DNA methylation mediates the link between adversity and depressive symptoms

Lussier, Alexandre A; Smith, Brooke J; Fisher, Jonah; Luo, Mannan; Cerutti, Janine; Schneper, Lisa; Smith, Trey; Cecil, Charlotte A M; Felix, Janine F; Mitchell, Colter; Notterman, Daniel A; Ressler, Kerry J; Schaid, Daniel J; Simpkin, Andrew J; Suderman, Matthew J; Walton, Esther; Smith, Andrew D A C; Dunn, Erin C

Abstract

Experiences of childhood adversity can double risk for depression. Although the mechanisms underlying this relationship remain unclear, DNA methylation (DNAm) has emerged as a potential pathway to explain the link between adversity and depression. Thus, we investigated whether epigenome-wide DNAm statistically mediates the association between childhood adversity and adolescent depressive symptoms. Specifically, we performed epigenome-wide mediation analyses to investigate the role of blood-based DNAm (age 7) in linking seven types of adversity (ages 1-7) to depressive symptoms (age 10.6). Primary analyses were conducted in the Avon Longitudinal Study of Parents and Children and replicated in the Future of Families and Child Wellbeing Study and Generation R Study. We identified 70 CpGs that mediated 10-73% of the correlation between adversity and depressive symptoms, with DNAm differences at 39 CpGs showing protective effects. Our findings suggest DNAm reflects a biological pathway linking childhood adversity to depression and a potential mechanism towards resilience.

• Journal Article Type: Article
• Acceptance Date: Oct 3, 2024
• Online Publication Date: Dec 2, 2024
• Publication Date: Dec 2, 2024
• Deposit Date: Dec 5, 2024
• Publicly Available Date: Jun 3, 2025
• Journal: Nature Mental Health
• Electronic ISSN: 2731-6076
• Publisher: Nature Research
• Peer Reviewed: Peer Reviewed
• Volume: 2
• Pages: 1476–1485
• DOI: https://doi.org/10.1038/s44220-024-00345-8
• Public URL: https://uwe-repository.worktribe.com/output/13507934
• Publisher URL: https://www.nature.com/articles/s44220-024-00345-8