A comprehensive computational morphometric analysis of the brain in neuroleptic-naive schizophrenia

Abstract

BACKGROUND: Neuroleptic treatment confounds the interpretation of studies of brain morphology in schizophrenia. We hypothesized that fronto-temporal and subcortico-limbic abnormalities, particularly the caudate nuclei, would be independent of neuroleptic treatment in first episode schizophrenia. METHODS: We performed a comprehensive computational morphometry analysis of the brain in 29 never-medicated individuals with first-episode schizophrenia and 40 healthy controls. Groups were balanced for age, sex, handedness, ethnicity, paternal socioeconomic status, and height. Patients were a consecutive series presenting to their local hospital for treatment for the first time. Healthy controls were recruited from the local community by advertisement. Voxel-based analysis of grey matter, white matter and CSF volumes was performed. RESULTS: Grey matter, white matter and CSF: global brain volume ratios were significantly smaller in patients. Patients had significantly less grey matter volume in bilateral caudate nuclei, right thalamus, right prefrontal cortex, bilateral cingulate gyrus, bilateral parahippocampal gyri, right superior temporal gyrus and bilateral cerebellum. They also had significantly less white matter volume in the right anterior limb of the internal capsule, right fronto-occipital fasciculus and bilateral fornices, and significantly greater CSF volume especially in the right lateral ventricle. CONCLUSIONS: Our data indeed suggest that fronto-temporal and subcortical-limbic circuits are morphologically abnormal in schizophrenia. Thus, unrelated to pharmacotherapy, periventricular changes, particularly smaller caudate volumes that are evident in neuroleptic naı¨ve patients, are likely to predate clinical expression of psychosis.