The Impact of developmental instability on voxel-based morphometry analyses of neuroanatomical abnormalities in Schizophrenia

The etiologic factors underlying schizophrenia have been conceptualized as reflecting two largely genetic components — those unique to schizophrenia and those representing vulnerability to neurodevelopmental deviation in general. The Developmental Instability (DI) approach suggests that the latter can be indexed by minor physical anomalies (MPAs), which assess early prenatal growth abnormalities, and fluctuating anatomic asymmetries (FA), which reflects later deviations. Individuals with schizophrenia (N = 19) had elevated scores on both measures as compared to healthy controls (N = 23). Further, MPAs and FA were very highly correlated in the sample of individuals with schizophrenia but not in controls. In order to identify neuroanatomic variation linked with the unique factor, we conducted gray matter Voxel Based Morphometry analyses of group membership, with and without treating a composite measure of DI (based on FA, and MPAs) as a covariate. When DI was treated as a covariate, many more gray matter regions were found to statistically differ as a function of diagnosis. These results support the DI approach and suggest that the unique etiologic factors associated with schizophrenia lead to widespread gray matter volume reductions.