Abstract
Major depression (MD) is associated with peripheral inflammation and increased cardiovascular risk. Regular physical exercise can have anti-inflammatory effects. The present study examined whether behavioral activation with exercise affects inflammatory processes in MD. Ninety-eight patients with MD were randomly assigned to cognitive-behavioral therapy (CBT) emphasizing exercise during behavioral activation (CBT-E), CBT with pleasurable low-energy activities as an active control condition (CBT-C) or a passive waiting list control group (WL). Plasma levels of C-reactive protein (CRP), interleukin (IL)-6, IL-10, lipopolysaccharide (LPS)-stimulated IL-6 production, and blood immune cell counts were analyzed at baseline and weeks 8 (post-behavioral activation) and 16 (post-treatment). Thirty non-depressed age- and sex-matched controls were included to examine potential immunological alterations in MD at baseline. Patients with MD exhibited higher levels of CRP, higher neutrophil and monocyte counts, lower IL-10 levels and reduced LPS-stimulated IL-6 production compared to controls (P<0.001−0.045). Multilevel modeling indicated that CBT-E was associated with increased anti-inflammatory IL-10 at weeks 8 and 16 compared to CBT-C and WL (P=0.004−0.018). CBT-E did not significantly affect other immunological makers in the total sample. A subgroup analysis including patients with potentially higher cardiovascular risk (CRP ⩾1 μg ml−1) indicated that CRP was reduced in CBT-E compared to CBT-C (P<0.007) and marginally reduced compared to WL (P<0.085) after week 16. The present findings provide new insights into immunological effects of behavioral treatments against depression. Behavioral activation in conjunction with exercise may have the potential to reverse, in part, immunological alterations in MD.
Highlights
Major depression (MD) is associated with low-grade inflammation as evident from elevated levels of pro-inflammatory cytokines (for example, interleukin (IL)-6, tumor necrosis factor (TNF)-α) and acute-phase proteins (that is, C-reactive protein (CRP)) in the circulation.[1,2] Longitudinal observations in humans and studies in experimental animals document a bidirectional loop in which peripheral inflammatory signals can induce depressive symptoms and vice versa.[3,4] Mechanistically, elevated peripheral inflammatory signaling leads to dysregulation of several mood-relevant neural processes via molecular, cellular and neural routes.[5]
Meta-analyses suggest that exercise has moderate to large antidepressant effects[21,22] and even reduces depressive symptom severity in patients who did not remit with pharmacological antidepressant treatment.[23]
Three participants were excluded because their CRP levels were above 10 μg ml − 1 at all measure points, invalid blood samples for almost all measures (n = 1), or a retrospective report showed chronic urinary tract infection during the study phase (n = 1)
Summary
Major depression (MD) is associated with low-grade inflammation as evident from elevated levels of pro-inflammatory cytokines (for example, interleukin (IL)-6, tumor necrosis factor (TNF)-α) and acute-phase proteins (that is, C-reactive protein (CRP)) in the circulation.[1,2] Longitudinal observations in humans and studies in experimental animals document a bidirectional loop in which peripheral inflammatory signals can induce depressive symptoms and vice versa.[3,4] Mechanistically, elevated peripheral inflammatory signaling leads to dysregulation of several mood-relevant neural processes via molecular, cellular and neural routes.[5]. Physical inactivity is associated with both inflammation and depression.[17,18,19,20] Meta-analyses suggest that exercise (that is, regular, planned and structured physical activity) has moderate to large antidepressant effects[21,22] and even reduces depressive symptom severity in patients who did not remit with pharmacological antidepressant treatment.[23] In addition, exercise induces anti-inflammatory effects mainly via the release of antiinflammatory cytokines, such as IL-10, and has been suggested as a beneficial treatment option for clinical conditions related to inflammation.[24,25,26,27,28,29,30] several studies document the anti-inflammatory effects of exercise in healthy individuals and patients with medical illness,[24] little research focuses on the impact of physical activity on immunity in patients with clinicallyrelevant depressive symptoms. These issues were discussed within treatment sessions and used to prepare an individualized schedule with at least four 40-min
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