Inflammatory and Cell-Mediated Immune Biomarkers in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Depression: Inflammatory Markers Are Higher in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome than in Depression

Abstract

Background: Depression is an inflammatory disorder while many authors declare myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) to be a functional disorder. The aim of the present study is to compare inflammatory and cell-mediated immune (CMI) responses between depression and ME/CFS. Methods: We measured two proinflammatory cytokines (PICs) in plasma, interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α), with enzyme-linked immunosorbent assays, and serum neopterin with a radioimmunoassay in controls, ME/CFS and depressive patients. Results: Plasma PICs were significantly higher in ME/CFS than in depression and higher in both patient groups than in controls. Increased PIC levels in depression were attributable to the presence of fatigue and physio-somatic symptoms. Serum neopterin did not differ significantly between depression and ME/CFS but was higher in both patient groups than in controls. The significant positive correlations between neopterin and either IL-1 or TNF-α were significantly greater in depression than in ME/CFS. Conclusions: Since PICs cause depression-like behaviors and fatigue/malaise, we suggest that inflammation may play a role in the pathophysiology of ME/CFS and depression. Increased neopterin also seems to contribute to the pathophysiology of both disorders. This study has detected a shared ‘pathway phenotype’, i.e. disorders in inflammatory and CMI pathways, which underpins both ME/CFS and depression and, therefore, may explain the co-occurrence of both disorders. ME/CFS and depression are discriminated from each other by increased PICs in ME/CFS and differences in the immune cell communication networks.

A review of peripheral biomarkers in major depression: The potential of inflammatory and oxidative stress biomarkers

“…Neopterin -levels of plasma neopterin are increased in depressed patients (Celik et al, 2010, Maes et al, 2013, Maes et al, 1994, Maes et al, 2012b, Rybka et al, 2013 and particularly in patients suffering from melancholic symptoms (Maes et al, 2012a, Maes et al, 1994. Greater concentrations of neopterin were also reported in patients suffering from two or more episodes of depression compared to first-episode populations (Celik et al, 2010).…”

Stability of Cellular Immune Parameters over 12 Weeks in Patients with Major Depression or Somatoform Disorder and in Healthy Controls

“…As values fluctuated significantly only in the MD group, an influence of this disease on the immune system also seems possible. Several studies have found characteristic alterations in the immune status of depressed persons [10, 11, 32, 47], suggesting a proinflammatory immune status in these patients. The female MD subgroup showed highly significant fluctuations in activated T lymphocytes (CD3 + CD25 + ), which is also an indicator of inflammation, once more suggesting an altered and possibly more fragile cellular immune status in depressed patients.…”

“…Several have tried to explain the etiology of SFD, such as childhood experiences of illness [5], high interoceptive awareness [6, 7], or misinterpretation of complaints as illness [7]. There are indications that the immune system may be causally involved, but study results vary [8-10]. Taking all these findings together, it is further strengthened that depression and SFD are two frequently overlapping clinical conditions having both been related to immunological changes [11].…”

“…Neopterin, a pyrazino-pyrimidine derivative [20], is released by macrophages after stimulation by interferon-γ released by activated T lymphocytes. Thus, it indicates an activated cellular immunity [10, 21-24]. …”

“…Several studies have compared at, one time point only, the immune status of patients with MD or SFD with that of healthy controls (HC) and found indications for psychoneuroimmunological differences [8-10, 32]. However, there is little evidence for the stability of or possible natural fluctuations in immunological parameters over the course of several weeks.…”