In a recent study published in eBioMedicine, researchers performed a meta-analysis to explore the impact of mood interventions on inflammatory disease activity in inflammatory bowel disease (IBD).
Background
The activity and progression of IBD, a chronic autoimmune inflammatory condition, are associated with psychological, neurological, and immunological mechanisms regulating the gut-brain connection. Depression and anxiety can worsen the IBD prognosis. Psychosocial interventions may reduce pro-inflammatory cytokines, potentially enhancing immune function and reducing inflammation. However, a recent meta-analysis found no improvement in disease activity and minor effects on anxiety, depression, and stress, indicating interventions with limited effects on mood may not improve the IBD prognosis.
About the study
In the present meta-analysis, researchers investigated whether mood-related interventions could improve inflammatory biomarker levels among IBD patients. They also assessed the potential moderating effects of intervention size, outcome, type, and disease subtype on inflammatory markers.
The team searched MEDLINE, EMBASE, PsycINFO, Global Health, and Web of Science databases for relevant studies published between 1947 and October 2023. They included randomized controlled trials (RCTs) in adults with IBD, focusing on mood and inflammation outcomes before and after intervention. The trial interventions included exercise, psychotropic therapy, antidepressants, and psychological therapy, with mood measures as primary or secondary outcomes for those with depression, anxiety, stress, distress, or poor emotional well-being.
Comparators included control groups (waitlist control, standard care, placebo controls, and active controls), and outcomes included inflammation-related biomarkers (such as C-reactive protein (CRP), fecal calprotectin, and inflammatory cytokines). The team excluded studies without IBD diagnosis, animal studies, drug interventions, mood measures not as a primary or secondary outcome, studies without comparators, self-reported clinical indices, non-inflammatory biomarkers, and non-randomized studies.
Two reviewers independently performed data screening, extraction, quality assessments, and data pooling to estimate standardized mean differences (SMDs), resolving disagreements by consensus. The researchers investigated intervention types, mood as study outcomes, effects on mood-related outcomes, and the subtypes of IBD as effect moderators. They performed random-effects modeling for analysis and estimated statistical heterogeneity using the I2 statistic.
The researchers assessed bias risks using Cochrane Handbook guidance, encompassing randomization processes, intervention deviations, missing data, outcome measurement and reported results selection. They evaluated publication bias using the Egger's test and the precision-effects test. Sensitivity analyses excluded influential points and results from psychotropic or antidepressant interventions. The researchers performed separate meta-analyses for biomarkers from ≥10 studies, including leave-one-out meta-analyses.
Results
The data search yielded 21,101 records and 15,631 references, of which 15,489 records were ineligible. After the title-abstract screening, the full text of 142 records was screened, and only 36 met the eligibility criteria. Nine RCTs reported complete data, 27 study authors were contacted for missing data, and five were unresponsive. As a result, the team analyzed 28 RCTs, including 1,789 individuals. Bias risk was low in four studies and high in 18 RCTs, with some concerns in six studies.
Inflammation-associated biomarkers ranged between one and 21 in the included studies, providing 116 effect estimates. The interventions showed a minor but significant impact on inflammatory biomarkers (-0.4) and a medium impact on mood-related outcomes (−0.5) without considerable inter-study heterogeneity and publication bias. Separate meta-analyses showed minor effects on fecal calprotectin (−0.2) and CRP (-0.3). The researchers observed large effect sizes for psychological interventions and in cases of influences (SMD ≥0.20) on mood.
The pooled analysis showed that mood-related interventions significantly reduced inflammatory biomarker levels (SMD, −0.4), denoting a reduction of 18% in inflammatory markers. Psychological therapies showed significant small-medium effects on inflammatory biomarkers (SMD, −0.5), while other interventions were insignificant. Studies with mood measures as primary and secondary outcomes showed medium (SMD, −0.6) and small (SMD, −0.3) effect sizes, respectively.
CRP was assessed in 16 study groups, demonstrating a small significant effect (SMD, −0.3). Significant heterogeneity (I2, 36%) and publication-type bias (Egger's test value = −0.9) existed. Across 17 intervention groups investigating fecal calprotectin, levels of the biomarker were significantly lowered by mood interventions compared to controls, with a 91 μg per gram reduction. The studies had low heterogeneity (I2 of 11%) and no publication-type bias. However, there were potential biases from minor sample effects. The sensitivity analyses showed similar findings.
Conclusion
The study findings showed that treatments targeting mood outcomes can reduce inflammation among IBD adults. Psychological interventions had a higher impact on the inflammatory biomarkers than antidepressants and exercises, with small-to-medium effect sizes, corroborating previous meta-analysis findings. The mechanisms underlying the biological effects of psychosocial treatments on inflammatory biomarkers among IBD patients involve mood enhancement, directly affecting the immune system or indirectly promoting self-management techniques.
Journal reference:
-
Natasha Seaton et al., Do interventions for mood improve inflammatory biomarkers in inflammatory bowel disease?: A systematic review and meta-analysis, eBioMedicine 2023; 104910. Published Online, doi: https://doi.org/10.1016/j.ebiom.2023. 104910