w i t h d i a g n o s t i c and sampling procedures a p p l i e d by i n d i v i d u a l i n v e s t i g a t o r s , as w e l l as the f a c t t h a t 'impairment' i s r e l a t i v i s t i c , not a b s o l u t e . To date t h e r e are no p u b l i s h e d r e p o r t s o f attempts t o s y s t e m a t i c a l l y c o l l e c t n e u r o p s y c h o l o g i c a l data from a l a r g e r e p r e s e n t a t i v e sample o f i n d i v i d u a l s who would be c u r r e n t l y diagnosed as s c h i z o p h r e n i c . Some o f the s t u d i e s reviewed do p r o v i d e e s t i m a t e s o f the r a t e s o f impairment i n t h e i r samples t h a t are based on c u t t i n g s c o r e s d e r i v e d from n e u r o l o g i c p o p u l a t i o n s . Donnelley e t a l . (1980) and R e i d e r e t a l . (1979) used the Average Impairment R a t i n g method t o a s s e s s d e g r e e o f i m p a i r m e n t on t h e HRB. Donnelley e t a l . (1980) c l a s s i f i e d 9/15 (60%) o f t h e i r sample o f young c h r o n i c s c h i z o p h r e n i c s as impaired and R e i d e r e t a l . 47 (1979) found 5/8 (62%) o f a s i m i l a r l y diagnosed sample were imp a i r e d . T a y l o r and Abrams (1984) and K o l b and Whishaw (1983) compared t h e i r samples t o normal c o n t r o l groups. ' T a y l o r and* Abrams f o u n d t h a t approximately 75% o f the 62 s c h i z o p h r e n i c s u b j e c t s e x h i b i t e d moderate to severe d y s f u n c t i o n r e l a t i v e to normals. Kolb and Whishaw (1983) r e p o r t t h a t o n l y 5 o f t h e i r 30 s c h i z o p h r e n i c s u b j e c t s performed i n the n o rmal range f o r the whole b a t t e r y o f t e s t s which assessed f r o n t a l and temporal l o b e f u n c t i o n ; however, i t does not n e c e s s a r i l y f o l l o w t h a t the remaining 25 would be c l a s s i f i e d as "impaired". While the authors r e p o r t t h a t mean l e v e l o f impairment was g r e a t e r i n the s c h i z o p h r e n i c group they do not attempt t o d i s t i n g u i s h or enumerate "impaired" vs "nonimpaired" i n d i v i d u a l s u b j e c t s so as t o p r o v i d e r a t e s . The above "prevalence r a t e s " are a c t u a l l y a r b i t r a r y and sample s p e c i f i c d e f i n i t i o n s o f impairment, e x c e p t f o r t h e 3 s t u d i e s which used standard impairment indexes w i t h the HRB. A more s a t i s f a c t o r y a p p r o a c h might be t h e d e v e l o p m e n t and a p p l i c a t i o n o f t e s t n o r m s d e r i v e d f r o m p s y c h i a t r i c p o p u l a t i o n s , s u c h t h a t one c o u l d compare t e s t s c o r e s t o standard performance o f other s i m i l a r l y diagnosed p a t i e n t s and determine the e x t e n t o f "impairment" i n a g i v e n i n d i v i d u a l . O b v i o u s l y an e v e n more i d e a l s i t u a t i o n w o u l d be t h e development o f t e s t s , f o r p s y c h i a t r i c d i s o r d e r p a t i e n t s , w i t h known n e u r o l o g i c c r i t e r i o n v a l i d i t y . At p r e s e n t , however, 48 impairment must i n g e n e r a l be d e f i n e d r e l a t i v e t o a s p e c i f i c c o n t r o l sample or t o c u t o f f sco r e s developed i n n e u r o l o g i c p a t i e n t samples, and p r e v a l e n c e r a t e s w i l l be t h e r e f o r e be a f u n c t i o n o f these d e f i n i t i o n s . M e d i c a t i o n and n e u r o p s y c h o l o g i c a l performance. Given the p o w e r f u l e f f e c t n e u r o l e p t i c d r u g s have on t h e p s y c h o t i c b e h a v i o r o f s c h i z o p h r e n i c p a t i e n t s , t h e p o s s i b i l i t y t h a t n e u r o p s y c h o l o g i c a l p e r f o r m a n c e d e f i c i t s a r e t h e r e s u l t o f m e d i c a t i o n must be s e r i o u s l y c o n s i d e r e d . E t h i c a l c o n s i d e r a -t i o n s p r e c l u d e f u l l e x p e r i m e n t a l i n v e s t i g a t i o n o f t h i s i s s u e over a time span s u f f i c i e n t t o address the e f f e c t o f c h r o n i c n e u r o l e p t i c u s e . Heaton and C r o w l e y (1981) s e l e c t i v e l y reviewed the l i t e r a t u r e on the e f f e c t s o f n e u r o l e p t i c drugs on n e u r o p s y c h o l o g i c a l performance. They i n d i c a t e d t h a t much o f the r e s e a r c h t o date i s flawed by the f a i l u r e o f r e s e a r c h e r s t o d i s t i n g u i s h the e f f e c t s o f drug c l a s s e s , f a i l u r e t o use d i a g n o s t i c a l l y homogeneous groups o f p a t i e n t s , i n a t t e n t i o n t o the complex r e l a t i o n s h i p s o f dose and blood l e v e l s o f medica-t i o n , and f a i l u r e t o c o n t r o l f o r other concomitant treatments. In a d d i t i o n , some s t u d i e s f a i l t o c o n s i d e r drug t o l e r a n c e and t e s t l e a r n i n g as p o s s i b l e f a c t o r s i n r e - t e s t p e r f o r m a n c e changes. The m a j o r i t y o f s t u d i e s o f acute or s h o r t - t e r m adminis-t r a t i o n o f n e u r o l e p t i c s t y p i c a l l y h a v e u t i l i z e d n o r m a l s u b j e c t s such as c o l l e g e s t u d e n t s . These s t u d i e s measure s i d e e f f e c t s o f acute a d m i n i s t r a t i o n o f n e u r o l e p t i c s a t v a r i o u s doses. Heaton and Crowley (1981) r e p o r t t h a t acute adminis-. t r a t i o n i n h i g h e r doses o f the n e u r o l e p t i c s w i t h s i g n i f i c a n t a n t i c h o l i n e r g i c p r o p e r t i e s (eg. c h l o r p r o m a z i n e and t h i o r i d a -z i n e ) impair performance on a v a r i e t y o f motor and c o g n i t i v e t e s t s . The n e u r o l e p t i c s i n t h e p i p e r a z i n e s g r o u p ( e g . t r i f l u o p e r a z i n e ) and h a l o p e r i d o l have l i t t l e a n t i c h o l i n e r g i c e f f e c t and do not seem to impair c o g n i t i v e f u n c t i o n or motor s p e e d , b u t a r e more l i k e l y t o produce acute e x t r a p y r a m i d a l s i d e e f f e c t s w h i c h i m p a i r p e r f o r m a n c e on some m o t o r c o o r d i n a t i o n t a s k s . The s t u d i e s suggest t h a t e a r l y i n the c ourse o f n e u r o l e p t i c drug a d m i n i s t r a t i o n , o r s h o r t l y a f t e r marked i n c r e a s e s i n dosage, t h e r e may be s i g n i f i c a n t drug-induced a b n o r m a l i t i e s i n n e u r o p s y c h o l o g i c a l performance which w i l l v a r y w i t h the type and dose o f n e u r o l e p t i c , and o f the a b i l i t y b e i n g t e s t e d (Heaton and Crowley 19 81). I n l o n g t e r n a d m i n i s t r a t i o n o f n e u r o l e p t i c s the e a r l y s i d e e f f e c t s d i m i n i s h as t o l e r a n c e d e v e l o p s and t h e r e i s f r e q u e n t l y a c l i n i c a l improvement i n p s y c h i a t r i c symptoms. A paradigm f o r a s s e s s i n g d r u g e f f e c t s on n e u r o p s y c h o l o g i c a l p e r f o r m a n c e i n p a t i e n t s t r e a t e d w i t h l o n g - t e r m courses o f n e u r o l e p t i c s i n v o l v e s a drug washout p e r i o d o f a t l e a s t one m onth f o l l o w e d by random a s s i g n m e n t t o d r u g and p l a c e b o c o n d i t i o n s . Heaton and Crowley (1981) c i t e 4 s t u d i e s o f t h i s s o r t . The f i n d i n g s s u g g e s t t h a t r e l a t i v e t o t h e p l a c e b o c o n d i t i o n t h e r e was a f a v o r a b l e e f f e c t o f n e u r o l e p t i c drugs on 50 a t t e n t i o n and simple i n f o r m a t i o n p r o c e s s i n g but not a measur-a b l e e f f e c t on more complex c o g n i t i v e p r o c e s s e s . S u b j e c t c h a r a c t e r i s t i c s ; e f f e c t o f age, e d u c a t i o n and  e t h n i c i t y on n e u r o p s y c h o l o g i c a l p e r f o r m a n c e . Age has r e -p e a t e d l y been shown t o i n t e r a c t w i t h p e r f o r m a n c e on n e u r o -p s y c h o l o g i c a l t e s t s (Bak and Greene, 1980; Karzmark, Heaton, Grant, & Matthews, 1984). Although t h i s i s an i s s u e t o be c o n s i d e r e d when r e s e a r c h i s conducted w i t h samples composed o f s u b j e c t s v a r y i n g w i d e l y i n age, marked e f f e c t s o f age on t e s t performance are most u s u a l l y noted i n s u b j e c t s e n t e r i n g t h e i r 70s and 80s. E d u c a t i o n l e v e l has been fou n d t o have a s i g n i f i c a n t e f f e c t on the a c c u r a c y o f t e s t - d e r i v e d c l a s s i f i c a t i o n s o f ' n o r m a l ' v s . ' b r a i n damaged' s t a t u s . N o n - b r a i n damaged i n d i v i d u a l s who a r e y o u n g e r , more i n t e l l i g e n t , and w e l l e d u c a t e d t e n d t o be c o r r e c t l y c l a s s i f i e d whereas l e s s w e l l educated i n d i v i d u a l s are more l i k e l y t o be m i s c l a s s i f i e d as b r a i n damaged. The c o n v e r s e i s t r u e f o r b r a i n damaged i n d i v i d u a l s (Adam, Boake, & G r a i n , 1982; Anthony, H e a t o n , & Lehman, 1980; F i n l a y s o n , Johnson, & R e i t a n , 1977). Karzmark e t a l . (1984), u s i n g 491 n e u r o l o g i c a l l y normal p e r s o n s , developed and c r o s s - v a l i d a t e d an e q u a t i o n t h a t uses d e m o g r a p h i c v a r i a b l e s t o p r e d i c t t h e A v e r a g e I m p a i r m e n t R a t i n g s on t h e HRB. They found t h a t i n t h i s sample o f normals, AIR c o r r e l a t e d s i g n i f i c a n t l y w i t h age (r=0.66), race (r=0.23), e d u c a t i o n (r=-0.54), and o c c u p a t i o n (r=-0.43). In a 51 r e g r e s s i o n a n a l y s i s u s i n g these v a r i a b l e s , 65% o f the v a r i a n c e i n AIR s c o r e s f o r the d e r i v a t i o n sample was accounted f o r and 59% i n a c r o s s v a l i d a t i o n sample. C l e a r l y , d e m o g r a p h i c v a r i a b l e s c a n n o t be i g n o r e d i n r e s e a r c h u t i l i z i n g n e u r o p s y c h o l o g i c a l t e s t s . S m a l l sample s t u d i e s t y p i c a l l y attempt t o o b t a i n f a i r l y homogeneous groups o r a l t e r n a t e l y u s e s t a t i s t i c a l t e c h n i q u e s s u c h as t h o s e a p p l i e d by T a y l o r e t a l . (1981, 1984) t o c o n t r o l f o r v a r i a n c e a t t r i b u t a b l e t o d i f f e r e n c e s i n s u b j e c t s t a t u s on demographic v a r i a b l e s . S i g n i f i c a n c e on Neuropsychological D e f i c i t s i n Schizophrenia The importance o f r e p o r t e d n e u r o p s y c h o l o g i c a l impairment i n s c h i z o p h r e n i c p a t i e n t s i s c r i t i c a l l y r e l a t e d t o two i s s u e s . F i r s t , i t must be determined whether d e v i a n t p e r f o r m a n c e on n e u r o p s y c h o l o g i c a l t e s t s i s indeed a v a l i d i n d i c a t i o n o f b r a i n d y s f u n c t i o n and not simply an a r t i f a c t o f c l i n i c a l , demogra-p h i c , or treatment f a c t o r s . F u r t h e r , i f t h e r e are grounds f o r r e a s o n a b l e c o n f i d e n c e t h a t n e u r o p s y c h o l o g i c a l d e f i c i t s are not s i m p l y s e c o n d a r y phenomena, then t h e r e remains the task o f d e t e r m i n i n g the c l i n i c a l s i g n i f i c a n c e o f t h e s e d e f i c i t s i n s c h i z o p h r e n i c p a t i e n t s - i e . are n e u r o p s y c h o l o g i c a l d e f i c i t s s y s t e m a t i c a l l y a s s o c i a t e d w i t h i m p o r t a n t e t i o l o g i c a l o r p r o g n o s t i c f a c t o r s ? The o c c u r r e n c e o f c o g n i t i v e impairment i n some s c h i z o -p h r e n i c p a t i e n t s and i t s a s s o c i a t i o n w i t h poor p r o g n o s i s are 52 o b s e r v a t i o n s as o l d as the d i a g n o s i s i t s e l f . N e u r o p s y c h o -l o g i c a l l i t e r a t u r e i s q u i t e c o n s i s t e n t i n demonstrating t h a t i m p a i r m e n t i s most common and s e v e r e i n c h r o n i c a l l y i l l p a t i e n t s . F u r t h e r r e s e a r c h must address the antecedents o f t h i s c o r r e l a t i o n , as i t i s s t i l l n o t c l e a r whether n e u r o -p s y c h o l o g i c a l i m p a i r m e n t i s c a u s a l l y i m p l i c a t e d i n t h e development o f severe and c h r o n i c psychopathology or i s a by-produ c t o f t h a t c l i n i c a l syndrome. D e s p i t e the pr e s e n t a m b i g u i t i e s i n the i n t e r p r e t a t i o n o f n e u r o p s y c h o l o g i c a l f i n d i n g s i n s c h i z o p h r e n i a , some r e c e n t s t u d i e s p r o v i d e v a l u a b l e d e s c r i p t i v e i n f o r m a t i o n and c o n t r i -b u t e t o t h e emergence o f a b r o a d l y based 'new lo o k ' at the s c h i z o p h r e n i a syndrome. Summary o f N e u r o p s y c h o l o g i c a l F i n d i n g s i n S c h i z o p h r e n i a S e v e r a l aspects o f the n e u r o p s y c h o l o g i c a l l i t e r a t u r e have b e e n d i s c u s s e d i n t h i s r e v i e w and may be summarized as f o l l o w s : 1) O v e r a l l , t h e c l a s s i f i c a t i o n o r d i f f e r e n t i a l d i a g n o s i s s t u d i e s show t h a t c h r o n i c s c h i z o p h r e n i c p a t i e n t s are very d i f f i c u l t t o d i s t i n g u i s h from i n d i v i d u a l s w i t h d i f f u s e b r a i n d y s f u n c t i o n . When popul a r n e u r o p s y c h o l o g i c a l s c r e e n i n g t e s t s and f u l l n e u r o p s y c h o l o g i c a l b a t t e r i e s a r e a p p l i e d t o g r o u p s w i t h p r i o r d i a g n o s e s o f b r a i n damage and c h r o n i c s c h i z o p h r e n i a , i n v e s t i g a t o r s r e p o r t e s s e n t i a l l y chance l e v e l o f c l a s s i f i c a t i o n accuracy. In c o n t r a s t , the median l e v e l o f c o r r e c t c l a s s i f i c a t i o n between b r a i n damaged p a t i e n t s and l e s s d i s t u r b e d s c h i z o p h r e n i c s o r o t h e r t y p e s o f p s y c h i a t r i c p a t i e n t s i s a p p r o x i m a t e l y 75%. 2) The m a j o r i t y o f d e s c r i p t i v e s t u d i e s o f the nat u r e o f the n e u r o p s y c h o l o g i c a l i m p a i r m e n t o c c u r r i n g i n s c h i z o p h r e n i c s , s u g g e s t t h a t t h e p a t t e r n o f impairment i n v o l v e s g e n e r a l i z e d d e f i c i t s on most common n e u r o p s y c h o l o g i c a l t e s t s . However r e s e a r c h i s not unanimous on t h i s m a t t e r . Some i n v e s t i g a t o r s r e p o r t t h a t i m p a i r m e n t i s most marked on t e s t s s e n s i t i v e t o f r o n t a l and temporal l o b e f u n c t i o n , and K o l b and Whishaw (1983) r e p o r t n o r m a l a t t a i n m e n t on p a r i e t a l l o b e t e s t s . 3) D i f f i c u l t i e s a s s o c i a t e d w i t h the d e f i n i t i o n o f n e u r o p s y c h o l o g i c a l i m p a i r -ment, and t h e c h o i c e o f a p p r o p r i a t e c o m p a r i s o n groups f o r s c h i z o p h r e n i c p a t i e n t s , make i t d i f f i c u l t t o a s s e s s t h e p r e v a l e n c e o f n e u r o p s y c h o l o g i c a l d y s f u n c t i o n i n samples o f s c h i z o p h r e n i c p a t i e n t s . Four s t u d i e s d i s c u s s e d e a r l i e r i n t h i s review r e p o r t the p r o p o r t i o n o f p a t i e n t s who perform i n an i m p a i r e d r ange r e l a t i v e t o e i t h e r s t a n d a r d i m p a i r m e n t c u t t i n g s c o r e s o r n o r m a l c o n t r o l g r o u p s . The A v e r a g e Impairment R a t i n g (AIR) i s a commonly used s c a l e f o r r e p o r t i n g t h e s e v e r i t y o f i m p a i r m e n t on t h e HRB. D o n n e l l e y e t a l . (1980) and R e i d e r e t a l . (1979) c l a s s i f i e d as impaired 60% and 6 2% r e s p e c t i v e l y o f t h e i r samples o f c h r o n i c s c h i z o p h r e n i c s . R e l a t i v e t o normal c o n t r o l s , T a y l o r and Abrams d e s c r i b e d 75% o f t h e i r sample o f s c h i z o p h r e n i c s as e x h i b i t i n g moderate t o s e v e r e i m p a i r m e n t . 4) Because d i a g n o s t i c p r a c t i c e s have changed over time, and r e s e a r c h r e p o r t s vary c o n s i d e r a b l y i n the e x t e n t to which the sample i s d e s c r i b e d on f a c t o r s such as c h r o n i c i t y and s e v e r i t y o f i l l n e s s , i t i s not p o s s i b l e to d e r i v e c u m u l a t i v e r a t e s o f n e u r o p s y c h o l o g i c a l i m p a i r m e n t i n c h r o n i c , vs. acute s c h i z o p h r e n i c p a t i e n t s . Nonetheless t h e r e i s c o n s i d e r a b l e c o n v e r g i n g evidence t h a t i m p a i r m e n t i s most f r e q u e n t i n c h r o n i c s e v e r e l y - i l l p a t i e n t s , and occurs at a lower r a t e i n groups o f a c u t e / r e a c t i v e s c h i z o p h r e n i c p a t i e n t s d e s p i t e t h e p r e s e n c e o f c l e a r p s y c h o t i c symptoms. 5) The r e l a t i o n s h i p o f n e u r o l e p t i c m e d i c a t i o n to n e u r o p s y c h o l o g i c a l p e r f o r m a n c e i s n o t w e l l u n d e r s t o o d . A v a i l a b l e r e s e a r c h s u g g e s t s t h a t t h e most m a r k e d d e t r i m e n t a l e f f e c t s o f n e u r o l e p t i c s may be e a r l y i n the course o f a d m i n i s t r a t i o n or s h o r t l y a f t e r marked i n c r e a s e s i n dosage ( i e . d u r i n g t i m e s when t h e s i d e e f f e c t s o f the medications are t y p i c a l l y most pronounced). There i s evidence t h a t a n t i p s y c h o t i c m e d i c a t i o n may have a p o s i t i v e e f f e c t on n e u r o p s y c h o l o g i c a l f u n c t i o n i n g ; p a t i e n t s who are s t a b i l i z e d on m e d i c a t i o n e x h i b i t i n c r e a s e d a b i l i t y on t e s t s o f a t t e n t i o n and s i m p l e i n f o r m a t i o n p r o c e s s i n g r e l a t i v e t o t h e i r p e r f o r m a n c e i n an u n m e d i c a t e d s t a t e . 6) Age, IQ, e d u c a t i o n l e v e l and e t h n i c i t y have a l l been a s s o c i a t e d w i t h attainment on n e u r o p s y c h o l o g i c a l t e s t s . Demographic v a r i a b l e s must be c o n s i d e r e d i n r e s e a r c h u t i l i z i n g n e u r o p s y c h o l o g i c a l t e s t s . 7) The s i g n i f i c a n c e o f f i n d i n g s o f n e u r o p s y c h o l o g i c a l impairment i n s c h i z o p h r e n i a awaits f u r t h e r r e s e a r c h . T h e r e r e m a i n s t h e p o s s i b i l i t y t h a t n e u r o p s y c h o l o g i c a l p e r f o r m a n c e d e f i c i t s a r e n o t v a l i d 55 i n d i c a n t s o f b r a i n d y s f u n c t i o n i n p s y c h i a t r i c p a t i e n t s . I t may be more r e a l i s t i c t o a t t r i b u t e i m p a i r e d s c o r e s t o g e n e r a l i z e d b e h a v i o r a l d i s o r d e r a s s o c i a t e d w i t h p s y c h i a t r i c d i s t u r b a n c e . T e s t i n g the c o r r e c t n e s s o f t h i s i n t e r p r e t a t i o n w i l l r e q u i r e c o n s i d e r a b l e f u r t h e r r e s e a r c h . P a r t i c u l a r l y u s e f u l w o u l d be a s s e s s m e n t i n h i g h r i s k s a m p l e s and l o n g i t u d i n a l i n v e s t i g a t i o n s o f p a t i e n t s who e v i d e n c e r e m i s s i o n s . However, as n e u r o p s y c h o l o g i c a l impairment appears t o be most common i n s e v e r e l y i l l , u n r e m i t t i n g p a t i e n t s , d e c o u p l i n g s e v e r e b e h a v i o r a l d i s t u r b a n c e from impairment on n e u r o p s y c h o l o g i c a l t e s t s i s o f t e n not p o s s i b l e . 