Brain-immune axis regulation is responsive to cognitive behavioral therapy and mindfulness intervention: Observations from a randomized controlled trial in patients with Crohn's disease

Anna Nemirovsky; Karny Ilan; Livnat Lerner; Liel Cohen-Lavi; Doron Schwartz; Ganit Goren; Ruslan Sergienko; Dan Greenberg; Vered Slonim-Nevo; Orly Sarid; Michael Friger; Shirley Regev; Shmuel Odes; Tomer Hertz; Alon Monsonego; Israeli IBD Research Nucleus (IIRN)

doi:10.1016/j.bbih.2021.100407

Brain-immune axis regulation is responsive to cognitive behavioral therapy and mindfulness intervention: Observations from a randomized controlled trial in patients with Crohn's disease

Brain Behav Immun Health. 2021 Dec 23:19:100407. doi: 10.1016/j.bbih.2021.100407. eCollection 2022 Feb.

Authors

Anna Nemirovsky^{1

2}, Karny Ilan¹, Livnat Lerner¹, Liel Cohen-Lavi^{2

3}, Doron Schwartz⁴, Ganit Goren⁵, Ruslan Sergienko⁶, Dan Greenberg⁷, Vered Slonim-Nevo⁵, Orly Sarid⁵, Michael Friger⁶, Shirley Regev⁵, Shmuel Odes⁴, Tomer Hertz^{1

2

8}, Alon Monsonego^{1

2}; Israeli IBD Research Nucleus (IIRN)

Affiliations

¹ The Shraga Segal Department of Microbiology, Immunology, and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, 8410501, Israel.
² The National Institute of Biotechnology in the Negev, Zlotowski Neuroscience Center, and Regenerative Medicine and Stem Cell Research Center, Ben-Gurion University of the Negev, Beer-Sheva, 8410501, Israel.
³ Department of Industrial Engineering and Management, Ben-Gurion University of the Negev, Beer-Sheva, 8410501, Israel.
⁴ Dept. of Gastroenterology and Hepatology, Soroka Medical Center, and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, 8410501, Israel.
⁵ Spitzer Department of Social Work Ben-Gurion University of the Negev, Beer Sheva, 8410501, Israel.
⁶ Department of Public Health, Ben-Gurion University of the Negev, Beer Sheva, 8410501, Israel.
⁷ Department of Health Systems Management, School of Public Health, Guilford Glazer Faculty of Business and Management, Ben-Gurion University of the Negev, Beer Sheva, 8410501, Israel.
⁸ Vaccine and Infectious Disease Division, Fred Hutch Cancer Research Center, Seattle, WA, USA.

Abstract

Background and aims: Crohn's disease (CD) is a chronic inflammatory bowel disease associated with psychological stress that is regulated primarily by the hypothalamus-pituitary-adrenal (HPA) axis. Here, we determined whether the psychological characteristics of CD patients associate with their inflammatory state, and whether a 3-month trial of cognitive-behavioral and mindfulness-based stress reduction (COBMINDEX) impacts their inflammatory process.

Methods: Circulating inflammatory markers and a wide range of psychological parameters related to stress and well-being were measured in CD patients before and after COBMINDEX. Inflammatory markers in CD patients were also compared to age- and sex-matched healthy controls (HCs).

Results: CD patients exhibited increased peripheral low-grade inflammation compared with HCs, demonstrated by interconnected inflammatory modules represented by IL-6, TNFα, IL-17, MCP-1 and IL-18. Notably, higher IL-18 levels correlated with higher score of stress and a lower score of wellbeing in CD patients. COBMINDEX was accompanied by changes in inflammatory markers that coincided with changes in cortisol: changes in serum levels of cortisol correlated positively with those of IL-10 and IFNα and negatively with those of MCP-1. Furthermore, inflammatory markers of CD patients at baseline predicted COBMINDEX efficacy, as higher levels of distinct cytokines and cortisol at baseline, correlated negatively with changes in disease activity (by Harvey-Bradshaw Index) and psychological distress (global severity index measure) following COBMINDEX.

Conclusion: CD patients have a characteristic immunological profile that correlates with psychological stress, and disease severity. We suggest that COBMINDEX induces stress resilience in CD patients, which impacts their well-being, and their disease-associated inflammatory process.

Keywords: CD, Crohn's disease; COBMINDEX, Cognitive-behavioral and mindfulness-based stress reduction; Crohn's disease; Cytokines; HC, Healthy controls; HPA axis; HPA, Hypothalamus-pituitary-adrenal; IBD; IBD, Inflammatory bowel disease; Mindfulness; Psychological intervention; Stress.