Brain abnormalities in relatives of schizophrenic patients identified by structural magnetic resonance imaging

Background: Schizophrenia is characterized by brain abnormalities in limbic-diencephalic and cortical regions. Increasing evidence indicates that nonpsychotic relatives of patients with schizophrenia ("Reis") manifest a milder syndrome which may also include brain abnormalities. In previous work we found that, compared with controls, Reis had significant volume reductions bilaterally in the amygdala-hippocampal region, thalamus, and cerebellum, and significantly increased volumes in the pallidum. The goal of this study was to further character-ize possible brain abnormalities in Reis. Methods: Subjects were 28 nonpsychotic first degree adult Rels and 26 matched normal controls. Sixty contiguous 3 mm coronal, T1-weighted 3D magnetic resonance images of the entire brain were acquired on a 1.5 Tesla magnet. Cortical and subcortical gray and white matter were segmented using a semiautomated intensity contour mapping algorithm. To assess expected regional alterations in cortical volumes, we used a new method to segment the entire cortex into 48 topographically-defined regions. Volumes were adjusted for total cortical volumes. Results: Findings showed that Rels had significant volumetric reductions in paralimbic cortices, particularly in the anterior cingulate and paracingulate gyri, the parahippocampal gyrus, and the insula. Rels also had reduced volumes in the inferior frontal gyrus, in and around Brocas area. Many of these areas had been found to be abnormal in a previous study of schizophrenic patients. Conclusions: Results indicate that nonpsychotic relatives of schizophrenic patients have abnormal brain structures, particularly in medial and paralimbic cortices. This supports the hypothesis that the genetic liability to schizophrenia is expressed as structural brain abnormalities.