UBC Theses and Dissertations
Basal ganglia structure and the effects of neuroleptic treatment in schizophrenia Lang, Donna Jane-Mai
Schizophrenia is a complex mental illness of unknown etiology. Clinical research has suggested that abnormalities of the basal ganglia are present in schizophrenia. Whether these abnormalities are present at the beginning of illness or progress with time remains controversial. Concomitantly, antipsychotic treatments, particularly traditional neuroleptics, may exert metabolic effects on the basal ganglia, but the effects of new atypical antipsychotic are unknown. To elucidate the nature of underlying basal ganglia structure and the effects of antipsychotic treatment on striatal morphology, clinical signs and symptoms, three MRI studies of basal ganglia volumes were conducted. In study A, baseline volumes in a cohort of drug-naive first episode psychosis (FEP) patients, chronically treated schizophrenia patients and healthy controls were assessed. Chronically treated patients had larger basal ganglia volumes compared to both never-medicated patients and healthy controls. Never-medicated patients' basal ganglia volumes were not different from controls. In study B, extrapyramidal symptoms (EPS) and their relationship to neuroleptics and striatal volumes were examined. Prior to neuroleptic treatment, 39% of FEP patients had EPS at baseline. FEP patients who presented with parkinsonism had larger left caudate volumes than those who did not. In study C, the effects on basal ganglia volumes and EPS after switching patients from risperidone or typical antipsychotics to olanzapine were examined. Patients previously treated with typicals had decreases in putamen and globus pallidus volume after switching. Patients previously on risperidone had a decrease in caudate volume after switching. Patients maintained on risperidone had no changes in basal ganglia volumes. Severity and prevalence of EPS were unchanged after switching. No underlying volumetric abnormalities of the basal ganglia in drug-naive first-episode schizophrenia were observed in the cohort of patients included in this thesis. However, movement disorders were seen in a notable portion of drug-naive schizophrenia patients, suggesting that abnormalities of the basal ganglia or circuits of the basal ganglia are present and may be subtle. Atypical neuroleptics do not induce additional EPS at clinically effective doses. Chonic exposure to atypical neuroleptics is not associated with striatal hypertrophy, and in the case of olanzapine, may reduce caudate volumes in some patients.
Item Citations and Data