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Riggott C, Fairbrass KM, Gracie DJ, Ford AC. Cumulative Impact of Clinical Disease Activity, Biochemical Activity and Psychological Health on the Natural History of Inflammatory Bowel Disease During 8 Years of Longitudinal Follow-Up. Aliment Pharmacol Ther 2025; 61:1635-1648. [PMID: 40057941 PMCID: PMC12013785 DOI: 10.1111/apt.70068] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2024] [Revised: 01/03/2025] [Accepted: 02/24/2025] [Indexed: 04/23/2025]
Abstract
BACKGROUND Common mental disorders, including anxiety and depression, are prevalent in patients with inflammatory bowel disease (IBD) and may be associated with adverse outcomes. However, whether increasing psychological co-morbidity, in combination with disease activity, exerts a cumulative effect on prognosis is uncertain. AIMS To assess this in a longitudinal follow-up study. METHODS We collected baseline demographic and IBD-related information, clinical activity using disease activity scores and biochemical activity using calprotectin. Patients were grouped according to the presence or absence of disease activity. Patients in remission or with active disease were subgrouped according to the presence or absence of symptoms of a common mental disorder at baseline. We recorded the occurrence of adverse outcomes over 8.1 years, comparing their occurrence across subgroups using Cox regression. RESULTS Among 717 participants with clinical activity data and 187 with clinical and biochemical activity data, rates of adverse outcomes increased with both disease activity and increasing psychological co-morbidity. Rates of flare or glucocorticosteroid prescription, escalation or death were higher with clinical activity (HR 2.89; 95% CI 1.68-4.93 and 2.52; 95% CI 1.55-4.10 and 6.97; 95% CI 2.43-20.0, respectively) or clinical and biochemical activity (HR 7.26; 95% CI 2.86-18.5, 3.62; 95% CI 1.59-8.25 and 57.3; 95% CI 7.58-433, respectively) and two common mental disorders. Rates of hospitalisation (HR 6.20; 95% CI 1.88-20.4) or hospitalisation and/or intestinal resection (HR 7.46; 95% CI 2.41-23.2) were higher with clinical and biochemical activity and two common mental disorders. CONCLUSION Psychological co-morbidity and active disease have a cumulative adverse impact on IBD prognosis.
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Affiliation(s)
- Christy Riggott
- Leeds Gastroenterology InstituteSt. James's University HospitalLeedsUK
- Leeds Institute of Medical Research at St. James'sUniversity of LeedsLeedsUK
| | - Keeley M. Fairbrass
- Leeds Gastroenterology InstituteSt. James's University HospitalLeedsUK
- Leeds Institute of Medical Research at St. James'sUniversity of LeedsLeedsUK
| | - David J. Gracie
- Leeds Gastroenterology InstituteSt. James's University HospitalLeedsUK
- Leeds Institute of Medical Research at St. James'sUniversity of LeedsLeedsUK
| | - Alexander C. Ford
- Leeds Gastroenterology InstituteSt. James's University HospitalLeedsUK
- Leeds Institute of Medical Research at St. James'sUniversity of LeedsLeedsUK
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Oh SJ, Choi CH, Jung SA, Song GA, Kim YJ, Koo JS, Shin SJ, Seo GS, Lee KM, Jang BI, Jung ES, Kim Y, Lee CK. Anxiety and Depression Are Associated with Poor Long-term Quality of Life in Moderate-to-Severe Ulcerative Colitis: Results of a 3-Year Longitudinal Study of the MOSAIK Cohort. Gut Liver 2025; 19:253-264. [PMID: 39506310 PMCID: PMC11907251 DOI: 10.5009/gnl240146] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2024] [Revised: 07/23/2024] [Accepted: 07/25/2024] [Indexed: 11/08/2024] Open
Abstract
Background/Aims We previously reported that patients with moderate-to-severe ulcerative colitis (UC) often experience common mental disorders (CMDs) such as anxiety and depression, necessitating immediate psychological interventions within the first 4 weeks of diagnosis. In this 3-year follow-up study of the MOSAIK cohort in Korea, we examined the effects of CMDs at initial diagnosis on clinical outcomes and health-related quality of life (HRQoL). Methods We examined differences in clinical outcomes (evaluated based on clinical response, relapse, hospitalization, and medication use) and HRQoL (assessed using the Inflammatory Bowel Disease Questionnaire [IBDQ] and Short Form 12 [SF-12]) according to Hospital Anxiety and Depression Scale (HADS) scores at diagnosis. Results In a study involving 199 UC patients, 47.7% exhibited significant psychological distress (anxiety and/or depression) at diagnosis. Clinical follow-up showed no major differences in outcomes, including remission rates, response rates, or hospitalization rates, between patients with anxiety or depression at diagnosis and patients without anxiety or depression at diagnosis. The HRQoL at the end of follow-up was notably lower in those with baseline CMDs, particularly anxiety, across all domains of the IBDQ and SF-12. Linear mixed-effect models revealed that higher HADS scores, as well as higher Mayo scores, were independently associated with lower IBDQ scores and both summary domains of the SF-12. Additionally, regular attendance at follow-up visits during the study period was also related to improvements in HRQoL (all p<0.05). Conclusions While CMDs present at the time of UC diagnosis did not influence long-term clinical outcomes, they persistently impaired HRQoL. Our findings support the routine incorporation of psychological interventions into the long-term management of moderate-to-severe UC.
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Affiliation(s)
- Shin Ju Oh
- Department of Gastroenterology, Center for Crohn’s and Colitis, College of Medicine, Kyung Hee University, Seoul, Korea
| | - Chang Hwan Choi
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Sung-Ae Jung
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
| | - Geun Am Song
- Department of Internal Medicine, Pusan National University School of Medicine, Busan, Korea
| | - Yoon Jae Kim
- Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea
| | - Ja Seol Koo
- Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Korea
| | - Sung Jae Shin
- Department of Internal Medicine, Ajou University Hospital, Suwon, Korea
| | - Geom Seog Seo
- Department of Internal Medicine, Wonkwang University Hospital, Iksan, Korea
| | - Kang-Moon Lee
- Department of Internal Medicine, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea
| | - Byung Ik Jang
- Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea
| | - Eun Suk Jung
- Medical Affairs, Janssen Korea Ltd., Seoul, Korea
| | - Youngdoe Kim
- Medical Affairs, Janssen Korea Ltd., Seoul, Korea
| | - Chang Kyun Lee
- Department of Gastroenterology, Center for Crohn’s and Colitis, College of Medicine, Kyung Hee University, Seoul, Korea
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Mekes-Adamczyk A, Gausmann N, Öznur Ö, Pfuhlmann K, Dziobaka J, Buer J, Langhorst J, Westendorf AM. Lifestyle Intervention Modulates the CD4+ T Cell Profile in the Blood of Crohn's Disease Patients. Inflamm Bowel Dis 2025; 31:200-209. [PMID: 39102712 DOI: 10.1093/ibd/izae154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Indexed: 08/07/2024]
Abstract
BACKGROUND Crohn's disease (CD) significantly affects patients' well-being and is influenced by stress and lifestyle factors, highlighting the importance of improving quality of life in CD management. An imbalance between pro- and anti-inflammatory CD4+ T cell responses is a key factor in CD, and stress has been shown to alter the function of CD4+ T cells. Therefore, this study aimed to evaluate the effect of a mind-body medicine stress management and lifestyle modification (MBM) program on the CD4+ T cell profile in CD patients. METHODS Circulating CD4+ T cells from CD patients were analyzed by flow cytometry following the MBM program. Patients were randomly assigned to either a guided intervention group (IG) or a self-guided waitlist control group (CG) over a 9-month trial and compared with healthy blood donors. RESULTS Lifestyle intervention reduced regulatory T cell (Treg) frequencies in the blood of CD patients. Notably, we observed a significant correlation between the quality of life improvement and Treg frequencies in the IG but not in the CG. Furthermore, differential activation and expression of the gut-homing molecules G protein-coupled receptor 15 and CCR9 on circulating Tregs and CD4+ effector T cells were detected in both the IG and CG. CONCLUSIONS The MBM program, whether guided or self-directed, has the potential to restore the CD4+ T cell profile of CD patients to levels comparable to healthy blood donors. Lifestyle interventions may benefit CD progression, symptoms, and immunological status, but further analysis is needed to substantiate these findings and to fully understand their clinical implications. (ClinicalTrials.gov: NCT05182645).
