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Browsing by Author "Hasin, Deborah"
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Item Alcohol metabolizing genes and alcohol phenotypes in an Israeli household sample(Wiley, 2013-11) Meyers, Jacquelyn L.; Shmulewitz, Dvora; Aharonovich, Efrat; Waxman, Rachel; Frisch, Amos; Weizman, Abraham; Spivak, Baruch; Edenberg, Howard J.; Gelernter, Joel; Hasin, Deborah; Biochemistry & Molecular Biology, School of MedicineBACKGROUND: 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.Item Subjective Responses to Alcohol in the Development and Maintenance of Alcohol Use Disorder(American Psychiatric Association, 2021) King, Andrea; Vena, Ashley; Hasin, Deborah; deWit, Harriet; O’Connor, Sean J.; Cao, Dingcai; Psychiatry, School of MedicineObjective: Alcohol use disorder (AUD) remains an urgent public health problem. Longitudinal data are needed to clarify the role of acute subjective responses to alcohol in the development and maintenance of excessive drinking and AUD. The authors report on 10 years of repeated examination of acute alcohol responses in the Chicago Social Drinking Project. Methods: Young adult drinkers (N=190) participated in an initial alcohol challenge (0.8 g/kg of alcohol compared with placebo) that was repeated 5 and 10 years later. They were also assessed on drinking behavior and AUD symptoms at numerous intervals across the decade. Retention was high, as 184 of the 185 (99%) nondeceased active participants completed the 10-year follow-up, and 91% (163 of 179) of those eligible for alcohol consumption engaged in repeated laboratory testing during this interval. Results: At the end of the decade, 21% of participants met criteria for past-year AUD. Individuals who reported the greatest alcohol stimulation, liking, and wanting at the initial alcohol challenge were most likely to have developed AUD 10 years later. Further, alcohol-induced stimulation and wanting increased in reexamination testing among those with the highest AUD symptoms as the decade progressed. Conclusions: Initial stimulant and rewarding effects of alcohol predicted heavy alcohol use, and the magnitude of these positive subjective effects increased over a 10-year period in those who developed AUD compared with those who did not develop the disorder. The findings demonstrate systematic changes in subjective responses to alcohol over time, providing an empirical basis for prevention, early intervention, and treatment strategies.