Page - (000141) - in Biomedical Chemistry: Current Trends and Developments

In the brain, stress-induced increased glucocorticoids enhances immune function, promotes microglia proliferation and activation, and a loss of astrocytes number and volume (Czeh, 2006). Increased concentrations of pro-inflammatory mediators can lead to hippocampal dendritic atrophy and neuronal death (Sapolsky, 1985; Woolley, 1990). Overall, antidepressants reduce Th1 cytokines production in vitro, promoting a shift towards Th2 patterns (Leonard, 2001). For instance, imipramine, clomipramine, fluoxetine, sertraline and venlafaxine amongst other antidepressants, significantly decrease the IFNγ/IL-10 ratio (Kubera, 2001; Maes, 1999; Szuster-Ciesielska, 2003). Amitriptylin and nortriptylin inhibit IL-1ß and TNF-α release in in vitro cultures of microglial and mixed glial cells (Obuchowicz, 2006). In MDD patients, decreases in circulating IL-6 levels and TNF-α (Basterzi, 2005; Frommberger, 1997; Narita, 2006; Sluzewska, 1995), and increases in anti-inflammatory Th3-cytokine transforming growth factor beta (TGF-ß) (Myint, 2005) have also been reported during antidepressant treatment. 2.2.4 Summary and Conclusions Optimal performance of the CNS requires that the core stress system be maintained within a particular range, and emotional responses involve the integration of several areas of the brain. Superb collaboration of several CNS and peripheral systems in a sequentially coordinated manner are required for the optimal response of the stress system, which will ultimately determine the ability of an organism to survive under a threat. Dysregulation of the stress system is implicated in MDD; melancholia involves the hyperactivity of the stress system and atypical features are related to the down-regulation of the stress response; likewise, dysregulation of the immune response implicates the activation or suppression of humoral and cellular immune components. The core stress and immune systems interact with other CNS pathways that have also been reported to be dysregulated in MDD, including the serotonergic, glutamatergic, and kynurenine pathways (Muller & Schwarz, 2007).