Alcohol metabolizing genes and alcohol phenotypes in an Israeli household sample

BACKGROUND: Alcohol dehydrogenase 1B and 1C (ADH1B and ADH1C) variants have been robustly associated with alcohol phenotypes in East Asian populations, but less so in non-Asian populations where prevalence of the most protective ADH1B allele is low (generally <5%). Further, the joint effects of ADH1B and ADH1C on alcohol phenotypes have been unclear. Therefore, we tested the independent and joint effects of ADH1B and ADH1C on alcohol phenotypes in an Israeli sample, with higher prevalence of the most protective ADH1B allele than other non-Asian populations. METHODS: A structured interview assessed lifetime drinking and alcohol use disorders (AUDs) in adult Israeli household residents. Four single nucleotide polymorphisms (SNPs) were genotyped: ADH1B (rs1229984, rs1229982, and rs1159918) and ADH1C (rs698). Regression analysis examined the association between alcohol phenotypes and each SNP (absence vs. presence of the protective allele) as well as rs698/rs1229984 diplotypes (also indicating absence or presence of protective alleles) in lifetime drinkers (n = 1,129). RESULTS: Lack of the ADH1B rs1229984 protective allele was significantly associated with consumption- and AUD-related phenotypes (OR = 1.77 for AUD; OR = 1.83 for risk drinking), while lack of the ADH1C rs698 protective allele was significantly associated with AUD-related phenotypes (OR = 2.32 for AUD). Diplotype analysis indicated that jointly ADH1B and ADH1C significantly influenced AUD-related phenotypes. For example, among those without protective alleles for ADH1B or ADH1C, OR for AUD was 1.87 as compared to those without the protective allele for ADH1B only and was 3.16 as compared to those with protective alleles for both ADH1B and ADH1C. CONCLUSIONS: This study adds support for the relationship of ADH1B and ADH1C and alcohol phenotypes in non-Asians. Further, these findings help clarify the mixed results from previous studies by showing that ADH1B and ADH1C jointly effect AUDs, but not consumption. Studies of the association between alcohol phenotypes and either ADH1B or ADH1C alone may employ an oversimplified model, masking relevant information

Alcohol consumption mediates the relationship between ADH1B and DSM-IV alcohol use disorder and criteria

OBJECTIVE: A single nucleotide variation in the alcohol dehydrogenase 1B (ADH1B) gene, rs1229984, produces an ADH1B enzyme with faster acetaldehyde production. This protective variant is associated with lower alcohol consumption and lower risk for alcohol use disorders (AUDs). Based on the premise that faster ADH1B kinetics decreases alcohol consumption, we formally tested if the association between ADH1B variant rs1229984 and AUDs occurs through consumption. We also tested whether the association between rs1229984 and each of the 11 Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), AUD criteria occurs through consumption. METHOD: A total of 1,130 lifetime drinkers from an Israeli household sample were assessed with a structured interview and genotyped for rs1229984 (protective allele frequency = 0.28). Logistic regression evaluated the association between rs1229984 and each phenotype (AUDs, 11 individual DSM-IV criteria). For phenotypes significantly related to rs1229984, the effect through consumption was tested with logistic regression and bootstrapping. RESULTS: ADH1B rs1229984 was significantly associated with AUDs and six criteria, with odds ratios ranging from 1.32 to 1.96. The effect through consumption was significant for these relationships, explaining 23%-74% of the total ADH1B effect. CONCLUSIONS: This is the first study to show that ADH1B rs1229984 is related to 6 of the 11 DSM-IV AUD criteria and that alcohol consumption explained a significant proportion of these associations and the association of ADH1B with AUDs. Better understanding of the relationship between ADH1B and the DSM-IV AUD criteria, including effects through consumption, will enhance our understanding of the etiologic model through which AUDs can occur

Identification of population substructure among Jews using STR markers and dependence on reference populations included

