Chunk #82 — Comorbidity of Post-traumatic stress disorder or major depressive disorder with alcohol use disorder and immune signaling — Major depressive disorder and alcohol use disorder
Postmortem human studies also indicate decreased numbers of astrocytes in cortical regions in subjects with depression (Peng et al., 2015; Rajkowska and Stockmeier, 2013), while preclinical studies have demonstrated an important role for cortical astrocyte function in mediating depressive-related phenotypes and anti-depressant functions. In rats, pharmacological ablation of PFC astrocytes is suffcient to drive depressive-like behaviors (Banasr and Duman, 2008), and intra-PFC blockade of astrocyte glutamate uptake induces anhedonia (John et al., 2012). Deficiencies in PFC astrocytic ATP release have been linked to depressive-like behaviors in adult mice (Cao et al., 2013). In addition, gap junction blockade in PFC astrocytes induces anxiety and anhedonia in rats (Sun et al., 2012). PFC astrocytes also show Ca2+ signaling in response to treatment with fluoxetine and citalopram, suggesting that these antidepressants may partly exert their effects via stimulation of astrocyte activity (Schipke et al., 2011). Several studies suggest that normal astrocyte function may be crucial for antidepressant treatment efficacy (Allaman et al., 2011; Etiévant et al., 2015; Sarrouilhe et al., 2018). Astrocyte activity and pro-inflammatory responses, particularly in the PFC, may thus contribute to behavioral symptoms of depression.
