Astrocytes have also been implicated in the aetiopathogenesis of preclinical models of despair and clinical depression (see Table I). Postmortem studies of major depressive disorder (MDD) demonstrate decreased glial cell density in several brain regions, including orbitofrontal cortex, dorsolateral PFC (dlPFC) (Rajkowska et al. 1999), ACC (Cotter et al. 2001), and amygdala (Bowley et al. 2002). An age-dependent reduction in GFAP-immunoreactive astrocyte density has also been observed in the PFC of younger individuals with MDD (Miguel-Hidalgo et al. 2000), but not in the supragenual ACC in late-life depression relative to age-matched controls (Khundakar et al. 2011). There is also a significant reduction in aquaporin-immunoreactive astrocytic end feet contacting gray matter vessels in the PFC of individuals with MDD, which suggests that blood-brain barrier permeability may be altered in depression (Rajkowska et al. 2013).