Background: Detecting population substructure is a critical issue for association studies of health behaviors and other traits. Whether inherent in the population or an artifact of marker choice, determining aspects of a population's genetic history as potential sources of substructure can aid in design of future genetic studies. Jewish populations, among which association studies are often conducted, have a known history of migrations. As a necessary step in understanding population structure to conduct valid association studies of health behaviors among Israeli Jews, we investigated genetic signatures of this history and quantified substructure to facilitate future investigations of these phenotypes in this population. Results: Using 32 autosomal STR markers and the program STRUCTURE, we differentiated between Ashkenazi (AJ, N = 135) and non-Ashkenazi (NAJ, N = 226) Jewish populations in the form of Northern and Southern geographic genetic components (AJ north 73%, south 23%, NAJ north 33%, south 60%). The ability to detect substructure within these closely related populations using a small STR panel was contingent on including additional samples representing major continental populations in the analyses. Conclusions: Although clustering programs such as STRUCTURE are designed to assign proportions of ancestry to individuals without reference population information, when Jewish samples were analyzed in the absence of proxy parental populations, substructure within Jews was not detected. Generally, for samples with a given grandparental country of birth, STRUCTURE assignment values to Northern, Southern, African and Asian clusters agreed with mitochondrial DNA and Y-chromosomal data from previous studies as well as historical records of migration and intermarriage

Pain, cannabis use, and physical and mental health indicators among veterans and nonveterans: results from the National Epidemiologic Survey on Alcohol and Related Conditions-III

AbstractChronic pain is associated with mental and physical health difficulties and is prevalent among veterans. Cannabis has been put forth as a treatment for chronic pain, and changes in laws, attitudes, and use patterns have occurred over the past 2 decades. Differences in prevalence of nonmedical cannabis use and cannabis use disorder (CUD) were examined across 2 groups: veterans or nonveterans and those reporting or not reporting recent pain. Data from the National Epidemiologic Survey on Alcohol and Related Conditions-III (2012-2013; n = 36,309) were analyzed using logistic regression. Prevalence differences (PDs) for 3 cannabis outcomes (1) past-year nonmedical cannabis use, (2) frequent (≥3 times a week) nonmedical use, and (3) DSM-5 CUD were estimated for those reporting recent moderate to severe pain (veterans or nonveterans) and veterans reporting or not reporting recent pain. Difference in differences was calculated to investigate PDs on outcomes associated with residence in a state with medical cannabis laws (MCLs). Associations between physical and mental health and cannabis variables were tested. The results indicated that the prevalence of recent pain was greater among veterans (PD = 7.25%, 95% confidence interval (CI) [4.90-9.60]). Among veterans, the prevalence of frequent cannabis use was greater among those with pain (PD = 1.92%, 98% CI [0.21-3.63]), and among veterans residing in a state with MCLs, the prevalence of CUD was greater among those reporting recent pain (PD = 3.88%, 98% CI [0.36-7.39]). Findings failed to support the hypothesis that cannabis use improves mental or physical health for veterans with pain. Providers treating veterans with pain in MCL states should monitor such patients closely for CUD

HealthCall for the smartphone: technology enhancement of brief intervention in HIV alcohol dependent patients

Background: Heavy drinking jeopardizes the health of patients in HIV primary care. In alcohol dependent patients in HIV primary care, a technological enhancement of brief intervention, HealthCall administered via interactive voice response (HealthCall-IVR) was effective at reducing heavy drinking. The smartphone offered a technology platform to improve HealthCall. Methods: Working with input from patients, technology experts, and HIV clinic personnel, we further developed HealthCall, harnessing smartphone technological capacities (HealthCall-S). In a pilot study, we compared rates of HealthCall-S daily use and drinking outcomes in 41 alcohol dependent HIV-infected patients with the 43 alcohol dependent HIV-infected patients who used HealthCall-IVR in our previous efficacy study. Procedures, clinic, personnel, and measures were largely the same in the two studies, and the two groups of patients were demographically similar (~90% minority). Results: Pilot patients used HealthCall-S a median of 85.0% of the 60 days of treatment, significantly greater than the corresponding rate (63.8%) among comparison patients using HealthCall-IVR (p < .001). Mean end-of-treatment drinks per drinking day was similar in the two groups. Patients were highly satisfied with HealthCall-S (i.e., 92% reported that they liked using HealthCall-S). Conclusions: Among alcohol dependent patients in HIV primary care, HealthCall delivered via smartphone is feasible, obtains better patient engagement than HealthCall-IVR, and is associated with decreased drinking. In HIV primary care settings, HealthCall-S may offer a way to improve drinking outcomes after brief intervention by extending patient engagement with little additional demands on staff time

Commitment Strength, Alcohol Dependence and Healthcall Participation: Effects On Drinking Reduction in HIV Patients

