Genome-wide meta-analysis of problematic alcohol use in 435,563 individuals yields insights into biology and relationships with other traits

BackgroundA number of studies reports reduced hippocampal volume in individuals who engage in problematic alcohol use. However, the magnitude of the difference in hippocampal volume between individuals with v. without problematic alcohol use has varied widely, and there have been null findings. Moreover, the studies comprise diverse alcohol use constructs and samples, including clinically significant alcohol use disorders and subclinical but problematic alcohol use (e.g. binge drinking), adults and adolescents, and males and females.MethodsWe conducted the first quantitative synthesis of the published empirical research on associations between problematic alcohol use and hippocampal volume. In total, 23 studies were identified and selected for inclusion in the meta-analysis; effects sizes were aggregated using a random-effects model.ResultsProblematic alcohol use was associated with significantly smaller hippocampal volume (d = −0.53). Moderator analyses indicated that effects were stronger for clinically significant v. subclinical alcohol use and among adults relative to adolescents; effects did not differ among males and females.ConclusionsProblematic alcohol use is associated with reduced hippocampal volume. The moderate overall effect size suggests the need for larger samples than are typically included in studies of alcohol use and hippocampal volume. Because the existing literature is almost entirely cross-sectional, future research using causally informative study designs is needed to determine whether this association reflects premorbid risk for the development of problematic alcohol use and/or whether alcohol has a neurotoxic effect on the hippocampus.

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Cessation and reduction in alcohol consumption and misuse after psychedelic use

Journal of Psychopharmacology ◽

10.1177/0269881119845793 ◽

2019 ◽

Vol 33 (9) ◽

pp. 1088-1101 ◽

Cited By ~ 19

Author(s):

Albert Garcia-Romeu ◽

Alan K Davis ◽

Fire Erowid ◽

Earth Erowid ◽

Roland R Griffiths ◽

...

Keyword(s):

Alcohol Consumption ◽

Alcohol Use ◽

Clinical Studies ◽

Online Survey ◽

Meta Analysis ◽

High Dose ◽

Clinical Settings ◽

Problematic Alcohol ◽

The Usa ◽

Problematic Alcohol Use

Background:Meta-analysis of randomized studies using lysergic acid diethylamide (LSD) for alcohol use disorder (AUD) showed large, significant effects for LSD efficacy compared to control conditions. Clinical studies suggest potential anti-addiction effects of LSD and mechanistically-related classic psychedelics for alcohol and other substance use disorders.Aims:To supplement clinical studies, reports of psychedelic use in naturalistic settings can provide further data regarding potential effects of psychedelics on alcohol use.Methods:An anonymous online survey of individuals with prior AUD reporting cessation or reduction in alcohol use following psychedelic use in non-clinical settings.Results:343 respondents, mostly White (89%), males (78%), in the USA (60%) completed the survey. Participants reported seven years of problematic alcohol use on average before the psychedelic experience to which they attributed reduced alcohol consumption, with 72% meeting retrospective criteria for severe AUD. Most reported taking a moderate or high dose of LSD (38%) or psilocybin (36%), followed by significant reduction in alcohol consumption. After the psychedelic experience 83% no longer met AUD criteria. Participants rated their psychedelic experience as highly meaningful and insightful, with 28% endorsing psychedelic-associated changes in life priorities or values as facilitating reduced alcohol misuse. Greater psychedelic dose, insight, mystical-type effects, and personal meaning of experiences were associated with a greater reduction in alcohol consumption, controlling for prior alcohol consumption and related distress.Conclusions:Although results cannot demonstrate causality, they suggest that naturalistic psychedelic use may lead to cessation or reduction in problematic alcohol use, supporting further investigation of psychedelic-assisted treatment for AUD.

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Meta-analysis of problematic alcohol use in 435,563 individuals identifies 29 risk variants and yields insights into biology, pleiotropy and causality

10.1101/738088 ◽

2019 ◽

Cited By ~ 5

Author(s):

Hang Zhou ◽

Julia M. Sealock ◽

Sandra Sanchez-Roige ◽

Toni-Kim Clarke ◽

Daniel Levey ◽

...

