Denise M. Scott

The 5-HTTLPR polymorphism moderates the effect of stressful life events on drinking behavior in college students of African descent†

Covault et al. [Covault et al. (2007); Biol Psychiatry 61(5): 609–616] reported that the common functional polymorphism, 5‐HTTLPR, in the serotonin transporter gene moderated the association between past‐year stressful events and daily reports of drinking in a sample of European‐American (EA) college students. We examined this effect in college students of African descent. Students recruited at a Historically Black University (n = 564) completed web‐based measures of past‐year stressful life experiences and daily reports of drinking and heavy drinking over a 30‐day period. Participants were genotyped for the tri‐allelic 5‐HTTLPR polymorphism and dichotomized as low‐activity S′ allele carriers or high‐activity L′ homozygotes. Generalized linear models were used to examine the effects of life stress, genotype, and their interaction on the two drinking measures. In students who completed 15 or more daily surveys (n = 393), there was a significant interaction of past‐year stressful events, 5‐HTTLPR genotype, and gender on the number of drinking days (P = 0.002). Similar findings were obtained in relation to heavy drinking days (P = 0.007). Men showed a main effect of past‐year stressful events on both drinking outcomes (Ps < 0.001), but no main or moderator effects of genotype. In women, the S′ allele moderated the impact of past‐year life stressors on the frequency of drinking and heavy drinking days (Ps < 0.001). In college students of African descent, past‐year stressful events were associated with more frequent drinking and heavy drinking, an effect that was moderated by the 5‐HTTLPR polymorphism. However, in contrast to the findings in EA students, in the current sample, 5‐HTTLPR moderated the association only among women.

Effects of an educational intervention on female biomedical scientists' research self-efficacy

Women and people of color continue to be underrepresented among biomedical researchers to an alarming degree. Research interest and subsequent productivity have been shown to be affected by the research training environment through the mediating effects of research self-efficacy. This article presents the findings of a study to determine whether a short-term research training program coupled with an efficacy enhancing intervention for novice female biomedical scientists of diverse racial backgrounds would increase their research self-efficacy beliefs. Forty-three female biomedical scientists were randomized into a control or intervention group and 15 men participated as a control group. Research self-efficacy significantly increased for women who participated in the self-efficacy intervention workshop. Research self-efficacy within each group also significantly increased following the short-term research training program, but cross-group comparisons were not significant. These findings suggest that educational interventions that target sources of self-efficacy and provide domain-specific learning experiences are effective at increasing research self-efficacy for women and men. Further studies are needed to determine the longitudinal outcomes of this effort.

Heritability of Level of Response and Association with Recent Drinking History in Nonalcohol‐Dependent Drinkers

BACKGROUND Level of response (LR) to alcohol has been shown to be associated with the risk of developing alcohol dependence and can be measured using the self-rating of the effects of alcohol (SRE) questionnaire. This study examined the heritability of the SRE-measured LR and the relationship between LR and recent alcohol drinking history (RDH) in a predominantly African American nonalcohol-dependent population. METHODS This was a sibling study of 101 social drinkers aged 21 to 35 years recruited from the Washington, DC metropolitan area. Participants were administered the SRE to assess LR and the timeline followback (TLFB) to assess RDH. The indices of SRE used were total SRE score (SRTT), early drinking SRE score (SRED), regular drinking SRE score (SRRD), and heavy drinking SRE score (SRHD). Pearsons product-moment correlation and linear regression were used to analyze SRE indices and RDH variables (quantity and drinks per drinking occasion). Heritability analysis was conducted using Sequential Oligogenic Linkage Analysis Routines (SOLAR) software with SRE indices as traits of interest. RESULTS There was a significant relationship between SRE and RDH measures. Drinks per drinking day, maximum drinks, and quantity of drinks were significantly associated with SRTT, SRHD, and SRRD (all p < 0.05). SRTT showed significant heritability (h(2) = 0.67, p = 0.025), however, the SRE subindices (SRED, SRRD, SRHD) were not significantly heritable. Analysis performed in the subset consisting of only African Americans (n = 86) showed similar trends. CONCLUSIONS LR, as measured by the SRE, is associated with RDH. The high level of heritability of the SRE total score suggests that genetics accounts for a significant proportion of the variation in the LR to alcohol in social drinkers.

