Genetic Risk Variants Associated With Comorbid Alcohol Dependence and Major Depression

Zhou, Hang; Polimanti, Renato; Yang, Bao Zhu; Wang, Qian; Han, Shizhong; Sherva, Richard; Nuñez, Yaira Z.; Zhao, Hongyu; Farrer, Lindsay A.; Kranzler, Henry R.; Gelernter, Joel

doi:10.1001/jamapsychiatry.2017.3275

Cited by 81 publications

(77 citation statements)

References 66 publications

(88 reference statements)

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“…For the remainder of this article, self‐medication (SM) will be defined as the self‐reported use of alcohol or drugs to help cope with feelings of depression or anxiety. While the SMH is one plausible mechanism to explain the comorbidity between MD/AD and SUD, other mechanisms include: (a) the reverse causal pathway, namely, substance use leading to a psychiatric disorder; (b) shared environmental or genetic vulnerability (i.e., childhood trauma) that may increase risk for both MD/AD and SUD (no causal relationship); and (c) a gene–environment interaction that may increase risk for SUD among those with MD/AD, or vice versa, through some third variable (indirect causal relationship) (Kraemer, Stice, Kazdin, Offord, & Kupfer, 2001; Zhou et al., 2017). …”

Section: Introductionmentioning

confidence: 99%

Self-medication with alcohol or drugs for mood and anxiety disorders: A narrative review of the epidemiological literature

et al. 2018

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BackgroundThe comorbidity of mood and anxiety disorders (MD and AD) with substance use disorders (SUD) is common. One explanation for this comorbidity is the self‐medication hypothesis, which posits that individuals with MD or AD use substances to cope with the difficult symptoms associated with the disorder. Over time, self‐medication (SM) can develop into an independent SUD. This narrative review will present the prevalence and correlates of SM with alcohol and/or drugs for MD and AD and the relationship between SM and subsequent SUD using both cross‐sectional and longitudinal epidemiological data.MethodsScopus and PsycINFO were searched from January 1997 to April 2018 to identify original research articles that examined the prevalence and correlates of SM and the temporal relationship between MD/AD and SUD in the general population (n = 22).ResultsThe prevalence of SM with alcohol and/or drugs among those with MD or AD ranged from 21.9% to 24.1%. Male sex, younger age, being separated, divorced or widowed, and being Caucasian were characteristics associated with higher proportions of respondents endorsing SM with alcohol/drugs for MD and AD. Longitudinal data supports the temporal onset of primary MD/AD and secondary SUD among those who self‐report SM.ConclusionProviding and promoting alternate coping strategies for those with MD/AD may reduce SM, the development of SUD, and the comorbidity of MD/AD with SUD. The concurrent treatment of MD/AD and substance use is the current “gold standard” model of care, and the results of this review support its use.

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Section: Introductionmentioning

confidence: 99%

Self-medication with alcohol or drugs for mood and anxiety disorders: A narrative review of the epidemiological literature

et al. 2018

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“…Covariates included sex and the first three principal components. For SAGE, birth cohorts as defined in COGA were included as covariates while for Yale-Penn AA, age was used (as recommended in prior publications of this sample 50,51 ). Effect sizes across COGA and replication samples were meta-analyzed in METAL.…”

Section: Replicationmentioning

confidence: 99%

Genome‐wide association study identifies loci associated with liability to alcohol and drug dependence that is associated with variability in reward‐related ventral striatum activity in African‐ and European‐Americans

Wetherill

Lai

Johnson

et al. 2019

Genes Brain and Behavior

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Genetic influences on alcohol and drug dependence partially overlap, however, specific loci underlying this overlap remain unclear. We conducted a genome‐wide association study (GWAS) of a phenotype representing alcohol or illicit drug dependence (ANYDEP) among 7291 European‐Americans (EA; 2927 cases) and 3132 African‐Americans (AA: 1315 cases) participating in the family‐based Collaborative Study on the Genetics of Alcoholism. ANYDEP was heritable (h 2 in EA = 0.60, AA = 0.37). The AA GWAS identified three regions with genome‐wide significant (GWS; P < 5E‐08) single nucleotide polymorphisms (SNPs) on chromosomes 3 (rs34066662, rs58801820) and 13 (rs75168521, rs78886294), and an insertion‐deletion on chromosome 5 (chr5:141988181). No polymorphisms reached GWS in the EA. One GWS region (chromosome 1: rs1890881) emerged from a trans‐ancestral meta‐analysis (EA + AA) of ANYDEP, and was attributable to alcohol dependence in both samples. Four genes (AA: CRKL, DZIP3, SBK3; EA: P2RX6) and four sets of genes were significantly enriched within biological pathways for hemostasis and signal transduction. GWS signals did not replicate in two independent samples but there was weak evidence for association between rs1890881 and alcohol intake in the UK Biobank. Among 118 AA and 481 EA individuals from the Duke Neurogenetics Study, rs75168521 and rs1890881 genotypes were associated with variability in reward‐related ventral striatum activation. This study identified novel loci for substance dependence and provides preliminary evidence that these variants are also associated with individual differences in neural reward reactivity. Gene discovery efforts in non‐European samples with distinct patterns of substance use may lead to the identification of novel ancestry‐specific genetic markers of risk.