8) Research most l i k e l y t o e s t a b l i s h t h e s i g n i f i c a n c e o f neuropsycho-l o g i c a l d e f i c i t s w i l l be i n the area o f documenting r e l a t i o n -s h i p s b e t w e e n n e u r o p s y c h o l o g i c a l p e r f o r m a n c e and o t h e r v a r i a b l e s o f c l i n i c a l , b i o l o g i c a l , e t i o l o g i c a l , and p r o g n o s t i c s i g n i f i c a n c e . Summary o f R e l a t i o n s h i p s Among Measures o f  Smooth P u r s u i t Eye Movements (SPEM),  L a t e r a l V e n t r i c l e Enlargement (LVE),  and N e u r o p s y c h o l o g i c a l T e s t Performance (NTP)  i n S c h i z o p h r e n i a T h i s f i n a l s e c t i o n o f the l i t e r a t u r e r e v i e w w i l l be a b r i e f summary o f s e v e r a l s t u d i e s c i t e d i n the p r e v i o u s t h r e e s e c t i o n s . The p u r p o s e o f t h i s s e c t i o n i s t o h i g h l i g h t r e s e a r c h w h i c h has examined a s s o c i a t i o n s between v a r i o u s 56 c o m b i n a t i o n s o f measures o f smooth p u r s u i t eye movements (SPEM), l a t e r a l v e n t r i c l e e n l a r g e m e n t (LVE), and neuropsy-c h o l o g i c a l t e s t performance (NTP). SPEM and LVE W e i n b e r g e r and Wyatt (1982) a s s e s s e d t h e a s s o c i a t i o n between t r a c k i n g p r o f i c i e n c y o f 20 p a t i e n t s w i t h n o r m a l v e n t r i c l e s , and 14 p a t i e n t s w i t h e n l a r g e d v e n t r i c l e s . S i x t y f o u r p e r c e n t o f the l a r g e v e n t r i c l e s u b j e c t s showed impaired t r a c k i n g compared w i t h t h i r t y p e r c e n t o f the s m a l l v e n t r i c l e s u b j e c t s . T h i s work by Weinberger and Wyatt was i n v e s t i g a t o r y i n n a t u r e . The eye movements were generated by a swinging pendulum and r a t e d q u a l i t a t i v e l y . Nonetheless i t does suggest t h a t e n l a r g e d v e n t r i c l e s may be a s s o c i a t e d w i t h impaired SPEM. The o t h e r i n v e s t i g a t i o n which assessed the a s s o c i a t i o n between SPEM and LVE was c a r r i e d out by B a r t f a i e t a l . (1985) (see the f o l l o w i n g s e c t i o n on SPEM, LVE and NTP, f o r a f u l l d e s c r i p t i o n o f t h i s s t u d y ) . They found t h a t few p a t i e n t s i n t h e i r sample had evidence o f m o r p h o l o g i c a l changes i n a n t e r i o r horn s i z e (a l i n e a r measure o f l a t e r a l v e n t r i c l e s i z e ) , but they noted a tendency f o r the most impaired eye t r a c k e r s t o have a l a r g e r a n t e r i o r h o r n i n d e x t h a n p a t i e n t s w i t h good o r s l i g h t l y impaired eye movements. 57 SPEM and NTP H o l z m a n (1974) and C e g a l i s and Sweeny (1979, 1982) addressed a s s o c i a t i o n s between Wechsler s c a l e IQs, e d u c a t i o n a l a t t a i n m e n t , and t r a c k i n g p e r f o r m a n c e . These i n v e s t i g a t o r s f a i l e d t o f i n d c o r r e l a t i o n s between p a r t i a l or f u l l s c a l e IQ or e d u c a t i o n a l a t t a i n m e n t and t r a c k i n g p r o f i c i e n c y . See f o l l o w i n g s e c t i o n on SPEM, LVE and NTP f o r d i s c u s s i o n o f the B a r t f a i e t a l . study. LVE and NTP T h e r e a r e s e v e r a l s t u d i e s w h i c h have a d d r e s s e d t h i s r e l a t i o n s h i p as i n d i c a t e d i n a p r e v i o u s s e c t i o n o f t h i s review ( s e e ' C o g n i t i v e / n e u r o p s y c h o l o g i c a l f u n c t i o n and CT s c a n a b n o r m a l i t i e s ' ) . I t was p o i n t e d out t h a t a s i z a b l e p r o p o r t i o n o f the l i t e r a t u r e on c o g n i t i v e impairment and b r a i n morphology has i n c l u d e d measures oth e r than l a t e r a l v e n t r i c l e s i z e ; most f r e q u e n t l y assessments o f s u l c a l prominence. S e v e r a l i n v e s t i -g a t o r s have r e p o r t e d a r e l a t i o n s h i p between marked s u l c a l p r o m i n e n c e and d e f i c i t s i n c o g n i t i v e f u n c t i o n i n g . Unfor-t u n a t e l y t h e r e i s no consensus i n the l i t e r a t u r e w i t h r e s p e c t t o a s s e s s i n g t h i s a s p e c t o f b r a i n s t r u c t u r e from CT scans; t h e r e i s evidence t h a t the l e v e l o f the upper most CT scan cut has c o n s i d e r a b l e i n f l u e n c e on r a t i n g s o f s u l c a l prominence and i s not s t a n d a r d i z e d a c r o s s s t u d i e s . In a d d i t i o n t o s t u d i e s which have focused on the r e l a t i o n s h i p between s u l c a l promi-nence and c o g n i t i v e f u n c t i o n i n g i n s c h i z o p h r e n i a t h e r e a r e 58 o t h e r i n v e s t i g a t i o n s which a s s e s s t h e r e l a t i o n s h i p between " s t r u c t u r a l a b n o r m a l i t y " (on s e v e r a l CT s c a n v i s u a l i z e d a s p e c t s o f b r a i n s t r u c t u r e ) and c o g n i t i v e i m p a i r m e n t . Thus w h i l e D o n n e l l y , W e i n b e r g e r , Waldman, and Wyatt (1980), and Weinberger e t a l . (1979b) found a s s o c i a t i o n s between s t r u c -t u r a l a b n o r m a l i t y and impaired c o g n i t i v e f u n c t i o n i n g , they do not r e p o r t the e x t e n t o f t h e r e l a t i o n s h i p between LVE and i m p a i r e d i n t e l l e c t u a l performance. In overview, i t appears t h a t many o f the s t r o n g e s t c l a i m s f o r an a s s o c i a t i o n between b r a i n s t r u c t u r e and l e v e l o f c o g n i t i v e f u n c t i o n i n g d e r i v e from i n v e s t i g a t i o n s i n v o l v i n g measures o f the s u l c i and combina-t i o n s o f s e v e r a l m o r p h o l o g i c a l measures. There are r e p o r t s o f a s i g n i f i c a n t r e l a t i o n s h i p between LVE and c o g n i t i v e impairment. Johnstone e t a l (1976) r e p o r t e d a c o r r e l a t i o n o f -.70 between Wi t h e r s - H i n t o n s c o r e s and VBR; G o l d e n e t a l . (1980a) r e p o r t e d a m u l t i p l e c o r r e l a t i o n c o e f -f i c i e n t o f 0.72 between e i g h t L u r i a Nebraska B a t t e r y s c a l e s and VBR. Golden e t a l . (19 82) found a m u l t i p l e c o r r e l a t i o n o f 0.76 between 14 L u r i a Nebraska s c a l e s and VBR. Some s t u d i e s a s s e s s i n g the r e l a t i o n s h i p between l a t e r a l v e n t r i c l e s i z e and n e u r o p s y c h o l o g i c a l / i n t e l l e c t u a l f u n c t i o n have f a i l e d t o f i n d s i g n i f i c a n t c o r r e l a t i o n s d e s p i t e reason-a b l e ranges i n l e v e l s o f c o g n i t i v e performance and a reason-a b l e p r o p o r t i o n o f i n d i v i d u a l s e v i d e n c i n g LVE ( N a s r a l l a h e t a l . , 1983a & 1983b; Weinberger e t a l . , 1979; W i l l i a m s e t a l . , 1985) .. Two r e c e n t a d d i t i o n s t o t h e l i t e r a t u r e have r e p o r t e d n o v e l r e l a t i o n s h i p s between measures o f c o g n i t i v e f u n c t i o n i n g and l a t e r a l v e n t r i c l e s i z e . DeMeyer e t a l . (1984) found s i g n i f i c a n t V B R/neuropsychological t e s t c o r r e l a t i o n s i n t h e d i r e c t i o n o p p o s i t e t o t h a t n o r m a l l y p r e d i c t e d f o r t o t a l summary s c o r e s and i n d i v i d u a l s u b t e s t s on the L u r i a Nebraska B a t t e r y , the H a l s t e a d - R e i t a n B a t t e r y , and the Wechsler A d u l t I n t e l l i g e n c e S c a l e . The c o r r e l a t i o n o f VBR w i t h the H a l s t e a d Impairment Index was -.77, VBR c o r r e l a t e d .79 w i t h WAIS v e r b a l IQ, .59 w i t h p e r f o r m a n c e IQ, and .73 w i t h f u l l s c a l e IQ. These c o r r e l a t i o n s were obtained u s i n g the s c o r e s o f a sample o f 13 t r e a t m e n t - r e s i s t a n t p s y c h i a t r i c p a t i e n t s o f m i x e d d i a g n o s e s ( h a l f were s c h i z o p h r e n i c ) . I n t h i s sample, the n o n s c h i z o p h r e n i c p a t i e n t s tended to have l a r g e r VBR's and had a s l i g h t l y h i g h e r mean IQ. O v e r a l l , the DeMeyer e t a l . study i s not s p e c i f i c t o s c h i z o p h r e n i a . R a t h e r i t a s s e s s e s t h e r e l a t i o n s h i p between VBR and n e u r o p s y c h o l o g i c a l performance i n a sample o f p s y c h i a t r i c p a t i e n t s s e l e c t e d by c h r o n i c i t y and poor r e s p o n s e to treatment r a t h e r than d i a g n o s i s . F i n a l l y , Owens e t a l . (1985) r e p o r t e d a s i g n i f i c a n t c u r v i l i n e a r r e l a -t i o n s h i p between VBR and s c o r e s on the Withers and H i n t o n t e s t i n a sample o f 110 i n s t i t u t i o n a l i z e d s c h i z o p h r e n i c p a t i e n t s . T h i s u n e x p e c t e d f i n d i n g o f an e x c e s s o f p a t i e n t s w i t h low Withers and H i n t o n s c o r e s at both extremes o f v e n t r i c l e s i z e s u g g e s t e d t o Owens e t a l . t h a t t h e r e may be two groups o f c o g n i t i v e l y impaired s c h i z o p h r e n i c p a t i e n t s . One group would 60 be expected t o e x h i b i t v e n t r i c u l a r enlargement, w h i l e another g r o u p o f c o g n i t i v e l y i m p a i r e d p a t i e n t s may have v e n t r i c l e s which are s m a l l compared t o the normal c o n t r o l mean. SPEM, LVE and NTP The s t u d y by B a r t f a i e t a l . (1985 ) i s o f p a r t i c u l a r i n t e r e s t as they examined the same s e t o f v a r i a b l e s as those u s e d i n t h e p r e s e n t r e s e a r c h study. B a r t f a i e t a l . r e p o r t t h a t most o f t h e i r sample o f 18 s c h i z o p h r e n i c p a t i e n t s e x h i b i t e d some degree o f eye t r a c k i n g impairment. They found t h a t SPEM impairment was r e l a t e d t o worse performance on the t h r e e n e u r o p s y c h o l o g i c a l measures a d m i n i s t e r e d . Eye movement re c o r d s were v i s u a l l y r a t e d f o r d e v i a n c e from t h e s t i m u l u s p a t t e r n on a 5-point s c a l e . The eye t r a c k i n g r a t i n g s o b t a i n e d by s u b j e c t s were t h e n c o r r e l a t e d w i t h t h e i r s c o r e s on t h e F i n g e r - T a p p i n g T e s t , T r a i l - M a k i n g T e s t , and r e v e r s a l s o f a Necker cube. They found the f o l l o w i n g c o r r e l a t i o n s between smooth p u r s u i t t r a c k i n g p r o f i c i e n c y o f a s i n u s o i d a l t a r g e t and the n e u r o p s y c h o l o g i c a l t e s t s : r = -.45 (p<0.10) f o r f i n g e r -t a p p i n g l e f t hand; r = -.49 (p<0.05) f o r f i n g e r - t a p p i n g r i g h t hand; r = .56 (p<0.01) f o r T r a i l - M a k i n g T e s t A; r = .37 (NS) f o r T r a i l - M a k i n g T e s t B; and r = -.5 3 (p<.05) f o r the number o f Necker Cube r e v e r s a l s . B a r t f a i e t a l . f a i l e d t o f i n d a s i g n i f i c a n c e d i f f e r e n c e i n a n t e r i o r horn index between groups o f s u b j e c t s c r e a t e d on the b a s i s o f eye t r a c k i n g p r o f i c i e n c y . However, t h e y suggest t h a t s u b j e c t s who t r a c k e d more p o o r l y 61 tended t o have wider l a t e r a l v e n t r i c l e s t h a n s u b j e c t s w i t h good o r s l i g h t l y impaired eye t r a c k i n g . The authors do not r e p o r t f i n d i n g s r e l a t i n g the n e u r o p s y c h o l o g i c a l t e s t s to t h e measure o f l a t e r a l v e n t r i c l e width. D e s p i t e apparent s i m i l a r i t i e s , the p r e s e n t study and the B a r t f a i e t a l . (1985) r e p o r t d i f f e r i n s e v e r a l s i g n i f i c a n t ways. The B a r t f a i e t a l . sample was a heterogeneous group o f s c h i z o p h r e n i c p a t i e n t s c o n s i s t i n g o f 18 s u b j e c t s (11 males, 7 females) r a n g i n g i n age from 23 t o 42 y e a r s . Two t h i r d s o f the sample were o u t p a t i e n t s , one h a l f o f the s u b j e c t s had o n l y one h o s p i t a l i z a t i o n , and one t h i r d were c l a s s i f i e d as c h r o n i c . In c o n t r a s t , the 30 s u b j e c t s p a r t i c i p a t i n g i n t h i s study were c o n s i d e r a b l y more homogeneous. A l l were male DSM-III c h r o n i c s c h i z o p h r e n i c s who were i n p a t i e n t s at the time o f t e s t i n g . There are advantages and drawbacks i m p l i c i t t o both types of samples. While the B a r t f a i e t a l . sample i s more l i k e l y t o be r e p r e s e n t a t i v e o f s c h i z o p h r e n i c s i n g e n e r a l , the h e t e r o g e n e i t y i n sex, age, d u r a t i o n o f i l l n e s s and h o s p i t a l i z a t i o n s t a t u s may i n t r o d u c e numerous confounds which obscure the r e l a t i o n -s h i p s between v a r i a b l e s . In a d d i t i o n , t h e p r e s e n t s t u d y d i f f e r s c o n s i d e r a b l y from t h a t o f B a r t f a i e t a l . w i t h r e s p e c t t o m e a s u r e m e n t and q u a n t i f i c a t i o n t e c h n i q u e s f o r smooth p u r s u i t eye t r a c k i n g , l a t e r a l v e n t r i c l e s i z e , and i n terms o f t h e e x t e n s i v e n e s s o f t h e n e u r o p s y c h o l o g i c a l b a t t e r y . The f o l l o w i n g r e p o r t d i s c u s s e s the r e s u l t s o f a r e s e a r c h p r o j e c t i n v o l v i n g 1 ) s o p h i s t i c a t e d measurement and c o m p u t e r i z e d s c o r i n g o f smooth p u r s u i t eye t r a c k i n g p e r f o r m a n c e ; 2) an e x t e n s i v e n e u r o p s y c h o l o g i c a l b a t t e r y i n c l u d i n g a f u l l Weschler I n t e l l i g e n c e s c a l e (WAIS-R) and 3) a measure o f l a t e r a l v e n t r i c l e s i z e e s t imated by mechanical p l a n i m e t r y i n conjunc-t i o n w i t h a l a r g e s e r i e s o f scans t h a t i n c l u d e a v o l u n t e e r n o r m a l c o n t r o l group. The above m e t h o d o l o g i c a l refinements stand somewhat i n c o n t r a s t to the measurement t e c h n i q u e s o f B a r t f a i e t a l . These i n v e s t i g a t o r s assessed smooth p u r s u i t t r a c k i n g p e r f o r m a n c e u s i n g v i s u a l r a t i n g s o f t r a c k i n g d e v i a n c e . L a t e r a l v e n t r i c l e s i z e was e s t i m a t e d by a l i n e a r w i d t h measurement o f t h e a n t e r i o r h o r n s o f t h e l a t e r a l v e n t r i c l e s . T h i s method has c o n s i s t e n t l y been found t o have the lowest i n t e r - r a t e r r e l i a b i l i t y , and the lowest c o r r e l a t i o n w i t h c r i t e r i o n measures o f v e n t r i c u l a r volume o f any o f the commonly used i n d e x e s o f l a t e r a l v e n t r i c l e s i z e ( R e v e l e y , 1985). The n e u r o p s y c h o l o g i c a l t e s t s were a d m i n i s t e r e d on a computer i n a s e s s i o n l a s t i n g 10 minutes. While two o f t h e t e s t s a r e r o u t i n e l y a d m i n i s t e r e d , the computerized p r e s e n t a -t i o n i s not standard and the r e s u l t s may not be comparable to o t h e r s t u d i e s . F i n a l l y , B a r t f a i e t a l . d i d n o t i n c l u d e c o n t r o l groups f o r any o f t h e i r measures; i t i s not p o s s i b l e to determine i f t h e i r sample were a c t u a l l y d e v i a n t on any o f the v a r i a b l e s , , hence the s i g n i f i c a n c e o f t h e i r f i n d i n g s i s unknown. O v e r a l l , d e s p i t e the s i m i l a r i t y o f purposes between t h i s s t u d y and t h e B a r t f a i e t a l . s t u d y , t h e r e a r e c o n s i d e r a b l e d i f f e r e n c e s i n s u b j e c t c h a r a c t e r i s t i c s , measure-ment t e c h n i q u e s , and t h e u s e o f c o n t r o l g r o u p s . T h e s e d i f f e r e n c e s make the p r e s e n t study and the r e p o r t o f B a r t f a i e t a l . , two d i s t i n c t approaches t o the i n v e s t i g a t i o n o f t h e r e l a t i o n s h i p s between smooth p u r s u i t eye t r a c k i n g , l a t e r a l v e n t r i c l e s i z e , and n e u r o p s y c h o l o g i c a l performance. C o n c l u s i o n s From L i t e r a t u r e Review The p r e c e d i n g review has d e a l t w i t h p r o g r e s s to date i n m a t t e r s o f d e f i n i t i o n / d e s c r i p t i o n , p r e v a l e n c e r a t e s and c l i n i c a l / t h e o r e t i c a l s i g n i f i c a n c e o f s m o o t h p u r s u i t e y e t r a c k i n g d y s f u n c t i o n , CT s c a n a b n o r m a l i t y , a n d n e u r o p s y c h o l o g i c a l p e r f o r m a n c e d e f i c i t s i n s c h i z o p h r e n i a . R e p e a t e d l y t h e r e s e a r c h has demonstrated t h a t some, but not a l l , s c h i z o p h r e n i c p a t i e n t s are d e v i a n t r e l a t i v e t o the normal range on these v a r i a b l e s . T h i s i s c o n s i s t e n t w i t h the contem-po r a r y view o f s c h i z o p h r e n i a as a heterogeneous d i s o r d e r which i s p r o b a b l y c o mposed o f a number o f more homogeneous subgroups. I t i s c l e a r t h a t f o r each o f the t h r e e v a r i a b l e s d i s c u s s e d , d e v i a n t s t a n d i n g would not be p r e d i c t e d f o r a l l i n d i v i d u a l s c u r r e n t l y diagnosed as s c h i z o p h r e n i c . However, i t i s e q u a l l y a p p a r e n t t h a t t h e m a j o r i t y o f s t u d i e s were not s p e c i f i c a l l y designed to address t h i s i s s u e . The f o l l o w i n g d i s c u s s i o n o f the subgroup i s s u e i s o f f e r e d as an attempt at s y n t h e s i s o f the r e s e a r c h f i n d i n g s and as a r a t i o n a l e f o r the p r e s e n t study. Attempts t o d e l i n e a t e and d e s c r i b e subgroups w i t h i n the d i a g n o s t i c c l a s s i f i c a t i o n ' s c h i z o p h r e n i a ' have a l o n g h i s t o r y . A t y p i c a l r e s e a r c h approach t o the subgroup i s s u e i s t o f i n d or p o s i t a v a r i a b l e or dimension on which groups o f s c h i z o -p h r e n i c s may be d i f f e r e n t i a t e d . Subgroups which d i f f e r w i t h r e s p e c t t o t h i s c l a s s i f i c a t i o n v a r i a b l e are then i n v e s t i g a t e d t o d e t e r m i n e t h e ways i n w h i c h t h e y d i f f e r f o r o t h e r c l i n i c a l l y s i g n i f i c a n t a spects o f the d i s o r d e r . H i s t o r i c a l l y s u b g r o u p s h a v e b e e n formed on t h e b a s i s o f c l i n i c a l o r p h e n o m e n o l o g i c a l d i c h o t o m i e s s u c h as p a r a n o i d v s . n o n -p a r a n o i d , or good premorbid vs. poor premorbid s t a t u s (Wyatt, P o t k i n , Kleinman, Weinberger, L u c h i n s , & J e s t e , 1981). As p o i n t e d o u t i n t h e i n t r o d u c t o r y s t a t e m e n t o f t h i s review, c u r r e n t r e s e a r c h i n s c h i z o p h r e n i a i s i n c r e a s i n g l y t u r n i n g t o b i o l o g i c a l v a r i a b l e s i n attempts t o understand the causes o f s c h i z o p h r e n i a , and when c h a r a c t e r i z i n g t h e u n d e r l y i n g dimensions which may d e l i n e a t e subgroups w i t h i n the d i a g n o s t i c c a t e g o r y . CT scans and eye movement measures are examples of what Wyatt e t a l . (1981) c a l l " b i o l o g i c a l t o o l s f o r s u b c l a s s i f i c a -t i o n " . They p o i n t o u t t h a t t o d a t e r e s e a r c h e r s have been unable t o d i v i d e s c h i z o p h r e n i a i n t o b i o l o g i c a l subtypes. In p a r t they a t t r i b u t e t h i s t o a l o n g h e l d b i a s toward a u n i t a r y d i s e a s e model. However, they add t h a t even when the concept o f subgroups i s s u b s c r i b e d t o , the success o f the endeavor i s compromised by "enormously h i g h v a r i a n c e i n almost a l l c u r r e n t 65 measures on s c h i z o p h r e n i c p a t i e n t s " . (Wyatt e t a l . , 1981, p. 100). At p r e s e n t i t appears t h a t s i n g l e b i o l o g i c a l measures are i n s u f f i c i e n t i n p r o v i d i n g a b a s i s f o r v a l i d i d e n t i f i c a t i o n o f homogeneous subgroups. An a l t e r n a t i v e approach might be the use o f combinations o f measures which are b e l i e v e d t o tap a s i m i l a r u n d e r l y i n g d i m e n s i o n . Use o f a c o m b i n a t i o n o f measures a l s o a i d s i n d e s c r i b i n g the c h a r a c t e r i s t i c s o f t h e p u t a t i v e subgroup i n a more adequate f a s h i o n than would r e s u l t from s i n g l e measures. However, i t c l e a r l y r e q u i r e s a m u l t i -stage r e s e a r c h s t r a t e g y t o v a l i d a t e the use o f a combination o f measures as a more adequate b a s i s o f c l a s s i f i c a t i o n . A p r e l i m i n a r y s t a g e i n t h i s e n d e a v o r i n v o l v e s s i m u l t a n e o u s measurement o f the v a r i a b l e s o f i n t e r e s t i n a s i n g l e sample o f s u b j e c t s i n order t o demonstrate an a s s o c i a t i o n . As i n d i c a t e d r e p e a t e d l y i n t h i s r e v i e w , many i n v e s t i -g a t o r s s p e c u l a t e t h a t t h e r e i s a subgroup o f s c h i z o p h r e n i c p a t i e n t s who s u f f e r from a b r a i n d i s o r d e r w h i c h m i g h t be c h a r a c t e r i z e d as a form o f dementia (Crow, C r o s s , Johnstone, & Owen, 1982; T a y l o r & Abrams, 1984). I t i s s p e c u l a t e d t h a t smooth p u r s u i t eye t r a c k i n g d y s f u n c t i o n , l a t e r a l v e n t r i c u l a r enlargement, and d e f i c i t s i n n e u r o p s y c h o l o g i c a l p e r f o r m a n c e a r e a l l p o t e n t i a l i n d i c a n t s o f p u t a t i v e b r a i n d i s o r d e r . F u r t h e r , i t i s assumed t h a t each measure has weaknesses i n s e n s i t i v i t y and s p e c i f i c i t y f o r d e t e c t i n g t h i s d i s o r d e r . The c u r r e n t p r o j e c t i s an i n v e s t i g a t i o n o f t h e c o v a r i a t i o n o f these measures i n a p o p u l a t i o n expected t o have a moderately h i g h p r e v a l e n c e o f t h e s e d y s f u n c t i o n s . C l e a r l y t h e major