Interactive effects of the BDNF Val66Met polymorphism and posttraumatic stress disorder on cognition in U.S. military veterans

Colton S. Rippey, Robert H. Pietrzak, Paul Maruff, Thomas G. Adams

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Posttraumatic stress disorder (PTSD) is associated with mild-to-moderate deficits in cognition. The Met allele of the brain-derived neurotrophic factor (BDNF) Val66Met gene may also be associated with deficits in cognition. However, findings are inconsistent and may be sensitive to moderating variables such as psychopathology. While emerging research suggests that PTSD and the Met allele may interact, few studies have replicated this effect or examined the interactive effect of PTSD and the Met allele on subjective cognition. To address this gap, the current study analyzed data from European-American (EA) U.S. military veterans (n = 1244) who participated in the National Health and Resilience in Veterans Study (NHRVS) to examine the main and interactive effects of BDNF Val66Met genotype and probable PTSD on objective and subjective cognition. Results revealed significant (p's < 0.001) interactions between Met allele carrier status and probable PTSD in objective and subjective cognition. Among individuals with probable PTSD (n = 131), the Met allele was associated with poorer objective (p < .001, d = 0.62) and subjective cognition (p = .001, d = 0.53). Among individuals without PTSD (n = 1113), the Met allele was not significantly associated with objective or subjective cognition. These findings suggest that PTSD may moderate the association between Met allele carrier status and cognition. Implications of these results for the mitigation of cognitive dysfunction in older veterans are discussed.

Original languageEnglish
Article number105820
StatePublished - Aug 2022

Bibliographical note

Funding Information:
The National Health and Resilience in Veterans Study (NHRVS) is supported by the U.S. Department of Veterans Affairs National Center for Posttraumatic Stress Disorder (NC-PTSD). Dr. Adams and Pietrzak were supported by the Clinical Neurosciences Division of the NC-PTSD. Dr. Adams is supported by the National Institute of Mental Health (NIMH; K23MH111977 and L30MH1110037 ). Dr. Maruff is a full-time employee of Cogstate Ltd. Mr. Rippey has no funding to disclose.

Publisher Copyright:
© 2022 Elsevier Ltd


  • Brain derived neurotrophic factor
  • Cognition
  • Elderly
  • PTSD
  • Trauma
  • Veterans

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Psychiatry and Mental health
  • Biological Psychiatry

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