Regional Gray Matter Volume in Monozygotic Twins Concordant and Discordant for Schizophrenia

Background: Alterations in gray matter volume (GMV) are a robust feature of schizophrenia. However, it is not clear to what extent these abnormalities are correlates of the genetic liability to the disorder, as opposed to environmental factors and the disorder itself. We investigated the influence of genetic and environmental risk on GMV in monozygotic (MZ) twin pairs concordant and discordant for schizophrenia. Methods: Total and regional GMVs were measured from magnetic resonance images of 80 twins: 14 MZ pairs concordant for schizophrenia, 9 pairs discordant for schizophrenia, and 17 healthy MZ twin pairs. Results: Total GMV was smaller in twins with schizophrenia (t = -3.17, p = .003) and nonpsychotic cotwins from discordant pairs (t = -2.66, p = .011) than in healthy control twins. Twin pairs concordant for schizophrenia displayed reduced regional GMV in the inferior frontal, medial frontal, and anterior cingulate gyri; the caudate; lingual gyrus; and cerebellum relative to healthy twins (p < .05, corrected). Within discordant pairs, twins with schizophrenia had less GMV than their nonpsychotic cotwins in the insula; superior/medial frontal, pre/postcentral, cingulate, and superior temporal gyri; and the paracentral lobule. There were no significant differences in regional GMV between nonpsychotic cotwins and healthy control subjects. Conclusions: The presence of schizophrenia was specifically related to reduced GMV in frontal, insular, cingulate, medial parietal, and temporal cortex, over and above effects of genetic risk for the disorder. These changes could be related to the pathophysiology of the disorder itself or to unique environmental factors acting etiologically or because of the illness.