Differential DNA Methylation Is Associated With Hippocampal Abnormalities in Pediatric Posttraumatic Stress Disorder

Recent findings in neuroimaging and epigenetics offer important insights into brain structures and biological pathways of altered gene expression associated with posttraumatic stress disorder (PTSD). However, it is unknown to what extent epigenetic mechanisms are associated with PTSD and its neurobi...

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Published in:	Biological psychiatry : cognitive neuroscience and neuroimaging Vol. 6; no. 11; pp. 1063 - 1070
Main Authors:	Ensink, Judith B.M., Keding, Taylor J., Henneman, Peter, Venema, Andrea, Papale, Ligia A., Alisch, Reid S., Westerman, Yousha, van Wingen, Guido, Zantvoord, Jasper, Middeldorp, Christel M., Mannens, Marcel M.A.M., Herringa, Ryan J., Lindauer, Ramon J.L.
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 01-11-2021
Subjects:	Biological pathways Child and adolescent psychiatry Epigenetics Imaging Methylation Posttraumatic stress disorder Biological pathways Epigenetics Child and adolescent psychiatry Posttraumatic stress disorder Methylation Imaging Posttraumatic Stress Disorder biological pathways child and adolescent psychiatry imaging epigenetics
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Summary:	Recent findings in neuroimaging and epigenetics offer important insights into brain structures and biological pathways of altered gene expression associated with posttraumatic stress disorder (PTSD). However, it is unknown to what extent epigenetic mechanisms are associated with PTSD and its neurobiology in youth. In this study, we combined a methylome-wide association study and structural neuroimaging measures in a Dutch cohort of youths with PTSD (8–18 years of age). We aimed to replicate findings in a similar independent U.S. cohort. We found significant methylome-wide associations for pediatric PTSD (false discovery rate p < .05) compared with non-PTSD control groups (traumatized and nontraumatized youths). Methylation differences on nine genes were replicated, including genes related to glucocorticoid functioning. In both cohorts, methylation on OLFM3 gene was further associated with anterior hippocampal volume. These findings point to molecular pathways involved in inflammation, stress response, and neuroplasticity as potential contributors to neural abnormalities and provide potentially unique biomarkers and treatment targets for pediatric PTSD.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Shared first authors Study supervision: R.L., R.H., M.M. Study concept and design: J.E, T.K., R.H., R.L, M.M. Drafting of the article: J.E, T.K. Critical revision of the article for important intellectual content: P.H., R.H, R.L, G.v.W, C.M., M.M Statistical analysis: J.E, T.K., A.V., P.H. Author Contributions Acquisition of data: J.E, T.K, J.Z Analysis and interpretation of data: J.E, T.K, P.H., R.H., J.Z, G.v.W.
ISSN:	2451-9022 2451-9030
DOI:	10.1016/j.bpsc.2021.04.016