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

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 dimensio

Supplementary Material for: Comparing the Efficacy of CBASP with Two Versions of CBT for Depression in a Routine Care Center: A Randomized Clinical Trial

<b><i>Background:</i></b> The cognitive-behavioral analysis system of psychotherapy (CBASP) was developed for the treatment of chronic, early-onset depression. However, it is unclear whether this approach can be recommended for depression in general (episodic and chronic), and no direct comparisons between CBASP with different versions of cognitive-behavioral therapy (CBT) exist. <b><i>Methods:</i></b> A randomized controlled trial compared 3 treatment conditions (all lasting 16 sessions) with a waiting list group (WL): CBASP, CBT with a focus on physical exercise (CBT-E), and CBT with a focus on pleasurable, low-energy and mindful activities (CBT-M). We included 173 patients and involved 41 therapists. Assessments were at baseline, after session 8, and at the end of treatment. <b><i>Results:</i></b> Our primary outcome Beck Depression Inventory-II indicated a general advantage of the CBT arms compared to CBASP [<i>F</i>(6, 154.5) = 4.2, <i>p</i> = 0.001], with significant contrasts in particular in favor of CBT-E. Effect sizes against WL were <i>d</i> = 0.91 (CBT-E), 0.87 (CBT-M), and 0.47 (CBASP). A triple interaction with an additional factor “chronic versus episodic depression” [<i>F</i>(6, 142.7) = 2.2, <i>p</i> = 0.048] indicated that the treatments resulted in different outcomes, with best results again for CBT-E in particular in episodic depression. Responder rates indicated significant improvements (56% in both CBT arms, 34% in the CBASP arm, 3.4% in WL; intention-to-treat samples). As compared to CBASP, response rates were significantly higher for CBT-E (OR = 2.48; 95% CI = 1.02–6.00) and CBT-M (OR = 2.46; 95% CI = 1.01–6.01). <b><i>Conclusions:</i></b> CBASP was more effective than WL, but less effective than the 2 CBT arms. This was mainly caused by an advantage of CBT interventions in episodic depression