Background: Schizophrenia is a severe illness whose clinical course is characterized by various numbers of psychotic episodes (PE). The neurotoxic hypothesis (NH) of schizophrenia assumes that psychosis is biologically toxic. The aim of the study was to investigate whether schizophrenia patients (SP) with multiple PE have greater grey matter volume (GMV) reduction compared to SP with fewer PE. Subjects and methods: We enrolled 106 adult SP and 63 healthy controls. Demographic and clinical data were collected and statistically analysed for all included subjects. Magnetic resonance imaging (MRI) of the brain was acquired on a 1.5 T scanner. SP were grouped according to the number of PE into a group with up to 3 PE (SCHG-1) and with 4 or more PE (SCHG-2). SCHG-1 was further subdivided into two groups regarding to disease duration (DD). Voxel-based morphometry (VBM) analyses were performed between SP groups as well as between SP groups and the healthy controls group (HCG). Results: No relevant GMV differences were detected between SP groups. Comparison between HCG and SCHG-1 showed only 3 regions with reduced GMV, while multiple regions with reduced GMV were detected when comparing HCG and SCHG-2. Conclusions: GMV reduction in schizophrenia varies depending on the number of PE when compared to HCG, regardless of disease duration (DD), but PE is not the only contributing factor that leads to neurotoxicity.
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