i s s u e o f whether a b r a i n d y s f u n c t i o n does or does not e x i s t cannot be determined i n t h i s manner. What can be assessed i s t h e e x t e n t o f r e l a t i o n s h i p between t h e s e v a r i a b l e s . T h i s should a l l o w an e s t i m a t e o f the l i k e l i h o o d t h a t t h e y m i g h t form a u s e f u l combination f o r d e f i n i n g a subgroup which might then be i n v e s t i g a t e d w i t h r e s p e c t to meaningful p s y c h o s o c i a l and c l i n i c a l parameters. RESEARCH OBJECTIVES The primary purpose o f t h i s study i s the i n v e s t i g a t i o n o f t h e r e l a t i o n s h i p between l a t e r a l v e n t r i c l e s i z e , smooth p u r s u i t eye t r a c k i n g , and n e u r o p s y c h o l o g i c a l t e s t performance i n a sample o f c a r e f u l l y d i a g n o s e d c h r o n i c s c h i z o p h r e n i c p a t i e n t s . The r e l a t i o n s h i p s among t h e s e m e a s u r e s i s o f i n t e r e s t b e c a u s e e a c h o f them i s c o n s i d e r e d t o be e i t h e r a s i g n o f , or s e n s i t i v e t o , b r a i n d y s f u n c t i o n . I f d e v i a t i o n s on t h e s e m e a s u r e s i s i n d e e d a f e a t u r e o f a s u b t y p e o f s c h i z o p h r e n i a i n v o l v i n g s i g n i f i c a n t neuropathology, one might e x p e c t t h i s s u b g r o u p t o be most h i g h l y r e p r e s e n t e d among s e r i o u s l y i l l i n s t i t u t i o n a l i z e d p a t i e n t s o f the s o r t assessed i n t h i s study. In o r d e r t o r e l a t e the r e s u l t s o f t h i s study t o ot h e r s i n the l i t e r a t u r e i t i s necessary t o assess the e x t e n t t o which the p r e s e n t sample e x h i b i t s d e v i a n t s t a t u s on the measures o f i n t e r e s t . To a d d r e s s t h i s i s s u e , two c o n t r o l g r o u p s a r e i n c l u d e d i n the d e s i g n . A group o f normal v o l u n t e e r c o n t r o l s serve as comparisons f o r VBR and eye t r a c k i n g . The n e u r o -p s y c h o l o g i c a l p e r f o r m a n c e o f t h e s c h i z o p h r e n i c g r o u p i s compared t o t h a t o f a group o f n o n - s c h i z o p h r e n i c p s y c h i a t r i c p a t i e n t s and to norms obtained from t e s t manuals. The i s s u e s i n v o l v e d i n s e l e c t i o n o f an a p p r o p r i a t e comparison group f o r n e u r o p s y c h o l o g i c a l t e s t s u s ed w i t h s c h i z o p h r e n i c s are not simple. The advantage o f u s i n g n o n - s c h i z o p h r e n i c p s y c h i a t r i c 68 p a t i e n t s i s t h a t t h i s group p r o v i d e s some measure o f c o n t r o l f o r p s y c h i a t r i c s t a t u s p e r s e , and i s a more c o n s e r v a t i v e comparison than would be obt a i n e d by u s i n g t e s t norms d e r i v e d f r o m n o r m a l s a m p l e s . The o b v i o u s drawback i s that* non-s c h i z o p h r e n i c p s y c h i a t r i c p a t i e n t s may e x h i b i t p e c u l i a r p a t t e r n s o f s t r e n g t h s and d e f i c i t s which make i n t e r p r e t a t i o n o f group d i f f e r e n c e s d i f f i c u l t . I n a d d i t i o n , r e l a t i o n s h i p s among the n e u r o p s y c h o l o g i c a l t e s t s i n the s c h i z o p h r e n i c sample w i l l be examined. The s m a l l sample s i z e p r e c l u d e s s o p h i s t i c a t e d m u l t i v a r i a t e and f a c t o r a n a l y t i c a n a l y s e s . N o n e t h e l e s s , e x a m i n a t i o n o f i n t e r c o r r e l a t i o n s i s a means o f l i n k i n g t h i s s t u d y t o t h e o r e t i c a l and e m p i r i c a l statements i n the l i t e r a t u r e . Hypotheses Group D i f f e r e n c e s I t i s p r e d i c t e d t h a t the sample o f s c h i z o p h r e n i c s u b j e c t s w i l l d i f f e r s i g n i f i c a n t l y from t h e c o n t r o l g r o u p s , i n t h e d i r e c t i o n o f g r e a t e r impairment, on the measures o f 1) VBR, 2) smooth p u r s u i t eye t r a c k i n g , and 3 ) n e u r o p s y c h o l o g i c a l t e s t performance. C o r r e l a t i o n s Among VBR, Smooth P u r s u i t Eye T r a c k i n g and  N e u r o p s y c h o l o g i c a l Performance I t i s p r e d i c t e d t h a t t h e r e w i l l be t h e f o l l o w i n g r e l a t i o n s h i p s among the p r i n c i p a l measures: 69 i ) V e n t r i c l e ' b r a i n r a t i o and smooth p u r s u i t eye t r a c k i n g performance w i l l be c o r r e l a t e d such t h a t i n d i v i d u a l s w i t h * l a r g e r v e n t r i c l e s w i l l be found t o have more impaired eye t r a c k i n g . i i ) V e n t r i c l e b r a i n r a t i o and n e u r o p s y c h o l o g i c a l performance w i l l be c o r r e l a t e d s u c h t h a t i n d i v i d u a l s w i t h l a r g e r v e n t r i c l e s w i l l b e m o r e i m p a i r e d o n t h e n e u r o p s y c h o l o g i c a l t e s t s t h a n t h o s e w i t h s m a l l e r ("normal") v e n t r i c l e s . i i i ) S m o o t h p u r s u i t e y e m o v e m e n t s ( S P E M ) a n d n e u r o p s y c h o l o g i c a l performance w i l l be c o r r e l a t e d s u c h t h a t i n d i v i d u a l s w i t h more impaired eye t r a c k i n g w i l l be more i m p a i r e d on t h e n e u r o p s y c h o l o g i c a l t e s t s . The r e l a t i o n s h i p b e t w e e n SPEM and n e u r o p s y c h o l o g i c a l performance c o u l d be o f two s o r t s : a) i f SPEM impairment i s a s s o c i a t e d w i t h a d i f f u s e b r a i n d i s o r d e r then one might e x p e c t SPEM im p a i r m e n t t o be r e l a t e d t o g l o b a l impairment on the n e u r o p s y c h o l o g i c a l t e s t s . b) i f SPEM impairment i s a r e s u l t o f a marked, or s p e c i f i c f r o n t a l l o b e d y s f u n c t i o n , i t might be expected t h a t impaired eye t r a c k i n g would be most s t r o n g l y a s s o c i a t e d w i t h t e s t s c o n s i d e r e d s e n s i t i v e t o f r o n t a l f u n c t i o n ( s i x o f ten i n b a t t e r y ) . C o r r e l a t i o n s W i t h i n B a t t e r y A l t h o u g h n o t c e n t r a l t o t h e m a j o r h y p o t h e s e s o f t h e study, t h e r e are c e r t a i n c o r r e l a t i o n s which might be p r e d i c t e d w i t h i n the n e u r o p s y c h o l o g i c a l t e s t b a t t e r y on the b a s i s o f the l i t e r a t u r e . i ) WAIS-R V e r b a l and Performance IQ's are p r e d i c t e d to be c o r r e l a t e d t h e o t h e r measures o f n e u r o p s y c h o l o g i c a l performance. i i ) The n e u r o p s y c h o l o g i c a l t e s t b a t t e r y i n c l u d e s the Category T e s t , F i n g e r T a p p i n g T e s t , T r i a l M a k i n g T e s t , Word F l u e n c y T e s t , and the Wisconsin Card S o r t T e s t . These t e s t s are b e l i e v e d s e n s i t i v e t o f r o n t a l l o b e f u n c t i o n i n g and would be expected to be c o r r e l a t e d i n the sample o f s c h i z o p h r e n i c p a t i e n t s . 71 METHOD Subj ects C h r o n i c s c h i z o p h r e n i c p a t i e n t s . T h i r t y male c h r o n i c s c h i z o p h r e n i c p a t i e n t s , r e c r u i t e d form a l a r g e p r o v i n c i a l m e n t a l h o s p i t a l ( R i v e r v i e w H o s p i t a l ) , s e r v e d as s u b j e c t s . Recruitment procedures were c a r e f u l l y designed and executed t o i n s u r e t h a t t h e o b t a i n e d sample was composed o f c o n s e n t i n g c o n s e c u t i v e a d m i s s i o n s , who s a t i s f i e d t h e i n c l u s i o n and e x c l u s i o n s e l e c t i o n c r i t e r i a f o r the study. I n d i v i d u a l s were i n c l u d e d i n the p r o j e c t i f they, i ) s a t i s f i e d D i a g n o s t i c and S t a t i s t i c a l M a n u a l I I I (DSM I I I ; A m e r i c a n P s y c h i a t r i c A s s o c i a t i o n , 1980) c r i t e r i a f o r d i a g n o s i s o f c h r o n i c s c h i z o p h r e n i a , i i ) were male and under 35 y e a r s o f age, i i i ) were s u f f i c i e n t l y v e r b a l and c o o p e r a t i v e t o p a r t i c i p a t e i n the d i a g n o s t i c i n t e r v i e w and g i v e w r i t t e n c o n s e n t , i v ) were without documented n e u r o l o g i c a l c o n d i t i o n s and, v) had n o t been t r e a t e d f o r substance dependence. I n i t i a l s c r e e n i n g o f t h e h o s p i t a l p o p u l a t i o n was done from a c o m p u t e r i z e d d a t a - b a n k w h i c h p r o v i d e d d e m o g r a p h i c i n f o r m a t i o n and p r i n c i p a l and s e c o n d a r y p s y c h i a t r i c and m e d i c a l diagnoses, u s i n g the I n t e r n a t i o n a l C l a s s i f i c a t i o n o f Disea s e s System ( n i n t h e d i t i o n ) . From the computer data base an i n i t i a l s u b j e c t p o o l o f males under age 35 w i t h diagnoses o f s c h i z o p h r e n i a was i d e n t i f i e d . The h o s p i t a l r e c o r d s o f t h e s e i n d i v i d u a l s were examined t o d e t e r m i n e d u r a t i o n o f i l l n e s s , p r e s e n c e o f n e u r o l o g i c a l d i a g n o s e s , h i s t o r y o f t r e a t m e n t f o r s u b s t a n c e d e p e n d e n c e , number o f p r e v i o u s h o s p i t a l i z a t i o n s , and t o r e c o r d i n f o r m a t i o n which would a s s i s t i n the d i a g n o s t i c i n t e r v i e w t h a t was conducted as p a r t o f the s e l e c t i o n procedures. I f , on the b a s i s o f c h a r t e d i n f o r m a t i o n t h e r e were no c l e a r grounds t o e x c l u d e t h e i n d i v i d u a l , h i s p s y c h i a t r i s t was c o n t a c t e d and p e r m i s s i o n t o d i s c u s s t h e p r o j e c t w i t h the p a t i e n t was requested. Using the s u b j e c t s e l e c t i o n procedure o u t l i n e d above, 10 3 c o n s e c u t i v e admissions were i d e n t i f i e d as p o t e n t i a l s u b j e c t s over the p e r i o d o f r e c r u i t m e n t and t e s t i n g (5 months). Due to a s e v e r a l week l a g time i n p r o c e s s i n g o f p a t i e n t d i s c h a r g e s t h r o u g h t h e h o s p i t a l computer data base, 25 p a t i e n t s i n the i n i t i a l g roup o f 103 had been d i s c h a r g e d b e f o r e i t was p o s s i b l e t o c o n t a c t them about the study. From a p o o l o f 78 i n p a t i e n t s , 35 were i n t e r v i e w e d and met the s e l e c t i o n c r i t e r i a f o r t h i s study. F i v e o f these p a t i e n t s c o u l d not be i n c l u d e d i n the study; one r e f u s e d t o c o n t i n u e a f t e r t h e s e l e c t i o n i n t e r v i e w , one r e f u s e d t o do the n e u r o p s y c h o l o g i c a l t e s t i n g , two were too s e r i o u s l y d i s t u r b e d t o be taken from the h o s p i t a l to the CT scanner l o c a t i o n and one was extremely h o s t i l e and expressed p a r a n o i d concerns about the experimenters d u r i n g the d i a g n o s t i c i n t e r v i e w . Of t h e remaining 43 i n d i v i d u a l s , 20 r e f u s e d t o p a r t i c i p a t e , 8 p a t i e n t s were i n t e r v i e w e d but d i d n o t meet the d i a g n o s t i c c r i t e r i a f o r the study, and 15 were f e l t t o be u n s u i t a b l e by t h e i r p h y s i c i a n s . In t h i s l a t t e r g r oup u n s u i t a b i l i t y was d e t e r m i n e d by a number of f a c t o r s 73 i n c l u d i n g ; i ) the p a t i e n t was c o n s i d e r e d an extreme elopement r i s k or had r e c e n t l y been v i o l e n t , i i ) the p a t i e n t was g r o s s l y d i s o r g a n i z e d o r i n a c c e s s i b l e , i i i ) t h e p a t i e n t was t o be d i s c h a r g e d b e f o r e a s e l e c t i o n i n t e r v i e w c o u l d be arranged or, ( i v ) t h e p a t i e n t had r e c e n t l y been r e d i a g n o s e d , o f t e n as having a n e u r o l o g i c a l d i s o r d e r . Comparisons between s u b j e c t s who r e f u s e d t o p a r t i c i p a t e (n=20) and those who took p a r t i n t h e s t u d y c o u l d be done u s i n g i n f o r m a t i o n a v a i l a b l e from the R i v e r v i e w H o s p i t a l data bank. S u b j e c t s who r e f u s e d had a mean age o f 27.9 (SD 4.27) and an average number o f admissions t o R i v e r v i e w H o s p i t a l o f 2.6 (SD 2.1) whereas those who p a r t i c i p a t e d had a mean age o f 28.2 (SD 3.71) and had an a v e r a g e number o f admissions to Ri v e r v i e w H o s p i t a l o f 1.9 (SD 2.3) admissions. The groups do not d i f f e r s i g n i f i c a n t l y on e i t h e r o f these v a r i a b l e s . The t h i r t y s c h i z o p h r e n i c p a t i e n t s who p a r t i c i p a t e d i n the study were g i v e n a s t r u c t u r e d d i a g n o s t i c i n t e r v i e w u s i n g the Pres e n t S t a t e Examination (PSE) (Wing, Cooper, & S a r t o r i u s , 1974 ) as a r o u t i n e p a r t o f t h e s e l e c t i o n procedure. T h i s i n t e r v i e w was conducted by one of two Ph.D. p s y c h o l o g i s t s w i t h e x t e n s i v e e x p e r i e n c e w i t h the PSE and the d i a g n o s t i c i s s u e s r e l e v a n t t o s e l e c t i n g s c h i z o p h r e n i c p a t i e n t s f o r r e s e a r c h . Symptom c h e c k l i s t s f o r DSM-III d i a g n o s t i c c r i t e r i a were completed f o r each p a t i e n t based on the PSE, and supplemented by c h a r t i n f o r m a t i o n r e l e v a n t t o d u r a t i o n o f i l l n e s s , p r e v i o u s diagnoses and d e c l i n e i n l e v e l o f f u n c t i o n i n g . The d i a g n o s i s o f DSM-III c h r o n i c s c h i z o p h r e n i a and the s c h i z o p h r e n i c subtype (see T a b l e 5) were determined on the b a s i s o f consensus on the above i s s u e s by the two d i a g n o s t i c i a n s . Thus e a c h p a t i e n t i n c l u d e d i n t h e p r o j e c t h a d an I C D - 9 d i a g n o s i s o f s c h i z o p h r e n i a a c c o r d i n g t o h o s p i t a l r e c o r d s and was a l s o i n d e p e n d e n t l y diagnosed f o r the study u s i n g DSM-III c r i t e r i a f o r c h r o n i c s c h i z o p h r e n i a based on an e x t e n s i v e d i a g n o s t i c i n t e r v i e w s u p p l e m e n t e d by c h a r t i n f o r m a t i o n . I t should be noted t h a t d e s p i t e the care taken i n d i a g n o s i s , some p a t i e n t s were found to be poor h i s t o r i a n s who presented c o n t r a d i c t o r y i n f o r m a t i o n , i n c o n s i s t e n c i e s i n p a t i e n t r e p o r t s were o f t e n recorded i n t h e i r c h a r t s as w e l l . T a b l e s 1 and 2 p r e s e n t age and e d u c a t i o n a l l e v e l s f o r a l l g r o u p s i n v o l v e d i n t h e s t u d y . T a b l e s 3 and 4 p r e s e n t a summary o f t h e number o f h o s p i t a l i z a t i o n s a n d t o t a l a c c u m u l a t e d l e n g t h o f i n s t i t u t i o n a l i z a t i o n f o r the c h r o n i c s c h i z o p h r e n i c p a t i e n t s . S e v e n t y s i x p e r c e n t (23) o f t h e s c h i z o p h r e n i c p a t i e n t s d i d not f i n i s h h i g h s c h o o l , one p a t i e n t completed one year o f a community c o l l e g e . The r ange f o r number o f h o s p i t a l i z a t i o n s was from 1 to 12, w i t h 80% o f the p a t i e n t s having 5 to 8 admissions. The range o f accumulated d u r a t i o n o f h o s p i t a l i z a t i o n spans s e v e r a l years (from 10 years t o 2 months.); 20% o f the sample had spent more than f o u r and one h a l f years i n mental i n s t i t u t i o n s , 50% had spent between two and f o u r and one h a l f years i n h o s p i t a l , and 30% had spent l e s s than two years i n h o s p i t a l . I t i s i n t e r e s t i n g t o note 75 / Table 1 Age of Participants Groups Schizophrenics Normal Psychiatric Controls controls (n-30) (n=29) (n=21) Mean SD Range 28.2 3.71 22-34 24.2 5.74 16-42 25.4 5.5 17-34 76 Table 2 Educational Attainment of Participants Groups Schizophrenics Normal Psychiatric Controls controls (n=30) (n=29) (n=21) Educational Leve I number (%) number (%) number (%) Grade 9 or less Grade 10 to 12 Post secondary training BA/BSc Post Graduate Not Known 9 (30%) 19 (63%) 1 (3%) 1 (3%) 7 (24%) 14 (48%) 5 (17%) 1 (3.3%) 2 (6.8%) 1 (5%) 15 (70%) 2 (10%) 2 (10%) 1 (5%) 77 Table 3 Number of Psychiatric Hospitalizations for Chronic  Schizophrenic Patients3 Number of Hospitalizations Number of Patients Mean Age of Group 1-3 hospitalizatIons 1 33.0 4-6 hospitalizations 15 28.5 7-9 hospitalizations 10 27.2 10-12 hospitalizations 4 30.3 Note. There are no significant differences in age between the groups aAverage number of admissions for entire sample is 6.7 (SD 2.6) 78 Table 4 Accumulated Duration of Institutionalization (In months) for  Chronic Schizophrenic Patients3 Duration Number Mean Duration Mean Age of Patients for Group of Group 2 i . to 23 m. 11 10. ,3 m. 28. ,3 24 m, . to 47 m. 12 33. .2 m. 27. .7 48 m. . to 83 m. 5 60. .4 m. 27. .8 84 r n. to 113 m. 2 92. .2 m. 32. .0 Note. There are no significant differences in age between the groups aAverage accumulated duration of hospitalizations for entire sample is 33.6 months (SD 25.69) 79 Table 5 DSM III Subtypes of Schizophrenia In Chronic Schizophrenic Sample Measure Groups Paranoid Disorganized Undifferentiated Subtype Subtype Subtype Number of Patients 21 Mean age (SD) 28.3 (3.72) Mean Cumulative 32.5 (27.4) Duration of HospitalIza-tions (SD) 28.2 (3.30) 44.2 (36.29) 28.0 (4.47) 29.0 (20.24) 80 t h a t t h e r e are no s i g n i f i c a n t age d i f f e r e n c e s between s u b j e c t s g r o u p e d o n t h e b a s i s o f n u m b e r o r d u r a t i o n o f h o s p i t a l i z a t i o n s . F i v e p a t i e n t s i n t h e s t u d y were on an e x t e n d e d c a r e l o c k e d ward, 12 were on wards d e s i g n a t e d f o r l o n g term p a t i e n t s , and 13 p a t i e n t s were on wards intended f o r admissions o f l e s s than s i x months. The e x c l u s i o n c r i t e r i a f o r t h i s study i n c l u d e d h i s t o r y o f t r e a t m e n t f o r s u b s t a n c e dependence. While no s u b j e c t s had s p e c i f i c a l l y been t r e a t e d f o r substance dependence, s e v e r a l s u b j e c t s had h i s t o r i e s o f e x t e n s i v e substance abuse and/or dependence i n v o l v i n g a l c o h o l , marijuana, LSD, and a v a r i e t y o f i l l i c i t s t r e e t drugs. Each s u b j e c t was i n t e r v i e w e d u s i n g the drug and a l c o h o l p o r t i o n s o f t h e NIMH D i a g n o s t i c I n t e r v i e w S c h e d u l e ( D I S - I I I : R o b i n s , H e l z e r , C roughan, W i l l i a m s , & S p i t z e r , 1981). The accuracy o f s e v e r a l p a t i e n t r e p o r t s i s q u e s t i o n a b l e , p a r t i c u l a r l y as t h e DIS r e q u i r e s s p e c i f i c i n f o r m a t i o n about the d u r a t i o n o f d a i l y use, number o f times v a r i o u s drugs were used, and the e f f e c t o f drug and a l c o h o l u s e on s o c i a l , f a m i l i a l , and work f u n c t i o n i n g . Some i n d i v i d u a l s appeared t o exaggerate t h e i r drug use h i s t o r i e s (e.g., one i n d i v i d u a l claimed t o be u s i n g v a s t q u a n t i t i e s o f s t r e e t drugs and d r i n k i n g l a r g e amounts d a i l y d u r i n g s e v e r a l months w i t h i n he was i n h o s p i t a l ; h o s p i t a l s t a f f denied t h a t t h i s o c c u r r e d ) , w h i l e s e v e r a l p a t i e n t s were b e l i e v e d t o minimize the exte n t o f t h e i r p a s t drug use. Based on m a t e r i a l recorded i n p a t i e n t s 1 c h a r t s and i n f o r m a t i o n o b t a i n e d from the 81 DIS i t i t estimated t h a t 11 o f the s u b j e c t s had h i s t o r i e s o f e x t e n s i v e a l c o h o l o r i l l i c i t drug abuse (e.g. d a i l y use o f m a r i j u a n a o v e r p e r i o d s o f s e v e r a l months, f r e q u e n t g l u e s n i f f i n g , extended p e r i o d s o f a l c o h o l use on a d a i l y b a s i s , e t c . ) ; 11 s u b j e c t s had experimented w i t h i l l i c i t d r u g s and a l c o h o l but had not used them f r e q u e n t l y or on a d a i l y b a s i s ; two p a t i e n t s had t r i e d marij.uana once; f i v e s a i d t h e y had never used i l l i c i t drugs and had r a r e l y used a l c o h o l ; and one p a t i e n t r e f u s e d t o answer the q u e s t i o n n a i r e a l t h o u g h i t was n o t e d i n h i s c h a r t t h a t he had u s e d m a r i j u a n a on s e v e r a l o c c a s i o n s . A l l s u b j e c t s i n t h i s s t u d y were t a k i n g a n t i p s y c h o t i c d r u g s ; t h e m a j o r i t y w e r e o n s e v e r a l m e d i c a t i o n s s i m u l t a n e o u s l y . C a l c u l a t i o n o f d a i l y m e d i c a t i o n dosage i n c h l o r p r o m a z i n e (CPZ) e q u i v a l e n t s was n o t a t t e m p t e d ; many p a t i e n t s were g i v e n 2 t o 3 d i f f e r e n t o r a l a n t i p s y c h o t i c s on a d a i l y b a s i s as w e l l as a m o n t h l y d e p o t i n j e c t i o n o f f l u p h e n a z i n e a n d a l s o h a d s t a n d i n g o r d e r s f o r PRN a d m i n i s t r a t i o n o f h a l o p e r i d o l and CPZ f o r a g i t a t i o n . Although m e d i c a t i o n l e v e l s were g e n e r a l l y h i g h , most p a t i e n t s who p a r t i c i p a t e d i n the study had been medicated f o r an extended p e r i o d and d i d not e x h i b i t the marked s i d e e f f e c t s o f t e n seen when m e d i c a t i o n i s f i r s t i n i t i a t e d . None o f the p a r t i c i p a n t s was t h o u g h t t o be s h o w i n g s i g n s o f t a r d i v e d y s k i n e s i a , a l t h o u g h m i l d p a r k i n s o n i a n movements and a k a t h i s i a were n o t 82 uncommon. Twenty s i x o f the s u b j e c t s were r i g h t handed and f o u r were l e f t handed. Normal C o n t r o l Group. A group o f 29 male v o l u n t e e r s r e c r u i t e d from f a m i l y p r a c t i c e c l i n i c s , employment c e n t e r s , community c e n t e r s , and community c o l l e g e s served as a c o n t r o l group o f the CT scan and smooth p u r s u i t eye t r a c k i n g measures. A l l the c o n t r o l s u b j e c t s were g i v e n a p s y c h i a t r i c s c r e e n i n g i n t e r v i e w t o i n s u r e t h a t t h e r e was no h i s t o r y o f treatment f o r p s y c h i a t r i c problems or a l c o h o l or drug abuse f o r e i t h e r the p a r t i c i p a n t or any o f h i s f i r s t degree r e l a t i v e s . Ages and e d u c a t i o n a l l e v e l s o f the v o l u n t e e r c o n t r o l sample are l i s t e d i n T a b l e s 1 a n d 2. T h e v o l u n t e e r c o n t r o l g r o u p i s s i g n i f i c a n t l y younger than the c h r o n i c s c h i z o p h r e n i c p a t i e n t s (t(57)=3.17 p<.01) and i s b e t t e r educated. Procedures f o r CT scanning, measurement o f VBR, and r e c o r d i n g and s c o r i n g eye t r a c k i n g a r e i d e n t i c a l f o r t h e s c h i z o p h r e n i c and v o l u n t e e r c o n t r o l p a t i e n t s . Both o f these s u b j e c t groups are p a r t o f a l a r g e s c a l e study o f s c h i z o p h r e n i a which has developed h i g h l y s t a n d a r d i z e d and very r e l i a b l e measurement and q u a n t i f i c a t i o n p r o c e d u r e s f o r v e n t r i c l e b r a i n r a t i o and smooth p u r s u i t eye t r a c k i n g . P s y c h i a t r i c C o n t r o l Group. C o n t r o l group s c o r e s f o r a l l n e u r o p s y c h o l o g i c a l t e s t s a d m i n i s t e r e d i n t h i s s t u d y were o b t a i n e d f o r a s a m p l e o f n o n s c h i z o p h r e n i c p s y c h i a t r i c p a t i e n t s . From a computerized data bank at the U.B.C. H e a l t h S c i e n c e s Center P s y c h i a t r i c Care U n i t (H.S.C.