PTSD, major depression, and advanced transcriptomic age in brain tissue

Background Psychiatric disorders have been associated with advanced epigenetic age in DNA methylation, yet this relationship has not been studied in the brain transcriptome. We examined transcriptomic age using an RNA‐based algorithm recently developed by Ren and Kuan (“RNAAgeCalc”) and the associat...

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Veröffentlicht in:Depression and anxiety 2022-12, Vol.39 (12), p.824-834
Hauptverfasser: Zhao, Xiang, Logue, Mark W., Hawn, Sage E., Neale, Zoe E., Zhou, Zhenwei, Huber, Bertrand R., Miller, Mark W., Wolf, Erika J.
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Sprache:eng
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Zusammenfassung:Background Psychiatric disorders have been associated with advanced epigenetic age in DNA methylation, yet this relationship has not been studied in the brain transcriptome. We examined transcriptomic age using an RNA‐based algorithm recently developed by Ren and Kuan (“RNAAgeCalc”) and the associations between posttraumatic stress disorder (PTSD), major depressive disorder (MDD), and alcohol use disorder with age‐adjusted RNA age (“RNA age residuals”) in three brain regions: dorsolateral prefrontal cortex, ventromedial prefrontal cortex (vmPFC), and motor cortex. Methods RNA sequencing was used to measure gene expression in postmortem brain tissue from the VA National PTSD Brain Bank (n = 94; 59% male). Results Linear models revealed that diagnoses of PTSD and/or MDD were positively associated with RNA age residuals in vmPFC only (p‐adj = 0.012). Three genes in the RNAAgeCalc algorithm (KCNJ16, HYAL2, and CEBPB) were also differentially expressed in association with PTSD/MDD in vmPFC (p‐adj = 6.45E−05 to 0.02). Enrichment analysis revealed that inflammatory and immune‐related pathways were overrepresented (p‐adj 
ISSN:1091-4269
1520-6394
DOI:10.1002/da.23289