Chunk #81 — Comorbidity of Post-traumatic stress disorder or major depressive disorder with alcohol use disorder and immune signaling — Major depressive disorder and alcohol use disorder
The discovery of immune imbalances in depressive illness led to the “macrophage hypothesis of depression ” (Neupane, 2016; Smith, 1991). As the resident macrophage of the CNS, microglia are major contributors to heightened pro-inflammatory states in MDD and SUDs. Postmortem analysis of brain tissue from subjects with depression and those who committed suicide show increased microglia activation in cortical areas related to depression (Steiner et al., 2008). In rodent models of depression, microglia isolated from stressed mice release higher levels of IL-1β and IL-6 following ex vivo exposure to LPS, suggesting stress/depression prime microglia for enhanced pro-inflammatory responses (Frank et al., 2007; Wohleb, 2016). Furthermore, transgenic mice lacking CX3CR1, a key microglia fractalkine receptor, have stunted neurodevelopment, deficient PFC-hippocampus connectivity, and impaired social interactions (Parkhurst et al., 2013; Zhan et al., 2014).