-P.C.U.) a group 83 o f 21 males u n d e r t h e age o f 35 were s e l e c t e d who, as i n p a t i e n t s a t t h e h o s p i t a l , h a d b e e n r e f e r r e d f o r n e u r o p s y c h o l o g i c a l t e s t i n g . T h i s group was composed o f 7 i n d i v i d u a l s diagnosed as depressed, 5 diagnosed as substance a b u s e r s , 2 as h a v i n g a n x i e t y d i s o r d e r s , 2 as p e r s o n a l i t y d i s o r d e r e d and 4 w i t h o t h e r u n s p e c i f i e d but n o n s c h i z o p h r e n i c p s y c h i a t r i c d i a g n o s i s . T e s t a d m i n i s t r a t i o n procedures f o r the p s y c h i a t r i c c o n t r o l s and the c h r o n i c s c h i z o p h r e n i c p a t i e n t s were w e l l s t a n d a r d i z e d a c r o s s s e t t i n g s as t h e ex a m i n e r f o r t h i s s t u d y had r e c e i v e d e x t e n s i v e t r a i n i n g a t the H.S.C.-P.C.U. and had i n f a c t worked as a t e s t i n g t e c h n i c i a n a t t h i s h o s p i t a l . For t h r e e o f the n i n e measures a d m i n i s t e r e d t h e r e were fewer than 21 p a t i e n t s w i t h c o n t r o l s c o r e s a v a i l a b l e . In the p s y c h i a t r i c c o n t r o l sample, 75% o f s u b j e c t s had grade 9 t o 12 e d u c a t i o n whereas 9 3% o f the c h r o n i c s c h i z o p h r e n i c s were i n t h i s c a t e g o r y . Only 1 s u b j e c t i n the s c h i z o p h r e n i c sample had any p o s t secondary e d u c a t i o n whereas 5 o f the c o n t r o l s u b j e c t s d i d . The two groups do not d i f f e r s i g n i f i c a n t l y i n age. Measures Smooth p u r s u i t eye movement r e c o r d i n g . Smooth p u r s u i t e y e movements were r e c o r d e d i n a p s y c h o p h y s i o l o g i c a l l a b o r a t o r y a t U.B.C. H.S.C-P.C.U. u s i n g a w e l l s t a n d a r d i z e d procedure. With head s t a b i l i z e d i n a c h i n and forehead r e s t s u b j e c t s observed a 5 mm luminous spot, d r i v e n by a s i n e wave gen e r a t o r at a frequency o f .4 hz f o r 20 c y c l e s o f t a r g e t 84 o s c i l l a t i o n , d i s p l a y e d on an o s c i l l o s c o p e s c r e e n p o s i t i o n e d 30 cm from t h e s u b j e c t ' s eyes. Eye movement were recorded by e l e c t r o - o c u l o g r a p h i c (EOG) t e c h n i q u e s u s i n g s i l v e r / s i l v e r c h l o r i d e e l e c t r o d e s p l a c e d a t the outer c a n t h i o f each eye. E l e c t r o d e s p l a c e d a t the s u p e r i o r and i n f e r i o r o r b i t a l rims o f t h e l e f t eye a l l o w e d b l i n k a r t i f a c t s t o be monitored. Eye movements and t a r g e t p o s i t i o n were recorded on a Beckman type R-612 D y n o g r a p h a n d a V e t t e r m o d e l FM r e c o r d e r f o r computerized a n a l y s i s . Accuracy o f eye t r a c k i n g was analysed by a computer-based s c o r i n g program which generates a v a l u e e q u a l t o t h e r o o t -mean-squared (RMS) d e v i a t i o n o f the eye movement wave form from the t a r g e t waveform f o r the 16 b e s t c y c l e s o f t r a c k i n g . The RMS d e v i a t i o n i s o b t a i n e d by u t i l i z i n g a computer program which a l i g n s the t a r g e t and eye t r a c k i n g c hannels, a d j u s t s f o r amplitude d i f f e r e n c e s and then computes the d i f f e r e n c e between the t a r g e t s i g n a l and the s u b j e c t ' s eye movements i n standard d e v i a t i o n u n i t s . The d i s t r i b u t i o n o f RMS s c o r e s i s t y p i c a l l y p o s i t i v e l y skewed making the l o g a r i t h m i c t r a n s f o r m a t i o n o f RMS s c o r e s a more a p p r o p r i a t e e x p r e s s i o n o f t r a c k i n g accuracy f o r use i n t e s t i n g group d i f f e r e n c e s . L a t e r a l v e n t r i c l e s i z e s . S u b j e c t s were scanned on a t h i r d g e n e r a t i o n , h i g h r e s o l u t i o n , t o t a l body scanner (Siemens Somatom DR2) l o c a t e d a t the U.B.C. H e a l t h S c i e n c e s Acute Care H o s p i t a l . Scanning o f a l l p a t i e n t s and v o l u n t e e r c o n t r o l s was done without i n j e c t i n g an enhancement c o n t r a s t medium and w i t h 85 a scanner window width s e t t i n g o f 80 a t a l e v e l o f 27; t h i s s e t t i n g a l l o w s p e r f e c t l y adequate v i s u a l i z a t i o n o f the l a t e r a l v e n t r i c l e s w h i l e m i n i m i z i n g the r a d i a t i o n dose. S u b j e c t s were s c a n n e d p a r a l l e l t o t h e c a n t h o - m e a t a l l i n e f o r 13 t o 16 s u c c e s s i v e a x i a l s e c t i o n s o f 8 mm t h i c k n e s s . The CT s c a n s e c t i o n which showed the l a t e r a l v e n t r i c l e s at t h e i r l a r g e s t was s e l e c t e d f o r ea c h s u b j e c t and e n l a r g e d on f i l m t o a 23.5 cm by 17.5 cm format f o r use i n measurement o f VBR. Measurement o f VBR v e n t r i c l e s i z e . The e n l a r g e d f i l m o f t h e s c a n s e c t i o n showing t h e l a t e r a l v e n t r i c l e s a t t h e i r l a r g e s t , was a t t a c h e d t o a l i g h t box, and a S o k k i s h 19908 compensating p o l a r p l a n i m e t e r was used t o measure the area o f the l a t e r a l v e n t r i c l e s and the area o f the b r a i n i n order t o c a l c u l a t e the v e n t r i c l e b r a i n r a t i o . The area o f each l a t e r a l v e n t r i c l e was measured t h r e e times, averaged, and then summed acr o s s the two v e n t r i c l e s t o g i v e v e n t r i c u l a r s i z e . The b r a i n a r e a was measured s i x t i m e s and a v e r a g e d t o p r o v i d e t h e denominator f o r the r a t i o . The r a t i o o f v e n t r i c l e t o b r a i n was m u l t i p l i e d by 100 to form the VBR as i t i s r e p o r t e d i n most p u b l i s h e d s t u d i e s . N e u r o p s y c h o l o g i c a l assessment. The n e u r o p s y c h o l o g i c a l a s s e s s m e n t was c a r r i e d o u t a t R i v e r v i e w H o s p i t a l u s i n g i n t e r v i e w rooms on t h e v a r i o u s w a r d s . T e s t i n g t o o k approximately t h r e e hours and was u s u a l l y completed i n one day comprised o f two s e s s i o n s o r g a n i z e d around a l u n c h break f o r the p a t i e n t . The f o l l o w i n g t e s t s were a d m i n i s t e r e d f o l l o w i n g 86 s t a n d a r d i z e d procedures o u t l i n e d i n the t e s t manuals; Weschler A d u l t I n t e l l i g e n c e S c a l e - Revised (WAIS-R - approximately 1.5 hours a d m i n i s t r a t i o n t i m e ) , Benton V i s u a l R e t e n t i o n T e s t , Form D, w i t h B a c k g r o u n d I n t e r f e r e n c e P r o c e d u r e ( B V R T -approximately 10 min a d m i n i s t r a t i o n t i m e ) , C a t e g o r i e s T e s t -V i c t o r i a R e v i s i o n (CAT - approximately 15 min a d m i n i s t r a t i o n t i m e ) , T r a i l Making T e s t A and B (TMT - approximately 10 min a d m i n i s t r a t i o n t i m e ) , R i g h t and L e f t Hand F i n g e r Tapping T e s t (TAPR & TAPL - approximately 10 min a d m i n i s t r a t i o n t i m e ) , Word Flu e n c y T e s t (WF - approximately 5 min a d m i n i s t r a t i o n t i m e ) , Rey A u d i t o r y V e r b a l L e a r n i n g T e s t (RAVLT - a p p r o x i m a t e l y 10 min a d m i n i s t r a t i o n t i m e ) , and the W i s c o n s i n Card S o r t i n g T e s t (WCST - approximately 20 min a d m i n i s t r a t i o n t i m e ) . S c o r i n g n e u r o p s y c h o l o g i c a l t e s t s . T e s t s were s c o r e d a c c o r d i n g t o s t a n d a r d p r o c e d u r e s d e s c r i b e d i n t h e t e s t manuals. For a number o f the n e u r o p s y c h o l o g i c a l t e s t s s e v e r a l d i f f e r e n t but r e l a t e d measures o f p e r f o r m a n c e a r e o f t e n o b t a i n e d from t h e same t e s t . For t h i s study the f o l l o w i n g s c o r e s were used: BVRT = t o t a l number o f e r r o r s on the Benton V i s u a l R e t e n t i o n t e s t , Form D w i t h Background I n t e r f e r e n c e Procedure; CAT = t o t a l number o f e r r o r s on the C a t e g o r i e s T e s t - V i c t o r i a R e v i s i o n ; TMT = t o t a l number o f seconds taken to c o m p l e t e p a r t s A and B o f t h e T r a i l Making T e s t ; TAPR = average number o f r i g h t hand index f i n g e r taps over f i v e , 10 second t r i a l s ; TAPL = average number o f l e f t hand index f i n g e r t a p s o v e r f i v e , 10 second t r i a l s ; WF = the t o t a l number o f 87 words generated i n response t o t h r e e d i f f e r e n t l e t t e r s o f the a l p h a b e t w i t h one m i n u t e allowed per l e t t e r ; RAVLT = t o t a l r e c a l l on f i v e immediate and 1 delayed r e c a l l t r i a l f o r the 16 item l i s t used i n the Rey A u d i t o r y V e r b a l R e c a l l T e s t ; WCST = the t o t a l number o f e r r o r s which o c c u r r e d d u r i n g p r e s e n t a t i o n o f the 128 car d s used i n the Wisc o n s i n Card S o r t i n g T e s t . Procedure S c h i z o p h r e n i c p a t i e n t s i d e n t i f i e d as p o t e n t i a l s u b j e c t s by the procedures o u t l i n e d e a r l i e r , and f o r whom the r e c r u i t e r had b e e n g i v e n p e r m i s s i o n t o d i s c u s s t h e s t u d y , were a p p r o a c h e d on t h e ward and r e q u e s t e d t o acco m p a n y t h e r e c r u i t e r t o an i n t e r v i e w room t o d i s c u s s t h e r e s e a r c h p r o j e c t . The study was d e s c r i b e d as c o n s i s t i n g o f f o u r major p o r t i o n s . T h e f i r s t s t a g e i n v o l v e d a 2 hour s e l e c t i o n i n t e r v i e w t o which the s u b j e c t gave w r i t t e n c o n s e n t ; a t t h e c o n c l u s i o n o f t h i s i n t e r v i e w a l l i n d i v i d u a l s were p a i d $5 whether or not they were s e l e c t e d f o r the r e s t o f the study. I f i n d i v i d u a l s met the d i a g n o s t i c c r i t e r i a and i f they wished to c o n t i n u e , a second consent form was u t i l i z e d which p r o v i d e d a d e t a i l e d d e s c r i p t i o n o f the remaining t h r e e stages o f the p r o j e c t ; ( i ) a 2.5 hour n e u r o p s y c h o l o g i c a l t e s t b a t t e r y , i i ) a CT s c a n and i i i ) a two hour b a t t e r y o f p s y c h o p h y s i o l o g i c a l t e s t s . S u b j e c t s were i n f o r m e d t h a t t h e y were f r e e t o t e r m i n a t e t e s t i n g a t any t i m e . Upon c o m p l e t i o n o f t h e r e s e a r c h p r o t o c o l the s u b j e c t s were p a i d $35. 88 N e u r o p s y c h o l o g i c a l t e s t i n g was done at R i v e r v i e w H o s p i t a l by a s i n g l e examiner, u s u a l l y w i t h i n a week o f the d i a g n o s t i c i n t e r v i e w . W i t h i n the next two weeks the s u b j e c t was d r i v e n t o t h e U n i v e r s i t y o f B r i t i s h C o l u m b i a by t h e R i v e r v i e w t r a n s p o r t s e r v i c e where p s y c h o p h y s i o l o g i c a l t e s t i n g and the CT scan were done. CT scans were done u s i n g h i g h l y s t a n d a r d i z e d procedures by h o s p i t a l r a d i o l o g i s t s . With few e x c e p t i o n s the time span from r e c r u i t m e n t t o completion o f t e s t i n g was l e s s than t h r e e weeks. For the normal c o n t r o l s , a l l p s y c h o p h y s i o l o g i c a l t e s t i n g procedures and CT scanning procedures were i d e n t i c a l t o those u s e d w i t h t h e p a t i e n t s . The p s y c h i a t r i c c o n t r o l group c o n s i s t e d o f i n p a t i e n t s r e f e r r e d f o r n e u r o p s y c h o l o g i c a l t e s t i n g . T h e s e i n d i v i d u a l s were t e s t e d by one o f two n e u r o p s y c h o l o g i c a l t e s t i n g t e c h n i c i a n s w o r k i n g u n d e r t h e s u p e r v i s i o n o f Dr. D. C r o c k e t t . The p a t i e n t s i n t h i s group were t y p i c a l l y t e s t e d over a t h r e e hour span ( w i t h a l u n c h break) u s i n g the same t e s t s and t e s t m a t e r i a l s as those used w i t h the s c h i z o p h r e n i c p a t i e n t s . Both groups o f s u b j e c t s were g i v e n the WAIS-R f i r s t , u s u a l l y f o l l o w e d by a break and then a d m i n i s t r a t i o n o f the r e s t o f the n e u r o p s y c h o l o g i c a l b a t t e r y . 89 RESULTS The r e s u l t s o f t h i s study are presented i n f i v e s e c t i o n s . The f i r s t s e c t i o n r e p o r t s r e l i a b i l i t y f o r the measurement o f v e n t r i c l e b r a i n r a t i o . The second s e c t i o n i s concerned w i t h t h e r e l a t i o n s h i p o f age, d u r a t i o n o f h o s p i t a l i z a t i o n , and substance abuse t o the p r i n c i p a l measures i n the study. I t i s important t o assess the e f f e c t o f these s u b j e c t v a r i a b l e s on the p r i n c i p a l measures as they might a f f e c t i n t e r p r e t a t i o n of d a t a p e r t i n e n t t o t h e major hypotheses. The t h i r d s e c t i o n a s s esses group d i f f e r e n c e s f o r comparisons between the c h r o n i c s c h i z o p h r e n i c sample and the c o n t r o l groups on the measures o f l a t e r a l v e n t r i c l e s i z e , smooth p u r s u i t eye t r a c k i n g and n e u r o p s y c h o l o g i c a l t e s t p e r f o r m a n c e . As the s c h i z o p h r e n i c group was p r e d i c t e d t o be more impaired than c o n t r o l s on a l l measures, 1 - t a i l e d t - t e s t s are u t i l i z e d . B o n f e r r o n i c o r r e c t e d p r o b a b i l i t y v a l u e s were u s e d t o a s s e s s mean d i f f e r e n c e s b e t w e e n t h e p s y c h i a t r i c c o n t r o l s and t h e s c h i z o p h r e n i c p a t i e n t s on the n e u r o p s y c h o l o g i c a l t e s t s . The f o u r t h s e c t i o n r e p o r t s r e l a t i o n s h i p s among the measures o f VBR, l o g r o o t mean s q u a r e ( L R M S ) d e v i a t i o n i n e y e t r a c k i n g , a n d n e u r o p s y c h o l o g i c a l t e s t p e r f o r m a n c e i n t h e s c h i z o p h r e n i c sample. C o r r e l a t i o n s p r e s e n t e d i n t h i s s e c t i o n a r e t e s t e d w i t h one t a i l e d , or d i r e c t i o n a l t e s t s , i n accord w i t h the h y p o t h e s i z e d r e l a t i o n s h i p s between VBR, smooth p u r s u i t eye t r a c k i n g and n e u r o p s y c h o l o g i c a l t e s t performance. Because 90 t h e r e w ere no s p e c i f i c a p r i o r i h y p o t h e s e s a b o u t t h e r e l a t i o n s h i p between any i n d i v i d u a l n e u r o p s y c h o l o g i c a l t e s t r e s u l t and the measures o f VBR and LRMS, an o v e r a l l B o n f e r r o n i a d j u s t m e n t was made by d i v i d i n g t h e p-value o f .05 by the number o f r e l a t i o n s h i p s examined f o r each v a r i a b l e . Because t h e r e w ere 10 n e u r o p s y c h o l o g i c a l t e s t s , t h e B o n f e r r o n i c o r r e c t e d p-value = .005. F i n a l l y , a f i f t h s e c t i o n p r e s e n t s f i n d i n g s r e l a t e d t o the r e l a t i o n s h i p s between t e s t s w i t h i n the n e u r o p s y c h o l o g i c a l b a t t e r y f o r the s c h i z o p h r e n i c sample. Means, standard d e v i a t i o n s , and t - v a l u e s f o r the measures o f v e n t r i c l e s i z e and eye t r a c k i n g accuracy are d i s p l a y e d i n T a b l e 7. M e a n s a n d s t a n d a r d d e v i a t i o n s f o r t h e n e u r o p s y c h o l o g i c a l t e s t s are d i s p l a y e d i n T a b l e 8. Note t h a t WAIS-R F u l l S c a l e IQ i s r e p o r t e d i n Tabl e 8 but not used i n f u r t h e r a n a l y s e s as i t i s redundant w i t h the WAIS-R V e r b a l and Performance IQs. R e l i a b i l i t y o f VBR measure The r e l i a b i l i t y o f t h e VBR measurement was a s s e s s e d d u r i n g measurement o f o v e r 200 CT s c a n s i n c l u d i n g t h e 30 c h r o n i c s c h i z o p h r e n i c s and 29 normal c o n t r o l s who p a r t i c i p a t e d i n t h i s s t u d y . I n t e r j u d g e r e l i a b i l i t y was o b t a i n e d by comparing the p l a n i m e t r y measures o f VBR f o r two independent r a t e r s f o r 25 CT scans. A P e a r s o n c o r r e l a t i o n o f .93 was obt a i n e d i n d i c a t i n g a h i g h l e v e l o f r e l i a b i l i t y . In a d d i t i o n 20 r a n d o m l y s e l e c t e d CT s c a n s were r a n k o r d e r e d by a 91 n e u r o r a d i o l o g i s t a c c o r d i n g t o l a t e r a l v e n t r i c l e s i z e ; t h e Spearman rank order c o r r e l a t i o n between the n e u r o r a d i o l o g i s t s r a n k i n g and the p l a n i m e t r y measure o f VBR was h i g h (r=.80) p r o v i d i n g an i n d i c a t i o n o f the v a l i d i t y o f p l a n i m e t r y o b t a i n e d VBR as a measure o f v e n t r i c l e s i z e . R e l a t i o n s h i p s Between D u r a t i o n o f H o s p i t a l i z a t i o n , Age and  Substance Abuse and the P r i n c i p a l Measures D e s p i t e c o n s i d e r a b l e r a n g e i n t o t a l d u r a t i o n o f h o s p i t a l i z a t i o n a c r o s s the sample o f s c h i z o p h r e n i c p a t i e n t s ( r a n g e 2 months t o 113 m o n t h s ) , t h i s v a r i a b l e was n o t s i g n i f i c a n t l y c o r r e l a t e d w i t h any o f the p r i n c i p a l measures u s e d i n t h i s s t u d y . D u r a t i o n o f h o s p i t a l i z a t i o n was c o r r e l a t e d r = .02 w i t h VBR, and r = .30 w i t h LRMS t r a c k i n g d e v i a t i o n . T a b l e 10 d i s p l a y s t h e c o r r e l a t i o n s b e t w e e n d u r a t i o n o f h o s p i t a l i z a t i o n a n d t h e t e s t s i n t h e n e u r o p s y c h o l o g i c a l b a t t e r y . The c o r r e l a t i o n between age and WAIS-R F u l l S c a l e IQ was r=.40, i n d i c a t i n g t h a t i n t h i s sample some o f t h e o l d