Categorical and Dimensional Deficits in Hippocampal Subfields Among Schizophrenia, Obsessive-Compulsive Disorder, Bipolar Disorder, and Major Depressive Disorder

BACKGROUND: The hippocampus is a core region of interest for all major mental disorders, and its subfields implement distinctive functions. It is unclear whether the mental disorders exhibit common patterns of hippocampal impairments, and we lack knowledge on whether and how hippocampal subfields represent deficit spectra across mental disorders. METHODS: Using brain images of 1123 individuals scanned on a single magnetic resonance imaging scanner, we examined the commonality, specificity, and symptom associations of the volume of hippocampal subfields across patients with schizophrenia, patients with obsessive-compulsive disorder, patients with bipolar disorder, patients with major depressive disorder, and healthy control subjects. We further performed a transdiagnostic analysis of the individual variability of the volume of hippocampal subfields to reflect cross-disease gradients in the hippocampus. RESULTS: We found common and disease-specific abnormalities in a few hippocampal fields and identified 2 reliable transdiagnostic factors in the hippocampal subfields, each reflecting a spectrum of mental disorders. The plane spanned by the 2 most reliable factors provided a clearer view of hippocampal volume abnormality spectra among the major mental disorders. In addition, functional and genetic enrichment analyses supported the different roles of the 2 hippocampal factors in mental disorders. CONCLUSIONS: The volume of hippocampal subfields reflected some commonality and specificity among the 3 major mental disorders. We propose a new pathophysiological dimensional view of the hippocampus, reflecting at least 2 spectra of mental disorders, suggesting multivariate links among the diseases. This work highlights the value of the complementary categorical and dimensional views of the hippocampal deficits in mental disorders. https://doi.org/10.1016/j.bpsc.2022.06.011