Keyword(s):

Substance Use ◽

Alcohol Use ◽

Genetic Relationships ◽

Meta Analysis ◽

European Ancestry ◽

Polygenic Risk Score ◽

Genome Wide Association Studies ◽

Problematic Alcohol ◽

Risk Variants ◽

Problematic Alcohol Use

AbstractProblematic alcohol use (PAU) is a leading cause of death and disability worldwide. Although genome-wide association studies (GWASs) have identified PAU risk genes, the genetic architecture of this trait is not fully understood. We conducted a proxy-phenotype meta-analysis of PAU combining alcohol use disorder and problematic drinking in 435,563 European-ancestry individuals. We identified 29 independent risk variants, 19 of them novel. PAU was genetically correlated with 138 phenotypes, including substance use and psychiatric traits. Phenome-wide polygenic risk score analysis in an independent biobank sample (BioVU, n=67,589) confirmed the genetic correlations between PAU and substance use and psychiatric disorders. Genetic heritability of PAU was enriched in brain and in genomic conserved and regulatory regions. Mendelian randomization suggested causal effects on liability to PAU of substance use, psychiatric status, risk-taking behavior, and cognitive performance. In summary, this large PAU meta-analysis identified novel risk loci and revealed genetic relationships with numerous other outcomes.

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Digital Interventions for People With Co-Occurring Depression and Problematic Alcohol Use: A Systematic Review and Meta-Analysis

Alcohol and Alcoholism ◽

10.1093/alcalc/agaa147 ◽

2021 ◽

Author(s):

Maria J E Schouten ◽

Carolien Christ ◽

Jack J M Dekker ◽

Heleen Riper ◽

Anna E Goudriaan ◽

...

Keyword(s):

Systematic Review ◽

Depressive Symptoms ◽

Alcohol Use ◽

Meta Analysis ◽

Assessment Development ◽

Digital Interventions ◽

Problematic Alcohol ◽

Meta Analyses ◽

Problematic Alcohol Use

Abstract Aims This systematic review and meta-analysis assessed the effectiveness of digital interventions addressing depressive symptoms and alcohol use simultaneously among people with co-occurring depression and problematic alcohol use. Methods Seven databases were searched for trials evaluating digital interventions aimed at depression and alcohol use. Random-effects meta-analyses were conducted to pool effects on depressive symptoms and alcohol use up to 3-month and 6-month follow-up. Overall quality for every outcome was assessed with GRADE (Grading of Recommendations Assessment, Development and Evaluation). Results The pooled effect of digital interventions compared to their comparators was in favour of digital interventions. Small but significant effects on depressive symptoms at 3-month follow-up were found (g = 0.34, 95% confidence interval (CI): 0.06–0.62, P = 0.02, k = 6) and non-significant effects at 6-month follow-up (g = 0.29, 95% CI: −0.16 to 0.73, P = 0.15, k = 5). For alcohol use, the pooled effect of digital interventions was small and non-significant at 3-month follow-up (g = 0.14, 95% CI: −0.02 to 0.30, P = 0.07, k = 6) and significant at 6-month follow-up (g = 0.14, 95% CI: 0.07–0.20, P = 0.005, k = 5). Sensitivity analysis indicated the latter finding to be sensitive to statistical estimator choice. Quality of evidence was moderate, except for depressive symptoms at 6-month follow-up for which it was low. Conclusion Based on the literature, digital interventions are effective in reducing depressive symptoms at 3-month follow-up and alcohol use at 6-month follow-up among people with comorbid depression and problematic alcohol use. More high-quality trials are needed to confirm the current findings.

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Supplemental Material for Predicting Problematic Alcohol Use With the DSM–5 Alternative Model of Personality Pathology

Personality Disorders Theory Research and Treatment ◽

10.1037/per0000131.supp ◽

2015 ◽

Keyword(s):

Alcohol Use ◽

Alternative Model ◽

Personality Pathology ◽

Dsm 5 ◽

Problematic Alcohol ◽

Problematic Alcohol Use

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A Developmental Perspective on the Genetic Basis of Alcohol Use Disorder

10.1093/oso/9780190676001.003.0004 ◽

2018 ◽

Author(s):

Elisa M. Trucco ◽

Gabriel L. Schlomer ◽

Brian M. Hicks

Keyword(s):

Alcohol Use ◽

Alcohol Use Disorder ◽

Developmental Perspective ◽

Relative Contribution ◽

Intermediate Phenotypes ◽

Problematic Alcohol ◽

Age Related ◽

Genetic And Environmental Factors ◽

Problematic Alcohol Use

Approximately 48–66% of the variation in alcohol use disorders is heritable. This chapter provides an overview of the genetic influences that contribute to alcohol use disorder within a developmental perspective. Namely, risk for problematic alcohol use is framed as a function of age-related changes in the relative contribution of genetic and environmental factors and an end state of developmental processes. This chapter discusses the role of development in the association between genes and the environment on risk for alcohol use disorder. Designs used to identify genetic factors relevant to problematic alcohol use are discussed. Studies examining developmental pathways to alcohol use disorder with a focus on endophenotypes and intermediate phenotypes are reviewed. Finally, areas for further investigation are offered.

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