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Affiliation(s)
- Alexandra Mekes-Adamczyk
- Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Nadine Gausmann
- Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Özlem Öznur
- Department of Internal and Integrative Medicine, Sozialstiftung Bamberg, Bamberg, Germany
- Department of Integrative Medicine, Medical Faculty, University of Duisburg-Essen, Bamberg, Germany
| | - Katrin Pfuhlmann
- Department of Internal and Integrative Medicine, Sozialstiftung Bamberg, Bamberg, Germany
- Department of Integrative Medicine, Medical Faculty, University of Duisburg-Essen, Bamberg, Germany
| | - Jan Dziobaka
- Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Jan Buer
- Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Jost Langhorst
- Department of Internal and Integrative Medicine, Sozialstiftung Bamberg, Bamberg, Germany
- Department of Integrative Medicine, Medical Faculty, University of Duisburg-Essen, Bamberg, Germany
| | - Astrid M Westendorf
- Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
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Anyane-Yeboa A, Casey K, Roberts AL, Lopes E, Burke K, Ananthakrishnan A, Richter J, Cozier YC, Koenen KC, Chan AT, Khalili H. Association of Childhood Abuse With Incident Inflammatory Bowel Disease. Clin Transl Gastroenterol 2024; 15:e00718. [PMID: 39450870 PMCID: PMC11671083 DOI: 10.14309/ctg.0000000000000718] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Accepted: 05/21/2024] [Indexed: 10/26/2024] Open
Abstract
INTRODUCTION A link between inflammatory bowel disease (IBD), stressful life events, and psychological factors has previously been reported. Our objective was to examine the relationship between emotional, physical, and sexual abuse of childhood and risk of IBD using a large cohort of female health professionals. METHODS We included participants in the Nurses' Health Study II who completed the Physical and Emotional Abuse Subscale of the Childhood Trauma Questionnaire and the Sexual Maltreatment Scale of the Parent-Child Conflict Tactics Scale in 2001. Diagnosis of IBD was determined by self-report and confirmed independently by 2 physicians through review of medical records. We used Cox proportional hazard modeling to estimate the risk of Crohn's disease (CD) and ulcerative colitis (UC) while adjusting for covariates. RESULTS Among 68,167 women followed from 1989 until 2017, there were 146 incident cases of CD and 215 incident cases of UC. Compared with women with no history of abuse, the adjusted hazard ratios of CD were 1.16 (95% confidence interval [CI] 0.67-2.02) for mild, 1.58 (95% CI 0.92-2.69) for moderate, and 1.95 (95% CI 1.22-3.10) for severe abuse ( Ptrend = 0.002). We did not observe an association between childhood abuse and risk of UC. DISCUSSION Women who reported early life severe abuse had an increased risk of CD. These data add to the growing body of evidence on the critical role of early life stressors in development of CD.
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Affiliation(s)
- Adjoa Anyane-Yeboa
- Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA
- Clinical, Translational, Epidemiology Unit (CTEU), The Mongan Institute, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Kevin Casey
- Clinical, Translational, Epidemiology Unit (CTEU), The Mongan Institute, Massachusetts General Hospital, Boston, Massachusetts, USA
| | | | - Emily Lopes
- Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA
- Clinical, Translational, Epidemiology Unit (CTEU), The Mongan Institute, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Kristin Burke
- Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA
- Clinical, Translational, Epidemiology Unit (CTEU), The Mongan Institute, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Ashwin Ananthakrishnan
- Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA
- Clinical, Translational, Epidemiology Unit (CTEU), The Mongan Institute, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - James Richter
- Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Yvette C. Cozier
- Slone Epidemiology Center at Boston University, Boston, Massachusetts, USA
| | | | - Andrew T. Chan
- Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA
- Clinical, Translational, Epidemiology Unit (CTEU), The Mongan Institute, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Hamed Khalili
- Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA
- Clinical, Translational, Epidemiology Unit (CTEU), The Mongan Institute, Massachusetts General Hospital, Boston, Massachusetts, USA
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Schlee C, Uecker C, Öznur Ö, Bauer N, Langhorst J. Participants' perspectives on a multimodal stress management and comprehensive lifestyle modification program for patients with Crohn's disease-A qualitative interview study. PLoS One 2024; 19:e0313127. [PMID: 39536026 PMCID: PMC11559982 DOI: 10.1371/journal.pone.0313127] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2024] [Accepted: 10/19/2024] [Indexed: 11/16/2024] Open
Abstract
BACKGROUND Crohn's disease (CD) is a type of inflammatory bowel disease (IBD) that is prevalent worldwide and associated with reduced quality of life for patients. Multimodal therapy approaches, which emphasize lifestyle modifications such as mindfulness and stress reduction, can be promising in enhancing health-related quality of life for IBD patients. However, research on multimodal therapy approaches for CD remains insufficient. METHOD This qualitative interview study is part of a mixed-methods approach that is embedded in a randomized controlled trial. It investigates the impact of a comprehensive 10-week day clinic lifestyle modification program on the health condition and quality of life of CD patients. Telephone interviews (n = 19) were conducted three months after the program to examine individuals' viewpoints on the intervention, including perceived changes and transfer of elements into daily life. Reflexive thematic analysis was performed using MAXQDA software. RESULTS The results indicate that CD can have very individual and comprehensive impacts (psychological, physical, social), leading to reduced perceived quality of life and well-being. By participating in the program, patients wanted to find self-help options to complement conventional pharmacotherapy and actively manage their disease. Patients expressed high satisfaction with the program, feeling it provided valuable support for daily disease management. They were able to integrate adequate therapy elements into their routines to complement their care. Patients recognized significant improvements in various domains, mainly in the psychological domain, e.g., improved self-efficacy, symptom management, and, also partly physical/symptomatic and social improvements. CONCLUSION A multimodal stress reduction and lifestyle modification day clinic appears to be beneficial as a complementary therapy for CD patients. It offers additional options and helps patients to address individual symptoms and needs, improve their understanding of the disease and their quality of life. Although promising, further research is needed to assess its long-term effects. TRIAL REGISTRATION ClinicalTrials.gov, identifier: NCT05182645.
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Affiliation(s)
- Christoph Schlee
- Department of Internal and Integrative Medicine, Sozialstiftung Bamberg, Bamberg, Germany
- Department of Integrative Medicine, Medical Faculty, University of Duisburg-Essen, Bamberg, Germany
- Institute for Sociology, University of Bamberg, Bamberg, Germany
| | - Christine Uecker
- Department of Internal and Integrative Medicine, Sozialstiftung Bamberg, Bamberg, Germany
- Department of Integrative Medicine, Medical Faculty, University of Duisburg-Essen, Bamberg, Germany
| | - Özlem Öznur
- Department of Internal and Integrative Medicine, Sozialstiftung Bamberg, Bamberg, Germany
- Department of Integrative Medicine, Medical Faculty, University of Duisburg-Essen, Bamberg, Germany
| | - Nina Bauer
- Department of Internal and Integrative Medicine, Sozialstiftung Bamberg, Bamberg, Germany
- Department of Integrative Medicine, Medical Faculty, University of Duisburg-Essen, Bamberg, Germany
| | - Jost Langhorst
- Department of Internal and Integrative Medicine, Sozialstiftung Bamberg, Bamberg, Germany
- Department of Integrative Medicine, Medical Faculty, University of Duisburg-Essen, Bamberg, Germany
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Riggott C, Ford AC, Gracie DJ. Review article: The role of the gut-brain axis in inflammatory bowel disease and its therapeutic implications. Aliment Pharmacol Ther 2024; 60:1200-1214. [PMID: 39367676 DOI: 10.1111/apt.18192] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Revised: 07/01/2024] [Accepted: 07/10/2024] [Indexed: 10/06/2024]
Abstract
BACKGROUND Treatments targeting the gut-brain axis (GBA) are effective at reducing symptom burden in irritable bowel syndrome (IBS). The prevalence of common mental disorders and IBS-type symptom reporting is significantly higher in inflammatory bowel disease (IBD) than would be expected, suggesting potential GBA effects in this setting. Manipulation of the GBA may offer novel treatment strategies in selected patients with IBD. We present a narrative review of the bi-directional effects of the GBA in IBD and explore the potential for GBA-targeted therapies in this setting. METHODS We searched MEDLINE, EMBASE, EMBASE Classic, PsychINFO, and the Cochrane Central Register of Controlled Trials for relevant articles published by March 2024. RESULTS The bi-directional relationship between psychological well-being and adverse longitudinal disease activity outcomes, and the high prevalence of IBS-type symptom reporting highlight the presence of GBA-mediated effects in IBD. Treatments targeting gut-brain interactions including brain-gut behavioural treatments, neuromodulators, and dietary interventions appear to be useful adjunctive treatments in a subset of patients. CONCLUSIONS Psychological morbidity is prevalent in patients with IBD. The relationship between longitudinal disease activity outcomes, IBS-type symptom reporting, and poor psychological health is mediated via the GBA. Proactive management of psychological health should be integrated into routine care. Further clinical trials of GBA-targeted therapies, conducted in selected groups of patients with co-existent common mental disorders, or those who report IBS-type symptoms, are required to inform effective integrated models of care in the future.
