Identification of a Diagnosis-Selective Neurobiological Substrate for Bipolar Disorder, Major Depressive Disorder, and Schizophrenia: A Meta-Analysis of 57,717 Subjects

Neuroimaging studies have consistently revealed neuroanatomical abnormalities in individuals with bipolar disorder, major depressive disorder, and schizophrenia. However, it remains unknown whether and to what extent disorder-selective gray matter variations occur in these prominent psychiatric disorders. This study conducted a meta-analysis of 25 years of published voxel-based morphometry research to assess the presence of selective and robust neuroanatomical substrates of gray matter variation in bipolar disorder, major depressive disorder, and schizophrenia. Peer-reviewed experiments encompassing subjects with target disorders were systematically searched in the MEDLINE database. Additionally, peer-reviewed data on 30 other psychiatric disorders and 65 neurological diseases were obtained from the BrainMap database. Experiments reporting whole-brain group comparisons between patients and healthy controls were included if they identified significant gray matter reductions. The data were analyzed using the Bayes fACtor mOdeliNg algorithm. 1,021 voxel-based morphometry experiments were included, comprising 29,540 patients and 28,177 healthy controls. Primary analyses of psychiatric data revealed strong evidence of gray matter reduction in the right middle temporal gyrus for bipolar disorder and the posterior dorsal anterior cingulate cortex for schizophrenia (P ≥ 95% selectivity). The robustness of these findings was confirmed using the fail-safe method tailored to the neuroimaging meta-analytic environment. No selective findings were observed in additional analyses that included neurological diseases. Taken together, these findings offer a framework that underscores the significance of diagnosis-selective neural substrates in psychopathology, a new perspective that could inform distinct pathophysiological processes and assist in diagnosis and treatment.