Long-Chain ω-3 Levels Are Associated With Increased Alcohol Sensitivity in a Population-Based Sample of Adolescents.

BACKGROUND: The levels of the ω-3 long-chain polyunsaturated fatty acids (ω-3 LC-PUFAs), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been associated with alcohol sensitivity in vertebrate and invertebrate model systems, but prior studies have not examined this association in human samples despite evidence of associations between ω-3 LC-PUFA levels and alcohol-related phenotypes. Both alcohol sensitivity and ω-3 LC-PUFA levels are impacted by genetic factors, and these influences may contribute to observed associations between phenotypes. Given the potential for using EPA and DHA supplementation in adjuvant care for alcohol misuse and other outcomes, it is important to clarify how ω-3 LC-PUFA levels relate to alcohol sensitivity. METHODS: Analyses were conducted using data from the Avon Longitudinal Study of Parents and Children. Plasma ω-3 LC-PUFA levels were measured at ages 15.5 and 17.5. Participants reported on their initial alcohol sensitivity using the early drinking Self-Rating of the Effects of Alcohol (SRE-5) scale, for which more drinks needed for effects indicates lower levels of response per drink, at ages 15.5, 16.5, and 17.5. Polygenic liability for alcohol consumption, alcohol problems, EPA levels, and DHA levels was derived using summary statistics from large, publicly available datasets. Linear regressions were used to examine the cross-sectional and longitudinal associations between ω-3 LC-PUFA levels and SRE scores. RESULTS: Age 15.5 ω-3 LC-PUFA levels were negatively associated with contemporaneous SRE scores and with age 17.5 SRE scores. One modest association (p = 0.02) between polygenic liability and SRE scores was observed, between alcohol problems-based polygenic risk scores (PRS) and age 16.5 SRE scores. Tests of moderation by genetic liability were not warranted. CONCLUSIONS: Plasma ω-3 LC-PUFA levels may be related to initial sensitivity to alcohol during adolescence. These data indicate that diet-related factors have the potential to impact humans' earliest responses to alcohol exposure.

Mediation of effects of the level of response to alcohol and impulsivity 15 years later in 36-year-old men: Implications for prevention efforts.

BACKGROUND: Although the prevalence of alcohol use disorders (AUDs) has increased in older individuals in the recent decade, there are few programs to mitigate that increase. The current analyses evaluate the feasibility of applying to older drinkers elements of an approach to prevent heavier drinking in young adults by focusing on mediators of effects of two risk factors for alcohol problems, low levels of response to alcohol (low LRs) and higher impulsivity. METHODS: Data were extracted from the San Diego Prospective Study (SDPS). Structural Equation Models evaluated relationships among age 36 low LRs and higher impulsivity; age 46 perceived peer drinking, alcohol expectancies, and drinking to cope; and age 51 alcohol problems, even after controlling for age 36 alcohol problems. RESULTS: Relationships of age 36 low LRs to later alcohol problems was both direct and linked to age 46 heavy drinking peers. LR also operated indirectly through peer drinking to alcohol expectancies and drinking to cope. Age 36 impulsivity had no direct path to later alcohol problems and operated primarily through mediation by alcohol expectancies and via expectancies to drinking to cope. After controlling for age 36 alcohol problems, the low LR and impulsivity results remained robust. CONCLUSIONS: Programs for mitigating increases in alcohol problems in middle-age drinkers should consider identifying individuals with low LRs and/or higher impulsivity and implementing prevention approaches similar to a program used in young adults. The approach should emphasize some different mediators for older drinkers with low LRs and those with higher impulsivity.

Evoked gamma band response in male adolescent subjects at high risk for alcoholism during a visual oddball task.

This study investigates early evoked gamma band activity in male adolescent subjects at high risk for alcoholism (HR; n=68) and normal controls (LR; n=27) during a visual oddball task. A time-frequency representation method was applied to EEG data in order to obtain stimulus related early evoked (phase-locked) gamma band activity (29-45 Hz) and was analyzed within a 0-150 ms time window range. Significant reduction of the early evoked gamma band response in the frontal and parietal regions during target stimulus processing was observed in HR subjects compared to LR subjects. Additionally, the HR group showed less differentiation between target and non-target stimuli in both frontal and parietal regions compared to the LR group, indicating difficulty in early stimulus processing, probably due to a dysfunctional frontoparietal attentional network. The results indicate that the deficient early evoked gamma band response may precede the development of alcoholism and could be a potential endophenotypic marker of alcoholism risk.