The interaction of BDNF Val66Met, PTSD, and child abuse on psychophysiological reactivity and HPA axis function in a sample of Gulf War Veterans

J Affect Disord. 2018 Aug 1;235:52-60. doi: 10.1016/j.jad.2018.04.004. Epub 2018 Apr 3.


Introduction: While the BDNF Val66Met polymorphism has been linked to various psychological disorders, limited focus has been on its relationship to posttraumatic stress disorder (PTSD) and early traumas such as child abuse. Therefore, we assessed whether Val66Met was associated with fear potentiated psychophysiological response and HPA axis dysfunction and whether PTSD status or child abuse history moderated these outcomes in a sample of Veterans.

Methods: 226 and 173 participants engaged in a fear potentiated acoustic startle paradigm and a dexamethasone suppression test (DST) respectively. Fear conditions included no, ambiguous, and high threat conditions. Psychophysiological response measures included electromyogram (EMG), skin conductance response (SCR), and heart rate. The Clinician Administered PTSD Scale (CAPS) and the Trauma History Questionnaire (THQ) were used to assess PTSD status and child abuse history respectively.

Results: Met allele carriers exhibited greater SCR magnitudes in the no and ambiguous threat conditions (p < 0.01 and p < 0.05 respectively). Met carriers with PTSD exhibited greater physiological response magnitudes in the ambiguous (SCR, p < 0.001) and high threat conditions (SCR and heart rate, both p ≤ 0.005). Met carrier survivors of child abuse exhibited blunted heart rate magnitudes in the high threat condition (p < 0.01). Met allele carries with PTSD also exhibited greater percent cortisol suppression (p < 0.005).

Limitations: Limitations included small sample size and the cross-sectional nature of the data.

Conclusions: The Val66met may impact PTSD susceptibility differentially via enhanced threat sensitivity and HPA axis dysregulation. Child abuse may moderate Val66Met's impact on threat reactivity. Future research should explore how neuronal mechanisms might mediate this risk.

Keywords: Child abuse; Dexamethasone suppression test; PTSD; Psychophysiological response; Val66Met.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adaptation, Psychological / physiology
  • Adult
  • Adult Survivors of Child Abuse / psychology*
  • Alleles
  • Brain-Derived Neurotrophic Factor / genetics*
  • Cross-Sectional Studies
  • Fear / psychology
  • Female
  • Genetic Predisposition to Disease
  • Gulf War
  • Humans
  • Hydrocortisone / metabolism
  • Hypothalamo-Hypophyseal System / physiopathology*
  • Male
  • Middle Aged
  • Pituitary-Adrenal System / physiopathology*
  • Polymorphism, Genetic
  • Stress Disorders, Post-Traumatic / genetics*
  • Stress Disorders, Post-Traumatic / physiopathology
  • Stress Disorders, Post-Traumatic / psychology
  • United States
  • Veterans / psychology*


  • Brain-Derived Neurotrophic Factor
  • BDNF protein, human
  • Hydrocortisone