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Affiliation(s)
- Christy Riggott
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK
| | - Alexander C Ford
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK
- Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
| | - David J Gracie
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK
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Sturm A, Atreya R, Bettenworth D, Bokemeyer B, Dignass A, Ehehalt R, Germer CT, Grunert PC, Helwig U, Horisberger K, Herrlinger K, Kienle P, Kucharzik T, Langhorst J, Maaser C, Ockenga J, Ott C, Siegmund B, Zeißig S, Stallmach A. Aktualisierte S3-Leitlinie „Diagnostik und Therapie des Morbus Crohn“ der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) (Version 4.1) – living guideline. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:1229-1318. [PMID: 39111333 DOI: 10.1055/a-2309-6123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/02/2024]
Affiliation(s)
- Andreas Sturm
- Klinik für Innere Medizin mit Schwerpunkt Gastroenterologie, DRK Kliniken Berlin Westend, Berlin, Deutschland
| | - Raja Atreya
- Medizinische Klinik 1, Universitätsklinikum Erlangen, Erlangen, Deutschland
| | | | - Bernd Bokemeyer
- Gastroenterologische Gemeinschaftspraxis Minden, Minden, Deutschland
| | - Axel Dignass
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt am Main, Deutschland
| | | | | | - P C Grunert
- Klinik für Innere Medizin IV (Gastroenterologie, Hepatologie und Infektiologie), Universitätsklinikum Jena, Deutschland
| | - Ulf Helwig
- Internistische Praxengemeinschaft, Oldenburg, Deutschland
| | - Karoline Horisberger
- Universitätsmedizin Johannes Gutenberg, Universität Klinik f. Allgemein-,Visceral- und Transplantationschirurgie, Mainz, Deutschland
| | | | - Peter Kienle
- Allgemein- und Viszeralchirurgie, Theresienkrankenhaus und Sankt Hedwig-Klinik GmbH, Mannheim, Deutschland
| | - Torsten Kucharzik
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Klinikum Lüneburg, Lüneburg, Deutschland
| | - Jost Langhorst
- Klinik für Integrative Medizin und Naturheilkunde, Klinikum am Bruderwald, Bamberg, Deutschland
| | - Christian Maaser
- Gastroenterologie, Ambulanzzentrum Lüneburg, Lüneburg, Deutschland
| | - Johann Ockenga
- Medizinische Klinik II, Klinikum Bremen Mitte - Gesundheit Nord, Bremen, Deutschland
| | - Claudia Ott
- Gastroenterologie Facharztzentrum, Regensburg, Deutschland
| | - Britta Siegmund
- Medizinische Klinik I, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Deutschland
| | - Sebastian Zeißig
- Medizinische Klinik und Poliklinik I, Universitätsklinikum Dresden, Deutschland
| | - Andreas Stallmach
- Klinik für Innere Medizin IV (Gastroenterologie, Hepatologie und Infektiologie), Universitätsklinikum Jena, Deutschland
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Ji Y, Li H, Dai G, Zhang X, Ju W. Systematic review and meta-analysis: Impact of depression on prognosis in inflammatory bowel disease. J Gastroenterol Hepatol 2024; 39:1476-1488. [PMID: 38655853 DOI: 10.1111/jgh.16568] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Revised: 01/19/2024] [Accepted: 03/25/2024] [Indexed: 04/26/2024]
Abstract
BACKGROUND AND AIM Depression is highly prevalent in patients with inflammatory bowel disease (IBD), which may affect the prognosis of IBD. This aimed to investigate the impact of depression on prognosis in IBD. METHODS A systematic literature search was performed in four databases (Medline, Embase, Web of Science, and PsycINFO) up to December 31, 2023. Studies were included if they investigated the impact of depression on prognosis in IBD. The primary outcome was flare in IBD, and secondary outcomes were hospitalization, readmission, emergency visits, surgery, and escalation of medical therapy. Relative risks (RRs) were utilized to estimate the risk in each of the above prognostic indicators. RESULTS Fourteen cohort and 10 case-control studies matched our entry criteria, comprising 630 408 patients with IBD. Twenty-two of included studies were considered to have a low risk of bias. Depression was found to significantly increase the risk of flare (RR = 1.37, 95% CI 1.16-1.63), hospitalization (RR = 1.11, 95% CI 1.00-1.23), readmission (RR = 1.32, 95% CI 1.04-1.67), emergency visits (RR = 1.33, 95% CI 1.12-1.59), surgery (1.38, 95% CI 1.08-1.76), and escalation of medical therapy (RR = 1.38, 95% CI 1.13-1.69) in IBD. Of note, patients with depression in ulcerative colitis had significant differences in readmission (RR = 1.38, 95% CI 1.19-1.60) and escalation of medical therapy (RR = 1.78, 95% CI 1.55-2.04). Additionally, the association was observed in patients with Crohn's disease in terms of flare (RR = 1.47, 95% CI 1.08-2.01) and hospitalization (RR = 1.20, 95% CI 1.03-1.40). CONCLUSIONS Current evidence suggested that depression could significantly increase the risk of poor prognosis worsening in patients with IBD. However, the association varied in IBD subtypes.
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Affiliation(s)
- Yuejin Ji
- Department of Clinical Pharmacology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Hongxiao Li
- College of Acupuncture Moxibustion and Tuina, Nanjing University of Chinese Medicine, Nanjing, China
| | - Guoliang Dai
- Department of Clinical Pharmacology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Xu Zhang
- School of Medicine and Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Wenzheng Ju
- Department of Clinical Pharmacology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
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Jacobs JP, Sauk JS, Ahdoot AI, Liang F, Katzka W, Ryu HJ, Khandadash A, Lagishetty V, Labus JS, Naliboff BD, Mayer EA. Microbial and Metabolite Signatures of Stress Reactivity in Ulcerative Colitis Patients in Clinical Remission Predict Clinical Flare Risk. Inflamm Bowel Dis 2024; 30:336-346. [PMID: 37650887 PMCID: PMC10906354 DOI: 10.1093/ibd/izad185] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Indexed: 09/01/2023]
Abstract
BACKGROUND Stress reactivity (SR) is associated with increased risk of flares in ulcerative colitis (UC) patients. Because both preclinical and clinical data support that stress can influence gut microbiome composition and function, we investigated whether microbiome profiles of SR exist in UC. METHODS Ninety-one UC subjects in clinical and biochemical remission were classified into high and low SR groups by questionnaires. Baseline and longitudinal characterization of the intestinal microbiome was performed by 16S rRNA gene sequencing and fecal and plasma global untargeted metabolomics. Microbe, fecal metabolite, and plasma metabolite abundances were analyzed separately to create random forest classifiers for high SR and biomarker-derived SR scores. RESULTS High SR reactivity was characterized by altered abundance of fecal microbes, primarily in the Ruminococcaceae and Lachnospiraceae families; fecal metabolites including reduced levels of monoacylglycerols (endocannabinoid-related) and bile acids; and plasma metabolites including increased 4-ethyl phenyl sulfate, 1-arachidonoylglycerol (endocannabinoid), and sphingomyelin. Classifiers generated from baseline microbe, fecal metabolite, and plasma metabolite abundance distinguished high vs low SR with area under the receiver operating characteristic curve of 0.81, 0.83, and 0.91, respectively. Stress reactivity scores derived from these classifiers were significantly associated with flare risk during 6 to 24 months of follow-up, with odds ratios of 3.8, 4.1, and 4.9. Clinical flare and intestinal inflammation did not alter fecal microbial abundances but attenuated fecal and plasma metabolite differences between high and low SR. CONCLUSIONS High SR in UC is characterized by microbial signatures that predict clinical flare risk, suggesting that the microbiome may contribute to stress-induced UC flares.
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Affiliation(s)
- Jonathan P Jacobs
- G. Oppenheimer Center for Neurobiology of Stress and Resilience, University of California Los Angeles, Los Angeles, CA, USA
- Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
- Goodman-Luskin Microbiome Center, University of California Los Angeles, Los Angeles, CA, USA
- Division of Gastroenterology, Hepatology and Parenteral Nutrition, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, USA
| | - Jenny S Sauk
- G. Oppenheimer Center for Neurobiology of Stress and Resilience, University of California Los Angeles, Los Angeles, CA, USA
- Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
- Goodman-Luskin Microbiome Center, University of California Los Angeles, Los Angeles, CA, USA
| | - Aaron I Ahdoot
- Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Fengting Liang
- Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - William Katzka
- Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Hyo Jin Ryu
- A.T. Still University School of Osteopathic Medicine in Arizona, Mesa, AZ, USA
| | - Ariela Khandadash
- G. Oppenheimer Center for Neurobiology of Stress and Resilience, University of California Los Angeles, Los Angeles, CA, USA
| | - Venu Lagishetty
- Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Jennifer S Labus
- G. Oppenheimer Center for Neurobiology of Stress and Resilience, University of California Los Angeles, Los Angeles, CA, USA
- Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
- Goodman-Luskin Microbiome Center, University of California Los Angeles, Los Angeles, CA, USA
| | - Bruce D Naliboff
- G. Oppenheimer Center for Neurobiology of Stress and Resilience, University of California Los Angeles, Los Angeles, CA, USA
- Goodman-Luskin Microbiome Center, University of California Los Angeles, Los Angeles, CA, USA
| | - Emeran A Mayer
- G. Oppenheimer Center for Neurobiology of Stress and Resilience, University of California Los Angeles, Los Angeles, CA, USA
- Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
- Goodman-Luskin Microbiome Center, University of California Los Angeles, Los Angeles, CA, USA
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10
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Öhlmann H, Lanters LR, Theysohn N, Langhorst J, Engler H, Icenhour A, Elsenbruch S. Distinct Alterations in Central Pain Processing of Visceral and Somatic Pain in Quiescent Ulcerative Colitis Compared to Irritable Bowel Syndrome and Health. J Crohns Colitis 2023; 17:1639-1651. [PMID: 37161902 PMCID: PMC10637045 DOI: 10.1093/ecco-jcc/jjad080] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Indexed: 05/11/2023]
Abstract
BACKGROUND AND AIMS Despite relevance to pain chronicity, disease burden, and treatment, mechanisms of pain perception for different types of acute pain remain incompletely understood in patients with inflammatory bowel disease [IBD]. Building on experimental research across pain modalities, we herein addressed behavioural and neural correlates of visceral versus somatic pain processing in women with quiescent ulcerative colitis [UC] compared to irritable bowel syndrome [IBS] as a patient control group and healthy women [HC]. METHODS Thresholds for visceral and somatic pain were assessed with rectal distensions and cutaneous thermal pain, respectively. Using functional magnetic resonance imaging, neural and behavioural responses to individually calibrated and intensity-matched painful stimuli from both modalities were compared. RESULTS Pain thresholds were comparable across groups, but visceral thresholds correlated with gastrointestinal symptom severity and chronic stress burden exclusively within UC. Upon experience of visceral and somatic pain, both control groups demonstrated enhanced visceral pain-induced neural activation and greater perceived pain intensity, whereas UC patients failed to differentiate between pain modalities at both behavioural and neural levels. CONCLUSIONS When confronted with acute pain from multiple bodily sites, UC patients' responses are distinctly altered. Their failure to prioritise pain arising from the viscera may reflect a lack of adaptive behavioural flexibility, possibly resulting from long-lasting central effects of repeated intestinal inflammatory insults persisting during remission. The role of psychological factors, particularly chronic stress, in visceral sensitivity and disease-specific alterations in the response to acute pain call for dedicated mechanistic research as a basis for tailoring interventions for intestinal and extraintestinal pain symptoms in IBD.
