Inflammatory Biomarkers in Chronic Fatigue Syndrome and Major Depression

render of DNAMajor depression is a mental disorder characterized by fatigue, low self-esteem, loss of interest in normally enjoyable activities, and lack of energy. Chronic Fatigue Syndrome (CFS) is a debilitating disorder that often presents with similar symptoms as depression. Importantly, both illnesses are accompanied by activation of cell mediated immunity. Because of these similarities researchers sought to investigate how similar the immune responses in major depression and CFS might be.

T cell mediated inflammation is associated with secretion of proinflammatory cytokines (PICs) and acute phase proteins which have been detected in many patients with major depression.1 Substantial research also suggests an inflammatory/immune response in the pathogenesis of CFS.2 Since both these conditions are accompanied by inflammation and cellular immune responses, shared pathways could explain the often disabling fatigue reported by patients with these disorders.

In order to investigate similarities of immune activation between major depression and CFS, researchers compared the concentration of PICs in the blood of patients with these disorders. 218 subjects participated in the study 3: 97 CFS participants, 85 depressed participants, and 26 control individuals. Researchers found the concentration of PICs in the CFS study population to be significantly higher than in the depressed population and both groups had higher PIC concentrations than the control group. Moreover, the inflammatory response was even more significant in those suffering from CFS than from depression.

As this study demonstrates, CFS and major depression do not only share fatigue but also inflammatory pathways that may contribute to the clinical symptoms seen in these patients. Specifically, PICs may cause depression-like behaviors as well as fatigue, and therefore inflammation may be very relevant for the pathogenesis of CFS as well as of depression.

Overall, the plasma concentrations of PICs were found to be elevated in CFS and depressed participants. In addition, CFS patients’ PIC levels were higher than those of depressed individuals. In the future PIC assays may be used as biomarkers for diagnosis and classification of both depression and CFS. It will be interesting to see whether decreasing the plasma concentrations of PICs will be useful for treating depression as well as CFS.


Meriem Mokhtech, BS
Senior Laboratory Technician
UF Center for Musculoskeletal Pain Research



  1. Howren MB, Lamkin DM, Suls J. Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis. PsychosomMed 2009; 71: 171–186.
  2. Maes M, Twisk FN. Chronic fatigue syndrome: Harvey and Wessely’s (bio)psychosocial model versus a bio(psychosocial) model based on inflammatory and oxidative and nitrosative stress pathways. BMC Med 2010; 8: 35.
  3. Maes M, Twisk FNM, Ringel K. 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. Psychother Psychosom 2012;81:286–295.