e r i n d i v i d u a l s t e n d e d t o h a v e h i g h e r I Q s . Age was n o t s i g n i f i c a n t l y c o r r e l a t e d w i t h any o t h e r p r i n c i p a l measure. The c o r r e l a t i o n between age and LRMS was r = .01; between age and VBR was r = .08; and b e t w e e n age and d u r a t i o n o f h o s p i t a l i z a t i o n was r = .20. The c o r r e l a t i o n c o e f f i c i e n t s between age and the 10 n e u r o p s y c h o l o g i c a l t e s t s r a nged from -.33 t o .24. I n o r d e r t o a d d r e s s t h e i m p o r t a n t p o s s i b i l i t y t h a t substance abuse might have a s i g n i f i c a n t e f f e c t on VBR, eye t r a c k i n g or n e u r o p s y c h o l o g i c a l t e s t performance, t - t e s t s were computed t o compare the group o f p a t i e n t s w i t h n o t a b l e h i s t o r y o f s u b s t a n c e abuse, t o those p a t i e n t s who had l i t t l e or no h i s t o r y o f substance use. As mentioned i n the method s e c t i o n , p a t i e n t r e p o r t s and c h a r t i n f o r m a t i o n on a l c o h o l and drug use were d i f f i c u l t t o e v a l u a t e . T h i s was p a r t i c u l a r l y t h e c a s e w i t h r e s p e c t t o d o c u m e n t i n g s p e c i f i c q u a n t i t i e s and a c t u a l d u r a t i o n o f use f o r each o f many i l l i c i t drugs covered i n the DIS s e c t i o n s f o r a s s e s s i n g drug and a l c o h o l use. However, i t i s l e s s d i f f i c u l t t o d i v i d e t h e p a t i e n t sample i n t o two g r o u p s , one w i t h ample e v i d e n c e ( b o t h by s e l f r e p o r t and c h a r t e d i n f o r m a t i o n ) o f s u b s t a n t i a l s u b s t a n c e a b u s e , and a n o t h e r g r o u p w h i c h , a c c o r d i n g t o p a t i e n t r e p o r t and c h a r t i n f o r m a t i o n , c o n s i s t s o f i n d i v i d u a l s w i t h m i n i m a l o r no e x p o s u r e t o i l l i c i t d r u g s or a l c o h o l . I n d i v i d u a l s i n t h i s sample who were c l a s s i f i e d as substance abusers or substance dependent o f t e n had h i s t o r i e s o f d a i l y use o f marijuana over p e r i o d s o f s e v e r a l months; t h e r e were two i n d i v i d u a l s who had been gl u e s h i f f e r s on a d a i l y b a s i s f o r more than two weeks, s e v e r a l had used a l c o h o l t o the p o i n t o f i n t o x i c a t i o n on a d a i l y b a s i s f o r p e r i o d s o f weeks t o months, and many were p o l y - d r u g a b u s e r s . Among t h e group c l a s s i f i e d as h a v i n g minimal, or no drug and a l c o h o l use, t h e r e were f i v e who had never used any i l l i c i t drugs; two who had used marijuana, but not more than f i v e times; and t h r e e who had u s e d m a r i j u a n a more than f i v e times but never on a d a i l y b a s i s or r e g u l a r l y over a p e r i o d o f weeks or months. Two i n d i v i d u a l s i n t h i s g r o u p had n e v e r been drunk; two had been drunk o n l y once; t h r e e had been drunk o c c a s i o n a l l y but d i d n o t u s e a l c o h o l r e g u l a r l y ; one i n d i v i d u a l had drunk two beers a week d u r i n g a p e r i o d o f s i x months but had s t o p p e d d r i n k i n g a l t o g e t h e r s e v e r a l years b e f o r e ; and two had a t some p o i n t s drunk as much as seven d r i n k s at l e a s t one evening a week but never f o r a p e r i o d g r e a t e r than two months. T a b l e 6 p r e s e n t s the r e s u l t s o f comparisons between 11 s u b j e c t s w i t h e x t e n s i v e h i s t o r i e s o f substance abuse and/or dependence (as recorded i n t h e i r c h a r t s and confirmed by i n t e r v i e w ) , and 10 s u b j e c t s whose d e n i a l o f more t h a n v e r y m i n i m a l use o f d r u g s o r a l c o h o l was n o t c o n t r a d i c t e d by c h a r t i n f o r m a t i o n . There were no s i g n i f i c a n t d i f f e r e n c e s between t h e s e groups f o r VBR, eye t r a c k i n g , or WAIS-R F u l l S c a l e IQ. Group Differences The s c h i z o p h r e n i c p a t i e n t s and normal c o n t r o l group d i d not d i f f e r s i g n i f i c a n t l y w i t h r e s p e c t to VBR, t(57)=.39 p>.l, (see T a b l e 7 f o r means and SD's). None o f the s c h i z o p h r e n i c s , and one o f the c o n t r o l group s u b j e c t s had a VBR > 2 SD above t h e c o n t r o l group mean ( c o n t r o l group x + 2SD i s a VBR of 11.57). Three o f the s c h i z o p h r e n i c p a t i e n t s and f o u r o f the c o n t r o l group s u b j e c t s had VBRs which were between 1 and 2 SD 94 Table 6 Means, Standard Deviations and t-test Values for VBR, LRMS Deviation In Eye Tracking and WAIS-R Full Scale IQ for Schizophrenic Patients with Histories of Alcohol and/or III I Icit Drug Abuse (n=11) Compared with Schizophrenic Patients with Little or No Use of I l l ic i t Drugs and Alcohol (n=10) Groups5 Drug and/or Little or Alcohol No Drug and/or Alcohol use (n-11) (n-10) Measure Mean (SD) Mean (SD) t-value VBR 6.99 (2.24) 6.83 (.57) .228 LRMS deviation in eye tracking 2.33 (.26) 2.22 (.21) .095 WAIS-R Full Scale IQ 84.18 (9.44) 82.10 (8.68) .053 Note: There are no significant differences between groups on any of the principle measures, all ps>.1, two tailed. a Groups were formed on the basis of information obtained from patient's charts and Interview on the drug and alcohol portions of the Diagnostic Interview Schedule. 95 Table 7 Means, Standard Deviations and t Values for VBR and Eye Tracking  Accuracy for Schizophrenic Patients and Normal Controls Groups Schizophrenics (M=30) Control (n=29) Measure Mean SD Mean SD t-value Ventricle Brain Ratio 6.75 1.70 6.53 2.52 .39 Log Root Mean Square Error (LRMS) in Eye Tracking 2.23 .25 2.04 .14 3.62* * p< 0.005, one tailed t test, df 57 96 above the c o n t r o l group mean ( c o n t r o l group x + 1SD i s a VBR o f 9.05). F i g u r e 1 i s a g r a p h i c d i s p l a y o f the d i s t r i b u t i o n s o f v e n t r i c l e b r a i n r a t i o s f o r the s c h i z o p h r e n i c s and c o n t r o l s u b j e c t s . I t i s c l e a r from t h i s f i g u r e t h a t the means, ranges and sta n d a r d e r r o r o f measurement f o r the two groups are very s i m i l a r . The s i t u a t i o n i s q u i t e d i f f e r e n t i n t h e c a s e o f eye t r a c k i n g . The s c h i z o p h r e n i c group e v i d e n c e d s i g n i f i c a n t l y l e s s a c c u r a t e eye t r a c k i n g than the normal c o n t r o l group (see Tab l e 7 ) . F i g u r e 2 i s a g r a p h i c r e p r e s e n t a t i o n o f the LRMS d e v i a t i o n s c o r e s f o r the s c h i z o p h r e n i c s and c o n t r o l s . N e u r o p s y c h o l o g i c a l p e r f o r m a n c e o f t h e s c h i z o p h r e n i c sample was compared t o t h a t o f the p s y c h i a t r i c c o n t r o l group. T a b l e 9 p r e s e n t s the r e s u l t s o f t - t e s t comparisons between the means o f the s c h i z o p h r e n i c sample and the p s y c h i a t r i c c o n t r o l g r o u p . S i x o f t h e 11 c o m p a r i s o n s were s i g n i f i c a n t w i t h B o n f e r r o n i c o r r e c t i o n f o r m u l t i p l e t - t e s t s . The c h r o n i c s c h i z o p h r e n i c group d i d s i g n i f i c a n t l y l e s s w e l l t h a n t h e p s y c h i a t r i c c o n t r o l s f o r WAIS-R Performance IQ, the C a t e g o r i e s T e s t , the Wisconsin Card S o r t i n g T e s t , the T r a i l Making T e s t , the Benton V i s u a l R e t e n t i o n T e s t , and the Rey A u d i t o r y V e r b a l L e a r n i n g T e s t . On 4 o f the t e s t s t h e r e were no s i g n i f i c a n t d i f f e r e n c e s b e t w e e n g r o u p s ; s c h i z o p h r e n i c p a t i e n t s and p s y c h i a t r i c c o n t r o l s d i d n o t d i f f e r f o r WAIS-R V e r b a l IQ, r i g h t and l e f t F i n g e r Tapping, and Word Flu e n c y . T a b l e 8 97 Table 8 Means, Standard Deviations and Ranges (where available) for Neuropsychological Tests for  Schizophrenic Patients, Psychiatric Controls and Normative Groups Reported in the Literature Groups Schizoprenlcs3 Controls Norms Reported in L iterature Neuropsychological Tests Mean (SD) Range Mean (SD) Range Mean (SD) WAIS-R Verbal IQ 87. .13 (12.9) 132-70 91.95° (14.8) 128-71 100 (15)f WAIS-R Performance IQ 80. .37 (9.2) 101-63 90.67° (15.4) 118-69 100 (15)f WAIS-R Ful1 Scale IQ 82. .13 (8.5) 102-66 90.76° (14.6) 126-72 100 (15)f Categories Test (errors) 43. .27 (13.4) 63-8 28.00° (16.0) 57-1 20.24 (9.5)9 FInger Tapping - Right 45. .67 (6.9) 59-29 45.95° (7.3) 61-32 46.7 (5.3)h Finger Tapping - Left 41. .73 (6.9) 51-20 40.37° (5.5) 53-30 43.2 (5.3)h Word Fluency Test 32. .23 (13.1) 58-6 33.81° (12.9) 67-9 33 (50% percentile) Wisconsin Card SortIng Test (errors) 49. .17 (16.8) 87-14 30.18d (20.9) 71-8 24.9 (19.4)J Trai1 Making Test -total time for A and B (seconds) 191. .07 (93.7) 562-85 129.24° (53.1) 284-61 86.3k Benton Visual Retention Test with background interference procedure (errors) 9, .90 (4.4) 18-1 4.36° (2.8) 10-1 Not avai table Rey Auditory Verbal Learning Test - total recal1 over 6 traiIs 33. .70 (12.5) 54-6 51.83 (10.1) 61-38 69.31 a n=30, b n-21, c n=20, d n=11, 6 n-6, f Weschler Adult Intelligence Scale-Revised Manual (1981) 9 Norms for Victoria Revision of the Halstead Categories. Labreche (1982). N = 50, mean age 37.2 years, mean Full scale I.Q. 116. n Norms for Finger Tapping Test from control study by Lome Yeudall (1978), n=46, ages 26-30. ' Taken from Spreen and Benton (1968), Neurosensory Center Comprehensive Examination for Aphasia, Edition A, Profile Form A (Normal Adults). Scores are listed on a percentile basis within the profile, a score of 33 falls at the 50th percentile while a score of 22 falls at the 10th and a score of 49 at the 90th percentile. J From Manual for Wisconsin Card Sorting Test, Heaton (1981) n=150. k Norm for Trail Making Test taken from Yeudall (1978) n=46, age 26-30. For comparison to the schizophrenic sample and psychiatric controls, times for the A form and B forms have been added together. ' From Lezak (1983). The value reported is the sum of the means for the six separate trials as reported by Lezak. Table 9 98 T-tests Between Schizophrenic Patients and Psychiatric Controls for the Neuropsychological Tests Neuropsychological Test t-value Degrees of Freedom Probabi1itya WAIS-R Verbal IQ 1.20 49 p > 0.1 WAIS-R Performance IQ 2.74 49 p < 0.005* Categories Test (errors) 3.57 48 p < 0.0005* Finger Tapping - Right .14 49 p > 0.1 Finger Tapping - Left .77 49 p > 0.1 Word Fluency Test .42 49 P > 0.1 Wisconsin Card Sorting Test (errors) 2.71 39 P < 0.005* Trail Making Test - total time for A and B 2.99 49 P < 0.0025* Benton Visual Retention Test with background Interference procedure (errors) 4.75 39 P < 0.0005* Rey Auditory Verbal Learning Test -total recall over 6 trials 3.84 34 P < 0.0005* * Starred entries are significant with one tai led probab i1 ities as I isted in table. a The t-tests are one tailed with Bonferronl adjustment for multiple comparisons. Bonferroni adjustment was made by dividing the p-value of 0.05 by the number of comparisons computed. Because there 10 neuropsychological tests, the Bonferroni corrected p-value = 0.005. 13.00 99 12.00 11.00 10.00 9.00 8.00 7.00 6.00 5.00 4.00 3.00 2.00 1.00 Schizophrenics Controls n=30 n=29 FIgure 1. Distribution of Ventricle Brain Ratios for Schizophrenic Patients and Volunteer Controls. Note 1. The horizontal bars denote the mean VBR for each group while the lines above and below the bar indicate the standard error of measurement. Mean for schizophrenia Is 6.75, standard error is .305. Mean for controls is 6.53, standard error is .460 units. 100 2.9 2.8 2.7 2.6 2.5 2.4 2.3 2.2 2.1 2.0 1.9 1.8 1.7 1.6 Schizophrenics Control n=30 n=29 Figure 2. Distribution of LRMS eye tracking accuracy scores for Schizophrenic Patients and Volunteer Controls. Note 1. The horizontal bars denote then mean LRMS for each group while the lines above and below the bar indicate the standard error of measurement. Mean for schizophrenics Is 2.23, standard error of measurement Is .25. Mean for control group Is 2.04, standard error of measurement is .14. 101 p r e s e n t s the means, standard d e v i a t i o n s , and ranges o f scores f o r t h e n e u r o p s y c h o l o g i c a l t e s t s f o r the s c h i z o p h r e n i c and c o n t r o l group; means and s t a n d a r d d e v i a t i o n s f o r n o r m a t i v e groups have been i n c l u d e d f o r comparison. R e l a t i o n s h i p s Among VBR, LRMS D e v i a t i o n i n Eye T r a c k i n g and  N e u r o p s y c h o l o g i c a l T e s t Performance A n a l y s e s i n t h i s s e c t i o n p e r t a i n t o t h e c e n t r a l hypotheses o f t h i s study.' VBR and eye t r a c k i n g . The p r e d i c t i o n t h a t v e n t r i c l e s i z e and eye t r a c k i n g would be r e l a t e d , such t h a t i n d i v i d u a l s w i t h l a r g e r v e n t r i c l e s would e x h i b i t l e s s a c c u r a t e eye t r a c k i n g , was n o t confirmed. The c o r r e l a t i o n between VBR and LRMS i n the s c h i z o p h r e n i c sample was l e s s t h a n z e r o (r= -.34) and i n d i c a t e s t h a t l a r g e r l a t e r a l v e n t r i c l e s i z e tended t o be a s s o c i a t e d w i t h b e t t e r e y e t r a c k i n g p e r f o r m a n c e . The c o r r e l a t i o n between VBR and LRMS i n t h e v o l u n t e e r c o n t r o l group was a l s o not s i g n i f i c a n t ( r = .18). VBR and N e u r o p s y c h o l o g i c a l T e s t Performance. None o f the hyp o t h e s i z e d r e l a t i o n s h i p s between l a t e r a l v e n t r i c l e s i z e and n e u r o p s y c h o l o g i c a l p e r f o r m a n c e were supported by the data. T a b l e 10 shows the c o r r e l a t i o n c o e f f i c i e n t s between t h e 10 n e u r o p s y c h o l o g i c a l t e s t s and VBR. None o f these c o r r e l a t i o n s i s s t a t i s t i c a l l y s i g n i f i c a n t . The two l a r g e s t c o e f f i c i e n t s are the c o r r e l a t i o n s between VBR and WAIS-R V e r b a l IQ, and VBR and the Word Fluency T e s t . These c o r r e l a t i o n s are i n a Table 10 102 Correlations Between VBR, LRMS Tracking Error, Duration of Hospitalization and the  Neuropsychological Tests for the Chronic Schizophrenic Sample (n=30) Neuropsychological Test WAIS-R Verbal IQ WAIS-R Performance IQ Categories Test (errors) Finger Tapping - Right Finger Tapping - Left Word Fluency Test Wisconsin Card Sorting Test (errors) Trail Making Test - total time for A and B Benton Visual Retention Test with background interference procedure (errors) Rey Auditory Verbal Learning Test -total recal I over 6 trials VBR LRMSa institutionalization 0 .40 -.17 .08 -.24 -.33 -.14 -.14 .37 .06 -.22 -.02 .08 .00 .12 -.11 .32 -.28 .09 .00 .19 .16 -.03 .22 -.08 -.02 .09 -.18 -.06 -.05 -.01 Note 1: No s igni f icant relationship were found between VBR, LRMS deviation or Institutionalization and any Neuropsychological Tests. Tests of the significance of correlations between the neuropsychological test battery and VBR, LRMS tracking deviation and institutionalization are directional one tailed tests as stated in hypotheses. Bonferroni correlated p-value = .005 a LRMS Is the log root mean square eye tracking error D Institutionalization was determined from the hospital records by adding the time spent in hospital for all recorded hospitalizations. The final figure was calculated to the nearest month. 103 d i r e c t i o n o p p o s i t e t o t h a t p r e d i c t e d , i n t h a t i n d i v i d u a l s w i t h l a r g e r v e n t r i c l e s tended t o have h i g h e r s c o r e s on the V e r b a l IQ s c a l e and t o perform b e t t e r on the Word Fl u e n c y T e s t . Eye T r a c k i n g and N e u r o p s y c h o l o g i c a l T e s t Performance. None o f the h y p o t h e s i z e d r e l a t i o n s h i p s between eye t r a c k i n g and n e u r o p s y c h o l o g i c a l performance was supported by the data. T a b l e 12 shows t h e c o r r e l a t i o n c o e f f i c i e n t s between LRMS t r a c k i n g d e v i a t i o n and t h e 10 t e s t s w h i c h make up t h e n e u r o p s y c h o l o g i c a l b a t t e r y . C o r r e l a t i o n s w i t h i n t h e N e u r o p s y c h o l o g i c a l T e s t B a t t e r y A t e n by t e n c o r r e l a t i o n m a t r i x c o n t a i n i n g 45 n o n -redundant Pearson c o e f f i c i e n t i s shown i n T a b l e 11. With such a l a r g e number o f c o r r e l a t i o n s i t i s i m p o r t a n t t o c o n s i d e r Type I e r r o r as c o n t r i b u t i n g t o t h e number o f s i g n i f i c a n t c o e f f i c i e n t s o b t a i n e d . S t e i g e r (1980) p r o v i d e s a method t o t e s t the n u l l h y p o t h e s i s t h a t a l l c o r r e l a t i o n s i n a m a t r i x are e q u a l t o z e r o . T h i s t e s t , w h i c h i s a s p e c i a l c a s e o f s t a t i s t i c X 2 i s d e s c r i b e d by S t e i g e r (1980) as a means o f o b t a i n i n g experiment wise e r r o r r a t e p r o t e c t i o n (see Appendix A f o r p r o c e d u r e ) . I n t h e c a s e o f a m a t r i x w i t h 45 non-r e d u n d a n t c o r r e l a t i o n s , a X 2 v a l u e o f 61.65 (df=45) (p<.05) would be r e q u i r e d i n order to r e j e c t the n u l l h y p o t h e s i s t h a t t h e m a t r i x i s an i d e n t i t y m a t r i x , or a l l c o r r e l a t i o n s are equal to z e r o . For the matrix d i s p l a y e d i n T a b l e 13 the X 2 v a l u e o b t a i n e d equals 100.7 (p<.05), a l l o w i n g r e j e c t i o n o f the n u l l h y p o t h e s i s . 104 Table 11 Correlation Matrix of Neuropsychological Tests for Schizophrenic Sample (n=30) 1 2 3 4 5 6 7 8 9 VIQ PIQ BVRT RAVLT TAPR TAPL TMT WCST CA" 1) VIQ 2) PIQ .25 3) BVRT -.17 -.46** 4) RAVLT .24 .09 -.15 5) TAPR .05 .16 -.16 .33* 6) TAPL .07 .02 -.011 .38* .63** 7) TMT -.28 -.36* .55** -.24 -.15 -.17 8) WCST -.33* -.47** .08 -.25 -.12 -.19 .08 9) CAT -.40* -.23 .33* -.23 -.07 -.19 .24 .42* 10) WF .43** .25 .00 .15 .21 -.08 -.33* .00 .08 Note. Abbreviations stand for the following tests ordered from 1 to 10. VIQ = WAIS-R Verbal IQ; PIQ = WAIS-R Performance IQ; BVRT = Benton Visual Retention Test, Form D, with Background Interference Procedure (errors); RAVLT = Rey Auditory Verbal Learning Test - total recall over six trials; TAPR = Finger Tapping Right; TAPL = Finger Tapping Left; TMT = Trial Making Test total time for A and B (seconds); WCST = Wisconsin Card Sorting Test (errors); CAT = Categories Test (errors); WF = Word Fluency Test. * p > 0.05 one-talled, df = 28 ** p > 0.01 one-tailed, df = 28 105 W i t h i n t h e ma t r i x o f 45 c o r r e l a t i o n s , 13 c o e f f i c i e n t s are s i g n i f i c a n t at a p r o b a b i l i t y o f .05 or l e s s , one t a i l e d . A l l s i g n i f i c a n t c o r r e l a t i o n s a r e d i r e c t i o n a l l y c o n s i s t e n t ; r e l a t i o n s h i p s between two t e s t s w h i c h a r e b o t h s c o r e d f o r a t t a i n m e n t o r b o t h s c o r e d f o r e r r o r s show p o s i t i v e c o e f f i c i e n t s , p a i r s o f t e s t s i n w h i c h one i s an a t t a i n m e n t s c o r e and the oth e r an e r r o r s c o r e show n e g a t i v e c o e f f i c i e n t s . The p r e d i c t i o n o f s i g n i f i c a n t r e l a t i o n s h i p s between WAIS-R V e r b a l a n d P e r f o r m a n c e I Q s a n d t h e r e m a i n i n g n e u r o p s y c h o l o g i c a l t e s t s i s supported by the da t a . Although R i g h t and L e f t F i n g e r T a p p i n g and t h e Rey A u d i t o r y V e r b a l L e a r n i n g T e s t are not c o r r e l a t e d w i t h e i t h e r IQ S c a l e , t h e r e m a i n i n g f i v e n e u r o p s y c h o l o g i c a l t e s t s a r e . V e r b a l IQ c o r r e l a t e s w i t h t h e W i s c o n s i n C a r d S o r t i n g T e s t , t h e C a t e g o r i e s T e s t and t h e Word Fluency T e s t . Performance IQ c o r r e l a t e s w i t h t h e T r a i l Making T e s t , t h e B e n t o n V i s u a l R e t e n t i o n T e s t and the Wisconsin Card S o r t i n g T e s t . Amoung the group o f s i x n e u r o p s y c h o l o g i c a l t e s t s thought t o be s e n s i t i v e t o f r o n t a l l o b e f u n c t i o n i n g ( F i n g e r Tapping R i g h t , F i n g e r Tapping L e f t , T r a i l Making T e s t , W i s c o n s i n Card S o r t i n g T e s t , C a t e g o r i e s T e s t , and Word Fluency T e s t ) t h e r e are t h r e e c o r r e l a t i o n s s i g n i f i c a n t at a p r o b a b i l i t y o f .05 or l e s s . When the X 2 t e s t o f the n u l l h y p o t h e s i s t h a t the e n t i r e m a t r i x o f c o r r e l a t i o n s equals zero i s a p p l i e d t o the 15 non-r e d u n d a n t c o r r e l a t i o n s amoung these t e s t s , the obtained X 2 v a l u e o f 31.4 i s compared wi t h a t a b l e d X 2 (p>.05) o f 24.99 106 a l l o w i n g r e j e c t i o n o f the n u l l h y p o t h e s i s . Among these t e s t s , R i g h t and L e f t h a n d e d F i n g e r T a p p i n g a r e s i g n i f i c a n t l y c o r r e l a t e d as are the Word Fluency T e s t and the T r a i l Making T e s t , and the Wis c o n s i n Card S o r t i n g T e s t and the C a t e g o r i e s T e s t . Summary of Results The r e s u l t s o f t h i s study f a i l e d t o show the p r e d i c t e d r e l a t i o n s h i p among the p r i n c i p a l measures o f i n t e r e s t i n the s c h i z o p h r e n i c sample. No s i g n i f i c a n t c o r r e l a t i o n s were found between any combination o f the measures o f VBR, eye t r a c k i n g a c c u r a c y and n e u r o p s y c h o l o g i c a l performance. Although the s c h i z o p h r e n i c group was impaired, r e l a t i v e t o t h e c o n t r o l s , f o r eye t r a c k i n g accuracy and on s e v e r a l n e u r o p s y c h o l o g i c a l t e s t s , they d i d not d i f f e r from the c o n t r o l group w i t h r e s p e c t t o l a t e r a l v e n t r i c l e s i z e . None o f t h e i n d i v i d u a l s c h i z o p h r e n i c p a t i e n t s had l a t e r a l v e n t r i c u l a r enlargement as d e f i n e d i n the l i t e r a t u r e (a VBR>_2 SD above the mean of the c o n t r o l group). No r e l a t i o n was found between d u r a t i o n o f h o s p i t a l i z a t i o n or substance abuse and any o f the p r i n c i p a l measures. Age was fo u n d t o be c o r r e l a t e d w i t h WAIS-R F u l l S c a l e IQ such t h a t o l d e r s u b j e c t s tended t o have h i g h e r IQ's. R e l a t i o n s h i p among t h e t e s t s i n the n e u r o p s y c h o l o g i c a l b a t t e r y conformed t o p r e v i o u s f i n d i n g s o f c o r r e l a t i o n s between WAIS-R IQs and other n e u r o p s y c h o l o g i c a l measures, i n d i c a t i n g t h a t t h e n e u r o p s y c h o l o g i c a l f i n d i n g a r e n o t e n t i r e l y anomalous. The p r e d i c t e d r e l a t i o n s h i p among t e s t s b e l i e v e d s e n s i t i v e t o f r o n t a l l o b e f u n c t i o n i n g was n o t s t r o n g l y supported: o f 15 non-redundant c o r r e l a t i o n s i n the m a t r i x o f f r o n t a l l o b e t e s t s , o n l y t h r e e were s i g n i f i c a n t . 