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


METHOD
A 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.


RESULTS
A 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.


CONCLUSIONS
This 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.
['Ellingson|J M|JM|', 'Richmond-Rakerd|L S|LS|', 'Statham|D J|DJ|', 'Martin|N G|NG|', 'Slutske|W S|WS|']
D000328:Adult D019973:Alcohol-Related Disorders D001315:Australia D015897:Comorbidity D003865:Depressive Disorder, Major D004644:Emotions D005260:Female D006801:Humans D008297:Male D010551:Personality D012042:Registries D000068356:Self-Control
Alcohol use disorder negative emotionality behavioral control internalizing externalizing major depressive disorder behavior genetics co-morbidity dual diagnosis research domain criteria