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Affiliation(s)
- Hanna Öhlmann
- Department of Medical Psychology and Medical Sociology, Ruhr University Bochum, Bochum, Germany
| | - Laura Ricarda Lanters
- Department of Neurology, Center for Translational Neuro- and Behavioral Sciences, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Nina Theysohn
- Institute of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Jost Langhorst
- Department for Internal and Integrative Medicine, Sozialstiftung Bamberg, Bamberg, Germany
- Department for Integrative Medicine, Medical Faculty, University of Duisburg-Essen, Essen, Germany
| | - Harald Engler
- Institute of Medical Psychology and Behavioral Immunobiology, Center for Translational Neuro- and Behavioral Sciences, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Adriane Icenhour
- Department of Medical Psychology and Medical Sociology, Ruhr University Bochum, Bochum, Germany
| | - Sigrid Elsenbruch
- Department of Medical Psychology and Medical Sociology, Ruhr University Bochum, Bochum, Germany
- Department of Neurology, Center for Translational Neuro- and Behavioral Sciences, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
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11
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Sauk JS, Ryu HJ, Labus JS, Khandadash A, Ahdoot AI, Lagishetty V, Katzka W, Wang H, Naliboff B, Jacobs JP, Mayer EA. High Perceived Stress is Associated With Increased Risk of Ulcerative Colitis Clinical Flares. Clin Gastroenterol Hepatol 2023; 21:741-749.e3. [PMID: 35952942 DOI: 10.1016/j.cgh.2022.07.025] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Revised: 07/14/2022] [Accepted: 07/18/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Although perceived stress (PS) has been associated with symptomatic flares in inflammatory bowel disease, clinical and physiological measures associated with perceived stress and flare are not known. The aim of this study was to identify physiological factors associated with perceived stress in ulcerative colitis (UC) subjects, and their relationship with flare. METHODS Patients with UC in clinical remission (Simple Colitis Clinical Activity Index [SCCAI] score <5) underwent clinical and behavioral assessments, morning salivary cortisol measurements, autonomic nervous system activity testing (heart rate variability, electrodermal activity) at baseline with patient-reported SCCAI every 2 weeks over 1 to 2 years and fecal calprotectin at time of flare. Clinical flares (SCCAI ≥5) and biochemical flares (SCCAI ≥5 with fecal calprotectin ≥250 μg/g) were evaluated. RESULTS One hundred ten patients with UC were enrolled, with mean follow-up of 65.6 weeks. Patients with UC with higher and lower PS were determined. Although the high PS group had 3.6 times higher odds of a clinical flare than the low PS group, no significant differences in biochemical flares were observed between the low and high PS groups. The high vs low PS group differed in tonic sympathetic arousal as indexed by significantly greater baseline electrodermal activity (4.3 vs 3.4 microsiemens; P = .026) in the high PS group, but not in terms of heart rate variability and morning cortisol levels. Increased fecal calprotectin was associated with cardioautonomic measures, suggesting lower parasympathetic activity. CONCLUSIONS Increased PS assessed at baseline is associated with tonic sympathetic arousal and greater odds of clinical flares in patients with UC.
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Affiliation(s)
- Jenny S Sauk
- G. Oppenheimer Center for Neurobiology of Stress and Resilience, Vatche and Tamar Manoukian Division of Digestive Diseases, University of California Los Angeles, Los Angeles, California; Vatche and Tamar Manoukian Division of Digestive Diseases, University of California Los Angeles, Los Angeles, California
| | - Hyo Jin Ryu
- G. Oppenheimer Center for Neurobiology of Stress and Resilience, Vatche and Tamar Manoukian Division of Digestive Diseases, University of California Los Angeles, Los Angeles, California
| | - Jennifer S Labus
- G. Oppenheimer Center for Neurobiology of Stress and Resilience, Vatche and Tamar Manoukian Division of Digestive Diseases, University of California Los Angeles, Los Angeles, California
| | - Ariela Khandadash
- G. Oppenheimer Center for Neurobiology of Stress and Resilience, Vatche and Tamar Manoukian Division of Digestive Diseases, University of California Los Angeles, Los Angeles, California
| | - Aaron I Ahdoot
- Vatche and Tamar Manoukian Division of Digestive Diseases, University of California Los Angeles, Los Angeles, California
| | - Venu Lagishetty
- Vatche and Tamar Manoukian Division of Digestive Diseases, University of California Los Angeles, Los Angeles, California
| | - William Katzka
- Vatche and Tamar Manoukian Division of Digestive Diseases, University of California Los Angeles, Los Angeles, California
| | - Hao Wang
- G. Oppenheimer Center for Neurobiology of Stress and Resilience, Vatche and Tamar Manoukian Division of Digestive Diseases, University of California Los Angeles, Los Angeles, California
| | - Bruce Naliboff
- G. Oppenheimer Center for Neurobiology of Stress and Resilience, Vatche and Tamar Manoukian Division of Digestive Diseases, University of California Los Angeles, Los Angeles, California
| | - Jonathan P Jacobs
- G. Oppenheimer Center for Neurobiology of Stress and Resilience, Vatche and Tamar Manoukian Division of Digestive Diseases, University of California Los Angeles, Los Angeles, California; Vatche and Tamar Manoukian Division of Digestive Diseases, University of California Los Angeles, Los Angeles, California; Division of Gastroenterology, Hepatology and Parenteral Nutrition, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California
| | - Emeran A Mayer
- G. Oppenheimer Center for Neurobiology of Stress and Resilience, Vatche and Tamar Manoukian Division of Digestive Diseases, University of California Los Angeles, Los Angeles, California; Vatche and Tamar Manoukian Division of Digestive Diseases, University of California Los Angeles, Los Angeles, California.
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12
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Rea KE, Cushman GK, Westbrook AL, Reed B. Trajectories of psychological stress in youth across the first year of inflammatory bowel disease diagnosis. J Psychosom Res 2023; 165:111143. [PMID: 36628854 PMCID: PMC9892289 DOI: 10.1016/j.jpsychores.2022.111143] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Revised: 12/28/2022] [Accepted: 12/29/2022] [Indexed: 01/02/2023]
Abstract
OBJECTIVE Youth newly diagnosed with inflammatory bowel diseases (IBD) may be physically impacted by their disease and experience increased psychological stress. Stress is known to relate to greater reported IBD symptoms, but little is known about the longitudinal experience of stress and clinical symptoms of youth newly diagnosed with IBD. METHODS Fifty-seven children (Mage = 14.26, range 8-17 years) diagnosed with IBD completed measures assessing psychological stress (PROMIS Psychological Stress Experiences), depressive symptoms (Children's Depression Inventory-2), and clinical disease symptoms (Self-Report Disease Activity) within 45 days of diagnosis and at 6-month and 1-year follow-ups. Group-based trajectory modeling was used to describe trajectory patterns of psychological stress over the first year of diagnosis and logistic regression identified predictors of group membership. RESULTS Two distinct groups of psychological stress trajectories were identified: 1) low prevalence over the first year of diagnosis (51%) and 2) moderate and increasing prevalence (49%). Membership in the moderate and increasing psychological stress group was associated with female sex and greater IBD symptoms at diagnosis. CONCLUSION Findings suggest roughly half of youth newly diagnosed with IBD would likely benefit from multidisciplinary assessment and intervention to promote adaptive stress management, given moderate and increasing stress levels. Future research is needed to evaluate specific intervention techniques most helpful to youth with IBD.
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Affiliation(s)
- Kelly E Rea
- University of Georgia, Department of Psychology, Athens, Georgia, United States
| | - Grace K Cushman
- Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, Rhode Island, United States
| | - Adrianna L Westbrook
- Pediatric Biostatistics Core, Department of Pediatrics, Emory University, Atlanta, Georgia, United States
| | - Bonney Reed
- Emory University Department of Pediatrics and Children's Healthcare of Atlanta, Atlanta, Georgia, United States.
