Species differences in comorbid alcohol use disorder and major depressive disorder: A narrative review

Alcohol use disorder (AUD) and major depressive disorder (MDD) are often comorbid, and it is estimated that between 15 % to 33% of people dependent on alcohol have an MDD diagnosis. Mood-related symptoms are also common in humans during acute withdrawal, but by most accounts, symptoms abate after 2-4 weeks of alcohol abstinence. Preclinical studies, important for understanding the etiology and finding treatments for this comorbidity, also find depression-like and anxiety-like phenotypes in early abstinence along with protracted negative affect detectable past 2 weeks postcessation. In this narrative review, we focus on the translational divergence of AUD and MDD comorbidity with a focus on the time line mismatch between species in concurrent AUD + MDD and MDD following AUD. We also highlight the preclinical success and clinical failure of classic antidepressants for AUD and the relative absence of withdrawal and negative affect in high-drinking selected lines of mice and rats. We suggest sources of these discrepancies, including discussion of relief/reward-driven drinking subpopulations and future directions for the field.