The predictive value of somatic and cognitive depressive symptoms for cytokine changes in patients with major depression

Abstract

Katharina Dannehl,1 Winfried Rief,1 Markus J Schwarz,2 Annika Hennings,1 Sabine Riemer,1 Verena Selberdinger,3 Theresa Stapf,3 Frank Euteneuer11Division of Clinical Psychology and Psychotherapy, Philipps Universität Marburg, Marburg, Germany; 2Institute for Laboratory Medicine, Ludwig-Maximilian Universität, Munich, Germany; 3Department of Psychiatry, Ludwig-Maximilian Universität, Munich, GermanyContext: Elevated concentrations of proinflammatory cytokines have been hypothesized as an important factor in the pathophysiology of depression. Depression itself is considered to be a heterogeneous disorder. Current findings suggest that “cognitive” and “somatic” symptom dimensions are related to immune function in different ways. So far, little research has been done on the longitudinal aspects of inflammation in patients with major depression, especially with respect to different symptom dimensions of depression. Therefore, we investigated which aspects of depression may predict changes in tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6 over 4 weeks. Methods: Forty-one patients with major depression diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), and 45 healthy controls were enrolled. Serum measurements of TNF-alpha and IL-6 were conducted at baseline and 4 weeks later. Psychometric measures included the assessment of cognitive-affective depressive symptoms and somatic symptoms during the last 7 days as well as somatic symptoms during the last 2 years. Results: Patients with depression showed increased levels of TNF-alpha (P<0.05) compared to healthy controls. Hierarchical regression analyses indicated that neither depressive nor somatic symptoms predict changes in proinflammatory cytokines in the whole sample of depressed patients. Moderation analyses and subsequent sex-stratified regression analyses indicated that higher somatoform symptoms during the last 2 years significantly predict an increase in TNF-alpha in women with major depression (P<0.05) but not in men. Exploratory ­analyses ­indicated that the stability of TNF-alpha and IL-6 (as indicated by intraclass correlation ­coefficients) over 4 weeks was high for TNF-alpha but lower for IL-6.Conclusion: The present study demonstrated that a history of somatoform symptoms may be important for predicting future changes in TNF-alpha in women with major depression. Keywords: interleukin-6, tumor necrosis factor-alpha, symptom dimension