There are several exciting avenues for future comorbidity research. First, preclinical models of co-occurring disorders, e.g., rodents exposed to both CUS and alcohol/illicit drugs, may expand our neuropathological understanding of this comorbidity. Ketamine’s improved antidepressant response in those with a family history of alcoholism suggests that subjects with comorbid depression and alcohol dependence may have enhanced antidepressant effects relative to non-alcohol dependent depressed patients. If efficacious, alternative non-parenteral NMDA receptor antagonists with lower addictive liability are better long-term strategies in this population (Ibrahim et al. 2012; Zarate et al. 2013). Despite the great wealth of preclinical data on glial-mediated glutamatergic dysregulation in DUDs (Kalivas et al. 2005, 2011), there are presently no pathophysiological or treatment studies in co-occurring MDD/bipolar depression and DUDs.