108 DISCUSSION Group D i f f e r e n c e s B e f o r e the c e n t r a l i s s u e o f the r e l a t i o n s h i p s between the t h r e e p r i n c i p a l measures can be m e a n i n g f u l l y addressed, i t i s u s e f u l t o examine the p a t t e r n o f impairments r e l a t i v e t o the c o n t r o l groups. The eye t r a c k i n g performance o f the s c h i z o p h r e n i c group was s i g n i f i c a n t l y impaired r e l a t i v e t o the c o n t r o l group (see F i g u r e 2 f o r g r a p h i c d i s p l a y o f t h e d i s t r i b u t i o n s o f LRMS d e v i a t i o n i n t r a c k i n g f o r t h e s c h i z o p h r e n i c and c o n t r o l g r o u p s ) . T h i s r e p l i c a t e s many p r e v i o u s f i n d i n g s i n t h e l i t e r a t u r e (e.g. Holzman e t a l . , 1974; Iacono e t a l . , 1982; L e v i n e t a l . , 1981). T h e s c h i z o p h r e n i c s a m p l e was f o u n d t o p e r f o r m s i g n i f i c a n t l y l e s s w e l l t h a n an age matched g r o u p o f non-s c h i z o p h r e n i c p s y c h i a t r i c p a t i e n t s on s i x o u t o f t h e 10 n e u r o p s y c h o l o g i c a l t e s t s ( s e e T a b l e 9 ) . The s c h i z o p h r e n i c sample made s i g n i f i c a n t l y more e r r o r s on the C a t e g o r i e s T e s t and W i s c o n s i n Card S o r t i n g T e s t . B o t h t h e s e t a s k s a s s e s s a b s t r a c t i n g a b i l i t y and co n c e p t u a l f l e x i b i l i t y . In a d d i t i o n , these t a s k s have a memory component. S u b j e c t s must remember from t r i a l t o t r i a l t h e c o n c e p t t h e y a r e u s i n g t o o b t a i n c o r r e c t c a t e g o r i z a t i o n o f i t e m s . B o t h t h e s e t e s t s a r e c o n s i d e r e d s e n s i t i v e t o f r o n t a l l o b e f u n c t i o n . Performance on t h e W i s c o n s i n C a r d S o r t i n g T e s t h a s b e e n r e p e a t e d l y demonstrated t o be i m p a i r e d i n p a t i e n t s w i t h f r o n t a l l o b e l e s i o n s (Lezak, 1983). However, as Lezak (1983) p o i n t s out, poor performance on the W i s c o n s i n Card S o r t i n g T e s t can r e s u l t from a v a r i e t y o f i n t e l l e c t u a l d e f i c i t s . The s c h i z o p h r e n i c sample was slower than the p s y c h i a t r i c c o n t r o l s i n completing t h e T r a i l M a k i n g T e s t . T h i s t e s t , w h i c h L e z a k (1983) c h a r a c t e r i z e s as being one o f t h e n e u r o p s y c h o l o g i c a l t e s t s most s e n s i t i v e t o t h e p r e s e n c e o f b r a i n damage, i n v o l v e s v i s u a l c o n c e p t u a l s k i l l s and v i s u a l m o t o r t r a c k i n g . The s c h i z o p h r e n i c sample was n o t a b l y i m p a i r e d r e l a t i v e t o the p s y c h i a t r i c c o n t r o l s on both a v i s u a l and an a u d i t o r y memory t a s k . F i n a l l y , t h e r e was a s i g n i f i c a n t d i f f e r e n c e between p s y c h i a t r i c c o n t r o l s and the s c h i z o p h r e n i c p a t i e n t s on WAIS-R performance IQ. T h e s c h i z o p h r e n i c g r o u p d i d n o t d i f f e r f r o m t h e p s y c h i a t r i c c o n t r o l s on V e r b a l IQ, Word F l u e n c y , and F i n g e r T a p p i n g R i g h t and L e f t . F u r t h e r , i t i s i n t e r e s t i n g t o note f r o m T a b l e 8 t h a t n e i t h e r t h e s c h i z o p h r e n i c s o r t h e p s y c h i a t r i c c o n t r o l s were impaired r e l a t i v e t o a normal sample on Word Fluency and F i n g e r Tapping R i g h t and L e f t . Both the F i n g e r Tapping T e s t and the Word Fluency T e s t are timed, and r e q u i r e a t t e n t i o n and c o n s i d e r a b l e c o o p e r a t i o n over r e p e a t e d t r i a l s . The l a c k o f d i f f e r e n c e between n o r m a l s and b o t h groups o f p a t i e n t s would suggest t h a t the d e f i c i t s i n o t h e r areas are not simply a r t i f a c t s o f i n a t t e n t i o n or i n s u f f i c i e n t e f f o r t . The f i n d i n g t h a t the s c h i z o p h r e n i c s and p s y c h i a t r i c 110 c o n t r o l s do not d i f f e r f o r V e r b a l IQ, Word Flue n c y , and F i n g e r T a p p i n g , would agai n suggest t h a t the d e f i c i t s evidenced by the s c h i z o p h r e n i c sample r e l a t i v e t o the p s y c h i a t r i c c o n t r o l s a r e n o t a t t r i b u t a b l e s i m p l y t o a g e n e r a l i z e d b e h a v i o r a l d e f i c i t i n the s c h i z o p h r e n i c sample. The s i m i l a r i t i e s i n V e r b a l I Q s b e t w e e n t h e s c h i z o p h r e n i c s a m p l e and t h e p s y c h i a t r i c c o n t r o l s suggest t h a t the d i f f e r e n c e s between the two groups on o t h e r t e s t s are not l i k e l y t o be a f u n c t i o n o f d i f f e r e n c e s i n g e n e r a l fund o f k n o w l e d g e o r a b i l i t y t o comprehend and respond t o v e r b a l i n s t r u c t i o n s . I n o v e r v i e w , t h e p e r f o r m a n c e o f t h e s c h i z o p h r e n i c p a t i e n t s shows an i n t e r e s t i n g p a t t e r n o f impairment r e l a t i v e t o p s y c h i a t r i c c o n t r o l s . The s c h i z o p h r e n i c sample does n o t d i f f e r s i g n i f i c a n t l y from p s y c h i a t r i c c o n t r o l s i n g e n e r a l v e r b a l a b i l i t y . However, t h e s c h i z o p h r e n i c p a t i e n t s a r e e s p e c i a l l y i m p a i r e d on t e s t s r e q u i r i n g a b s t r a c t r e a s o n i n g a b i l i t y ( C a t e g o r i e s T e s t and Wisconsin Card S o r t i n g T e s t ) ; i n t a s k s which r e q u i r e c o o r d i n a t i o n o f v i s u o p e r c e p t u a l s k i l l s and motor responses (Benton v i s u a l R e t e n t i o n T e s t , most s u b t e s t s on the WAIS-R Performance IQ s c a l e and the T r a i l Making T e s t ) ; and on t h e memory t a s k s i n t h e b a t t e r y ( B e n t o n V i s u a l R e t e n t i o n T e s t and the Rey A u d i t o r y V e r b a l Memory T e s t ) . In the c o n t e x t o f the l i t e r a t u r e r e v i e w e d f o r t h i s s t u d y , t h e s c h i z o p h r e n i c p a t i e n t s would be c h a r a c t e r i z e d as showing d i f f u s e n e u r o p s y c h o l o g i c a l i m p a i r m e n t s d e s p i t e some non-s i g n i f i c a n t d i f f e r e n c e s from p s y c h i a t r i c c o n t r o l . As a group, I l l s c h i z o p h r e n i c p a t i e n t s were impaired on s e v e r a l f r o n t a l l o b e t e s t s ; on WAIS-R Pe r f o r m a n c e IQ; on memory t e s t s which are a s s o c i a t e d w i t h b o t h t e m p o r a l and p a r i e t a l l o b e f u n c t i o n s ( K o l b and Whishaw, 1980); and on s p a t i a l and c o n s t r u c t i o n a l t a s k s r e q u i r i n g i n t e g r a t i o n o f p e r c e p t u a l a n d m o t o r f u n c t i o n i n g which are a s s o c i a t e d w i t h p a r i e t a l l o b e f u n c t i o n . The t h i r d p r i n c i p a l measure i n t h i s s t u d y was l a t e r a l v e n t r i c l e s i z e . The s c h i z o p h r e n i c sample and normal v o l u n t e e r c o n t r o l s d i d not d i f f e r s i g n i f i c a n t l y on t h i s v a r i a b l e (see F i g u r e l ) . The r a n g e s o f s c o r e s a r e v i r t u a l l y i d e n t i c a l , a l t h o u g h t h e r e i s a t e n d e n c y f o r t h e s c o r e s o f t h e s c h i z o p h r e n i c g r o u p t o c l u s t e r a b o v e t h e mean o f t h e d i s t r i b u t i o n . T h i s n e g a t i v e f i n d i n g , w i t h r e s p e c t t o l a t e r a l v e n t r i c l e e n l a r g e m e n t , runs c o u n t e r t o t h e hypotheses put f o r w a r d i n t h i s s t u d y and t o s e v e r a l s t u d i e s i n t h e l i t e r a t u r e , p a r t i c u l a r l y the r e s e a r c h conducted i n the l a t e 1970s and e a r l y 1980s. However, the f i n d i n g s are c o n s i s t e n t w i t h a number o f p u b l i s h e d r e p o r t s which have f a i l e d t o d e t e c t l a t e r a l v e n t r i c u l a r enlargement i n s c h i z o p h r e n i c p a t i e n t s . A c o m m u n i c a t i o n by Smith and Iacono (1986) suggests t h a t some p r e v i o u s r e p o r t s o f l a t e r a l v e n t r i c u l a r e n l a r g e m e n t i n s c h i z o p h r e n i c s may have been an a r t i f a c t o f u n r e p r e s e n t a t i v e l y s m a l l v e n t r i c u l a r s i z e i n t h e c o n t r o l g r o u p s . S m i t h and I a c o n o (1986) r e p o r t t h a t t h e mean VBR o f s c h i z o p h r e n i c p a t i e n t groups f o r seven s t u d i e s which f a i l e d t o f i n d l a t e r a l v e n t r i c l e e n l a r g e m e n t was 6.75, w h i l e 14 s t u d i e s w h i c h r e p o r t e d v e n t r i c u l a r e n l a r g e m e n t i n t h e i r s a m p l e had an o v e r a l l mean VBR o f 6.86. The s t u d i e s which f a i l e d t o f i n d e n l a r g e d v e n t r i c l e s i n t h e i r s c h i z o p h r e n i c samples had c o n t r o l g r o u p s w i t h a mean VBR o f 6.34 whereas t h e 14 s t u d i e s r e p o r t i n g p o s i t i v e f i n d i n g s had c o n t r o l groups w i t h mean VBRs o f 3.95. Thus, the d i f f e r e n c e between s e v e r a l s t u d i e s w i t h p o s i t i v e and n e g a t i v e f i n d i n g s appears t o be a f u n c t i o n o f the v e n t r i c l e s i z e s i n t h e c o n t r o l g r o u p s and n o t i n t h e s c h i z o p h r e n i c p a t i e n t s . The sample o f s c h i z o p h r e n i c s u b j e c t s a s s e s s e d i n t h i s s t u d y has a mean VBR o f 6.75, w h i l e the c o n t r o l g r o u p has a mean VBR o f 6.53. These v a l u e s a r e p r a c t i c a l l y i n d i s t i n g u i s h a b l e from those r e p o r t e d by Smith and Iacono (1986) f o r s t u d i e s which f a i l e d t o f i n d v e n t r i c u l a r enlargement. A q u e s t i o n w h i c h might be r a i s e d i n r e s p o n s e t o t h e n e g a t i v e f i n d i n g s i s whether t h e sample o f s c h i z o p h r e n i c s u b j e c t s used i n t h i s study might not be an u n u s u a l l y i n t a c t group, which d i f f e r s i n some s y s t e m a t i c way from samples used i n p r e v i o u s r e s e a r c h . T h i s seems an u n l i k e l y e x p l a n a t i o n i n v i r t u e o f a number o f i s s u e s . F i r s t , the sample was found to be i m p a i r e d f o r eye t r a c k i n g a c c u r a c y and on a number of n e u r o p s y c h o l o g i c a l t e s t s , r e l a t i v e t o c o n t r o l s . Second, t h e sample c o n s i s t s o f c o n s e n t i n g c o n s e c u t i v e admissions t o a l a r g e , p u b l i c mental i n s t i t u t i o n . As s e v e r a l o t h e r s t u d i e s i n the l i t e r a t u r e r e p o r t u s i n g c o n s e n t i n g c o n s e c u t i v e admissions t o s i m i l a r i n s t i t u t i o n s , s u b j e c t s e l e c t i o n procedures s h o u l d not account f o r d i f f e r e n c e s between t h i s s t u d y and o t h e r s . T h i r d , a l t h o u g h a l l s u b j e c t s were under the age o f 35, the average accumulated d u r a t i o n o f h o s p i t a l i z a t i o n f o r the sample was two y e a r s , ' n i n e months. H a l f t h e s u b j e c t s had spent between 2 and 4 y e a r s i n m e n t a l i n s t i t u t i o n s , and twenty p e r c e n t o f t h e s a m p l e had s p e n t more t h a n 4 y e a r s i n h o s p i t a l . F i n a l l y , i n d i v i d u a l s w i t h h i s t o r i e s o f e x t e n s i v e s u b s t a n c e abuse were n o t e x c l u d e d from the sample p r o v i d e d they had not been s p e c i f i c a l l y t r e a t e d f o r d r u g o r a l c o h o l dependence. Although t h e r e may be good reasons t o attempt t o exclude substance abusers, h i g h p r e v a l e n c e o f substance abuse among young c h r o n i c s c h i z o p h r e n i c s would suggest t h a t a sample composed o n l y o f i n d i v i d u a l s without a h i s t o r y o f s u b s t a n c e abuse would be a very u n r e p r e s e n t a t i v e sample. In any case, t h e i n c l u s i o n o f t h e s e i n d i v i d u a l s would be e x p e c t e d t o i n c r e a s e the l i k e l i h o o d o f f i n d i n g v e n t r i c u l a r enlargement i n the sample i f i t has any e f f e c t a t a l l . Thus o v e r a l l , t h e r e i s no r e a s o n t o s u s p e c t t h a t some a s p e c t o f t h e sample s e l e c t i o n procedure, or p a r t i c u l a r s u b j e c t v a r i a b l e s , make t h i s s a m p l e u n r e p r e s e n t a t i v e o f young i n s t i t u t i o n a l i z e d c h r o n i c s c h i z o p h r e n i c s . N e i t h e r i s t h e r e any i n d i c a t i o n t h a t t h e c h a r a c t e r i s t i c s o f t h i s p a r t i c u l a r sample would b i a s toward s m a l l e r v e n t r i c l e s i z e s . I n summary, t h i s s c h i z o p h r e n i c group was found t o have i m p a i r e d smooth p u r s u i t eye t r a c k i n g p e r f o r m a n c e and t o p e r f o r m s i g n i f i c a n t l y l e s s w e l l then p s y c h i a t r i c c o n t r o l s on s e v e r a l n e u r o p s y c h o l o g i c a l t e s t s . T h e s e f i n d i n g s a r e c o n s i s t e n t w i t h t h e p r e d i c t i o n s o f g r e a t e r i m p a i r m e n t h y p o t h e s i z e d i n t h i s s t u d y , and w i t h p r e v i o u s r e s e a r c h f i n d i n g s i n s c h i z o p h r e n i c samples. The s c h i z o p h r e n i c sample d i d not show l a t e r a l v e n t r i c u l a r enlargement r e l a t i v e t o the normal v o l u n t e e r c o n t r o l s . Although t h i s n e g a t i v e f i n d i n g i s i n c o n t r a d i c t i o n t o the study h y p o t h e s i s and to a p r o p o r t i o n o f p r e v i o u s l i t e r a t u r e , i t i s c o n s i s t e n t w i t h f i n d i n g s o f more r e c e n t s t u d i e s . The average VBR f o r the sample o f p a t i e n t s i s s i m i l a r t o the mean VBRs f o r many c o n t r o l l e d s t u d i e s t h a t have obt a i n e d both p o s i t i v e and n e g a t i v e f i n d i n g s . Thus, w h i l e v e n t r i c u l a r e n l a r g e m e n t was not found, n e i t h e r would i t be s a i d t h a t the p r e s e n t sample has s m a l l e r v e n t r i c l e s than many o f the p r e v i o u s l y r e p o r t e d samples o f s c h i z o p h r e n i c p a t i e n t s . R e l a t i o n s h i p s Among VBR, LRMS D e v i a t i o n i n Eye T r a c k i n g , and  N e u r o p s y c h o l o g i c a l T e s t Performance The p r i n c i p a l purpose o f t h i s study was the i n v e s t i g a t i o n o f r e l a t i o n s h i p s among the measures o f l a t e r a l v e n t r i c l e s i z e , eye t r a c k i n g accuracy, and n e u r o p s y c h o l o g i c a l t e s t performance w i t h i n t h e group o f c h r o n i c s c h i z o p h r e n i c p a t i e n t s . I t was hy p o t h e s i z e d t h a t t h e r e would be c o r r e l a t i o n s between t h e measures such t h a t low attainment on one measure would tend t o be a s s o c i a t e d w i t h low a t t a i n m e n t on e a c h o f t h e o t h e r m e a s u r e s . None o f the p r e d i c t e d r e l a t i o n s h i p s between VBR, 115 eye t r a c k i n g or any o f the n e u r o p s y c h o l o g i c a l t e s t s were found i n t h i s study. VBR and eye t r a c k i n g . No s i g n i f i c a n t r e l a t i o n s h i p was found between these measures. The c o r r e l a t i o n between these v a r i a b l e s was l e s s than zero and i n d i r e c t i o n o p p o s i t e t o t h a t p r e d i c t e d . T h e r e a r e two s t u d i e s w h i c h h a v e a s s e s s e d t h e r e l a t i o n s h i p between l a t e r a l v e n t r i c l e s i z e and eye t r a c k i n g ( W e i n b e r g e r and Wyatt, 1982; and B a r t f a i e t a l . , 1985); the f i n d i n g s were thought by the i n v e s t i g a t o r s t o be s u g g e s t i v e o f a r e l a t i o n s h i p between l a r g e v e n t r i c l e s i z e and i m p a i r e d t r a c k i n g . Both s t u d i e s have m e t h o d o l o g i c a l flaws which make i t d i f f i c u l t t o i n t e r p r e t t h e d a t a w i t h r e s p e c t t o t h e a s s o c i a t i o n between eye t r a c k i n g and v e n t r i c u l a r s i z e . The W e i n b e r g e r a n d W y a t t ( 1 9 8 2 ) r e p o r t was b a s e d on an i n v e s t i g a t o r y p r o j e c t . Two groups o f p a t i e n t s s e l e c t e d on the b a s i s o f having " l a r g e " and "normal" v e n t r i c l e s , were g i v e n an eye t r a c k i n g task which i n v o l v e d watching a swinging pendulum. They found t h a t 30% o f the p a t i e n t s w i t h normal v e n t r i c l e s had markedly d i s o r d e r e d eye t r a c k i n g (a r a t i n g g r e a t e r than 3 on a 5 p o i n t s c a l e ) , w h i l e 64% o f t h e p a t i e n t s w i t h l a r g e v e n t r i c l e s had d i s o r d e r e d t r a c k i n g . U n f o r t u n a t e l y they do not d e s c r i b e the p a t i e n t s , nor g i v e an i n d i c a t i o n o f the mean VBRs f o r each group. The B a r t f a i e t a l . (1985) study had a s m a l l sample (n = 18) and used a r a t h e r u n s o p h i s t i c a t e d measures o f both eye t r a c k i n g and l a t e r a l v e n t r i c l e s i z e . They found few 116 p a t i e n t s w i t h evidence o f en l a r g e d l a t e r a l v e n t r i c l e a n t e r i o r h o r n s , but they concluded t h a t t h e r e was a tendency f o r the most impaired t r a c k e r s t o have a l a r g e r a n t e r i o r h o r n i n d e x t h a n p a t i e n t s w i t h b e t t e r t r a c k i n g . T h e i r f i n d i n g o f a s s o c i a t i o n between l a t e r a l v e n t r i c l e s i z e and eye t r a c k i n g was not s t a t i s t i c a l l y s i g n i f i c a n t when they compared groups or when they c o r r e l a t e d v e n t r i c l e s i z e and eye t r a c k i n g r a t i n g s (r=.35, df=15, not s i g n i f i c a n t a t 0.05, one t a i l e d ) . The p o s s i b i l i t y t h a t a r e l a t i o n s h i p between v e n t r i c l e s i z e and eye t r a c k i n g e x i s t s , but was undetected by t h i s study cannot be completely r u l e d out. None o f the s u b j e c t s i n the s c h i z o p h r e n i c sample showed l a t e r a l v e n t r i c u l a r enlargement r e l a t i v e t o the c o n t r o l group. I f eye t r a c k i n g impairment and v e n t r i c u l a r enlargement are a s s o c i a t e d o n l y when v e n t r i c u l a r e n l a r g e m e