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13
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Balestrieri P, Cicala M, Ribolsi M. Psychological distress in inflammatory bowel disease. Expert Rev Gastroenterol Hepatol 2023; 17:539-553. [PMID: 37254523 DOI: 10.1080/17474124.2023.2209723] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Accepted: 04/28/2023] [Indexed: 06/01/2023]
Abstract
INTRODUCTION Mental health disorders are common in inflammatory bowel disease (IBD) and affect patients' quality of life, impacting on disease outcomes and health care-related costs. AREAS COVERED Even if psychological issues in IBD patients are highly burdened in terms of quality of life, psychiatric comorbidities still receive less attention into routine care than the physical symptoms of the disease. The present review provides an overview of recent literature, focusing on the association between perceived stress and IBD outcomes. For this purpose, the epidemiology of more common psychological comorbidities in IBD and their potential effect on the onset and disease course have been examined. Moreover, therapeutic interventions in the management of these patients have also been evaluated. EXPERT OPINION Screening of patients at high risk of psychological issues is currently an unmet, clinical need in the management of IBD. Under-diagnosed and under-treated mental health disorders in IBD patients may impact outcomes, leading to increased disability and health-care utilization and associated costs. A patient-tailored, integrated model of care in the management of IBD is required to optimize disease outcomes and improve patients' quality of life.
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Affiliation(s)
- Paola Balestrieri
- Unit of Gastroenterology and Digestive Endoscopy, Campus Bio Medico University, Rome, Italy
| | - Michele Cicala
- Unit of Gastroenterology and Digestive Endoscopy, Campus Bio Medico University, Rome, Italy
| | - Mentore Ribolsi
- Unit of Gastroenterology and Digestive Endoscopy, Campus Bio Medico University, Rome, Italy
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14
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Shah R, Kelley J, Amundsen T, Coggins K, Edwards A, Johnson CM. Medical and social determinants of health as predictors of adverse outcomes in patients with inflammatory bowel disease. Proc AMIA Symp 2023; 36:165-170. [PMID: 36876274 PMCID: PMC9980680 DOI: 10.1080/08998280.2022.2156025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
There is a growing recognition that social determinants of health (SDOH) influence outcomes in patients with chronic diseases. This study aimed to investigate the influence of SDOH on outcomes in patients with inflammatory bowel disease (IBD). We conducted a retrospective cohort study of adult patients with IBD from 1996 to 2019. Patients were identified using ICD-10 codes for ulcerative colitis and Crohn's disease, and chart review was performed to validate the diagnosis and extract clinical information. SDOH factors including food security, financial resources, and transportation were self-reported by the patient. Random forest models were trained and tested in R to predict either IBD-related hospitalization or surgery. A total of 175 patients were studied, and the majority reported no financial resource, food security, or transportation concerns. For the model using clinical predictors, the sensitivity was 0.68 and specificity was 0.77 with an area under the receiver operating characteristic curve (AUROC) of 0.77. The model's performance did not significantly improve with the addition of SDOH information (AUROC of 0.78); however, model performance did vary by phenotype (AUROC of 0.86 for patients with Crohn's disease and AUROC of 0.68 for patients with ulcerative colitis). Further research is needed to understand the role of SDOH factors and IBD-related outcomes.
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Affiliation(s)
- Rajesh Shah
- Division of Gastroenterology, Baylor Scott and White Medical Center - Austin, Austin, Texas
| | - John Kelley
- Department of Medicine, Baylor Scott and White Medical Center - Temple, Temple, Texas
| | - Tyson Amundsen
- Department of Medicine, Baylor Scott and White Medical Center - Temple, Temple, Texas
| | - Kenneth Coggins
- Department of Medicine, Baylor Scott and White Medical Center - Temple, Temple, Texas
| | - Audrene Edwards
- Department of Biostatistics, Baylor Scott and White Health Research Institute, Temple, Texas
| | - Christopher M Johnson
- Division of Gastroenterology, Department of Medicine, Baylor Scott and White Medical Center
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15
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Oyama H, Moroi R, Tarasawa K, Shimoyama Y, Naito T, Sakuma A, Shiga H, Kakuta Y, Fushimi K, Fujimori K, Kinouchi Y, Masamune A. Depression is associated with increased disease activity in patients with ulcerative colitis: A propensity score-matched analysis using a nationwide database in Japan. JGH Open 2022; 6:876-885. [PMID: 36514494 PMCID: PMC9730723 DOI: 10.1002/jgh3.12836] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Revised: 10/03/2022] [Accepted: 10/15/2022] [Indexed: 11/17/2022]
Abstract
Background and Aim The incidence and prevalence of psychiatric disorders are elevated in patients with inflammatory bowel disease (IBD). Whether psychiatric disorders could affect the clinical course of IBD is uncertain and controversial. We aimed to evaluate the impact of psychiatric disorders, particularly depression, on the clinical course of IBD using a nationwide database in Japan. Methods We collected data on admissions with IBD using the Diagnosis Procedure Combination database system introduced in Japan. We divided eligible admissions into IBD with and without depression groups using propensity score matching and compared the rates of surgery, use of molecular targeted drugs and biologics, systemic steroid administrations, and in-hospital death. We also conducted a logistic regression analysis to identify clinical factors affecting surgery, the use of molecular targeted drugs and biologics, and systemic steroid administrations. Results The rates of surgery, use of two or more molecular targeted drugs, systemic steroid administrations, and in-hospital deaths in the ulcerative colitis (UC) with depression group were higher than in the UC without depression group. Multivariate analysis of UC showed that depression increased the odds of systemic steroid administrations, use of two or more molecular targeted drugs, and surgery. However, analysis of Crohn's disease showed that only steroid administrations were associated with depression. Conclusion Our study demonstrated an association between a worse clinical course of UC and depression. Although this result indicates that depression might be associated with increased disease activity in patients with UC, the causal relationship is still unclear. Further prospective studies are warranted.
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Affiliation(s)
- Hideaki Oyama
- Division of GastroenterologyTohoku University Graduate School of MedicineSendaiJapan
| | - Rintaro Moroi
- Division of GastroenterologyTohoku University Graduate School of MedicineSendaiJapan
| | - Kunio Tarasawa
- Department of Health Administration and PolicyTohoku University Graduate School of MedicineSendaiJapan
| | - Yusuke Shimoyama
- Division of GastroenterologyTohoku University Graduate School of MedicineSendaiJapan
| | - Takeo Naito
- Division of GastroenterologyTohoku University Graduate School of MedicineSendaiJapan
| | - Atsushi Sakuma
- Department of PsychiatryTohoku University HospitalSendaiJapan
| | - Hisashi Shiga
- Division of GastroenterologyTohoku University Graduate School of MedicineSendaiJapan
| | - Yoichi Kakuta
- Division of GastroenterologyTohoku University Graduate School of MedicineSendaiJapan
| | - Kiyohide Fushimi
- Department of Health Policy and InformaticsTokyo Medical and Dental University Graduate School of MedicineBunkyo CityJapan
| | - Kenji Fujimori
- Department of Health Administration and PolicyTohoku University Graduate School of MedicineSendaiJapan
| | - Yoshitaka Kinouchi
- Division of GastroenterologyTohoku University Graduate School of MedicineSendaiJapan
| | - Atsushi Masamune
- Division of GastroenterologyTohoku University Graduate School of MedicineSendaiJapan
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16
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Black J, Sweeney L, Yuan Y, Singh H, Norton C, Czuber‐Dochan W. Systematic review: the role of psychological stress in inflammatory bowel disease. Aliment Pharmacol Ther 2022; 56:1235-1249. [PMID: 36082403 PMCID: PMC9825851 DOI: 10.1111/apt.17202] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Revised: 02/27/2022] [Accepted: 08/21/2022] [Indexed: 01/30/2023]
Abstract
BACKGROUND Psychological stress is a possible factor in the disease course and poor psychosocial outcomes in inflammatory bowel disease (IBD). Understanding the exact relationship between stress and health has been hampered by methodological issues and how stress has been defined and measured. AIMS To explore the association between stress and disease outcomes, investigate the impact of stress on psychosocial outcomes, and evaluate the efficacy of interventions in reducing stress for people with IBD METHODS: We performed a systematic review, searching Medline, CINAHL, Embase and PsycInfo databases on 21 January 2021. We included prospective studies that recruited people with IBD who were aged 16 or over and that measured psychological stress or distress. Analyses included Critical Appraisal Skills Programme quality assessments of included studies and narrative analyses against each research question. RESULTS We reviewed 38 studies with 4757 people with IBD, and included 23 observational and 15 interventional studies using 36 different instruments to measure stress. Perceived stress was the most frequently studied concept and preceded IBD exacerbation. Only three studies examined the relationship between stress and psychosocial factors. Cognitive behavioural interventions may reduce stress and other interventions with disease-specific stress, but more studies are needed where groups have comparable baseline characteristics and potential harms are considered alongside benefits. CONCLUSION Psychological stress appears to precede IBD exacerbation, although what role it plays in psychosocial outcomes and how it is best managed is unclear. Further research needs to examine the differential effects of stress on disease subtypes and IBD in flare and remission.
