Mental Health Interventions Reduce Inflammatory Biomarkers in IBD by 18%

Published on: 

Interventions designed to improve mood, especially psychological therapy, may also have notable effects on C-reactive protein, fecal calprotectin, and other inflammatory biomarkers in IBD.

The clinical impact of treatment interventions for mood may span beyond mental health, according to findings from a recent systematic review and meta-analysis published in eBiomedicine.1

Results showed treatments addressing mood outcomes also demonstrated beneficial effects for general inflammation and inflammatory bowel disease (IBD)-specific biomarkers, further detailing the greater impact of psychological interventions for accentuating the effect on biomarkers and objective disease outcomes.1

“Interventions for mood show considerable promise for the management of IBD in improving mental health, inflammation, and disease outcomes. Integrated mental health support alongside pharmacological treatments may offer a more holistic approach to IBD care, potentially leading to reduced disease and healthcare costs,” said Rona Moss-Morris, head of the department of psychology at King’s College London, in a press release.2

Psychological stress has previously been linked to increases in inflammatory activity, although the reciprocal relationships between different types of stressors, emotional attention, and inflammation are not well understood. Speculation about the potential neurobiological mechanisms underlying these interactions has led many to hypothesize the therapeutic role of mood intervention for reducing inflammation, especially in conditions like IBD.3

Investigators set out to address several research questions about the interplay between mood and inflammation, specifically looking at whether interventions targeting mood outcomes impact inflammation levels in IBD. Additionally, they explored whether the intervention type, the size of its effect on mood, and the disease subtype moderate the effect on inflammatory markers.1

Investigators began by conducting a systematic literature search using MEDLINE, EMBASE, PsycINFO, Global Health, and Web of Science databases for relevant randomized controlled trials from 1947 to October 2023. Eligible studies involved adults with IBD, tested mood intervention as a primary or secondary income, and assessed inflammatory outcomes pre- and post-intervention.1

The initial search yielded 21,101 articles, which resulted in 15,631 original references after removing duplicates. A further 15,489 studies were deemed ineligible, leaving 142 studies for full-text screening. A total of 36 eligible studies were identified, of which 28 were included in the final analysis.1

These studies involved a collective 1789 participants and comprised 20 studies testing psychological therapy, 3 studies testing antidepressants, and 5 studies testing exercise interventions.1

Investigators assessed intervention type, mood as a primary or secondary outcome, effect on mood outcomes, and IBD subtype as treatment effect moderators. The primary a-priori effect size outcome of interest was the standardized mean difference (SMD) between the psychosocial intervention and control groups post-intervention.1

Upon analysis, interventions treating mood significantly reduced levels of inflammatory biomarkers compared with controls (SMD, −0.349; 95% Confidence interval [CI], −0.48 to −0.22; z = −5.44; P <.001), corresponding to an 18% reduction in inflammatory biomarkers. Fecal calprotectin levels were also significantly lower following interventions treating mood compared with controls (SMD, −0.186; 95% CI, −0.34 to −0.03; z = −2.38; P = .018), corresponding to a 91 μg/g reduction.1

A small but significant effect was also observed for C-reactive protein (SMD, −0.289; 95% CI, −0.47 to −0.10; z = −3.06; P = .002) and reflected a 2.44 mg/dL reduction with interventions treating mood. Unlike inflammatory biomarkers and fecal calprotectin, investigators called attention to significant heterogeneity (I2 = 36.3%; P = .073) and evidence of publication bias (Egger’s = −1.815; P = .013) but noted the effect size did not significantly change during leave-one-out analysis.1

The interventions included in the review significantly improved mood outcomes (SMD, −0.501; 95% CI, −0.73 to −0.27; z = −4.47; P <.001). Further analysis revealed interventions with effects ≥0.2 showed significantly greater post-intervention effects on inflammation (SMD, −0.376; 95% CI, −0.61 to −0.15; P = .003) and interventions with at least a small effect on mood had a medium-sized effect on inflammation (SMD, 0.480; 95% CI, −0.67 to −0.29; P <.001).1

Of note, effect sizes were larger for psychological therapy interventions (SMD, −0.455; 95% CI, −0.61 to −0.30; P <.001) compared with exercise (SMD, −0.047; 95% CI, −0.25 to 0.15; P = .583) and antidepressants (SMD, −0.236; 95% CI, −0.56 to −0.09; P = .154).1

“Our study suggests that improvements in mood can influence physical diseases through modulation of the immune system,” concluded Valeria Mondelli, clinical professor of psychoneuroimmunology at King’s College London.2 “This adds to the growing body of research demonstrating the role of inflammation in mental health and suggests that interventions working to improve mood could also have direct physical effects on levels of inflammation. However, more research is needed to understand exact mechanisms in IBD.”


  1. Seaton N, Hudson J, Harding S, et al. Do interventions for mood improve inflammatory biomarkers in Inflammatory Bowel Disease?: A Systematic Review and Meta-Analysis. eBiomedicine. doi:10.1016/j.ebiom.2023.104910.
  2. King’s College London. Mood interventions may reduce inflammation in Crohn’s and Colitis. EurekAlert! January 24, 2024. Accessed January 24, 2024.
  3. Maydych V. The Interplay Between Stress, Inflammation, and Emotional Attention: Relevance for Depression. Front Neurosci. doi:10.3389/fnins.2019.00384