Search

Background: Psychiatric conditions show overlap in their symptoms, genetics, and involvement in brain areas and circuits. Structural alterations in the brain have been found to run in parallel with expression profiles of risk genes at the level of the brain transcriptome, which may point toward a potential transdiagnostic vulnerability of the brain to disease processes., Methods: We characterized the transcriptomic vulnerability of the cortex across 4 major psychiatric disorders based on collated data from patients with psychiatric disorders (n = 390) and matched control participants (n = 293). We compared normative expression profiles of risk genes linked to schizophrenia, bipolar disorder, autism spectrum disorder, and major depressive disorder to examine cross-disorder overlap in spatial expression profiles across the cortex and their concordance with a magnetic resonance imaging-derived cross-disorder profile of structural brain alterations., Results: We showed high expression of psychiatric risk genes converging on multimodal cortical regions of the limbic, ventral attention, and default mode networks versus primary somatosensory networks. Risk genes were found to be enriched among genes associated with the magnetic resonance imaging cross-disorder profile, suggestive of a common link between brain anatomy and the transcriptome in psychiatric conditions. Characterization of this cross-disorder structural alteration map further shows enrichment for gene markers of astrocytes, microglia, and supragranular cortical layers., Conclusions: Our findings suggest that normative expression profiles of disorder risk genes confer a shared and spatially patterned vulnerability of the cortex across multiple psychiatric conditions. Transdiagnostic overlap in transcriptomic risk suggests a common pathway to brain dysfunction across psychiatric disorders., (Copyright © 2023 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

The human brain is a highly complex system, with a large variety of microscale cellular morphologies and macroscale global properties. Working at multiple scales, it forms an efficient system for processing and integration of multimodal information. Studies have repeatedly demonstrated strong associations between modalities of both microscales and macroscales of brain organization. These consistent observations point toward potential common organization principles where regions with a microscale architecture supportive of a larger computational load have more and stronger connections in the brain network on the macroscale. Conversely, disruptions observed on one organizational scale could modulate the other. First neuropsychiatric micro-macro comparisons in, among other conditions, Alzheimer's disease and schizophrenia, have, for example, shown overlapping alterations across both scales. We give an overview of recent findings on associations between microscale and macroscale organization observed in the healthy brain, followed by a summary of microscale and macroscale findings reported in the context of brain disorders. We conclude with suggestions for future multiscale connectome comparisons linking multiple scales and modalities of organization and suggest how such comparisons could contribute to a more complete fundamental understanding of brain organization and associated disease-related alterations., (Copyright © 2018 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)