Effects of Religious vs. Conventional Cognitive-Behavioral Therapy on Inflammatory Markers and Stress Hormones in Major Depression and Chronic Medical Illness: A Randomized Clinical Trial

Background: Depressive disorder is often accompanied by physiological changes that may adversely affect the course of medical illness, including an increase in pro-inflammatory cytokines. Methods: We examine the effects of religious cognitive behavioral therapy (RCBT) vs. conventional CBT (CCBT) on pro-/anti-inflammatory indicators and stress hormones in 132 individuals with major depressive disorder (MDD) and chronic medical illness who were recruited into a multi-site randomized clinical trial. Biomarkers (C-reactive protein and pro-inflammatory cytokines TNF-α, IL-1β, IFN-γ, IL-6, IL-12-p70), anti-inflammatory cytokines (IL1ra, IL-4, IL-10), and stress hormones (urinary cortisol, epinephrine, norepinephrine) were assessed at baseline, 12 weeks, and 24 weeks. Differential effects of baseline religiosity on treatment response were also examined, along with effects of religiosity on changes in biomarkers over time independent of treatment group. Biomarker levels were log transformed where possible to normalize distributions. Mixed models were used to examine trajectories of change. Results: CRP increased and IL-4, IL-10, and epinephrine decreased over time, mostly in the opposite direction expected (except epinephrine). No significant difference between RCBT and CCBT was found on average trajectory of change in any biomarkers. Religiosity interacted with treatment group in effects on IL-6, such that CCBT was more effective than RCBT in lowering lL-6 in those with low religiosity whereas RCBT appeared to be more effective than CCBT in those with high religiosity. Higher baseline religiosity also tended to predict an increase in pro-inflammatory cytokines INF-γ and IL-12 (p70) and urinary cortisol over time. Conclusions: RCBT and CCBT had similar effects on stress biomarkers. CCBT was more effective in reducing IL-6 levels in those with low religiosity, whereas RCBT tended to be more effective in those with high religiosity. Unexpectedly, higher baseline religiosity was associated with an increase in several stress biomarkers.

Religious Involvement, Inflammatory Markers and Stress Hormones in Major Depression and Chronic Medical Illness

Background: Religious practices/experiences (RPE) may produce positive physiological changes in patients with major depressive disorder (MDD) and chronic medical illness. Here, we report cross-sectional relationships between depressive symptoms, RPE and stress biomarkers (pro-/anti-inflammatory measures and stress hormones), hypothesizing positive associations between depressive symptoms and stress biomarkers and inverse associations between RPE and stress biomarkers. Methods: We recruited 132 individuals with both MDD and chronic illness into a randomized clinical trial. First, stress biomarkers in the baseline sample were compared to biomarker levels from a community sample. Second, relationships between depressive symptoms and biomarkers were examined, and, finally, relationships between RPE and biomarkers were analyzed, controlling for demographics, depressive symptoms, and physical functioning. Results: As expected, inflammatory markers and stress hormones were higher in our sample with MDD compared to community participants. In the current sample, however, depressive symptoms were largely unrelated to stress biomarkers, and were unexpectedly inversely related to proinflammatory cytokine levels (TNF-α, IL-1β). Likewise, while RPE were largely unrelated to stress biomarkers, they were related to the anti-inflammatory cytokine IL-1RA and the stress hormone norepinephrine in expected directions. Unexpectedly, RPE were also positively related to the proinflammatory cytokine IFN-γ and to IFN-γ/IL-4 and IFN-γ/IL-10 ratios. Conclusions: Little evidence was found for a consistent pattern of relationships between depressive symptoms or religiosity and stress biomarkers. Of the few significant relationships, unexpected findings predominated. Future research is needed to determine whether religious interventions can alter stress biomarkers over time in MDD.