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.