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Functionally relevant basal ganglia subdivisions in first-episode schizophrenia Khorram, Babak

Abstract

Schizophrenia is among the most debilitating mental disorders, yet the pathophysiology remains unclear. The basal ganglia, a region of the brain involved in motor, cognitive, and sensory processes, may be involved in the pathophysiology of schizophrenia. Some, but not all, neuroimaging studies suggest abnormalities of the basal ganglia in schizophrenia. However, previous studies have examined whole basal ganglia nuclei as opposed to using a unified basal ganglia complex that incorporates anterior-posterior divisions, dorsal-ventral divisions, and gray-white matter segmentation. The hypothesis for the present study was that basal ganglia sub-regions forming functionally relevant subdivisions might be different in schizophrenia. Magnetic resonance imaging scans were acquired from 25 first-episode schizophrenia subjects and 24 healthy subjects. Using manual and automated neuroimaging techniques, total and segmented (gray-white matter) volumes were obtained for the caudate, putamen, and globus pallidus. For the striatum (caudate and putamen), total and segmented volumes were obtained for their respective sub-regions. These sub-regions were restructured into associative, limbic, and sensorimotor subdivisions. Schizophrenia subjects had 6% smaller gray matter volumes for the caudate and 8% smaller gray matter volumes for the associative striatum relative to healthy subjects. Basal ganglia function was studied by examining performance on a neuropsychological test that assesses frontostriatal functioning. For male subjects there was a significant negative correlation between volume of the associative striatum and performance on the neuropsychological test (r=-0.57, p=0.03). Smaller volumes of the associative striatum were associated with more errors on the neuropsychological test. This test was specific to the associative striatum, as another neuropsychological test did not reveal any correlation. In schizophrenia subjects, the relationship between basal ganglia volumes and motor symptoms severity was examined. For antipsychotic-naive subjects there was a significant negative correlation between volume of the motor striatum and severity of Parkinsonism (r=-0.65, p=0.03). The present study suggests that total basal ganglia nuclei volumes are not different in schizophrenia, but gray matter volumes of total basal ganglia nuclei and subdivisions forming functional units may be different in schizophrenia. Structural abnormalities involving the basal ganglia may lead to disrupted functional circuits in schizophrenia.

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