Abstract
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.