Purpose of review The comorbidity between psychiatric and substance use disorders remains an important phenomenon to understand, and an active area of investigation. The purpose of this review is to highlight key 2011 issues and novel findings on psychiatric and substance disorders comorbidity from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), a large national survey of the US general population. Recent findings Topics of active investigation included the internalizing/externalizing meta-structure of common mental disorders; the 10 Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) personality disorders; the 3-year incidence and persistence of disorders; treatment of major depression; and many other topics not as easily categorized. Summary Meta-structure may increasingly offer a parsimonious way of addressing comorbidity, although adding new disorders adds complexity and the value of etiologic analyses utilizing broad dimensions of psychopathology rather than individual disorders is not yet fully known. Expanding the range of personality disorders beyond antisocial personality disorder appears essential in understanding the incidence and persistence of substance use disorders. Substance use disorders have low rates of treatment relative to major depression, but increase the likelihood of depression treatment among comorbid cases, a phenomenon that needs to be understood. These comorbidity studies provide much novel information, and indicate many potentially fruitful directions for new research.

ABSTRACT. Objective: A single nucleotide variation in the alcohol dehydrogenase 1B (ADH1B) gene, rs1229984, produces an ADH1B enzyme with faster acetaldehyde production. This protective variant is associated with lower alcohol consumption and lower risk for alcohol use disorders (AUDs). Based on the premise that faster ADH1B kinetics decreases alcohol consumption, we formally tested if the association between ADH1B variant rs1229984 and AUDs occurs through consumption. We also tested whether the association between rs1229984 and each of the 11 Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), AUD criteria occurs through consumption. Method: A total of 1,130 lifetime drinkers from an Israeli household sample were assessed with a structured interview and genotyped for rs1229984 (protective allele frequency = 0.28). Logistic regression evaluated the association between rs1229984 and each phenotype (AUDs, 11 individual DSM-IV criteria). For phenotypes signifi cantly related to rs1229984, the effect through consumption was tested with logistic regression and bootstrapping. Results: ADH1B rs1229984 was signifi cantly associated with AUDs and six criteria, with odds ratios ranging from 1.32 to 1.96. The effect through consumption was signifi cant for these relationships, explaining 23%-74% of the total ADH1B effect. Conclusions: This is the fi rst study to show that ADH1B rs1229984 is related to 6 of the 11 DSM-IV AUD criteria and that alcohol consumption explained a significant proportion of these associations and the association of ADH1B with AUDs. Better understanding of the relationship between ADH1B and the DSM-IV AUD criteria, including effects through consumption, will enhance our understanding of the etiologic model through which AUDs can occur. (J. Stud. Alcohol Drugs, 75, 635-642, 2014)