(Invited review) genetic research on alcohol use outcomes in African American populations: A review of the literature, associated challenges, and implications

BACKGROUND AND OBJECTIVES There have been remarkable advances in understanding genetic influences on complex traits; however, individuals of African descent have been underrepresented in genetic research. METHODS We review the limitations of existing genetic research on alcohol phenotypes in African Americans (AA) including both twin and gene identification studies, possible reasons for underrepresentation of AAs in genetic research, the implications of the lack of racially diverse samples, and special considerations regarding conducting genetic research in AA populations. RESULTS There is a marked absence of large-scale AA twin studies so little is known about the genetic epidemiology of alcohol use and problems among AAs. Individuals of African descent have also been underrepresented in gene identification efforts; however, there have been recent efforts to enhance representation. It remains unknown the extent to which genetic variants associated with alcohol use outcomes in individuals of European and African descent will be shared. Efforts to increase representation must be accompanied by careful attention to the ethical, legal, and social implications of genetic research. This is particularly true for AAs due to the history of abuse by the biomedical community and the persistent racial discrimination targeting this population. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE Lack of representation in genetic studies limits our understanding of the etiological factors that contribute to substance use and psychiatric outcomes in populations of African descent and has the potential to further perpetuate health disparities. Involving individuals of diverse ancestry in discussions about genetic research will be critical to ensure that all populations benefit equally from genetic advances. (Am J Addict 2017;26:486-493).

Clinical Course of Alcohol Dependence in African Americans

ABSTRACT Objective: The sequence and progression of alcohol related life events were investigated in a sample of African Americans and compared with findings from a predominantly Caucasian sample. Methods: Alcohol dependent participants were recruited from treatment facilities. Participants completed the Semi-Structured Assessment for the Genetics of Alcoholism to assess the physical, psychological and social manifestations of alcoholism and related disorders. Results: The sequence and mean age of appearance of alcohol-related life events were similar for this sample of African-American men and women. While there were similarities in the progression of alcohol related life problems between the African American and the Caucasian samples, the frequency of symptom endorsement for most problems was significantly higher in the Caucasian sample. Conclusions: Identifying ethnic differences in the clinical course of alcohol dependence may be of importance in developing treatment plans and assist in the development of culturally sensitive intervention and prevention programs.

Alterations in Ethyl Alcohol Pharmacokinetics During Oral Consumption of Malt Liquor Beverages in African Americans

BACKGROUND Malt liquor (ML) beverages have become increasingly popular among urban minority groups, due partly to their inexpensive price and targeted advertising. We hypothesized that nonfermented by-products contained in ML beverages will alter the pharmacokinetics (PK) and pharmacodynamic (PD) effects of its ethanol content. In addition, we determined the effect of alcohol dehydrogenase (ADH) genotypes on the PK following consumption of ML beverages. METHODS The study was conducted in 31 healthy adult African-American social drinkers, mean +/- SD age of 22.3 +/- 1.3 years, and weight of 70.7 +/- 10.9 kg. Participants were administered ethanol, in randomized order, 2-weeks apart, in the form of oral ML beverage (6%v/v), or isocaloric solution of diet soda-ethanol (DS-Etoh) beverage (6%v/v). During each session the beverage was consumed over 4 minutes and breath alcohol concentrations (BrAC) as well as subjective and behavioral effects of ethanol were evaluated over 180 minutes. Pharmacokinetic parameters of ethanol were calculated using Michaelis-Menten elimination kinetics. The effect of ML and ADH genotype on PK was evaluated using the Wilcoxon rank-sum test and the Wilcoxon signed rank test, respectively. RESULTS Results show a slower mean rate of absorption, K(a), (0.12 vs. 0.15 min(-1), p = 0.03) and a longer time to reach maximum concentration, T(max), (28 vs. 23 minute, p < 0.01) for the ML compared with DS-Etoh beverage. The ML beverage resulted in a larger area under the BrAC-time curve compared with DS-Etoh beverage (8.4 vs. 6.8 min g/dl, p = 0.02). There was no difference in the subjective PD effects between the 2 beverages. CONCLUSION Results show that exposure to ethanol following the consumption of ML beverages is different compared to that following nonmalt beverages in African-Americans. These differences may be related to nonfermented by-products present in commercially available ML products. These PK differences do not appear to result in significant perceived alcohol PD changes, nor are they related to ADH genotype.

FKBP5 genotype interacts with early life trauma to predict heavy drinking in college students

Alcohol use disorder (AUD) is debilitating and costly. Identification and better understanding of risk factors influencing the development of AUD remain a research priority. Although early life exposure to trauma increases the risk of adulthood psychiatric disorders, including AUD, many individuals exposed to early life trauma do not develop psychopathology. Underlying genetic factors may contribute to differential sensitivity to trauma experienced in childhood. The hypothalamic‐pituitary‐adrenal (HPA) axis is susceptible to long‐lasting changes in function following childhood trauma. Functional genetic variation within FKBP5, a gene encoding a modulator of HPA axis function, is associated with the development of psychiatric symptoms in adulthood, particularly among individuals exposed to trauma early in life. In the current study, we examined interactions between self‐reported early life trauma, past‐year life stress, past‐year trauma, and a single nucleotide polymorphism (rs1360780) in FKBP5 on heavy alcohol consumption in a sample of 1,845 college students from two university settings. Although we found no effect of early life trauma on heavy drinking in rs1360780*T‐allele carriers, rs1360780*C homozygotes exposed to early life trauma had a lower probability of heavy drinking compared to rs1360780*C homozygotes not exposed to early life trauma (P < 0.01). The absence of an interaction between either current life stress or past‐year trauma, and FKBP5 genotype on heavy drinking suggests that there exists a developmental period of susceptibility to stress that is moderated by FKBP5 genotype. These findings implicate interactive effects of early life trauma and FKBP5 genetic variation on heavy drinking.

