Regional, circuit, and network heterogeneity of brain abnormalities in psychiatric disorders

ABSTRACT The substantial individual heterogeneity that characterizes mental illness is often ignored by classical case-control designs that rely on group mean comparisons. Here, we present a comprehensive, multiscale characterization of individual heterogeneity of brain changes in 1294 cases diagnosed with one of six conditions and 1465 matched healthy controls. Normative models identified that person-specific deviations from population expectations for regional grey matter volume were highly heterogeneous, affecting the same area in <7% of people with the same diagnosis. However, these deviations were embedded within common functional circuits and networks in up to 56% of cases. The salience/ventral attention system was implicated transdiagnostically, with other systems selectively involved in depression, bipolar disorder, schizophrenia, and ADHD. Our findings indicate that while phenotypic differences between cases assigned the same diagnosis may arise from heterogeneity in the location of regional deviations, phenotypic similarities are attributable to dysfunction of common functional circuits and networks.