Most of the genetic covariation between major depressive and alcohol use disorders is explained by trait measures of negative emotionality and behavioral control

Abstract

BackgroundMental health disorders commonly co-occur, even between conceptually distinct syndromes, such as internalizing and externalizing disorders. The current study investigated whether phenotypic, genetic, and environmental variance in negative emotionality and behavioral control account for the covariation between major depressive disorder (MDD) and alcohol use disorder (AUD).MethodA total of 3623 members of a national twin registry were administered structured diagnostic telephone interviews that included assessments of lifetime histories of MDD and AUD, and were mailed self-report personality questionnaires that assessed stress reactivity (SR) and behavioral control (CON). A series of biometric models were fitted to partition the proportion of covariance between MDD and AUD into SR and CON.ResultsA statistically significant proportion of the correlation between MDD and AUD was due to variance specific to SR (men = 0.31, women = 0.27) and CON (men = 0.20, women = 0.19). Further, genetic factors explained a large proportion of this correlation (0.63), with unique environmental factors explaining the rest. SR explained a significant proportion of the genetic (0.33) and environmental (0.23) overlap between MDD and AUD. In contrast, variance specific to CON accounted for genetic overlap (0.32), but not environmental overlap (0.004). In total, SR and CON accounted for approximately 70% of the genetic and 20% of the environmental covariation between MDD and AUD.ConclusionsThis is the first study to demonstrate that negative emotionality and behavioral control confer risk for the co-occurrence of MDD and AUD via genetic factors. These findings are consistent with the aims of NIMH's RDoC proposal to elucidate how transdiagnostic risk factors drive psychopathology.

Reciprocal relationships between substance use and disorders and suicidal ideation and suicide attempts in the Collaborative Study of the Genetics of Alcoholism

“…However, adjustment for MDD did not abolish our association suggesting that this shared liability may be more general than MDD (e.g. Ellingson et al, 2016). Third, increased likelihood of substance use disorders in those with a prior history of SA may reflect a general predisposition towards impulsive and aggressive behaviors (Turecki, 2005).…”

Socio-economic inequalities in the association between alcohol-use disorder and depressive disorder among Thai adults: a population-based study

“…However, our results do not provide support for the evidence of a stronger association between depressive symptoms and alcohol use among people with lower SES, but rather indicate that the SES impact on mental disorders is controversial which may vary between countries [19] and the types of measurements used for either depressive and alcohol use disorders or SES variables [31]. The signi cant relationship between MDE and AUD could be explained in terms of shared common genetic and environmental factors in the comorbidity of depressive disorder and AUD, as investigated in other studies [34][35][36]. It could also be explained in terms of causality where depressed persons may turn to alcohol as self-medication for their symptoms and develop AUD afterwards [37].…”

Serial Progression from Attention-Deficit/Hyperactivity Disorder to Alcohol Use Disorder: Serial Multiple Mediated Effects of Externalizing Disorders and Depression

“…Interestingly, the latest theoretical models predict that depression shares a common potential endophenotype, or reward dysfunction, with the impulsivity-based disorders including substance abuse, which is substantiated by accumulating physiological grounds 38–41). Also, a large-scale twin study reported that the genetic covariation between depression and AUD could be explained by negative emotionality and behavioral control 42). In other studies, it was demonstrated that insulin-like growth factor-1 (IGF-1) was significantly higher in patients with AUD accompanied with depressive symptoms than ones without the symptoms, which shows IGF-1 would be a biomarker of AUD accompanied with depression 43).…”