APOE & BDNF polymorphisms interact to affect memory performance at baseline in adolescent athletes.

Although several single-nucleotide polymorphisms have been associated with cognitive functioning in a variety of healthy and clinical samples, the influence of gene × gene interactions on cognition is poorly understood. The purpose of this study was to examine interactive relationships between apolipoprotein E (APOE) and brain-derived neurotrophic factor (BDNF) polymorphisms on cognitive functioning in a sample of healthy adolescent athletes. Participants of this cross-sectional study included 78 student-athletes (52.6% male; age: M = 13.31, SD = 1.23). Athletes completed the Immediate Post-Concussion and Cognitive Testing (ImPACT) computerized battery at baseline. APOE and BDNF genotypes were determined with buccal samples (APOE ε4+: n = 26; APOE ε4-: n = 52; BDNF Met+: n = 23; BDNF Met-: n = 55). Two-way analyses of variance (ANOVAs) were used to evaluate the associations among APOE (ε4+ vs. ε4-) and BDNF (Met+ vs. Met-) genotypes and the ImPACT cognitive composites and two-factor model. No main effects were observed for either APOE or BDNF genotypes across the cognitive outcomes. However, there was a significant APOE × BDNF genotype interaction for the verbal (p=.009, ηp2=.091) and visual (p = .012, ηp2=.082) memory composites and the memory factor (p = .001, ηp2=.133), such that ε4+/Met+ carriers demonstrated poorer performance relative to other allele combinations. No significant interactions were observed for the visual motor speed (p = .263, ηp2=.017) or reaction time (p = .825, ηp2=.001) composites or the speed factor (p = .205, ηp2=.022). Our findings suggest an important relationship between APOE and BDNF genotypes on verbal and visual memory performance in healthy adolescent athletes. Clinicians may use this information to offer individualized concussion management based on individual athlete characteristics related to genetics and cognition.

A pilot study examining BDNF Val66Met polymorphism and biological sex: Relationships with baseline cognitive functioning in adolescent athletes.

The purpose of this exploratory study was to examine interactive relationships between a common brain-derived neurotrophic factor (BDNF) polymorphism (Val66Met) and biological sex on cognitive functioning in a sample of healthy adolescent athletes. Participants included 82 student athletes (age: M = 12.85 years, SD = 1.13) who were involved in a clinically-based sports-concussion management program. Athletes completed the ImPACT computerized battery at baseline and provided buccal samples for determination of their BDNF genotype. Two-way ANOVAs were used to evaluate the effect of BDNF genotype (Met+ vs. Met-) and sex (male vs. female) on cognitive functioning (subgroup n's: Female/Met+ = 12, Female/Met- = 26, Male/Met+ = 12, Male/Met- = 32). ANOVAs revealed non-significant main effects for both BDNF genotype and sex across all four cognitive composites. However, there was a significant BDNF genotype by sex interaction for the visual-motor speed composite (p = .015; ηp2 = .073), such that female Met carriers demonstrated better performance than male Met carriers. In contrast, no differences were found on visual-motor speed performance between females and males without a Met allele. Although these results will need to be replicated using larger samples, our preliminary findings lend support to the view that the Met allele may be somewhat neuroprotective in healthy adolescent females.

Subjective cognitive and psychiatric well-being in U.S. Military Veterans screened for deployment-related traumatic brain injury: A Million Veteran Program Study.

The purpose of this study was to examine subjective cognitive and psychiatric functioning in post-deployed military Veterans who underwent the Veterans Health Administration's Traumatic Brain Injury (TBI) Screening and Evaluation Program and enrolled in the VA's Million Veteran Program (MVP). Veterans (N = 7483) were classified into three groups based on outcomes from the TBI Screening and Evaluation Program: (1) negative TBI screen ('Screen-'), (2) positive TBI screen but no TBI diagnosis ('Screen+/TBI-'), or (3) positive TBI screen and TBI diagnosis ('Screen+/TBI+'). Chi-square analyses revealed significant group differences across all self-reported cognitive and psychiatric health conditions (e.g., memory loss, depression), and ANCOVAs similarly showed a significant association between group and subjective symptom reporting. Specifically, the relationship between TBI group and clinical outcome (i.e., health conditions and symptoms) was such that the Screen+/TBI+ group fared the worst, followed by the Screen+/TBI- group, and finally the Screen- group. However, evaluation of effect sizes suggested that Veterans in the two Screen+ groups (Screen+/TBI+ and Screen+/TBI-) are faring similarly to one another on subjective cognitive and psychiatric functioning, but that both Screen+ groups are faring significantly worse than the Screen- group. Our results have meaningful clinical implications and suggest that Veterans who screen positive for TBI, regardless of ultimate TBI diagnosis, be eligible for similar clinical services so that both groups can benefit from valuable treatments and therapeutics. Finally, this research sets the stage for follow-up work to be conducted within MVP that will address the neurobiological underpinnings of cognitive and psychiatric distress in this population.