Oxytocin receptor genes moderate BDNF epigenetic methylation by childhood trauma

Abstract

Objectives: Gene-Environment (G × E) interaction is of increasing importance in understanding the pathophysiology of posttraumatic stress disorder (PTSD). This study investigated the interaction effect of childhood traumatic experience and epigenetic methylation of brain-derived neurotrophic factor (BDNF) and a possible moderating effect of oxytocin receptor (OXTR) gene rs53576.

Methods: Ninety-nine patients with PTSD and 81 healthy controls (HCs) were recruited. Clinical assessments, including the childhood trauma questionnaire (CTQ) and posttraumatic stress disorder Checklist (PCL) were performed. BDNF methylation and OXTR genotyping (A vs. G allele) were conducted through blood sampling. A two-way multivariate analysis and a moderated regression analysis were conducted to investigate the moderating effect of the OXTR gene on the relationship between CTQ and BDNF methylation.

Results: As for the HC group, the interaction effect of the CTQ and OXTR genotype was significant on BDNF methylation, and the moderation model showed that CTQ and OXTR group are significant predictors of BDNF methylation. In the G-OXTR type, the high CTQ group showed a greater BDNF methylation level. As for the PTSD group, no interaction or moderation effects were found.

Limitations: The present study did not control the dosage, duration of medications, and different trauma types and the assessment of childhood trauma was based on self-report.

Conclusions: These results suggested that childhood traumatic experience showed a significant impact on BDNF methylation, and OXTR genes have a moderating effect on this epigenetic mechanism in people who have experienced the childhood traumatic episodes.

Keywords: BDNF methylation; Childhood trauma; Epigenetics; Gene × environment; Genotype-coding; Oxytocin receptor gene.