Chad E Shenk1,2, Kieran J O'Donnell3,4, Irina Pokhvisneva3, Michael S Kobor4,5, Michael J Meaney3,4,6, Heather E Bensman7, Elizabeth K Allen1, Anneke E Olson1. 1. Department of Human Development and Family Studies, The Pennsylvania State University. 2. Department of Pediatrics, The Pennsylvania State University College of Medicine. 3. The Douglas Hospital Research Centre, Department of Psychiatry, McGill University. 4. Child and Brain Developmental Program, Canadian Institute for Advanced Research. 5. Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia. 6. Agency for Science, Technology and Research, Singapore Institute of Clinical Sciences. 7. Department of Pediatrics, The University of Cincinnati College of Medicine.
Abstract
OBJECTIVE: Child maltreatment is among the strongest predictors of posttraumatic stress disorder (PTSD). However, less than 40% of children who have been maltreated are ever diagnosed with PTSD, suggesting that exposure to child maltreatment alone is insufficient to explain this risk. This study examined whether epigenetic age acceleration, a stress-sensitive biomarker derived from DNA methylation, explains variation in PTSD diagnostic status subsequent to child maltreatment. METHOD: Children and adolescents (N = 70; 65.7% female), 8-15 years of age (M = 12.00, SD = 2.37) and exposed to substantiated child maltreatment within the 12 months prior to study entry, were enrolled. Participants provided epithelial cheek cells via buccal swab for genotyping and quantification of epigenetic age acceleration within a case-control design. PTSD diagnostic status was determined using the Child PTSD Symptoms Scale according to the DSM-IV-TR algorithm. RESULTS: Epigenetic age acceleration predicted current PTSD status, revealing an effect size magnitude in the moderate range, OR = 2.35, 95% CI: 1.22- 4.51, after adjusting for sample demographics, polygenic risk for PTSD, and lifetime exposure to other childhood adversities. Supplemental analyses demonstrated that epigenetic age acceleration was related to a greater severity of PTSD arousal symptoms (r =.29, p =.015). There were no differential effects for child maltreatment subtype on epigenetic age acceleration or PTSD status. CONCLUSIONS: The biological embedding of child maltreatment may explain variation in PTSD diagnostic status and serve as a novel approach for informing selective prevention or precision-based therapeutics for those at risk for PTSD.
OBJECTIVE: Child maltreatment is among the strongest predictors of posttraumatic stress disorder (PTSD). However, less than 40% of children who have been maltreated are ever diagnosed with PTSD, suggesting that exposure to child maltreatment alone is insufficient to explain this risk. This study examined whether epigenetic age acceleration, a stress-sensitive biomarker derived from DNA methylation, explains variation in PTSD diagnostic status subsequent to child maltreatment. METHOD: Children and adolescents (N = 70; 65.7% female), 8-15 years of age (M = 12.00, SD = 2.37) and exposed to substantiated child maltreatment within the 12 months prior to study entry, were enrolled. Participants provided epithelial cheek cells via buccal swab for genotyping and quantification of epigenetic age acceleration within a case-control design. PTSD diagnostic status was determined using the Child PTSD Symptoms Scale according to the DSM-IV-TR algorithm. RESULTS: Epigenetic age acceleration predicted current PTSD status, revealing an effect size magnitude in the moderate range, OR = 2.35, 95% CI: 1.22- 4.51, after adjusting for sample demographics, polygenic risk for PTSD, and lifetime exposure to other childhood adversities. Supplemental analyses demonstrated that epigenetic age acceleration was related to a greater severity of PTSD arousal symptoms (r =.29, p =.015). There were no differential effects for child maltreatment subtype on epigenetic age acceleration or PTSD status. CONCLUSIONS: The biological embedding of child maltreatment may explain variation in PTSD diagnostic status and serve as a novel approach for informing selective prevention or precision-based therapeutics for those at risk for PTSD.
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