Framing Ethnic Variations in Alcohol Outcomes from Biological Pathways to Neighborhood Context

BACKGROUND Health disparities research seeks to eliminate disproportionate negative health outcomes experienced in some racial/ethnic minority groups. This brief review presents findings on factors associated with drinking and alcohol-related problems in racial/ethnic groups. METHODS Those discussed are as follows: (i) biological pathways to alcohol problems, (ii) gene × stress interactions, (iii) neighborhood disadvantage, stress, and access to alcohol, and (iv) drinking cultures and contexts. RESULTS These factors and their interrelationships are complex, requiring a multilevel perspective. CONCLUSIONS The use of interdisciplinary teams and an epigenetic focus are suggested to move the research forward. The application of multilevel research to policy, prevention, and intervention programs may help prioritize combinations of the most promising intervention targets.

Evaluation of the Influence of Alcohol Dehydrogenase Polymorphisms on Alcohol Elimination Rates in African Americans

INTRODUCTION The relationship between alcohol dehydrogenase (ADH) polymorphisms and alcohol use disorders in populations of African descent has not been clearly established. This study examined the effect of ADH1B polymorphisms on alcohol metabolism and subjective response, following intravenous (IV) alcohol administration, and the influence of gender, recent drinking history, and family history of alcoholism (FHA), in nondependent African American drinkers. MATERIALS The sample included eighty-seven 21- to 35-year-old, light social drinkers of African descent. Participants included 39 sib pairs, 2 sibships with 3 siblings each, and 3 individuals who were not part of a sibship. Participants received infusions via the use of the clamp method that refers to the goal of controlling breath alcohol concentration in 2 randomized sessions at 0.06 g% ethanol and 0 mg% (placebo), and a battery of subjective scales at predefined time points. Dependent measures included alcohol elimination rates (AERs), alcohol disappearance rates (ADRs), subjective measures peak scores, and area under the curve. General linear model and mixed models were performed to examine the relationship between ADH1B genotype, dependent measures, and influence of covariates. RESULTS Participants with ADH1B1/1 genotypes showed higher number of drinks (p = 0.023) and drinks per drinking day (p = 0.009) compared with the persons with ADH1B1/3 genotype. AER (adjusted for body weight) was higher in ADH1B*1 homozygotes (p = 0.045) compared with ADH1B1/3 heterozygotes. ADR differed significantly between males and females (p = 0.002), regardless of body weight (p = 0.004) and lean body mass (p < 0.001) adjustments. Although a few subjective measures differed across genotype, all measures were higher in alcohol sessions compared with placebo sessions (p < 0.001). These observations were mediated by drinks per drinking day, gender, and FHA. CONCLUSIONS ADH1B polymorphism had a marginal effect on alcohol pharmacokinetics following IV alcohol administration in nondependent drinkers of African descent. Session (alcohol vs. placebo) and ADH1B genotype did, however, influence subjective response to alcohol with some variation by gender, FHA, and drinks per drinking day.

Alcohol Dependence and Health Care Utilization in African Americans

OBJECTIVE Ethnic and cultural differences in patterns of alcohol use disorders must be understood in order to address improvement in prevention of such disorders and accessibility to health care services. The purpose of this study was to evaluate factors that influence the utilization of medical and mental health services among alcohol-dependent and non-alcohol-dependent African Americans. METHOD A cohort of 454 African Americans was evaluated. Alcohol-dependent participants were recruited from various inpatient treatment facilities in the Washington, DC, metropolitan area and through advertisement and word of mouth. Non-alcohol-dependent participants were recruited by advertisements. Each participant was administered the Semi-Structured Assessment for the Genetics of Alcoholism to assess alcohol dependency and the Family History Assessment module to access family history of alcoholism. Xl Test and analysis of variance were used to analyze the data. RESULTS Alcohol dependence was more prevalent among men, those with lower income, those with less education, and they utilized mental health counseling as opposed to medical-based therapy. Increased reports of medical conditions such as migraine (p<.001), loss of consciousness (p=.001), and sexually transmitted diseases: (p<.001) were also associated with alcohol dependency. Other factors, including visits to inpatient treatment programs, were directly related to incidence of alcohol dependency regardless of gender status (p<.001). CONCLUSIONS This study suggests an association exists among alcohol dependence, medical conditions, health care, and mental care utilization among African Americans. Future research may benefit from investigating if an association exists between alcohol use disorders and health care utilization for other ethnic groups.