Background: The role of three factors in drinking outcome after brief intervention among heavily drinking HIV patients were investigated: strength of commitment to change drinking, alcohol dependence, and treatment type: brief Motivational Interview (MI) only, or MI plus HealthCall, a technological extension of brief intervention. Methods: HIV primary care patients (N= 139) who drank ≥4 drinks at least once in the 30 days before study entry participated in MI-only or MI. +. HealthCall in a randomized trial to reduce drinking. Patients were 95.0% minority; 23.0% female; 46.8% alcohol dependent; mean age 46.3. Outcome at end of treatment (60 days) was drinks per drinking day (Timeline Follow-Back). Commitment strength (CS) was rated from MI session recordings. Results: Overall, stronger CS predicted end-of-treatment drinking (p\u3c. .001). After finding an interaction of treatment, CS and alcohol dependence (p= .01), we examined treatment. ×. CS interactions in alcohol dependent and non-dependent patients. In alcohol dependent patients, the treatment. ×. commitment strength interaction was significant (p= .006); patients with low commitment strength had better outcomes in MI. +. HealthCall than in MI-only (lower mean drinks per drinking day; 3.5 and 4.6 drinks, respectively). In non-dependent patients, neither treatment nor CS predicted outcome. Conclusions: Among alcohol dependent HIV patients, HealthCall was most beneficial in drinking reduction when MI ended with low commitment strength. HealthCall may not merely extend MI effects, but add effects of its own that compensate for low commitment strength. Thus, HealthCall may also be effective when paired with briefer interventions requiring less skill, training and supervision than MI. Replication is warranted

Adult transition from at-risk drinking to alcohol dependence: The relationship of family history and drinking motives. Alcohol Clin

Background: Prospective studies have not previously examined whether a family history of alcoholism and drinking motives conjointly predict a diagnosed DSM-IV alcohol abuse or dependence in adults, despite a large literature that each is associated with alcohol consumption. The focus of this study is the conjoint, prospective examination of these risk factors in a 10-year longitudinal study of adults who were at-risk drinkers at baseline. Methods: Prospective, population-based cohort of drinkers aged 18 or older from a Northeastern U.S. area initially evaluated for history of alcohol use disorders and drinking motives in 1991 to 1992. New onset dependence was studied in those who never met the criteria for alcohol dependence at baseline (n = 423), and new onset abuse was studied in those who never met the criteria for alcohol abuse at baseline (n = 301) and who did not develop dependence during the follow-up. Results: Family history significantly interacted with 2 baseline drinking motives in predicting new onsets of DSM-IV alcohol dependence: drinking to reduce negative affect (OR 3.38; 95% CI 1.05, 10.9) and drinking for social facilitation (OR 3.88; CI 1.21, 12.5). Effects were stronger after conditioning the drinking motives on having a positive family history of alcoholism. In contrast, in predicting new onsets of alcohol abuse, drinking motives did not have direct effects or interact with family history. Conclusions: Those who drank to reduce negative affect or for social facilitation at baseline were at greater risk of alcohol dependence 10 years later if they also had a family history of alcoholism. These results suggest an at-risk group that can be identified prior to the development of alcohol dependence. Further, the findings suggest utility in investigating the interaction of drinking motives with measured genetic polymorphisms in predicting alcohol dependence

Cognition, Commitment Language, and Behavioral Change Among Cocaine-Dependent Patients

Patients\u27 cognitive abilities and verbal expressions of commitment to behavioral change predict different aspects of substance abuse treatment outcome, but these 2 traits have never been examined conjointly. The authors therefore investigated patients\u27 cognitive abilities and verbal expressions of commitment to behavioral change as predictors of retention and drug use outcomes in an outpatient cognitive behavioral treatment (CBT) of adult cocaine-dependent patients. A neuropsychological battery was administered at baseline. Two independent raters used recordings of CBT sessions to code commitment language strength across the temporal segments (e.g., beginning, middle, and end) of 1 session per patient. Better cognitive abilities predicted treatment retention (p \u3c .01) but not drug use, whereas mean commitment strength across the session segments predicted reduced drug use (p = .01). Results indicate that although commitment to behavioral changes such as abstinence may occur independently of patients\u27 cognitive abilities, engagement in the behavioral intervention process appears to depend on cognitive abilities. Future clinical studies should further investigate the relations between cognition and commitment to change and their differential contributions to treatment processes and outcome