A significant amount of evidence from structural brain imaging studies provide new insights into the neuroanatomical basis of schizophrenia.

To investigate whole brain gray matter (GM) differences between schizophrenia patients grouped according to the number of psychotic episodes and normal controls (NC).

To determine regions of GM differences in schizophrenia patients grouped according to the number of psychotic episodes.

A group of 53 schizophrenia patients (23 with up to 3 psychotic episodes, 15 with 4 to 6 and 15 with 7 or more psychotic episodes) and 35 age and gender matched NC were included. Voxel-based morphometry (VBM) is an adaptation of the statistical parametric mapping technique that allows investigators to quantitatively examine brain structural changes. VBM data of schizophrenia patients divided into 3 groups: up to 3, 4 to 6 and 7 or more episodes were compared with NC.

Patients with up to 3 episodes had reduced gray matter volume (GMV) in the right claustrum, right Brodmann areas 6 and 13 and left Brodmann area 10, patients with 4 to 6 episodes in left Brodmann areas 25, 35 and 37 and in right Brodmann area 13, and those with 7 or more episodes showed decreased GMV in left substantia nigra and left Brodmann area 10 compared with NC.

GMV reduction in schizophrenia varies depending on the number of psychotic episodes. The affection of different brain areas indicates separated neurobiological mechanisms underlying the stage and the progression of illness.