Dissociation of BDNF Val66Met polymorphism on neurocognitive functioning in military veterans with and without a history of remote mild traumatic brain injury

Abstract

Objective

Since neurocognitive functioning following mild traumatic brain injury (mTBI) may be influenced by genetic factors that mediate synaptic survival and repair, we examined the influence of a common brain-derived neurotrophic factor (BDNF) polymorphism (Val66Met) on cognition using a well-defined sample of military Veterans with and without a history of mTBI.

Method

Participants included 138 Veterans (mTBI = 75; military controls [MCs] = 63) who underwent neuropsychological testing, including completion of self-report measures assessing psychiatric distress, and BDNF genotyping. The mTBI group was tested roughly 66.7 months following their most recent mTBI. Veterans were divided into two groups—Met+ (Met/Met and Met/Val; n = 49) and Met− (Val/Val; n = 89) and compared on domain-specific cognitive composite scores representing memory, executive functioning, and visuospatial speed.

Results

ANCOVAs adjusting for psychiatric distress, sex, years of education, and ethnicity/race revealed a significant group (mTBI vs. MC) by BDNF genotype (Met + vs. Met−) interaction for the memory (p = .024; η_p² = .039) and executive functioning (p = .010; η_p² = .050) composites, such that Met+ mTBI Veterans demonstrated better performance than Met− mTBI Veterans on the cognitive measures, whereas Met+ MCs demonstrated worse performance relative to Met− MCs on the cognitive measures. No significant interaction was observed for the visuospatial speed composite (p = .938; η_p² < .001).

Conclusions

These findings offer preliminary evidence to suggest that the Met allele may be protective in the context of remote mTBI. Findings need to be replicated using larger samples, and future studies are necessary to elucidate the precise mechanisms and neural underpinnings of this interaction.

Keywords:

• Brain-derived neurotrophic factor
• cognition
• mild traumatic brain injury
• neuropsychological assessment
• military Veterans

Note

Disclosure statement

The authors have no conflict of interests to report.

Notes

1 The PCL-M and BDI-II total scores were highly associated with one another; as a result, only one measure of psychiatric distress was used as a covariate in the main analyses. In this case, the PCL-M was selected as a covariate due to its overall greater associations with the independent and dependent variables (see Table 4).

Additional information

Funding

This work was supported by Veterans Affairs grants awarded to Drs. Delano-Wood (829-MR-NB-25860) and Schiehser (CDA-2-065-10S). This work was further supported by grants awarded by the Department of Defense (W81XWH-10-2-0169) to Dr. Delano-Wood and the National Institute of Neurological Disorders and Stroke of the National Institutes of Health (F31NS09870) to Dr. Clark. Finally, Drs. Merritt and Sorg received salary support during this work from Career Development Awards from the VA Clinical Science Research & Development Service (IK2 CX001952 and CDA-2-CX001508, respectively).