PER1 rs3027172 genotype interacts with early life stress to predict problematic alcohol use, but not reward-related ventral striatum activity

Increasing evidence suggests that the circadian and stress regulatory systems contribute to alcohol use disorder (AUD) risk, which may partially arise through effects on reward-related neural function. The C allele of the PER1 rs3027172 single nucleotide polymorphism reduces PER1 expression in cells incubated with cortisol and has been associated with increased risk for adult AUD and problematic drinking among adolescents exposed to high levels of familial psychosocial adversity. Using data from undergraduate students who completed the ongoing Duke Neurogenetics Study (n=665), we tested whether exposure to early life stress (ELS; Childhood Trauma Questionnaire) moderates the association between rs3027172 genotype and later problematic alcohol use (Alcohol Use Disorders Identification Test) as well as ventral striatum (VS) reactivity to reward (card-guessing task while functional magnetic resonance imaging data were acquired). Initial analyses found that PER1 rs3027172 genotype interacted with ELS to predict both problematic drinking and VS reactivity; minor C allele carriers, who were also exposed to elevated ELS reported greater problematic drinking and exhibited greater ventral striatum reactivity to reward-related stimuli. When gene x covariate and environment x covariate interactions were controlled for, the interaction predicting problematic alcohol use remained significant (p<0.05, corrected) while the interaction predicting VS reactivity was no longer significant. These results extend our understanding of relationships between PER1 genotype, early life stress, and problematic alcohol use, and serve as a cautionary tale on the importance of controlling for potential confounders in studies of moderation including gene x environment interactions

Validation of HeadCount-2w for estimation of two-week heading: Comparison to daily reporting in adult amateur player

Objectives: To validate the HeadCount-2w questionnaire for estimation of 2-week soccer heading by comparison to daily electronic diary reporting over the same two-week period. Design: Prospective observational study. Methods: Adult amateur soccer players completed HeadCount-daily, comprising 14 daily at-home assessments of soccer play and heading via a tablet PC. Following the 14 day period, players completed HeadCount-2w, a web-based two-week-recall questionnaire on soccer and heading. intraclass correlation coefficient (ICC) was estimated between HeadCount-daily, the reference standard, and HeadCount-2w estimates of heading during the same 2-week period. Results: 53 participants (38 men) reported a mean of 24.36 (median = 11.76) headers during 2 weeks via HeadCount-daily and a mean of 38.34 (median = 15.0) headers for the same 2 weeks via HeadCount-2w. The ICC comparing 2-week heading from HeadCount-daily and HeadCount-2w was 0.85. Linear regression of the log-transformed Headcount-daily on HeadCount-2w data yielded a slope of 0.71 (p < 0.001; 95% CI 0.54–0.82), suggesting that heading tends to be over-estimated by HeadCount-2w relative to HeadCount-daily. Slope estimates for men (0.65) and women (0.71) were similar. Conclusions: HeadCount, a self-administered web-based survey, is valid for self-reporting 2-week heading in adult amateur players, supporting its use in future research and as a simple and low-cost technique for exposure monitoring

Heading Frequency Is More Strongly Related to Cognitive Performance Than Unintentional Head Impacts in Amateur Soccer Players

ObjectiveCompared to heading, unintentional head impacts (e.g., elbow to head, head to head, head to goalpost) in soccer are more strongly related to risk of moderate to very severe Central Nervous System (CNS) symptoms. But, most head impacts associated with CNS symptoms that occur in soccer are mild and are more strongly related to heading. We tested for a differential relation of heading and unintentional head impacts with neuropsychological (NP) test performance.MethodActive adult amateur soccer players were recruited in New York City and the surrounding areas for this repeated measures longitudinal study of individuals who were enrolled if they had 5+ years of soccer play and were active playing soccer 6+ months/year. All participants completed a baseline validated questionnaire (“HeadCount-2w”), reporting 2-week recall of soccer activity, heading and unintentional head impacts. In addition, participants also completed NP tests of verbal learning, verbal memory, psychomotor speed, attention, and working memory. Most participants also completed one or more identical follow-up protocols (i.e., HeadCount-2w and NP tests) at 3- to 6-month intervals over a 2-year period. Repeated measures General Estimating Equations (GEE) linear models were used to determine if variation in NP tests at each visit was related to variation in either heading or unintentional head impacts in the 2-week period before testing.Results308 players (78% male) completed 741 HeadCount-2w. Mean (median) heading/2-weeks was 50 (17) for men and 26 (7) for women. Heading was significantly associated with poorer performance on psychomotor speed (p &lt; 0.001) and attention (p = 0.02) tasks and was borderline significant with poorer performance on the working memory (p = 0.06) task. Unintentional head impacts were not significantly associated with any NP test. Results did not differ after excluding 22 HeadCount-2w with reported concussive or borderline concussive symptoms.ConclusionPoorer NP test performance was consistently related to frequent heading during soccer practice and competition in the 2 weeks before testing. In contrast, unintentional head impacts incurred during soccer were not related to cognitive performance