TY - JOUR
T1 - Convergence of Brain Transcriptomic and Neuroimaging Patterns in Schizophrenia, Bipolar Disorder, Autism Spectrum Disorder, and Major Depressive Disorder
AU - Ardesch, Dirk Jan
AU - Libedinsky, Ilan
AU - Scholtens, Lianne H.
AU - Wei, Yongbin
AU - van den Heuvel, Martijn P.
N1 - Funding Information:
This study was supported by VIDI (Grant No. 452-16-015 [to MPvdH]) and Aard- en levenswetenschappen (Grant No. ALWOP.179 [to MPvdH]) from the Netherlands Organization for Scientific Research and Consolidator (Grant No. 101001062 [to MPvdH]) on cross-disorder connectomics from the European Research Council.
Publisher Copyright:
© 2023 Society of Biological Psychiatry
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - Cortex
KW - Cross-disorder
KW - Gene expression
KW - MRI
KW - Microarray
KW - Psychiatry
UR - http://www.scopus.com/inward/record.url?scp=85152356455&partnerID=8YFLogxK
U2 - 10.1016/j.bpsc.2022.12.013
DO - 10.1016/j.bpsc.2022.12.013
M3 - Article
SN - 2451-9022
JO - Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
JF - Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
ER -