TY - JOUR
T1 - Differential DNA Methylation Is Associated With Hippocampal Abnormalities in Pediatric Posttraumatic Stress Disorder
AU - Ensink, Judith B. M.
AU - Keding, Taylor J.
AU - Henneman, Peter
AU - Venema, Andrea
AU - Papale, Ligia A.
AU - Alisch, Reid S.
AU - Westerman, Yousha
AU - van Wingen, Guido
AU - Zantvoord, Jasper
AU - Middeldorp, Christel M.
AU - Mannens, Marcel M. A. M.
AU - Herringa, Ryan J.
AU - Lindauer, Ramon J. L.
N1 - Funding Information: This project was partly funded by the Augeo Foundation (Grant No. 21362 [to RJLL]), National Institute of Mental Health (Grant No. K08 MH100267, R01MH115910, R01MH117141 to [RJH]), NARSAD Young Investigator Grant (to RJH, LAP), University of Wisconsin Institute for Clinical and Translational Research Translational Pilot Grant Award (NIH/NCATS Grant No. UL1TR000427 [to RJH]), and National Science Foundation Graduate Research Fellowship Award (Grant No. DGE 1747503 [to TJK]). The funders had no role in the design and conduct of the study; the collection, management, analysis, or interpretation of data; or article preparation. JBME, TJK, RJH, RJLL, and MMAMM were involved in study concept and design. JBME, TJK, and JZ were involved in acquisition of data. JBME, TJK, PH, RJH, JZ, LAP, RSA, and GvW were involved in analysis and interpretation of data. JBME and TJK were involved in drafting of the article. PH, RJH, RJLL, GvW, CMM, and MMAMM were involved in critical revision of the article for important intellectual content. JBME, TJK, AV, and PH were involved in statistical analysis. RJLL, RJH, and MMAMM were involved in study supervision. We thank Rosanne op den Kelder, M.Sc. psychologist at the Bascule, Academic Centre for Child an Adolescent Psychiatry, for her help with the collection of the clinical data. The authors report no biomedical financial interests or potential conflicts of interest. Funding Information: This project was partly funded by the Augeo Foundation (Grant No. 21362 [to RJLL]), National Institute of Mental Health (Grant No. K08 MH100267, R01MH115910, R01MH117141 to [RJH]), NARSAD Young Investigator Grant (to RJH, LAP), University of Wisconsin Institute for Clinical and Translational Research Translational Pilot Grant Award (NIH/NCATS Grant No. UL1TR000427 [to RJH]), and National Science Foundation Graduate Research Fellowship Award (Grant No. DGE 1747503 [to TJK]). The funders had no role in the design and conduct of the study; the collection, management, analysis, or interpretation of data; or article preparation. Publisher Copyright: © 2021 Society of Biological Psychiatry Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/11
Y1 - 2021/11
N2 - Background: 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. Methods: 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. Results: 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. Conclusions: 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.
AB - Background: 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. Methods: 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. Results: 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. Conclusions: 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.
KW - Biological pathways
KW - Child and adolescent psychiatry
KW - Epigenetics
KW - Imaging
KW - Methylation
KW - Posttraumatic stress disorder
UR - http://www.scopus.com/inward/record.url?scp=85111292523&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.bpsc.2021.04.016
DO - https://doi.org/10.1016/j.bpsc.2021.04.016
M3 - Article
C2 - 33964519
SN - 2451-9022
VL - 6
SP - 1063
EP - 1070
JO - Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
JF - Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
IS - 11
ER -