Publication Type Academic Article
Authors Talishinsky A, Downar J, Vértes P, Seidlitz J, Dunlop K, Lynch C, Whalley H, McIntosh A, Vila-Rodriguez F, Daskalakis Z, Blumberger D, Liston C
Journal Nat Commun
Volume 13
Issue 1
Pagination 5692
Date Published 09/28/2022
ISSN 2041-1723
Keywords Brain Mapping, Transcriptome
Abstract The neural substrates of depression may differ in men and women, but the underlying mechanisms are incompletely understood. Here, we show that depression is associated with sex-specific patterns of abnormal functional connectivity in the default mode network and in five regions of interest with sexually dimorphic transcriptional effects. Regional differences in gene expression in two independent datasets explained the neuroanatomical distribution of abnormal connectivity. These gene sets varied by sex and were strongly enriched for genes implicated in depression, synapse function, immune signaling, and neurodevelopment. In an independent sample, we confirmed the prediction that individual differences in default mode network connectivity are explained by inferred brain expression levels for six depression-related genes, including PCDH8, a brain-specific protocadherin integral membrane protein implicated in activity-related synaptic reorganization. Together, our results delineate both shared and sex-specific changes in the organization of depression-related functional networks, with implications for biomarker development and fMRI-guided therapeutic neuromodulation.
DOI 10.1038/s41467-022-32617-1
PubMed ID 36171190
PubMed Central ID PMC9519925
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