Serotonin-Immune Interactions in Major Depression

A series of studies over the last decade has demonstrated that depression is associated with alterations in immune functions. Most of the initial research indicated that depression is accompanied by signs of in vitro immunosuppression, such as decreased mitogen-stimulated lymphocyte proliferation (Kronfol et al. 1983) and natural killer cell activity (Irwin et al. 1987). Recently, a large body of evidence has been reported suggesting that major depression is associated with activation of cell-mediated immunity (for reviews, see Smith 1991; Maes et al. 1995; Maes 1997). The evidence for this includes the following: activation of in vivo cell-mediated immunity, as indicated by 1) a significantly increased CD4+/CD8+ ratio, which is determined by an increased percentage of T helper (CD4+) and T memory cells (CD4+CD45RO+) and/or by lowered percentage of T-suppressor cells (CD8+CD57); 2) significantly increased numbers of activated T cells (CD25+ and HLA-DR+ T cells) in the peripheral blood and increased concentrations of serum soluble interleukin- 2 receptor (sIL-2R); 3) enhanced production of mono- and T-lymphocytic products, such as interleukin-(IL-1β), IL-β and interferon-y(IFN-y) by mitogen-stimulated peripheral blood mononuclear cells (PBMCs), as well as increased plasma concentrations of IL-6 and sIL-6R; and 4) elevated plasma and urine neopterin concentrations. Moreover, there is strong evidence that the acute episode of major depression is accompanied by activation of the inflammatory response system (IRS; for reviews, see Maes 1993, 1997).

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