Genetic predisposition to major depressive disorder differentially impacts alcohol consumption and high-risk drinking situations in men and women with alcohol use disorder. (1st February 2023)

• Record Type: Journal Article
• Authors: Karpyak, Victor M.; Coombes, Brandon J.; Geske, Jennifer R.; Pazdernik, Vanessa M.; Schneekloth, Terry; Kolla, Bhanu Prakash; Oesterle, Tyler; Loukianova, Larissa L.; Skime, Michelle K.; Ho, Ada Man-Choi; Ngo, Quyen; Skillon, Cedric; Ho, Ming-Fen; Weinshilboum, Richard; Biernacka, Joanna M.
• Is Part Of: Drug and alcohol dependence. Volume 243(2023)
• Publication Date: 2023-02-01
• Subjects: Alcohol use disorder -- Alcohol consumption -- Depression -- Polygenic risk scores -- Sex differences; Drug abuse -- Periodicals; Alcoholism -- Periodicals; 616.86
• DOI: 10.1016/j.drugalcdep.2022.109753
• Languages: English
• ISSNs: 0376-8716

Abstract

Abstract: Lifetime history of major depressive disorder (MDD) has a sex-specific association with pretreatment alcohol consumption in patients with alcohol dependence. Here, we investigated the association of genetic load for MDD estimated using a polygenic risk score (PRS) with pretreatment alcohol consumption assessed with Timeline Follow Back in a sample of 287 men and 156 women meeting DSM-IV-TR criteria for alcohol dependence. Preferred drinking situations were assessed using the Inventory of Drug Taking Situations (IDTS). Linear models were used to test for association of normalized alcohol consumption measures with the MDD-PRS, adjusting for ancestry, age, sex, and number of days sober at baseline. We fit models both with and without adjustment for MDD history and alcohol-use-related PRSs as covariates. Higher MDD-PRS was associated with lower 90-day total alcohol consumption in men (β = −0.16, p = 0.0012) but not in women (β = 0.11, p = 0.18). The association of MDD-PRS with IDTS measures was also sex-specific: higher MDD-PRS was associated with higher propensity to drink in temptation-related situations in women, while the opposite (negative association)was found in men. MDD-PRS was not associated with lifetime MDD history in our sample, and adjustment for lifetime MDD and alcohol-related PRSs did not impact the results. Our results suggest that genetic load for MDD impacts pretreatment alcohol consumption in a sex-specific manner, which is similar to, but independent from, the effect of history of MDD. The clinical implications of these findings and contributing biological and psychological factors should be investigated in future studies. Highlights: History of major depressive disorder has sex-specific association with alcohol use. Genetic load for MDD was inversely associated with alcohol use in men but not women. Genetic load for MDD inversely correlated with temptation-driven use in women and men. MDD history and genetic load for MDD were associated with alcohol use independently. Clinical implications of these findings and their mechanisms should be investigated.