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Background and Aims  Depression and anxiety are often comorbid with alcoholism and contribute to craving and relapse. We aimed to estimate the prevalence of life‐time diagnoses of major depressive disorder (MDD), substance‐induced depression (SID), anxiety disorder (AnxD) and substance‐induced anxiety (SIA), the effects of these comorbidities on the propensity to drink in negative emotional states (negative craving), and test whether these effects differ by sex.    Design  Secondary analyses of baseline data collected in a single‐arm study of pharmacogenetic predictors of acamprosate response.    Setting  Academic medical center and affiliated community‐based treatment programs in the American upper mid‐west.    Participants  A total of 287 males and 156 females aged 18–80 years, meeting DSM‐IV criteria for alcohol dependence.    Measurements  The primary outcome measure was ‘propensity to drink in negative emotional situations’ (determined by the Inventory of Drug Taking Situations) and the key predictors/covariates were sex and psychiatric comorbidities, including MDD, SID, AnxD and SIA (determined by Psychiatric Research Interview of Substance and Mood Disorders).    Findings  The prevalence of the MDD, SID and AnxD was higher in females compared with males (33.1 versus 18.4%, 44.8 versus 26.4% and 42.2 versus 27.4%, respectively;  P  < 0.01, each), while SIA was rare (3.3%) and did not differ by sex. Increased propensity to drink in negative emotional situations was associated with comorbid MDD (β = 6.6,  P  = 0.013) and AnxD (β = 4.8,  P  = 0.042) as well as a SID × sex interaction effect ( P  = 0.003), indicating that the association of SID with propensity to drink in negative emotional situations differs by sex and is stronger in males (β = 7.9,  P  = 0.009) compared with females (β = −6.6,  P  = 0.091).    Conclusions  There appears to be a higher prevalence of comorbid depression and anxiety disorders as well as propensity to drink in negative emotional situations in female compared with male alcoholics. Substance‐induced depression appears to have a sex‐specific effect on the increased risk for drinking in negative emotional situations in males.

Gender‐specific effects of comorbid depression and anxiety on the propensity to drink in negative emotional states