Brain structural correlates of familial risk for mental illness: a meta-analysis of voxel-based morphometry studies in relatives of patients with psychotic or mood disorders

Schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD) are heritable psychiatric disorders with partially overlapping genetic liability. Shared and disorder-specific neurobiological abnormalities associated with familial risk for developing mental illnesses are largely unknown. We performed a meta-analysis of structural brain imaging studies in relatives of patients with SCZ, BD, and MDD to identify overlapping and discrete brain structural correlates of familial risk for mental disorders. Search for voxel-based morphometry studies in relatives of patients with SCZ, BD, and MDD in PubMed and Embase identified 33 studies with 2292 relatives and 2052 healthy controls (HC). Seed-based d Mapping software was used to investigate global differences in gray matter volumes between relatives as a group versus HC, and between those of each psychiatric disorder and HC. As a group, relatives exhibited gray matter abnormalities in left supramarginal gyrus, right striatum, right inferior frontal gyrus, left thalamus, bilateral insula, right cerebellum, and right superior frontal gyrus, compared with HC. Decreased right cerebellar gray matter was the only abnormality common to relatives of all three conditions. Subgroup analyses showed disorder-specific gray matter abnormalities in left thalamus and bilateral insula associated with risk for SCZ, in left supramarginal gyrus and right frontal regions with risk for BD, and in right striatum with risk for MDD. While decreased gray matter in right cerebellum might be a common brain structural abnormality associated with shared risk for SCZ, BD, and MDD, regional gray matter abnormalities in neocortex, thalamus, and striatum appear to be disorder-specific.