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

Published version
Peer-reviewed

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Authors

Talishinsky, Aleksandr 
Downar, Jonathan 
Dunlop, Katharine 

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.

Description

Keywords

Article, /631/378/1689/1414, /692/699/476/1414, /59/36, /45, /45/23, /45/91, article

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

Publisher

Springer Science and Business Media LLC
Sponsorship
U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) (MH109685)