Immune-inflammatory response changes in patients with major depressive disorder

Objectives: It has been hypothesized that major depression is accompanied by alterations in cell-mediated and innate immunity. Moreover, major depression appears to be associated with increased plasma concentrations of positive "acute-phase" proteins and increased production of cytokines. It has been suggested that an altered production of cytokines may underlie numerous recognized changes of immune or inflammatory markers. The aim of our study was to evaluate the usefulness of high-sensitivity C-reactive protein (hs-CRP) values in identifying a state of immune-inflammatory activation in patients with major depressive disorder. In particular, in order to assess the reliability of this inflammatory parameter in depression, we measured changes in hs-CRP values as well as its correlation with both the levels of some cytokines [interleukin 6 (IL-6), soluble interleukin 6 receptor (sIL-6R) and Tumor Necrosis Factor (TNF-α)] and the clinical characteristics of the sample (severity of symptoms, specific psychopathological dimensions, etc.). Methods: 24 outpatients (M/F = 8/16; mean age = 46.79 ± 12.97) with a Major Depressive Disorder (MDD) during a Major Depressive Episode (MDE) and 20 healthy controls (M/F = 8/12, mean age = 40.05 ± 11.02) were recruited at the Institute of Psychiatry of the Catholic University in Rome. Depression severity was assessed with 21-items-Hamilton Depression Rating Scale (HDRS), while anhedonia and psychomotor retardation were evaluated with Snaith-Hamilton Pleasure Scale (SHAPS) and Depression Retardation Rating Scale (DRRS). Blood samples for the determination of hs-CRP, TNF-α, IL-6 and sIL-6R were collected. Cytokines were measured using commercial enzyme linked immunosorbent assays (ELISA). Levels of hs-CRP were measured using nephelometric assay. Results: The patients included in the study mostly had moderate depressive symptoms at baseline. Plasma concentrations of IL-6 (0.59 ± 1.14 vs. 0.06 ± 0.27 pg/ml) and hs-CRP (3.28 ± 3.59 vs. 1.33 ± 1.48 mg/ml) were significantly higher in depressed patients compared to healthy controls. sIL-6R levels along with receptor-ligand binding activity (product IL-6 x sIL6R) were higher in depressed patients compared to healthy controls, though not significantly. In contrast, TNF-α levels appeared reduced in depressed patients compared to healthy subjects. A significant positive correlation between hs-CRP and IL-6 (r = 0.25, p = 0.047) was found. The analysis of a possible correlation between different inflammatory markers (hs-CRP, IL-6, sIL-6R and TNF-α) and scores on psychometric scales (HDRS, BPRS, DRRS and SHAPS) showed no statistical significance. Immune system and acute phase response activation, therefore, shows no correlation with severity of depressive symptoms and psychopathological profile (anhedonia and psychomotor retardation). Conclusions: Although plasma cytokine assays are highly specific and sensitive measurs in defining immune profile, they are quite expensive. The use of hs-CRP in our study has, on the contrary, proven to be sufficiently reliable and potentially applicable to routine clinical practice, so to identify those subjects with the highest levels of immune dysregulation. Further studies on larger samples, more adequately characterized with respect to clinical course and characteristics, are necessary to increase our understanding of the role played by immune activation in major depression.