Regional gene expression signatures are associated with sex-specific functional connectivity changes in depression.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
28 09 2022
28 09 2022
Historique:
received:
12
09
2020
accepted:
09
08
2022
entrez:
28
9
2022
pubmed:
29
9
2022
medline:
1
10
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 36171190
doi: 10.1038/s41467-022-32617-1
pii: 10.1038/s41467-022-32617-1
pmc: PMC9519925
doi:
Substances chimiques
Protocadherins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
5692Subventions
Organisme : NIMH NIH HHS
ID : F30 MH124317
Pays : United States
Informations de copyright
© 2022. The Author(s).
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