Common neuroanatomical differential factors underlying heterogeneous gray matter volume variations in five common...

Multifaceted evidence has shown that psychiatric disorders share common neurobiological mechanisms. However, the tremendous inter-individual heterogeneity among patients with psychiatric disorders limits trans-diagnostic studies with case-control designs, aimed at identifying clinically promising neuroimaging biomarkers. This study aims to identify neuroanatomical differential factors (ND factors) underlying gray matter volume variations in five psychiatric disorders. We leverage 4 independent datasets of 878 patients diagnosed with psychiatric disorders and 585 healthy controls (HCs) to identify shared ND factors underlying individualized gray matter volume variations. Individualized gray matter volume variations are represented with the linear weighted sum of ND factors, and each case is assigned a unique factor composition, thus preserving interindividual variation. We identify four robust ND factors that can be generalized to unseen disorders. ND factors show significant association with group-level morphological abnormalities, reconciling individual- and group-level morphological abnormalities, and are characterized by dissociable cognitive processes, molecular signatures, and connectome-informed epicenters. Moreover, using factor compositions as features, we discover two robust transdiagnostic subtypes with opposite gray matter volume variations relative to HCs. In conclusion, we identify four reproducible and shared neuroanatomical factors that underlie the highly heterogeneous morphological abnormalities in psychiatric disorders.