Regional gene expression signatures are associated with sex-specific functional connectivity changes in depression.

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