Currently, the cause and the temporal order of the development of comorbid MDD and AUD is lively debated,46 highlighting the role of alcohol abuse as a risk factor for depression and vice versa.47 In this discussion, genetic and environmental factors, as well as their interaction, are considered crucial for the emergence of comorbidity.48, 49 We report that individual variability to the effects of chronic stress, which precipitates or precludes the development of a chronic depressive‐like state,21 is related to the emergence or absence of AUD‐like manifestations, respectively. In our model, maladaptive stress coping, which leads to propensity to primary depression, exaggerates several secondary AUD‐like behaviors. Notably, depression resilience limits the emergence of the full comorbid phenotype, protecting from changes in extinction learning, persistent alcohol seeking, and relapse vulnerability. Our data might be explained by (a) a common (epi) genetic predisposition underlying the two diseases, (b) depression as a factor that confers vulnerability to alcohol abuse, and (c) a combination of the two. For example, increased alcohol preference in the SDPS‐prone individuals might reflect a genetic vulnerability to alcohol50 in the same individuals that show depression susceptibility,48 especially when these individuals are exposed to adverse environmental conditions.51, 52
