Chunk #79 — Comorbidity of Post-traumatic stress disorder or major depressive disorder with alcohol use disorder and immune signaling — Major depressive disorder and alcohol use disorder
Like individuals with AUD, patients with MDD have higher levels of pro-inflammatory cytokines and circulating leukocytes, leading to the hypothesis that inflammatory/immune processes also mediate the development and progression of depressive illnesses (for review, see (Lotrich, 2015; Miller and Raison, 2016)). Genome-wide association studies suggest immune-related genetic polymorphisms may mediate depression vulnerability, severity of symptoms, and response to anti-depressant treatment (Barnes et al., 2017). Meta-analyses of un-stimulated measurements of cytokines in patients with MDD show higher concentrations of TNF-α, IL-1β, IL-6, and IFN-γ—many of the same cytokines that are related to PTSD symptomology and AUD progression (García-Marchena et al., 2017; Glaus et al., 2017; Montesinos et al., 2016b). Additional support for a relationship between systemic inflammation and depression comes from cancer patients undergoing cytokine immunotherapy with IFN-α and IL-2, who show increased risk of developing depressive symptoms (Capuron and Dantzer, 2003). Clinical findings link increases in peripheral inflammatory markers with decreases in the functional connectivity of PFC–striatum pathways (Felger et al., 2015). For instance, the inflammatory marker CRP is associated with decreased connectivity between ventral striatum and ventromedial PFC, which