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Affiliation(s)
- Jacqueline Black
- King's College LondonFlorence Nightingale Faculty of Nursing, Midwifery, and Palliative CareJames Clerk Maxwell BuildingLondonUK
| | - Louise Sweeney
- King's College LondonFlorence Nightingale Faculty of Nursing, Midwifery, and Palliative CareJames Clerk Maxwell BuildingLondonUK,King's College LondonInstitute of Psychiatry, Psychology & NeuroscienceLondonUK
| | - Yuhan Yuan
- King's College LondonFlorence Nightingale Faculty of Nursing, Midwifery, and Palliative CareJames Clerk Maxwell BuildingLondonUK
| | | | - Christine Norton
- King's College LondonFlorence Nightingale Faculty of Nursing, Midwifery, and Palliative CareJames Clerk Maxwell BuildingLondonUK
| | - Wladyslawa Czuber‐Dochan
- King's College LondonFlorence Nightingale Faculty of Nursing, Midwifery, and Palliative CareJames Clerk Maxwell BuildingLondonUK
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17
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Bauer N, Kairey L, Schlee C, Uecker C, Öznur Ö, Langhorst J. Use of complementary and alternative medicine (CAM) in patients with inflammatory bowel disease (IBD): results from a German nationwide survey of 2019 compared to a previous survey of 2002. Scand J Gastroenterol 2022; 57:1209-1215. [PMID: 35722930 DOI: 10.1080/00365521.2022.2078667] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
INTRODUCTION In 2002, 50% of patients with Inflammatory Bowel Disease (IBD) had used complementary and alternative medicine (CAM) in Germany. This survey aimed to examine changes from 2002 to 2019 and predictors of CAM use in 2019. MATERIALS AND METHODS In 2019, a questionnaire was sent randomly to 1000 members of the German Crohn's Colitis Association, the same sampling strategy was chosen 2002. Items assessed included, demographic characteristics, IBD diagnosis and disease history, medication use, patients' symptoms/quality of life, anxiety/depression and use of complementary therapies. RESULTS The 2019 sample only differed slightly in case of gender (55% women) and disease (43% Ulcerative Colitis) from the 2002 sample. In 2019, 54% (227/417) reported having ever used CAM and 75% (396/417) planned to use CAM for their IBD in the future, whereby there was an evidence of a decrease in exclusive CAM use from 2002 (28%; 96/344) to 2019 (16%, 37/277; BF<.01). In logistic regression analyses, ulcerative colitis compared to Crohn's Disease (OR 0.59, p=.005), side effects of standard therapy (OR 1.94, p=.012), the use of corticosteroids (OR 0.54, p=.038) or biologics (OR 1.90, p = .020) and lower quality of life (OR 0.96, p=.002) were associated with CAM use in 2019. CONCLUSIONS Every other patient with IBD used CAM and has thus indicated a need for a safe and evidence-based combination of conventional and complementary approaches. This would further support the desired decrease in exclusive -alternative- CAM use.
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Affiliation(s)
- Nina Bauer
- Department of Internal and Integrative Medicine, Sozialstiftung Bamberg, Bamberg, Germany.,Department of Integrative Medicine, Medical Faculty, University of Duisburg-Essen, Bamberg, Germany
| | - Lana Kairey
- Department of Internal and Integrative Medicine, Sozialstiftung Bamberg, Bamberg, Germany.,Department of Integrative Medicine, Medical Faculty, University of Duisburg-Essen, Bamberg, Germany
| | - Christoph Schlee
- Department of Internal and Integrative Medicine, Sozialstiftung Bamberg, Bamberg, Germany.,Department of Integrative Medicine, Medical Faculty, University of Duisburg-Essen, Bamberg, Germany.,Department of Sociology, University of Bamberg, Bamberg, Germany
| | - Christine Uecker
- Department of Internal and Integrative Medicine, Sozialstiftung Bamberg, Bamberg, Germany.,Department of Integrative Medicine, Medical Faculty, University of Duisburg-Essen, Bamberg, Germany
| | - Özlem Öznur
- Department of Internal and Integrative Medicine, Sozialstiftung Bamberg, Bamberg, Germany.,Department of Integrative Medicine, Medical Faculty, University of Duisburg-Essen, Bamberg, Germany
| | - Jost Langhorst
- Department of Internal and Integrative Medicine, Sozialstiftung Bamberg, Bamberg, Germany.,Department of Integrative Medicine, Medical Faculty, University of Duisburg-Essen, Bamberg, Germany
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18
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Fairbrass KM, Lovatt J, Barberio B, Yuan Y, Gracie DJ, Ford AC. Bidirectional brain-gut axis effects influence mood and prognosis in IBD: a systematic review and meta-analysis. Gut 2022; 71:1773-1780. [PMID: 34725197 DOI: 10.1136/gutjnl-2021-325985] [Citation(s) in RCA: 99] [Impact Index Per Article: 33.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Accepted: 10/20/2021] [Indexed: 02/07/2023]
Abstract
OBJECTIVE The role of the brain-gut axis is of increasing interest in IBD, as the link between common mental disorders and GI inflammation may be bidirectional. We performed a systematic review examining these issues. DESIGN We searched EMBASE Classic and EMBASE, Medline, and APA PsychInfo (to 11 July 2021) for longitudinal follow-up studies examining effect of symptoms of anxiety or depression on subsequent adverse outcomes in IBD, or effect of active IBD on subsequent development of symptoms of anxiety or depression. We pooled relative risks (RRs) and HRs with 95% CIs for adverse outcomes (flare, escalation of therapy, hospitalisation, emergency department attendance, surgery or a composite of any of these) according to presence of symptoms of anxiety or depression at baseline, or RRs and HRs with 95% CIs for new onset of symptoms of anxiety or depression according to presence of active IBD at baseline. RESULTS We included 12 separate studies, recruiting 9192 patients. All 12 studies examined brain-to-gut effects. Anxiety at baseline was associated with significantly higher risks of escalation of therapy (RR=1.68; 95% CI 1.18 to 2.40), hospitalisation (RR=1.72; 95% CI 1.01 to 2.95), emergency department attendance (RR=1.30; 95% CI 1.21 to 1.39), or a composite of any adverse outcome. Depression at baseline was associated with higher risks of flare (RR=1.60; 95% CI 1.21 to 2.12), escalation of therapy (RR=1.41; 95% CI 1.08 to 1.84), hospitalisation (RR=1.35; 95% CI 1.17 to 1.57), emergency department attendance (RR=1.38; 95% CI 1.22 to 1.56), surgery (RR=1.63; 95% CI 1.19 to 2.22) or a composite of any of these. Three studies examined gut-to-brain effects. Active disease at baseline was associated with future development of anxiety or depression (RR=2.24; 95% CI 1.25 to 4.01 and RR=1.49; 95% CI 1.11 to 1.98, respectively). CONCLUSION Bidirectional effects of the brain-gut axis are present in IBD and may influence both the natural history of the disease and psychological health.
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Affiliation(s)
- Keeley M Fairbrass
- Leeds Gastroenterology Institute, St James's University Hospital, Leeds, UK.,Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
| | - Jessica Lovatt
- Leeds Gastroenterology Institute, St James's University Hospital, Leeds, UK
| | - Brigida Barberio
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padova, Italy
| | - Yuhong Yuan
- Division of Gastroenterology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada
| | - David J Gracie
- Leeds Gastroenterology Institute, St James's University Hospital, Leeds, UK.,Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
| | - Alexander C Ford
- Leeds Gastroenterology Institute, St James's University Hospital, Leeds, UK .,Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
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19
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Bauer N, Löffler C, Öznur Ö, Uecker C, Keil T, Langhorst J. Mind-body-medicine and comprehensive lifestyle-modification in patients with Crohn's disease—Feasibility of a randomized controlled trial under pandemic circumstances. Front Integr Neurosci 2022; 16:960301. [PMID: 36081609 PMCID: PMC9447476 DOI: 10.3389/fnint.2022.960301] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Accepted: 07/08/2022] [Indexed: 11/21/2022] Open
Abstract
Introduction Mind-body medicine (MBM) focuses on stress reduction and lifestyle changes. The primary objective of this pilot trial was to test study feasibility of a complex integrative MBM program for patients with Crohn's disease (CD), especially in rural regions, and under pandemic conditions. Methods Patients were stratified and randomized to the intervention group (IG) or the control group (CG). The intervention included a weekly 6-h session for 10 weeks. The CG (waiting list) received an initial 90-min workshop and started the intervention 9 months later. The primary outcome for study feasibility was recruitment and retention rates, as well as reasons for drop-out. The trial took place in Bamberg, Germany (September 2020 to December 2021). Results Totally 700 members of the German Crohn's and Colitis Organization—DCCV—were contacted. A total of 15% (102/700; 95% CI 12–17%) expressed interest to participate. Following screening, 41% (95% CI 32–50) were randomized to IG (n = 22) and CG (n = 20). The patients were on average (±standard deviation) 48 ± 13 years old, 67% were female, and have been suffering from CD for 20 ± 12 years. Patients traveled 71.5 ± 48.7 km (range: 9–227 km) to the intervention with no differences between IG and CG. At the 6-month follow-up, 36/42 (86%, 95% CI 74–95%) participants completed final assessment and 19/22 (86%, 95% CI 70–100%) the intervention. The most important reasons for non-responding were work-related (12/60; 20%) and for or drop-out pandemic-related anxiety (3/6). No patient and staff member became infected with SARS-CoV-2 during the study. Conclusion The feasibility of the MBM study was confirmed in terms of predefined recruitment and retention criteria, both despite difficult conditions (including the rural setting) and patients' fears associated with the pandemic. It was crucial to develop appropriate hygiene and safety concepts that enable chronically ill patients to participate in helpful group-based interventions even under pandemic conditions. Clinical trial registration ClinicalTrials.gov, identifier: NCT05182645.