n t i s e x t r e m e , t h e n t h i s s t u d y w o u l d f a i l t o d e m o n s t r a t e t h e r e l a t i o n s h i p . I t should, however, be noted t h a t t h e s c h i z o p h r e n i c g r o u p i n t h i s s t u d y h a s a mean v e n t r i c u l a r s i z e t h a t i s comparable t o t h a t found i n other s a m p l e s o f s c h i z o p h r e n i c p a t i e n t s , who, by v i r t u e o f comparison w i t h d i f f e r e n t c o n t r o l samples have been l a b e l e d as having s i g n i f i c a n t v e n t r i c u l a r e n l a r g e m e n t . The group o f p a t i e n t s i n t h i s study d i d e x h i b i t eye t r a c k i n g impairment. The r a n g e s a n d d i s t r i b u t i o n s f o r VBR a n d LRMS a r e a p p r o x i m a t e l y n o r m a l . T h e r e f o r e , t h e r e i s no r e a s o n t o b e l i e v e t h a t t h i s p a r t i c u l a r sample would be any l e s s l i k e l y t o demonstrate a t r u e r e l a t i o n s h i p between v e n t r i c l e s i z e and 117 eye t r a c k i n g than other samples o f s c h i z o p h r e n i c p a t i e n t s f o r whom measures o f v e n t r i c u l a r s i z e are a v a i l a b l e . In summary, t h e r e was no s i g n i f i c a n t r e l a t i o n s h i p between l a r g e r l a t e r a l v e n t r i c l e s and i m p a i r e d eye t r a c k i n g . The l i t e r a t u r e r e l e v a n t t o t h i s r e l a t i o n s h i p i s s m a l l . One study found t h a t more p a t i e n t s w i t h l a r g e v e n t r i c l e s t r a c k e d p o o r l y than d i d p a t i e n t s w i t h s m a l l v e n t r i c l e s . The o t h e r s t u d y f a i l e d t o show a s i g n i f i c a n t r e l a t i o n s h i p between the two. Although i t i s p o s s i b l e t h a t t h i s s t u d y f a i l e d t o f i n d t h e p r e d i c t e d r e l a t i o n s h i p due t o t h e a b s e n c e o f e x t r e m e v e n t r i c u l a r enlargement i n the p a t i e n t s , t h i s argument i s not f e l t t o be a s t r o n g c h a l l e n g e t o the v a l i d i t y o f the pres e n t f i n d i n g s as a p p l i e d t o s c h i z o p h r e n i c p a t i e n t s who, as a group, do n o t show extreme v e n t r i c u l a r e n l a r g e m e n t . I t can be concluded t h a t , although i t i s p o s s i b l e t h a t i n a sample w i t h more v e n t r i c u l a r enlargement a c o r r e l a t i o n between VBR and eye t r a c k i n g might emerge, i t i s c l e a r l y not the case t h a t bad eye t r a c k i n g i s c a u s a l l y a s s o c i a t e d w i t h v e n t r i c u l a r enlargement. VBR and N e u r o p s y c h o l o g i c a l T e s t Performance. There were no s i g n i f i c a n t r e l a t i o n s h i p s between VBR and p e r f o r m a n c e on any o f the n e u r o p s y c h o l o g i c a l t e s t s (see T a b l e 10). The i s s u e s i n v o l v e d i n d i s c u s s i o n o f t h i s f i n d i n g a r e very s i m i l a r t o those d i s c u s s e d i n some d e t a i l i n the p r e v i o u s s e c t i o n on the r e l a t i o n s h i p between VBR and eye t r a c k i n g . As t h i s s a m p l e was n o t f o u n d t o h a v e a b n o r m a l l y e n l a r g e d v e n t r i c l e s r e l a t i v e t o the c o n t r o l group, t h i s i n v e s t i g a t i o n 118 i s not a b l e t o address the i s s u e o f the e f f e c t o f abnormally l a r g e v e n t r i c l e s on n e u r o p s y c h o l o g i c a l performance. However, as was p o i n t e d out i n d i s c u s s i o n of VBR and eye t r a c k i n g , t h i s sample showed l a t e r a l v e n t r i c l e s i z e s i n the same range as s e v e r a l o t h e r s t u d i e s o f s c h i z o p h r e n i c p a t i e n t s w h i c h have r e p o r t e d v e n t r i c u l a r enlargement. There are c l e a r i n d i c a t i o n s t h a t t h e s a m p l e e x h i b i t s i m p a i r m e n t on a n u m b e r o f n e u r o p s y c h o l o g i c a l t e s t s . Examination o f the ranges o f scores f o r the s c h i z o p h r e n i c p a t i e n t s (see T a b l e 8) show t h a t a l l the r a n g e s span t h e means f o r b o t h p s y c h i a t r i c c o n t r o l s and l i t e r a t u r e norms. Taking the above i s s u e s i n t o c o n s i d e r a t i o n , i t w o u l d seem t h a t t h e r e i s no r e a s o n t o e x p e c t t h i s p a r t i c u l a r study to be l e s s l i k e l y than o t h e r s t o demonstrate a t r u e r e l a t i o n s h i p b e t w e e n v e n t r i c l e s i z e a n d n e u r o p s y c h o l o g i c a l performance i n s c h i z o p h r e n i c p a t i e n t s , i f one e x i s t s . E x a m i n i n g t h e l i t e r a t u r e r e l a t e d t o t h e a s s o c i a t i o n between l a t e r a l v e n t r i c l e s i z e and n e u r o p s y c h o l o g i c a l t e s t performance suggests on l y moderate support f o r an a s s o c i a t i o n between c o g n i t i v e f u n c t i o n i n g and l a t e r a l v e n t r i c l e s i z e . The s t u d i e s which r e p o r t the s t r o n g e s t a s s o c i a t i o n between VBR and c o g n i t i v e f u n c t i o n i n g are those o f Johnstone e t a l . (1976) and Golden e t a l . (1980a and 1982). The average VBR f o r p a t i e n t s i n the Johnstone e t a l . (1976) (n=18) s t u d y was 18.7. The measure o f c o g n i t i v e f u n c t i o n i n g was the W i t h e r s - H i n t o n s c a l e , which i s s i m i l a r i n content t o a n e u r o l o g i c a l m e n t a l s t a t e exam. These i n v e s t i g a t o r s found a c o r r e l a t i o n o f -.70 between v e n t r i c l e s i z e and W i t h e r s - H i n t o n s c o r e s . A more r e c e n t r e p o r t by t h i s r e s e a r c h group (Owen e t a l . , 1985) which uses a much l a r g e r sample ( a l t h o u g h i t a p p e a r s t h a t the s u b j e c t s r e p o r t e d on i n t h e 1976 s t u d y a r e a l s o p a r t o f t h e group d e s c r i b e d i n the 1985 paper) found a s i g n i f i c a n t c u r v i l i n e a r r e l a t i o n s h i p between W i t h e r s - H i n t o n s c o r e s and v e n t r i c u l a r s i z e . B o t h p a p e r s p r e s e n t anomalous f i n d i n g s compared to o t h e r r e s e a r c h . I t seems l i k e l y t h a t t h e v e n t r i c l e s i z e s r e p o r t e d i n t h e i r f i r s t s t u d y are d e r i v e d from measurement tec h n i q u e s which d i f f e r from those used i n most VBR s t u d i e s . The c u r v i l i n e a r r e l a t i o n s h i p between v e n t r i c u l a r s i z e and W i t h e r s - H i n t o n s c o r e s i s p u z z l i n g . The two o t h e r s t u d i e s w h i c h show a r e l a t i o n s h i p between VBR and n e u r o p s y c h o l o g i c a l f u n c t i o n i n g are those o f Golden e t a l . (1980a and 1982). They r e p o r t m u l t i p l e c o r r e l a t i o n c o e f f i c i e n t s between the L u r i a Nebraska B a t t e r y and VBR o f 0.72 ( f o r VBR and e i g h t s c a l e s from the L u r i a Nebraska), and 0.76 ( f o r VBR and 14 s c a l e s from the L u r i a Nebraska). A c c o r d i n g to the d e s c r i p t i o n o f t h e i r method, the m u l t i p l e c o r r e l a t i o n c o e f f i c i e n t s were c a l c u l a t e d u s i n g o n l y those s c a l e s which s i g n i f i c a n t l y c o r r e l a t e d w i t h VBR. Thus, u n l i k e t h e p r e s e n t s t u d y , t h e G o l d e n e t a l . s t u d i e s found a s i z a b l e c o r r e l a t i o n a l r e l a t i o n s h i p between VBR and n e u r o p s y c h o l o g i c a l f u n c t i o n i n g . There are a t l e a s t s i x p u b l i s h e d r e p o r t s w h i c h have f a i l e d t o f i n d r e l a t i o n s h i p s between l a t e r a l v e n t r i c u l a r s i z e and v a r i o u s measures o f 120 c o g n i t i v e f u n c t i o n i n g . T he r e s u l t s o f t h i s s t u d y a r e c o n s i s t e n t w i t h the m a j o r i t y o f r e s e a r c h on l a t e r a l v e n t r i c l e s i z e and c o g n i t i v e f u n c t i o n i n g . The f i n d i n g s o f Golden e t a l . w o u l d b e n e f i t f r o m s y s t e m a t i c r e p l i c a t i o n by a g r o u p independent o f the Nebraska group. Should t h e i r f i n d i n g s be r e p l i c a t e d i t may i m p l y t h a t i n v e s t i g a t o r s , i n c l u d i n g the p r e s e n t a u t h o r , have used t e s t s w h i c h a r e i n s e n s i t i v e t o v a r i a t i o n s i n v e n t r i c l e s i z e , and t h a t t h e L u r i a Nebraska B a t t e r y has some s p e c i a l q u a l i t i e s w h i c h make i t v e r y s e n s i t i v e t o t h e e f f e c t s o f v e n t r i c u l a r e n l a r g e m e n t on c o g n i t i v e f u n c t i o n i n g . Eye T r a c k i n g and N e u r o p s y c h o l o g i c a l T e s t Performance. There were no r e l a t i o n s h i p s between eye t r a c k i n g accuracy and performance on any o f the n e u r o p s y c h o l o g i c a l t e s t s (see Tab l e 10). The hypotheses f o r t h i s study proposed two a l t e r n a t i v e f o r m s f o r r e l a t i o n s h i p s b e t w e e n e y e t r a c k i n g a nd n e u r o p s y c h o l o g i c a l performance. One p a t t e r n which might have emerged would i n v o l v e an a s s o c i a t i o n o f eye t r a c k i n g w i t h impairment on many o f t h e n e u r o p s y c h o l o g i c a l t e s t s . T h i s would suggest t h a t eye t r a c k i n g impairment might be r e l a t e d t o g l o b a l n e u r o p s y c h o l o g i c a l d e f i c i t s , and hence, might serve as an i n d i c a n t o f " d i f f u s e " b r a i n d y s f u n c t i o n , w h i c h some i n v e s t i g a t o r s b e l i e v e t o be a c h a r a c t e r i s t i c o f a subgroup o f s c h i z o p h r e n i c s . On the other hand, some i n v e s t i g a t o r s b e l i e v e t h a t both eye t r a c k i n g impairment and s c h i z o p h r e n i a i n v o l v e d i s r u p t i o n s o f f r o n t a l l o b e f u n c t i o n i n g . I f t h i s were t o be 121 the case, one might have expected eye t r a c k i n g impairment to be p a r t i c u l a r l y r e l a t e d t o d e f i c i t s on the f r o n t a l l o b e t e s t s i n the n e u r o p s y c h o l o g i c a l t e s t b a t t e r y . N e i t h e r o f t h e s e p a t t e r n s emerged. T h e r e i s l i t t l e p r e v i o u s r e s e a r c h on the r e l a t i o n s h i p between n e u r o p s y c h o l o g i c a l t e s t s and eye t r a c k i n g . B a r t f a i e t a l . ( 1985) f o u n d c o r r e l a t i o n s between eye t r a c k i n g and two t e s t s which were used i n t h i s study — the T r a i l Making T e s t and F i n g e r Tapping-Right. These f i n d i n g s were not r e p l i c a t e d i n t h i s study. Holzman (1974) and C e g a l i s and Sweeny (1979, 1982) f a i l e d t o f i n d s i g n i f i c a n t c o r r e l a t i o n s between IQ measures and eye t r a c k i n g p r o f i c i e n c y . I n summary, t h e h y p o t h e s i s t h a t impaired eye t r a c k i n g would be r e l a t e d t o impairment on n e u r o p s y c h o l o g i c a l t e s t s was n o t c o n f i r m e d . A l t h o u g h t h e r e was no c o n c o r d a n c e f o r i m p a i r m e n t on t h e n e u r o p s y c h o l o g i c a l measures and on t h e m e a s u r e o f eye t r a c k i n g , s u b j e c t s were i m p a i r e d on b o t h r e l a t i v e t o c o n t r o l s . G i v e n t h e s c o r e r a n g e s a n d approximately normal d i s t r i b u t i o n s f o r most o f the measures i t seems improbable t h a t the data analyses would f a i l t o uncover s y s t e m a t i c r e l a t i o n s h i p s i f they were p r e s e n t . S u b j e c t v a r i a b l e s The p o s s i b i l i t y o f c o n f o u n d i n g r e l a t i o n s h i p s between d u r a t i o n o f i n s t i t u t i o n a l i z a t i o n , substance abuse, and age and t h e p r i n c i p a l m e a s u r e s was e x a m i n e d . T h e r e were no 122 s i g n i f i c a n t c o r r e l a t i o n s b e t w e e n d u r a t i o n o f i n s t i t u t i o n a l i z a t i o n and VBR, LRMS, age o r any o f t h e n e u r o p s y c h o l o g i c a l t e s t s . Past h i s t o r y o f s u b s t a n c e abuse, f o r approximately one t h i r d o f the sample, i s not b e l i e v e d t o have a f f e c t e d the f i n d i n g s . There were no d i f f e r e n c e s between t h e g r o u p o f s u b s t a n c e abusers and a group o f t e n p a t i e n t s w i t h l i t t l e or no drug or a l c o h o l use f o r VBR, eye t r a c k i n g , or WAIS-R F u l l S c a l e IQ. Age was r e l a t e d t o o n l y one v a r i a b l e i n the study; WAIS-R F u l l S c a l e IQ and age were c o r r e l a t e d .40. In t h i s p a r t i c u l a r sample the o l d e r s u b j e c t s tended to have some o f the h i g h e r IQ's measured i n the group. T h e r e was no c o n t r o l f o r m e d i c a t i o n e f f e c t s on eye t r a c k i n g or n e u r o p s y c h o l o g i c a l t e s t performance. However, i t i s i n t e r e s t i n g t o note t h a t the s c h i z o p h r e n i c p a t i e n t s were not impaired r e l a t i v e t o normals on a t e s t o f motor speed and c o o r d i n a t i o n ( F i n g e r Tapping), or on a timed t e s t o f v e r b a l f l u e n c y (Word F l u e n c y ) . T h i s suggests t h a t the s c h i z o p h r e n i c p a t i e n t s were not abnormally slowed i n e i t h e r motor responses or p r o d u c t i o n o f v e r b a l responses - b o t h o f w h i c h o c c u r i f m e d i c a t i o n s a r e c a u s i n g s i g n i f i c a n t s e d a t i o n (Heaton & Crowley, 1981). C o r r e l a t i o n s w i t h i n t h e N e u r o p s y c h o l o g i c a l T e s t B a t t e r y The p a t t e r n o f p o s i t i v e and n e g a t i v e c o r r e l a t i o n s w i t h i n the t e s t b a t t e r y are d i r e c t i o n a l l y c o n s i s t e n t w i t h s c o r i n g ( i e . attainment vs. e r r o r scored t e s t s produce c o r r e l a t i o n s i n 123 the expected d i r e c t i o n s ) . There were s i g n i f i c a n t c o r r e l a t i o n s between f i v e o f t h e non-IQ t e s t s and t h e IQ s c a l e s . The i n d i v i d u a l t e s t s which do and do not c o r r e l a t e w i t h the two IQ s c a l e s a r e , i n t h e main, c o n s i s t e n t w i t h t h e o r i e s o f t h e a b i l i t i e s t hese t e s t s measure. For i n s t a n c e the Benton V i s u a l R e t e n t i o n T e s t and the T r a i l Making T e s t both c o r r e l a t e w i t h Performance IQ and not V e r b a l IQ. These two t a s k s i n v o l v e v i s u o p e r c e p t u a l and motor performance, as do s e v e r a l tasks which c o n t r i b u t e t o t h e P e r f o r m a n c e IQ s c o r e . C o n c e p t u a l r e a s o n i n g t e s t s ( C a t e g o r i e s T e s t s and Wis c o n s i n Card S o r t i n g Test) and the v e r b a l f l u e n c y t e s t (Word Fluency) c o r r e l a t e d w i t h V e r b a l IQ. The f a c t t h a t the F i n g e r Tapping T e s t does n o t c o r r e l a t e w i t h IQ i s a l s o a f i n d i n g w h i c h w o u l d be expected. D e m o n s t r a t i n g t h e s e r e l a t i o n s h i p s i n t h i s sample i s u s e f u l , i n d i c a t i n g t h a t the s u b j e c t s ' performance shows some o f the expected i n t e r - c o r r e l a t i o n t y p i c a l l y found among these t e s t s i n many d i f f e r e n t p a t i e n t samples. The s u b j e c t s i n t h i s s t u d y were i n s t i t u t i o n a l i z e d p a t i e n t s many o f whom were a c t i v e l y p s y c h o t i c at the time o f t e s t i n g . I t i s c o n c e i v a b l e t h a t the t e s t performance o f these i n d i v i d u a l s might be h i g h l y e r r a t i c , p r e c l u d i n g any s y s t e m a t i c r e l a t i o n s h i p between t h e n e u r o p s y c h o l o g i c a l t e s t s a n d o t h e r m e a s u r e s . T h e r e l a t i o n s h i p s between the v a r i o u s t e s t s i n the b a t t e r y and the c o n s i s t e n c y o f the d i r e c t i o n s o f the c o r r e l a t i o n c o e f f i c i e n t s makes i t u n l i k e l y t h a t f a i l u r e t o f i n d r e l a t i o n s h i p s between 124 n e u r o p s y c h o l o g i c a l performance and the oth e r measures i s due to e r r a t i c or random t e s t behavior by the p a t i e n t s . A l t h o u g h the c o n s i s t e n c y i n responses i s t h o u g h t t o be s u f f i c i e n t t o r u l e o u t t h e l i k e l i h o o d o f random or i n v a l i d t e s t b e h a v i o r , s e v e r a l expected c o r r e l a t i o n s d i d not emerge. More c o v a r i a t i o n was e x p e c t e d between t e s t s s e n s i t i v e t o f r o n t a l l o b e f u n c t i o n . The f a c t t h a t t h e r e i s not a s t r o n g e r r e l a t i o n s h i p between t h e s e t a s k s m i g h t be t h e r e s u l t o f numerous f a c t o r s . F i r s t , s e v e r a l o f the t e s t s d e s i g n a t e d as ' f r o n t a l t e s t s ' a r e known t o i n v o l v e complex c o g n i t i v e f u n c t i o n s which are not e x c l u s i v e t o the f r o n t a l l o b e s ; hence, the ' f r o n t a l t e s t s ' may not be s p e c i f i c a l l y measuring f r o n t a l l o b e f u n c t i o n i n g i n t h e s e p a t i e n t s . Second, i t i s h i g h l y l i k e l y t h a t the ' f r o n t a l t e s t s ' are not e q u a l l y s e n s i t i v e t o f r o n t a l l o b e f u n c t i o n i n g , o r a r e s e n s i t i v e t o d i f f e r e n t a s p e c t s o f the f u n c t i o n i n g o f the f r o n t a l l o b e s , and t h e r e f o r e should not be expected t o i n t e r c o r r e l a t e h i g h l y . F i n a l l y , i t i s p o s s i b l e t h a t t h e r e i s n o t a s p e c i f i c f r o n t a l l o b e d y s f u n c t i o n i n the s u b j e c t s who p a r t i c i p a t e d i n t h i s study and hence, t h e r e i s no reason t o expect covergence o f performance among the f r o n t a l t e s t s . As no o b j e c t i v e c r i t e r i o n o f f r o n t a l l o b e i n t e g r i t y i s a v a i l a b l e f o r t h e s e s u b j e c t s , i t i s not p o s s i b l e t o choose between the above a l t e r n a t i v e s . F i n a l l y i t i s noteworthy t h a t V e r b a l and Performance IQs a r e n o t s i g n i f i c a n t l y c o r r e l a t e d . I n t h e WAIS-R s t a n d a r d i z a t i o n s a m p l e o f 300 s u b j e c t s age 25-34, t h e 125 c o r r e l a t i o n between V e r b a l and P e r f o r m a n c e IQ was .76. I n t h i s sample i t i s .25. In comparison w i t h the p s y c h i a t r i c c o n t r o l group t h e s c h i z o p h r e n i c p a t i e n t s do n o t d i f f e r i n V e r b a l IQ but d i d s i g n r f i c a n t l y l e s s w e l l on Performance IQ. The low c o r r e l a t i o n between t h e two s c a l e s may r e f l e c t a s e l e c t i v e impairment o f some o f the a b i l i t i e s assessed by the WAIS-R P e r f o r m a n c e S c a l e . The p a t t e r n o f s i g n i f i c a n t d e p r e s s i o n o f P e r f o r m a n c e IQ r e l a t i v e t o V e r b a l IQ i s c o n s i s t e n t w i t h the s o r t o f impairment found i n d i f f u s e b r a i n damage. S t a t i s t i c a l I s s u e s The a n a l y s e s o f t h e d a t a i n t h i s study were conducted u s i n g m u l t i p l e t - t e s t s and c o r r e l a t i o n s . E x c e p t f o r t h e e x a m i n a t i o n o f i n t e r - c o r r e l a t i o n s i n the n e u r o p s y c h o l o g i c a l t e s t b a t t e r y , o t h e r m u l t i p l e c o m p a r i s o n s were done a g a i n s t B o n f e r r o n i c o r r e c t e d p r o b a b i l i t y v a l u e s . T h i s approach seems the most a p p r o p r i a t e one f o r a study e x a m i n i n g many i n t e r -r e l a t i o n s h i p s i n a r e l a t i v e l y s m a l l sample. F u r t h e r , the l i t e r a t u r e on t h e r e l a t i o n s h i p s between t h e m e a s u r e s i s r e l a t i v e l y s m a l l , c o n t a i n s i n c o n s i s t e n c i e s , and does not have a w e l l developed t h e o r e t i c a l base f o r l i n k i n g t h e measures. In accord w i t h t h i s i t seems a d v i s a b l e t o use a c o n s e r v a t i v e approach t o Type I e r r o r . T h i s study f a i l e d t o d e monstrate any s t a t i s t i c a l l y s i g n i f i c a n t r e l a t i o n s h i p s among t h e p r i n c i p a l measures. Examining the c o r r e l a t i o n t a b l e s makes i t 126 c l e a r t h a t t h e r e are no c o n s i s t e n t t r e n d s t o suggest t h a t the data are r e l a t e d as h y p o t h e s i z e d , but miss s i g n i f i c a n c e by a s l i m margin. In f a c t , were the B o n f e r r o n i procedure not used, the i n t e r p r e t a t i o n o f r e s u l t s would not change. Of the twenty c o r r e l a t i o n c o e f f i c i e n t s between the n e u r o p s y c h o l o g i c a l t e s t s and VBR and eye t r a c k i n g , two would be s i g n i f i c a n t a t a l i