Retrospective self-reports of sensitivity to the effects of alcohol: Trait-like stability and concomitant changes with alcohol involvement.

OBJECTIVE: Lower sensitivity to the acute effects of alcohol is known to confer risk for the development of alcohol use disorder. Alcohol sensitivity, or level of response to alcohol's subjective effects, is heritable but also can change as a result of persistent alcohol exposure (i.e., acquired tolerance). Here, we examined how changes over time in four indices of alcohol involvement affected scores on two validated, retrospective self-report measures of alcohol response-the Self-Rating of the Effects of Alcohol (SRE) form and the Alcohol Sensitivity Questionnaire (ASQ)-in a sample of emerging adult drinkers. METHOD: Participants (N = 173; Mage = 19.5 years; 60% assigned female at birth) completed the ASQ, SRE, and measures of alcohol use and problems at two time points separated by a median of 0.77 years (range: 0.30-2.54 years). RESULTS: Multiple linear regression showed that increases in drinking over this period accounted for increases in SRE and ASQ scores (i.e., in reported numbers of drinks needed to experience subjective effects of alcohol). Increased drinking accounted for more variance in the number of drinks needed to experience lighter drinking versus heavier drinking effects, and increases in the number of drinks consumed per occasion had a larger effect than did changes in total numbers of drinks consumed, number of binge-drinking occasions, or drinking-related problems. CONCLUSIONS: Findings suggest that both SRE and ASQ capture some stable, trait-like variability in alcohol response as well as some state-dependent, within-person variability in alcohol response acquired through increases in alcohol involvement. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Predicting disordered gambling across adolescence and young adulthood from polygenic contributions to Big 5 personality traits in a UK birth cohort.

BACKGROUND AND AIMS: Previous research has demonstrated phenotypical associations between disordered gambling (DG) and Big 5 personality traits, and a twin study suggested that shared genetic influences accounted for a substantial portion of this relation. The present study examined associations between DG and polygenic scores (PSs) for Big 5 traits to measure the shared genetic underpinnings of Big 5 personality traits and DG. DESIGN: Zero-inflated negative binomial regression models estimated associations between Big 5 PSs and past-year and life-time assessments of DG in a longitudinally assessed population-based birth cohort. SETTING: United Kingdom. PARTICIPANTS: A total of 4729 unrelated children of European ancestry from the Avon Longitudinal Study of Parents and Children (ALSPAC) with both phenotypical and genetic data. MEASUREMENTS: Phenotypical outcomes included past-year assessment of DG using the problem gambling severity index (PGSI) and life-time assessment of DSM-IV pathological gambling symptoms (DPG) across the ages of 17, 20 and 24 years. Polygenic scores were derived for the Big 5 personality traits of agreeableness, extraversion, conscientiousness, openness and neuroticism using summary statistics from genome-wide association studies (GWAS). FINDINGS: PSs for agreeableness [ß= - 0.25, standard error (SE) = 0.054, P = 3.031e-6, ΔR2 = 0.008] and neuroticism (ß=0.14, SE = 0.046, P = 0.0017, ΔR2 = 0.002) significantly predicted PGSI scores over and above included covariates (i.e. sex and first five ancestral principal components). PSs for agreeableness (ß= - 0.20, SE = 0.056, P = 0.00036, ΔR2 = 0.003) and neuroticism, when interactions with age were taken into account (ß = 0.29, SE = 0.090, P = 0.002, ΔR2 = 0.004), also predicted DPG scores. CONCLUSIONS: Polygenic contributions to low agreeableness and high neuroticism appear to predict two measures of disordered gambling (problem gambling severity index and life-time assessment of DSM-IV pathological gambling symptoms). Polygenic scores for neuroticism interact with age to suggest that the positive association becomes stronger from adolescence through young adulthood.

Effects of genetic risk for alcohol dependence and onset of regular drinking on the progression to alcohol dependence: A polygenic risk score approach.

BACKGROUND: Prior studies have established the importance of genetic contributions to the etiology of alcohol dependence (AD), and suggested an early onset of alcohol use represents an initial marker of this genetic risk, which is associated with a more rapid progression to AD and increased risk for AD itself. Building on prior work, the current study examined whether the additive effects of AD risk variants predicted the rate of progression to AD from the onset of regular drinking, a drinking milestone with high clinical relevance to AD prevention. METHODS: Data from 1501 European-ancestry adults from the University of California - San Francisco Family Alcoholism Study were used to examine whether polygenic risk scores for AD (PRSAD) and age-at-onset of regular drinking contributed uniquely to the likelihood of having a lifetime AD diagnosis and the rate of progression from regular drinking to AD. Mixed effects logistic regression and Cox proportional hazards regression analyses were employed. RESULTS: Increases in PRSAD were associated with a faster progression from regular drinking to AD independent of age-at-onset of regular drinking. An independent effect of age-at-onset of regular drinking was also observed indicating that a one-year delay in regular drinking was associated with a 7% decrease in the hazard of progression to AD among drinkers with an early onset (≤ 18), but a 3% increase among drinkers with a late onset (> 18) of regular drinking. CONCLUSIONS: These results broaden our understanding of the contributions of measured genotypes underlying AD-risk on the etiology and clinical course of AD.