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Affiliation(s)
- Nina Bauer
- Department of Internal and Integrative Medicine, Sozialstiftung Bamberg, Bamberg, Germany
- Department of Integrative Medicine, Medical Faculty, University of Duisburg-Essen, Bamberg, Germany
| | - Claudia Löffler
- Department of Internal Medicine II, University Hospital of Würzburg, Würzburg, Germany
| | - Özlem Öznur
- Department of Internal and Integrative Medicine, Sozialstiftung Bamberg, Bamberg, Germany
- Department of Integrative Medicine, Medical Faculty, University of Duisburg-Essen, Bamberg, Germany
| | - Christine Uecker
- Department of Internal and Integrative Medicine, Sozialstiftung Bamberg, Bamberg, Germany
- Department of Integrative Medicine, Medical Faculty, University of Duisburg-Essen, Bamberg, Germany
| | - Thomas Keil
- Institute of Clinical Epidemiology and Biometry, Julius Maximilians University of Würzburg, Würzburg, Germany
- State Institute of Health, Bavarian Health and Food Safety Authority, Erlangen, Germany
- Institute of Social Medicine, Epidemiology and Health Economics, Charité – Universitätsmedizin Berlin, Berlin, Germany
| | - Jost Langhorst
- Department of Internal and Integrative Medicine, Sozialstiftung Bamberg, Bamberg, Germany
- Department of Integrative Medicine, Medical Faculty, University of Duisburg-Essen, Bamberg, Germany
- *Correspondence: Jost Langhorst
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20
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Fairbrass KM, Gracie DJ, Ford AC. Relative Contribution of Disease Activity and Psychological Health to Prognosis of Inflammatory Bowel Disease During 6.5 Years of Longitudinal Follow-Up. Gastroenterology 2022; 163:190-203.e5. [PMID: 35339461 DOI: 10.1053/j.gastro.2022.03.014] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Revised: 02/02/2022] [Accepted: 03/04/2022] [Indexed: 12/30/2022]
Abstract
BACKGROUND & AIMS Symptoms of common mental disorders, such as anxiety or depression, are common in inflammatory bowel disease (IBD) and may affect prognosis. However, unlike clinical or biochemical markers of disease activity, psychological health is not a recommended therapeutic target. We assessed relative contribution of poor psychological health and clinical or biochemical activity to prognosis. METHODS Demographic features, IBD subtype, treatments, and anxiety and depression scores were recorded at baseline for 760 adults, with clinical activity determined using validated scoring systems. Fecal calprotectin was analyzed in 379 (49.9%) patients (≥250 μg/g used to define biochemical activity). Glucocorticosteroid prescription or flare, escalation, hospitalization, intestinal resection, or death were assessed during 6.5 years of follow-up. Occurrence was compared using multivariate Cox regression across 4 patient groups according to presence of disease remission or activity, with or without symptoms of a common mental disorder, at baseline. RESULTS In total, 718 (94.5%) participants provided data. Compared with clinical remission without symptoms of a common mental disorder at baseline, need for glucocorticosteroid prescription or flare (hazard ratio [HR], 2.36; 95% confidence interval [CI], 1.58-3.54), escalation (HR, 1.65; 95% CI, 1.14--2.40), and death (HR, 4.99; 95% CI, 1.80-13.88) were significantly higher in those with clinical activity and symptoms of a common mental disorder. Rates in those with clinical remission and symptoms of a common mental disorder at baseline or those with clinical activity without symptoms of a common mental disorder were not significantly higher. Similarly, with biochemical activity and symptoms of a common mental disorder, rates of glucocorticosteroid prescription or flare (HR, 2.48; 95% CI, 1.38-4.46), escalation (HR, 2.97; 95% CI, 1.74-5.06), hospitalization (HR, 3.10; 95% CI, 1.43-6.68), and death (HR, 6.26; 95% CI, 2.23-17.56) were significantly higher. CONCLUSIONS Psychological factors are important determinants of poor prognostic outcomes in IBD and should be considered as a therapeutic target.
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Affiliation(s)
- Keeley M Fairbrass
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, United Kingdom; Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, United Kingdom
| | - David J Gracie
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, United Kingdom; Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, United Kingdom
| | - Alexander C Ford
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, United Kingdom; Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, United Kingdom.
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21
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Sturm A, Atreya R, Bettenworth D, Bokemeyer B, Dignaß A, Ehehalt R, Germer C, Grunert PC, Helwig U, Herrlinger K, Kienle P, Kreis ME, Kucharzik T, Langhorst J, Maaser C, Ockenga J, Ott C, Siegmund B, Zeißig S, Stallmach A. Aktualisierte S3-Leitlinie „Diagnostik und Therapie des Morbus Crohn“ der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) – August 2021 – AWMF-Registernummer: 021-004. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:332-418. [PMID: 35263784 DOI: 10.1055/a-1713-3941] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Andreas Sturm
- Klinik für Innere Medizin mit Schwerpunkt Gastroenterologie, DRK Kliniken Berlin Westend, Berlin, Deutschland
| | - Raja Atreya
- Medizinische Klinik 1, Universitätsklinikum Erlangen, Deutschland
| | | | - Bernd Bokemeyer
- Gastroenterologische Gemeinschaftspraxis Minden, Deutschland
| | - Axel Dignaß
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt am Main, Deutschland
| | | | - Christoph Germer
- Chirurgische Klinik I, Universitätsklinikum Würzburg, Deutschland
| | - Philip C Grunert
- Klinik für Innere Medizin IV (Gastroenterologie, Hepatologie und Infektiologie), Universitätsklinikum Jena, Deutschland
| | - Ulf Helwig
- Internistische Praxengemeinschaft, Oldenburg, Deutschland
| | | | - Peter Kienle
- Allgemein- und Viszeralchirurgie, Theresienkrankenhaus und Sankt Hedwig-Klinik GmbH, Mannheim, Deutschland
| | - Martin E Kreis
- Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Charité Campus Benjamin Franklin - Universitätsmedizin Berlin, Deutschland
| | - Torsten Kucharzik
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Klinikum Lüneburg, Deutschland
| | - Jost Langhorst
- Klinik für Integrative Medizin und Naturheilkunde, Klinikum am Bruderwald, Bamberg, Deutschland
| | | | - Johann Ockenga
- Medizinische Klinik II, Klinikum Bremen Mitte - Gesundheit Nord, Bremen, Deutschland
| | - Claudia Ott
- Gastroenterologie Facharztzentrum, Regensburg, Deutschland
| | - Britta Siegmund
- Medizinische Klinik I, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Deutschland
| | - Sebastian Zeißig
- Medizinische Klinik und Poliklinik I, Universitätsklinikum Dresden, Deutschland
| | - Andreas Stallmach
- Klinik für Innere Medizin IV (Gastroenterologie, Hepatologie und Infektiologie), Universitätsklinikum Jena, Deutschland
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22
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Chen R, Zheng J, Li L, Li C, Chao K, Zeng Z, Chen M, Zhang S. Metabolomics facilitate the personalized management in inflammatory bowel disease. Therap Adv Gastroenterol 2021; 14:17562848211064489. [PMID: 34987610 PMCID: PMC8721420 DOI: 10.1177/17562848211064489] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2021] [Accepted: 11/15/2021] [Indexed: 02/04/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a gastrointestinal disorder characterized by chronic relapsing inflammation and mucosal lesions. Reliable biomarkers for monitoring disease activity, predicting therapeutic response, and disease relapse are needed in the personalized management of IBD. Given the alterations in metabolomic profiles observed in patients with IBD, metabolomics, a new and developing technique for the qualitative and quantitative study of small metabolite molecules, offers another possibility for identifying candidate markers and promising predictive models. With increasing research on metabolomics, it is gradually considered that metabolomics will play a significant role in the management of IBD. In this review, we summarize the role of metabolomics in the assessment of disease activity, including endoscopic activity and histological activity, prediction of therapeutic response, prediction of relapse, and other aspects concerning disease management in IBD. Furthermore, we describe the limitations of metabolomics and highlight some solutions.
