Mood interventions show promise for the management of IBD

In a recent study published in eBioMedicineresearchers performed a meta-analysis to examine 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 linked to psychological, neurological and immunological mechanisms regulating the gut-brain connection. Depression and anxiety can worsen the prognosis of IBD. Psychosocial interventions can reduce proinflammatory 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 that interventions with limited effects on mood may not improve prognosis in IBD.

About the research

In the current meta-analysis, researchers investigated whether mood-related interventions could improve levels of inflammatory biomarkers among patients with IBD. They also assessed the potential moderating effects of intervention size, outcome, disease type, and subtype on inflammatory markers.

The team searched the MEDLINE, EMBASE, PsycINFO, Global Health and Web of Science databases for relevant studies published between 1947 and October 2023. These included randomized controlled trials (RCTs) in adults with IBD, focusing on outcomes of mood and inflammation before and after the intervention. Trial interventions included exercise, psychotropic therapy, antidepressants, and psychological therapy, with measures of mood as primary or secondary outcomes for those with depression, anxiety, stress, distress, or poor emotional well-being.

Comparison groups included controls (waiting list controls, standard care, placebo controls, and active controls), and outcomes included biomarkers related to inflammation (such as C-reactive protein (CRP), faecal calprotectin, and inflammatory cytokines). The team excluded studies without a diagnosis of IBD, animal studies, drug interventions, measures of mood that were not a primary or secondary outcome, studies without comparators, clinical self-report indices, non-inflammatory biomarkers and non-randomized studies.

Two reviewers independently performed data screening, extraction, quality assessments and data pooling to assess standardized mean differences (SMDs), resolving disagreements by consensus. Investigators examined intervention types, mood as study outcomes, effects on mood-related outcomes, and IBD subtypes as effect moderators. They performed random effects modeling for analysis and assessed statistical heterogeneity using the I2 statistic.

Investigators assessed risks of bias using Cochrane Handbook guidelines covering randomisation processes, intervention bias, missing data, outcome measurement and selection of reported outcomes. They assessed publication bias using Egger’s test and the precision effects test. Sensitivity analyzes excluded influential points and outcomes from psychotropic or antidepressant interventions. Investigators performed separate meta-analyses for biomarkers from ≥10 studies, including meta-analyses with exclusions.

Results

The data search yielded 21,101 records and 15,631 references, of which 15,489 records were inappropriate. After screening the title and abstract, the full text of 142 records was reviewed and only 36 met the eligibility criteria. Nine RCTs reported complete data, 27 study authors were contacted for missing data, and five did not respond. As a result, the team analyzed 28 RCTs including 1,789 individuals. The risk of bias was low in four trials and high in 18 RCTs, with some concerns in six trials.

The inflammation-related biomarkers ranged between 1 and 21 in the included studies, providing 116 effect estimates. The interventions showed a small but significant effect on inflammatory biomarkers (−0.4) and a medium effect on mood-related outcomes (−0.5), without significant between-study heterogeneity and publication bias. Separate meta-analyses showed non-significant effects on faecal calprotectin (-0.2) and CRP (-0.3). The researchers observed large effect sizes for psychological interventions and in cases of influence (SMD ≥0.20) on mood.

Pooled analysis showed that mood interventions significantly reduced inflammatory biomarker levels (SMD, -0.4), representing an 18% reduction in inflammatory markers. Psychological therapies showed significant small to medium effects on inflammatory biomarkers (SMD, -0.5), while other interventions were nonsignificant. Studies with mood measures as primary and secondary outcomes showed medium (SMD, -0.6) and small (SMD, -0.3) effect sizes, respectively.

CRP was evaluated in 16 study groups, demonstrating a small significant effect (SMD, -0.3). There was significant heterogeneity (I2, 36%) and publication type bias (Egger’s test value = -0.9). In 17 intervention groups examining fecal calprotectin, levels of the biomarker were significantly reduced by mood interventions compared to controls, with a reduction of 91 μg per gram. Studies had low heterogeneity (I2 of 11%) and no publication bias. However, there were potential biases from minor sample effects. Sensitivity analyzes showed similar findings.

Conclusion

The study results suggest that treatments targeting mood outcomes can reduce inflammation in adults with IBD. Psychological interventions had a greater impact on inflammatory biomarkers than antidepressants and exercise, with small to medium effect sizes confirming previous meta-analysis findings. Mechanisms underlying the biological effects of psychosocial treatments on inflammatory biomarkers among IBD patients include improving mood, directly affecting the immune system, or indirectly promoting self-management techniques.