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“…Participants for the second replication sample from the Yale–Penn study were recruited from three sites in the eastern United States, for studies of the genetics of drug or alcohol dependence‐study (Gelernter, Kranzler, Sherva, Almasy et al, ; Gelernter, Kranzler, Sherva, Koesterer et al, ; Gelernter, Sherva et al, ; Zhou et al, ). All participants were interviewed using the Semi‐Structured Assessment for Drug Dependence and Alcoholism (SSADDA; Pierucci‐Lagha et al, ), a structured, polydiagnostic clinical interview, and completed the computerized version of the Wisconsin Card Sorting Test (WCST), as described below…”

Section: Methodsmentioning

confidence: 99%

“…Participants for the second replication sample from the Yale-Penn study were recruited from three sites in the eastern United States, for studies of the genetics of drug or alcohol dependence-study Zhou et al, 2017). All participants were interviewed using the Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA; Pierucci-Lagha et al, 2005), a structured, polydiagnostic clinical interview, and completed the computerized version of the Wisconsin Card Sorting Test (WCST), as described below WCST is a well-validated and widely-used test of cognitive reasoning and flexibility first published by Grant andBerg in 1948 (Grant andBerg, 1948).…”

Section: Yale-penn Study Replication Samplementioning

confidence: 99%

Apolipoprotein E gene polymorphism, posttraumatic stress disorder, and cognitive function in older U.S. veterans: Results from the National Health and Resilience in Veterans Study

et al. 2019

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Background Although the ε4 allele of the apolipoprotein E (APOE) gene and posttraumatic stress disorder (PTSD) have been linked to cognitive dysfunction and dementia risk, it is unknown whether they interact to predict cognitive dysfunction. Methods We analyzed data from European‐American (EA) veterans who participated in the National Health and Resilience in Veterans Study (NHRVS): main sample (n = 1,386) and primary replication sample (n = 509). EAs from the Yale–Penn Study cohort (n = 948) served as a second replication sample. Multivariable analyses were conducted to evaluate the predictive effects of ε4 carrier status and PTSD on cognitive functioning, with a focus on whether PTSD moderates the effect of ε4 carrier status. Results APOE ε4 allele carrier status (d = 0.15 and 0.17 in the main and primary replication NHRVS samples, respectively) and PTSD (d = 0.31 and 0.17, respectively) were independently associated with lower cognitive functioning. ε4 carriers with PTSD scored lower than those without PTSD (d = 0.68 and 1.29, respectively) with the most pronounced differences in executive function (d's = 0.75–1.50) and attention/concentration (d's = 0.62–1.33). A significant interaction was also observed in the Yale–Penn sample, with ε4 carriers with PTSD making more perseverative errors on a measure of executive function than those without PTSD (24.7% vs. 17.6%; d = 0.59). Conclusions APOE ε4 allele carriers with PTSD have substantially greater cognitive difficulties than ε4 carriers without PTSD. These results underscore the importance of assessing, monitoring, and treating PTSD in trauma‐affected individuals who are at genetic risk for cognitive decline and dementia.

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Genetic Risk Variants Associated With Comorbid Alcohol Dependence and Major Depression

Cited by 81 publications

References 66 publications

Self-medication with alcohol or drugs for mood and anxiety disorders: A narrative review of the epidemiological literature

Self-medication with alcohol or drugs for mood and anxiety disorders: A narrative review of the epidemiological literature

Genome‐wide association study identifies loci associated with liability to alcohol and drug dependence that is associated with variability in reward‐related ventral striatum activity in African‐ and European‐Americans

Apolipoprotein E gene polymorphism, posttraumatic stress disorder, and cognitive function in older U.S. veterans: Results from the National Health and Resilience in Veterans Study

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