Voxel-based morphometry of patients with schizophrenia or bipolar I disorder: a matched control study

Abstract

Controlled trials provide critical tests of hypotheses generated by meta-analyses. Two recent meta-analyses have reported that gray matter volumes of schizophrenia and bipolar I patients differ in the amygdala, hippocampus, or perigenual anterior cingulate. The present magnetic resonance imaging study tested these hypotheses in a cross-sectional voxel-based morphometry (VBM) design of 17 chronic schizophrenia and 15 chronic bipolar patients and 21 healthy subjects matched for age, gender and duration of illness. Whole brain gray matter volume of both the schizophrenia and bipolar groups was smaller than among healthy control subjects. Regional voxel-wise comparisons showed that gray matter volume was smallest within frontal and temporal regions of both patient groups. Region of interest analyses found moderately large to large differences between schizophrenia and healthy subjects in the amygdala and hippocampus. There were no group differences in the perigenual anterior cingulate. When schizophrenia and bipolar groups were directly compared, the schizophrenia group showed smaller gray matter volumes in right subcortical regions involving the right hippocampus, putamen, and amygdala. The hippocampal and amygdala findings confirm predictions derived from recent meta-analyses. These structural abnormalities may be important factors in the differential manifestations of these two functional psychotic disorders.

Figure 1

Voxel-by-voxel comparison map of bipolar I disorder (n=15), schizophrenia(n=17) and healthy control(n=21) subjects, rendered on a T1-weighted anatomic image^{a a}Statistically significant differences in gray matter volume were defined p≤.001, with a cluster size of 200 and corrected cluster level significance p<0.05. The location of the significant difference results from each comparison was plotted as a dot (Montreal Neurological Institute coordinates are provided in Table 2). Green dot signifies location of gray matter reduction in schizophrenic patients compared with bipolar patients. Blue dot signifies location of gray matter reduction in bipolar I patients compared with control subjects. Red dot signifies location of gray matter reduction in schizophrenic patients compared with control subjects.