b e r a l p - v a l u e o f .05 one t a i l e d ( P e r f o r m a n c e IQ i s c o r r e l a t e d -.3 3 w i t h eye t r a c k i n g and the C a t e g o r i e s T e s t i n c o r r e l a t e d .37 w i t h eye t r a c k i n g ) . T he p u r p o s e o f t h e i n v e s t i g a t i o n was t o assess the p o s s i b i l i t y o f u s i n g VBR, eye t r a c k i n g accuracy, and n e u r o p s y c h o l o g i c a l t e s t performance, as a s o r t o f b a t t e r y f o r i n v e s t i g a t i o n o f hypotheses r e l a t e d t o b i o l o g i c a l subgrouping o f s c h i z o p h r e n i c p a t i e n t s . The weak r e l a t i o n s h i p s between two o f the n e u r o p s y c h o l o g i c a l t e s t s and e y e t r a c k i n g do n o t p r o v i d e c o n v i n c i n g e v i d e n c e t h a t performance on these measures share a common e t i o l o g y , or t h a t e i t h e r would be p a r t i c u l a r l y u s e f u l t o p r e d i c t the occurrence o f the o t h e r . C o n c l u s i o n . T h e r e i s no i n d i c a t i o n from t h e pr e s e n t s t u d y t h a t l a t e r a l v e n t r i c u l a r e n l a r g e m e n t , eye t r a c k i n g impairment, and n e u r o p s y c h o l o g i c a l t e s t d e f i c i t s would, as a group, form a u s e f u l s e t o f measures f o r i d e n t i f i c a t i o n o f a sub g r o u p o f c h r o n i c s c h i z o p h r e n i c p a t i e n t s f o r f u r t h e r r e s e a r c h . The sample d i d not show l a t e r a l v e n t r i c u l a r enlargement as p r e d i c t e d . I n l i g h t o f t h e most r e c e n t r e s e a r c h 127 l i t e r a t u r e , s i g n i f i c a n t l a t e r a l v e n t r i c u l a r e n l a r g e m e n t i n s c h i z o p h r e n i c s may be l e s s common t h a n e a r l i e r f i n d i n g s suggested. S e v e r a l i n v e s t i g a t o r s a r e s u g g e s t i n g t h a t t h e t h i r d v e n t r i c l e , not the l a t e r a l v e n t r i c l e s , are abnormal i n s c h i z o p h r e n i c p a t i e n t s (e.g. Boronow e t a l . , 1985). T h i r d v e n t r i c l e s i z e was not analyzed i n t h i s r e p o r t . A l though the p r e s e n t sample showed d e f i c i t s i n both eye t r a c k i n g and n e u r o p s y c h o l o g i c a l performance, t h e s e impairments were n o t r e l a t e d . I t m i g h t be t h a t m e a s u r e m e n t o f a r e l a t i o n s h i p between these two v a r i a b l e s was hampered by u s i n g a sample which was e x c e s s i v e l y i m p a i r e d on b o t h . T h i s i s thought t o be u n l i k e l y . D e s p i t e the o v e r a l l impairment o f the group on both measures, i t does not appear t h a t the ranges o f s c o r e s were so r e s t r i c t e d as t o p r e c l u d e the demonstration o f a r e l a t i o n s h i p . The most parsimonious i n t e r p r e t a t i o n o f the f i n d i n g s on eye t r a c k i n g and n e u r o p s y c h o l o g i c a l performance would be t h a t performance on these v a r i a b l e s i s u n r e l a t e d i n s c h i z o p h r e n i c p a t i e n t s . Nonetheless, i t may be t h a t the sample i n t h i s study i s a subgroup i n i t s e l f , and hence t h e measures a r e r e l a t e d by s i m p l e v i r t u e o f t h e i r c o - o c c u r r e n c e i n t h i s g r o u p . The p o s s i b i l i t y e x i s t s , t h a t had these measures o f eye t r a c k i n g and n e u r o p s y c h o l o g i c a l performance been a p p l i e d t o a b r o a d l y heterogeneous sample of s c h i z o p h r e n i c p a t i e n t s , a subgroup o f i n d i v i d u a l s w i t h abnormal attainment on both would emerge and the measures would be found to be r e l a t e d . F u r t h e r r e s e a r c h 128 along these l i n e s might be u s e f u l . Were such work t o be done, i t would be a d v i s a b l e t o c o l l e c t i n f o r m a t i o n on a wider range o f c l i n i c a l parameters than were c o n s i d e r e d i n t h i s study. I t may be t h a t l i n k s between t h e v a r i a b l e s a r e m e d i a t e d by s u b j e c t c h a r a c t e r i s t i c s which went unmeasured i n t h i s study. F i n a l l y , l i t t l e s p e c i f i c i n f o r m a t i o n i s known about f a c t o r s w h i c h c o v a r y w i t h n e u r o p s y c h o l o g i c a l d e f i c i t s i n s c h i z o p h r e n i a . These d e f i c i t s c l e a r l y e x i s t i n the c h r o n i c p a t i e n t group i n t h i s study, and i n many o t h e r s r e p o r t e d i n t h e l i t e r a t u r e . L o n g i t u d i n a l i n v e s t i g a t i o n o f n e u r o p s y c h o l o g i c a l d e f i c i t s would be p a r t i c u l a r l y i n t e r e s t i n g . Some o f the p a t i e n t s who p a r t i c i p a t e d i n t h i s study had been n e u r o p s y c h o l o g i c a l ^ assessed e a r l i e r i n the course o f t h e i r i l l n e s s . In some cases i t appeared t h a t t h e r e had been l i t t l e change i n t h e i r performance over a p e r i o d o f y e a r s . I t would be v e r y i n t e r e s t i n g t o i n v e s t i g a t e t h e p r e v a l e n c e o f n e u r o p s y c h o l o g i c a l d e f i c i t s i n f i r s t episode p a t i e n t s on whom fo l l o w - u p assessments o f both c l i n i c a l and n e u r o p s y c h o l o g i c a l f u n c t i o n i n g were c a r r i e d out. 129 REFERENCES Adams, R.L., Boake, C , & C r a i n , C. ( 1 9 8 2 ) . B i a s i n a n e u r o p s y c h o l o g i c a l t e s t c l a s s i f i c a t i o n r e l a t e d t o e d u c a t i o n , age, and e t h n i c i t y . J o u r n a l o f C o u n s u l t i n g  and C l i n i c a l Psychology, 50, 143-145. 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The v e n t r i c u l a r system i n c h r o n i c s c h i z o p h r e n i c p a t i e n t s : A c o n t r o l l e d c o m p u t e d t o m o g r a p h y s t u d y . B r i t i s h J o u r n a l o f P s y c h i a t r y , 144, 172-176. P e n n , R.D., B e l a n g e r , M.G., & Y a s n o f f , W.A., ( 1 9 7 8 ) . V e n t r i c u l a r v o l ume i n man computed from CAT s c a n s . Annals o f Neurology, 3_, 216-233. P u r i s c h , A.D., G o l d e n , C . J . , & Hammeke, T.A. ( 1 9 7 8 ) . D i s c r i m i n a t i o n o f s c h i z o p h r e n i c and b r a i n - i n j u r e d p a t i e n t s b y a s t a n d a r d v e r s i o n o f L u r i a 1 s n e u r o p s y c h o l o g i c a l t e s t s . J o u r n a l o f C o n s u l t i n g and  C l i n i c a l Psychology, 46, 1266-1273. 135 R e v e l e y , M.A. (1 9 8 5 ) . CT scans i n s c h i z o p h r e n i a . B r i t i s h  J o u r n a l o f P s y c h i a t r y , 146, 367-371. R i e d e r , R.O., Mann, L.S., Weinberger, D.R., Van Rammer, D.P. & P o s t , R.M. ( 1 9 8 3 ) . Computed t o m o g r a p h i c s c a n s i n p a t i e n t s w i t h s c h i z o p h r e n i a , s c h i z o a f f e c t i v e , and b i p o l a r a f f e c t i v e d i s o r d e r . A r c h i v e s o f Gener a l P s y c h i a t r y , 40, 735-739. R i e d e r , R.O., D o n n e l l y , E.F., Herdt, J.R., & Waldman, I.N. (1979). S u i c a l prominence i n young c h r o n i c s c h i z o p h r e n i c p a t i e n t s : CT scan f i n d i n g s a s s o c i a t e d w i t h impairment on n e u r o p s y c h o l o g i c a l t e s t s . P s y c h i a t r y Research, l _ , 1-8. Robins, L.N., H e l z e r , J.E., Croughan, J . , W i l l i a m s , J.B. & S p i t z e r , R.L. ( 1 9 8 1 ) . NIMH D i a g n o s t i c I n t e r v i e w  S c h e d u l e : V e r s i o n I I I . ( C o n t r a c t MH 278-79-00 170B). W a s h i n g t o n , DC: N a t i o n a l I n s t i t u t e o f M e n t a l H e a l t h D i v i s i o n o f Biometry and Epidemiology. R u s s e l l , E.W., N e u r i n g e r , C , & G o l d s t e i n , G. (1970). A s s e s s m e n t o f brain-damage: A n e u r o p s y c h o l o g i c a l key  approach. New York: W i l e y - I n t e r s c i e n c e . S c h u l z , S.C., K o l l e r , M.M., K i s h o r e , P.R., Hamer, R.M., Gehl, J . J . , & F r i e d e l , R.O. (1983). V e n t r i c u l a r enlargement i n t e e n a g e p a t i e n t s w i t h s c h i z o p h r e n i a spectrum d i s o r d e r . American J o u r n a l P s y c h i a t r y , 140, 1592-1983. Seidman, L . J . (1983). S c h i z o p h r e n i a and b r a i n d y s f u n c t i o n : An i n t e g r a t i o n o f r e c e n t n e u r o d i o g r o s t i c f i n d i n g s . P s y c h o l o g i c a l B u l l e t i n , 94, 195-238. Shima, S., Kanba, S., Masuda, Y., Tsukumo, T., Kitamura, T., & A s a i , M. ( 1 9 8 5 ) . N o r m a l v e n t r i c l e s i n c h r o n i c s c h i z o p h r e n i c s . A c t a P s y c h o l o g i c a S c a n d i n a v i a , 71, 25-29. Smith, G.N., & Iacono, W.G. (1986). L a t e r a l v e n t r i c l e s i z e i n s c h i z o p h r e n i a and c h o i c e o f c o n t r o l group. Lancet, 8, 1450. Spohn, H.E. (1983). Is eye t r a c k i n g d y s f u n c t i o n s p e c i f i c t o s c h i z o p h r e n i a ? S c h i z o p h r e n i a B u l l e t i n , 9_, 50-54. S t e i g e r , J.H. (1 9 8 0 ) . T e s t s f o r c o m p a r i n g e l e m e n t s o f a c o r r e l a t i o n m a t r i x . P s y c h o l o g i c a l B u l l e t i n , 87, 245-251. Synek, v., & Reuben, J.R. (1976). The v e n t r i c u l a r - b r a i n r a t i o u s i n g p l a n i m e t r i c measurement o f EMI s c a n s . B r i t i s h  J o u r n a l o f Radi o l o g y , 49, 233-237. 136 T a y l o r , M.A., & Abrams, R. (1984). C o g n i t i v e impairment i n s c h i z o p h r e n i a . American J o u r n a l o f P s y c h i a t r y , 141,• 196-201. T a y l o r , M.A., R e d f i e l d , J . & A b r a m s , R. ( 1 9 8 1 ) . N e u r o p s y c h o l o g i c a l d y s f u n c t i o n i n s c h i z o p h r e n i a and a f f e c t i v e d i s e a s e . B i o l o g i c a l P s y c h i a t r y , 16, 467-478. T r i m b l e , M., & K i n g s l e y , D. (1978). C e r e b r a l v e n t r i c u l a r s i z e i n c h r o n i c s c h i z o p h r e n i a . Lancet, 1_, 278-279. Weinberger, D.R., Bigelow, B., Kleinman, J . E . , K l e i n , S.T., R o s e n b l a t t , J . E . , & Wyatt, R.J. ( 1 9 8 0 a ) . C e r e b r a l v e n t r i c u l a r e n l a r g e m e n t i n c h r o n i c s c h i z o p h r e n i a . A r c h i v e s o f General P s y c h i a t r y , 37, 11-13. Weinberger, D.R., Cannon-Spoor, E., P o t k i n , S.G. & Wyatt, R.D. ( 1 9 8 0 b ) . P o o r p r e m o r b i d a d j u s t m e n t and CT s c a n a b n o r m a l i t i e s i n c h r o n i c s c h i z o p h r e n i a . American J o u r n a l  o f P s y c h i a t r y , 137, 1410-1413. W e i n b e r g e r , D.R., D e L i s i , L.E., Perman, G.P. Targum, S., & W y a t t , R . J . (1 9 8 2) . C o m p u t e d t o m o g r a p h y i n s c h i z o p h r e n i f o r m d i s o r d e r and o t h e r acute p s y c h i a t r i c d i s o r d e r s . A r c h i v e s o f General P s y c h i a t r y , 39, 778-783. Weinberger, D.R., T o r r e y , E.F., Neophytides, A.N., & Wyatt, R . J . (1979a). L a t e r a l c e r e b r a l v e n t r i c u l a r enlargement i n c h r o n i c s c h i z o p h r e n i a . A r c h i v e s o f G e n e r a l  P s y c h i a t r y , 36, 735-739. W e i n b e r g e r , D.R. , T o r r e y , E.F., Neophytides, A.N., & Wyatt, R.J. (1979b). S t r u c t u r a l a b n o r m a l i t i e s i n the c e r e b r a l c o r t e x o f c h r o n i c s c h i z o p h r e n i c p a t i e n t s . A r c h i v e s of  Gen e r a l P s y c h i a t r y , 36, 735-739. W e i n b e r g e r , D.R., Wagner, R.L., & W y a t t , R.S. (1983). N e u r o p s y c h o l o g i c a l s t u d i e s o f s c h i z o p h r e n i a : A s e l e c t i v e review. S c h i z o p h r e n i a B u l l e t i n , 9_ 193-212. Weinberger, D.R., & Wyatt, R.J. (1982). C e r e b r a l V e n t r i c u l a r S i z e : A b i o l o g i c a l m a r k e r f o r s u b - t y p i n g c h r o n i c s c h i z o p h r e n i a . In I . Hanin & E. Usdin ( E d s . ) , B i o l o g i c a l  M a r k e r s i n p s y c h i a t r y & neurology. New York: Pergamon Pr e s s . W i l l i a m s , A.O., R e v e l y , M.A., Kolakowska, T., Arden, M., & Mandelbrote, B.M. (1985). S c h i z o p h r e n i a w i t h good and p o o r outcome. I I C e r e b r a l v e n t r i c u l a r s i z e and i t s c l i n i c a l s i g n i f i c a n c e . B r i t i s h J o u r n a l o f P s y c h i a t r y , 146, 239-246. 137 W ing, J.K., C o o p e r , J . E . , & S a r t o r i u s , N. ( 1 9 7 4 ) . The  measurement and c l a s s i f i c a t i o n o f p s y c h i a t r i c symptoms. London: Cambridge U n i v e r s i t y P r e s s . Yee, R.D., (1983). Eye movement r e c o r d i n g as a c l i n i c a l t o o l Ophthalmology, 90, 221-222. Za t z , L.M., J e r n i g a n , T.L., & Ahumada, A . J . (198s). Changes on computed c r a n i a l tomography w i t h aging: I n t r a c r a n i a l f l u i d volume. American J o u r n a l o f N e u r o r a d i o l o g y , 3, 1-11. 138 APPENDIX A T e s t i n g t h e I d e n t i t y M a t r i x H y p o t h e s i s The c a l c u l a t i o n o f t h e X 2 v a l u e u s e d i n t e s t i n g t h e o v e r a l l n u l l h y p o t h e s i s t h a t a m a t r i x o f c o r r e l a t i o n s i s an i d e n t i t y m a t r i x i s done w i t h the f o l l o w i n g formula: X 2 = (N-3) Z i j 2 j < i where Z i j 2 are the squares o f the F i s h e r Z t r a n s f o r m a t i o n s f o r the non-redundant c o r r e l a t i o n c o e f f i c i e n t s i n the m a t r i x and N-3 corresponds t o the sample s i z e minus 3. The degrees o f f r e e d o m f o r t h e c r i t i c a l X 2 v a l u e a r e t h e number o f non-redundant c o r r e l a t i o n s i n the m a t r i x . In the case o f the 10x10 m a t r i x o f c o e f f i c i e n t s f o r the n e u r o p s y c h o l o g i c a l b a t t e r y , t h e r e a r e 45 n o n - r e d u n d a n t c o r r e l a t i o n s . The sum o f the squared F i s h e r Z t r a n s f o r m a t i o n s f o r t h e s e 45 c o r r e l a t i o n s i s 3.73. When t h i s v a l u e i s m u l t i p l i e d by N-3 (N-3 = 30-3, i n t h i s sample) the obtained v a l u e f o r the X 2 i s 100.7. T h i s i s compared to a t a b l e d value o f X 2 w i t h 45 degrees o f freedom (p=.05) which equals 61.656, t h e r e f o r e the n u l l h y p o t h e s i s can be r e j e c t e d . T h i s method i s p r o p o s e d by S t e i g e r (1980) as a way o f o b t a i n i n g experiment wise e r r o r r a t e p r o t e c t i o n . APPENDIX B l MARKERS AND PREDICTORS (MAP) PROJECT CONSENT FORM I n v e s t i g a t o r s : W i l l i a m G. Iacono, Ph.D. Karen Tallman, B.Sc. Consent t o be i n t e r v i e w e d : A r e s e a r c h p r o j e c t i n v o l v i n g p s y c h o l o g i c a l t e s t i n g , p h y s i o l o g i c a l r e cords and a CAT scan has been d e s c r i b e d t o me. I u n d e r s t a n d t h a t b e f o r e anyone i s i n c l u d e d i n the r e s e a r c h study they are i n t e r v i e w e d . T h i s i n t e r v i e w i s c a r r i e d o ut because the r e s e a r c h p r o j e c t needs t o c a r e f u l l y s e l e c t people w i t h c e r t a i n types o f p r o b l e m s . I n f o r m a t i o n t h a t w i l l be h e l p f u l t o my treatment may be conveyed t o my t h e r a p i s t (or to ). Otherwise a l l the i n f o r m a t i o n obtained i n t h i s p r o j e c t w i l l be kept c o n f i d e n t i a l and used on l y f o r the purposes o f t h i s study. I understand t h a t I w i l l be p a i d $5.00 at the end o f the i n t e r v i e w whether I am s e l e c t e d f o r the r e s e a r c h p r o j e c t or not. I a l s o u n d e r s t a n d t h a t I may withdraw from the i n t e r v i e w at any time without p r e j u d i c e t o pr e s e n t and f u t u r e care and treatment. In s i g n i n g t h i s form I h e r e b y acknowledge r e c e i v i n g a copy o f my own use. Witness S i g n a t u r e P r i n t Name Date 140 APPENDIX B2 MARKERS AND PREDICTORS (MAP) PROJECT CONSENT FORM I n v e s t i g a t o r s : W i l l i a m G . I a c o n o , P h . D . K a r e n T a l l m a n , B . S c . The r e s e a r c h p r o j e c t you have been asked to p a r t i c i p a t e i n has t h r e e p a r t s . None o f the t h i n g s we w i l l be d o i n g w i l l cause you any p a i n . One p a r t o f the study w i l l take p l a c e at R i v e r v i e w and t h e o t h e r two p a r t s w i l l h a p p e n a t t h e U n i v e r s i t y o f B r i t i s h C o l u m b i a . The t e s t i n g done a t t h e u n i v e r s i t y takes about two and a h a l f hours. A member o f the p r o j e c t s t a f f w i l l d r i v e you t o the U n i v e r s i t y , s t a y w i t h you d u r i n g the t e s t i n g and then d r i v e you back t o R i v e r v i e w . You w i l l be away from the h o s p i t a l f o r about 5 or 6 yours on the day you go t o the U n i v e r s i t y f o r t e s t i n g . P l e a s e r e a d t h e r e s t o f t h i s form c a r e f u l l y so you understand what you w i l l be doing i f you d e c i d e t o p a r t i c i p a t e i n the study. PART ONE: P s y c h o l o g i c a l T e s t i n g at R i v e r v i e w : about 3 hours In t h i s p a r t o f the study, you w i l l be g i v e n t e s t s o f memory, word d e f i n i t i o n s , concept p u z z l e s , had c o o r d i n a t i o n t a s k s and o t h e r more d i f f i c u l t f o r you. You w i l l be asked to c o n c e n t r a t e and t r y your best to answer each q u e s t i o n . We w i l l take a r e s t a t the end o f each hour. PART TWO: P h y s i o l o g i c a l Recording a t U.B.C.: about 2 hours In t h i s p a r t of the study your body responses such as eye movements, h e a r t beat, b r a i n waves and the a c t i v i t y o f your sweat glands w i l l be measured w h i l e you perform s e v e r a l simple t a s k s . T h e s e t a s k s i n c l u d e c o m f o r t a b l y r e l a x i n g w h i l e l i s t e n i n g t o b e l i e f tones, watching b r i e f f l a s h e s o f l i g h t , watching a spot o f l i g h t move back and f o r t h on a s c r e e n and attempting to produce s i m i l a r movements by t u r n i n g a knob back and f o r t h . To make these r e c o r d i n g s , sensors w i l l be attached to your arms, l e g s , and head but no d i s c o m f o r t or danger t o you i s i n v o l v e d . In another p a r t o f t h i s study a drop o f o i l s i m i l a r t o cooking o i l w i l l be p l a c e d on your s k i n near your f i n g e r n a i l s and a photograph o f your s k i n w i l l be made. 141 PART THREE: CAT Scan a t U.B.C. about 1/2 hour In t h i s p a r t o f the study, p i c t u r e s o f your head w i l l be made w i t h a machine c a l l e d a CAT o r body image s c a n n e r . Having a CAT scan made i s a r o u t i n e h o s p i t a l p r o c e d u r e t h a t takes about 20 minutes. There i s n o t h i n g u n p l e a s a n t about a CAT scan; a l l you have t o do i s l i e s t i l l on a bed w h i l e the machine takes the p i c t u r e . A CAT scan i s very much l i k e an X-ray and makes i t p o s s i b l e t o look at the s t r u c t u r e s o f b r a i n s t r u c t u r e s t h a t are r e l a t e d t o the kin d s o f problems you had been h a v i n g or t h a t a r e r e l a t e d t o t h e m e a s u r e s o f e y e movements, sweat gland, and b r a i n wave a c t i v i t y . We hope you have c a r e f u l l y read the d e s c r i p t i o n o f t h e t h r e e p a r t s o f t h e s t u d y . T h i s i s a good t i m e t o ask q u e s t i o n s i f th e r e i s anything you don't understand. I f you f e e l you understand what you w i l l be doi n g , and i f you s t i l l w ish t o t a k e p a r t i n t h e p r o j e c t p l e a s r e a d and s i g n t h e f o l l o w i n g consent form. I have read the above e x p l a n a t i o n o f a r e s e a r c h p r o j e c t and been g i v e n a copy o f t h i s consent form f o r my own use. I u n d e r s t a n d t h e p r o j e c t w i l l i n v o l v e p s y c h o l o g i c a l t e s t i n g , p h y s i o l o g i c a l r e c o r d i n g s and a CAT scan. I am aware t h a t I w i l l t r a v e l by c a r to the U n i v e r s i t y o f B r i t i s h Columbia w i t h one o f the r e s e a r c h s t a f f . I n f o r m a t i o n t h a t w i l l be h e l p f u l t o my t r e a t m e n t may be c o n v e y e d t o my t h e r a p i s t ( o r to ) . Otherwise, a l l the i n f o r m a t i o n o b t a i n e d i n t h i s p r o j e c t w i l l be kept c o n f i d e n t i a l and used o n l y f o r the p u r p o s e s o f t h i s s t u d y . I u n d e r s t a n d I am f r e e t o a s k q u e s t i o n s about the procedure at any time. By s i g n i n g t h i s form, I agree t o p a r t i c i p a t e , although I. r e a l i z e I am f r e e t o with d r a w from t h i s s t u d y a t any t i m e w i t h o u t p r e j u d i c e t o p r e s e n t and f u t u r e c a r e and t r e a t m e n t . when I f i n i s h a l l p a r t s o f the study I w i l l be p a i d $35.00. Witness S i g n a t u r e P r i n t Name Date 

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