Abstract: Background: imaging evidence indicates that brain alterations are primary to the full-blown onset of schizophrenia and seem to progress across time. The potential effects of antipsychotic medication on brain structure represent a key factor in understanding brain changes in psychosis. We aimed to investigate the effects of low doses of haloperidol, risperidone and olanzapine on cortical thickness. Method: we investigated the effects of risperidone (N=16), olanzapine (N= 18) and low doses of haloperidol (N= 18) in cortical thickness changes during 1-year follow-up period in a large and heterogeneous sample of schizophrenia spectrum patients. The relationship between cortical thickness changes and clinical and cognitive outcome was also assessed. A group of 45 healthy volunteers was also longitudinally evaluated. Magnetic resonance imaging brain scans (1.5 T) were obtained and images were analyzed by using BRAINS2. Results: there were no significant effects of time (F1,47b1.66; P>0.204), treatment group (F2,47 b1.47; P> 0.242) or group-by-time interaction (F2,47b1.82; P> 0.174) for any of the cortical thickness variables. When the group of healthy controls was included in the analyses, it is of note that group-by-time interaction showed a significant result for the frontal lobe at trend level (F3,81= 2.686; P= 0.052). After the Bonferroni adjustment for multiple comparisons, there were no significant associations between changes in cortical thickness and clinical and cognitive outcome. Conclusions: low doses of haloperidol, risperidone, and olanzapine seem to equally affect gray matter cortical thickness, overall and lobes, at the medium-term (1 year). The clinical effectiveness of treatments was not significantly related to changes in cortical thickness.

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