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Affiliation(s)
- Rirong Chen
- Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, P.R. China
| | - Jieqi Zheng
- Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, P.R. China
| | - Li Li
- Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan Road 2, Guangzhou 510080, P.R. China
| | - Chao Li
- Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, P.R. China
| | - Kang Chao
- Division of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, P.R. China
| | - Zhirong Zeng
- Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, P.R. China
| | - Minhu Chen
- Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan Road 2, Guangzhou 510080, P.R. China
| | - Shenghong Zhang
- Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan Road 2, Guangzhou 510080, P.R. China
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23
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Öhlmann H, Koenen LR, Labrenz F, Engler H, Theysohn N, Langhorst J, Elsenbruch S. Altered Brain Structure in Chronic Visceral Pain: Specific Differences in Gray Matter Volume and Associations With Visceral Symptoms and Chronic Stress. Front Neurol 2021; 12:733035. [PMID: 34744973 PMCID: PMC8564184 DOI: 10.3389/fneur.2021.733035] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Accepted: 09/21/2021] [Indexed: 12/12/2022] Open
Abstract
Structural brain alterations in chronic pain conditions remain incompletely understood, especially in chronic visceral pain. Patients with chronic-inflammatory or functional bowel disorders experience recurring abdominal pain in concert with other gastrointestinal symptoms, such as altered bowel habits, which are often exacerbated by stress. Despite growing interest in the gut-brain axis and its underlying neural mechanisms in health and disease, abnormal brain morphology and possible associations with visceral symptom severity and chronic stress remain unclear. We accomplished parallelized whole-brain voxel-based morphometry analyses in two patient cohorts with chronic visceral pain, i.e., ulcerative colitis in remission and irritable bowel syndrome, and healthy individuals. In addition to analyzing changes in gray matter volume (GMV) in each patient cohort vs. age-matched healthy controls using analysis of covariance (ANCOVA), multiple regression analyses were conducted to assess correlations between GMV and symptom severity and chronic stress, respectively. ANCOVA revealed reduced GMV in frontal cortex and anterior insula in ulcerative colitis compared to healthy controls, suggesting alterations in the central autonomic and salience networks, which could however not be confirmed in supplemental analyses which rigorously accounted for group differences in the distribution of sex. In irritable bowel syndrome, more widespread differences from healthy controls were observed, comprising both decreased and increased GMV within the sensorimotor, central executive and default mode networks. Associations between visceral symptoms and GMV within frontal regions were altered in both patient groups, supporting a role of the central executive network across visceral pain conditions. Correlations with chronic stress, on the other hand, were only found for irritable bowel syndrome, encompassing numerous brain regions and networks. Together, these findings complement and expand existing brain imaging evidence in chronic visceral pain, supporting partly distinct alterations in brain morphology in patients with chronic-inflammatory and functional bowel disorders despite considerable overlap in symptoms and comorbidities. First evidence pointing to correlations with chronic stress in irritable bowel syndrome inspires future translational studies to elucidate the mechanisms underlying the interconnections of stress, visceral pain and neural mechanisms of the gut-brain axis.
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Affiliation(s)
- Hanna Öhlmann
- Department of Medical Psychology and Medical Sociology, Ruhr University Bochum, Bochum, Germany
| | - Laura Ricarda Koenen
- Institute of Medical Psychology and Behavioral Immunobiology, Center for Translational Neuro-and Behavioral Sciences, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Franziska Labrenz
- Department of Medical Psychology and Medical Sociology, Ruhr University Bochum, Bochum, Germany
| | - Harald Engler
- Institute of Medical Psychology and Behavioral Immunobiology, Center for Translational Neuro-and Behavioral Sciences, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Nina Theysohn
- Institute of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Jost Langhorst
- Department for Internal and Integrative Medicine, Sozialstiftung Bamberg, Bamberg, Germany.,Department for Integrative Medicine, Medical Faculty, University of Duisburg-Essen, Essen, Germany
| | - Sigrid Elsenbruch
- Department of Medical Psychology and Medical Sociology, Ruhr University Bochum, Bochum, Germany.,Department of Neurology, Center for Translational Neuro- and Behavioral Sciences, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
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24
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Koch AK, Schöls M, Haller H, Anheyer D, Cinar Z, Eilert R, Kofink K, Engler H, Elsenbruch S, Cramer H, Dobos G, Langhorst J. Comprehensive Lifestyle Modification Influences Medium-Term and Artificially Induced Stress in Ulcerative Colitis-A Sub-Study within a Randomized Controlled Trial Using the Trier Social Stress Test. J Clin Med 2021; 10:5070. [PMID: 34768588 PMCID: PMC8584874 DOI: 10.3390/jcm10215070] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Revised: 10/20/2021] [Accepted: 10/26/2021] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVE The present study presents long-term results of stress-related outcomes of a prospective RCT that evaluated effects of a ten-week comprehensive lifestyle-modification program (LSM) in patients with inactive ulcerative colitis (UC). In addition, exploratory results of a sub-study applying a laboratory stress protocol (Trier Social Stress Test; TSST) conducted within the RCT are reported. METHODS Ninety-seven patients with inactive UC were randomized to LSM (n = 47; 50.28 ± 11.90 years; 72.3% female) or self-care (n = 50; 45.54 ± 12.49 years; 70% female). Patients' perceived stress, anxiety, flourishing and depression were assessed at week 0, 12, 24 and 48. After the respective intervention, 16 female patients (LSM: n = 8; 44.6 ± 14.3 years; Self-care: n = 8; 49.25 ± 4.30 years) additionally underwent the TSST. State anxiety, blood pressure, pulse, complete blood counts, adrenocorticotropic hormone (ACTH), cortisol, adrenalin and noradrenalin were measured at baseline (-15 min), stress (+10 min), recovery1 (+20 min) and recovery2 (+55 min). Statistical significance was set at p < 0.05; for the exploratory sub-study using the TSST, p-values < 0.10 were considered significant. RESULTS Patients' perceived stress declined significantly after the LSM (p < 0.001) compared with control. This lasted until week 24 (p = 0.023) but did not persist until week 48 (p = 0.060). After 48 weeks, patients' flourishing was significantly increased compared with control (p = 0.006). In response to the TSST, significant group differences were evident for pulse (p = 0.015), adrenaline (p = 0.037) and anxiety (p = 0.066). After 55 min, group differences were found for ACTH (p = 0.067) and systolic blood pressure (p = 0.050). CONCLUSIONS LSM has a medium-term positive effect on perceived stress. First indications show that it is promising to investigate these effects further under laboratory conditions. It is also desirable to find out how the effects of LSM can be maintained in the long term.
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Affiliation(s)
- Anna K. Koch
- Department of Internal and Integrative Medicine, Evang. Kliniken Essen-Mitte, Faculty of Medicine, University of Duisburg-Essen, 45276 Essen, Germany; (A.K.K.); (M.S.); (H.H.); (D.A.); (Z.C.); (R.E.); (K.K.); (H.C.); (G.D.)
- Department of Internal and Integrative Medicine, Klinikum Bamberg, Sozialstiftung Bamberg, 96049 Bamberg, Germany
| | - Margarita Schöls
- Department of Internal and Integrative Medicine, Evang. Kliniken Essen-Mitte, Faculty of Medicine, University of Duisburg-Essen, 45276 Essen, Germany; (A.K.K.); (M.S.); (H.H.); (D.A.); (Z.C.); (R.E.); (K.K.); (H.C.); (G.D.)
| | - Heidemarie Haller
- Department of Internal and Integrative Medicine, Evang. Kliniken Essen-Mitte, Faculty of Medicine, University of Duisburg-Essen, 45276 Essen, Germany; (A.K.K.); (M.S.); (H.H.); (D.A.); (Z.C.); (R.E.); (K.K.); (H.C.); (G.D.)
| | - Dennis Anheyer
- Department of Internal and Integrative Medicine, Evang. Kliniken Essen-Mitte, Faculty of Medicine, University of Duisburg-Essen, 45276 Essen, Germany; (A.K.K.); (M.S.); (H.H.); (D.A.); (Z.C.); (R.E.); (K.K.); (H.C.); (G.D.)
- National Centre for Naturopathic Medicine, Southern Cross University, Lismore, NSW 2480, Australia
| | - Zehra Cinar
- Department of Internal and Integrative Medicine, Evang. Kliniken Essen-Mitte, Faculty of Medicine, University of Duisburg-Essen, 45276 Essen, Germany; (A.K.K.); (M.S.); (H.H.); (D.A.); (Z.C.); (R.E.); (K.K.); (H.C.); (G.D.)
| | - Ronja Eilert
- Department of Internal and Integrative Medicine, Evang. Kliniken Essen-Mitte, Faculty of Medicine, University of Duisburg-Essen, 45276 Essen, Germany; (A.K.K.); (M.S.); (H.H.); (D.A.); (Z.C.); (R.E.); (K.K.); (H.C.); (G.D.)
| | - Kerstin Kofink
- Department of Internal and Integrative Medicine, Evang. Kliniken Essen-Mitte, Faculty of Medicine, University of Duisburg-Essen, 45276 Essen, Germany; (A.K.K.); (M.S.); (H.H.); (D.A.); (Z.C.); (R.E.); (K.K.); (H.C.); (G.D.)
| | - Harald Engler
- Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany;
| | - Sigrid Elsenbruch
- Department of Medical Psychology and Medical Sociology, Faculty of Medicine, Ruhr University, 44801 Bochum, Germany;
| | - Holger Cramer
- Department of Internal and Integrative Medicine, Evang. Kliniken Essen-Mitte, Faculty of Medicine, University of Duisburg-Essen, 45276 Essen, Germany; (A.K.K.); (M.S.); (H.H.); (D.A.); (Z.C.); (R.E.); (K.K.); (H.C.); (G.D.)
- National Centre for Naturopathic Medicine, Southern Cross University, Lismore, NSW 2480, Australia
| | - Gustav Dobos
- Department of Internal and Integrative Medicine, Evang. Kliniken Essen-Mitte, Faculty of Medicine, University of Duisburg-Essen, 45276 Essen, Germany; (A.K.K.); (M.S.); (H.H.); (D.A.); (Z.C.); (R.E.); (K.K.); (H.C.); (G.D.)
| | - Jost Langhorst
- Department of Internal and Integrative Medicine, Klinikum Bamberg, Sozialstiftung Bamberg, 96049 Bamberg, Germany
- Department for Integrative Medicine and Translational Gastroenterology, Medical Faculty, University of Duisburg-Essen, Sozialstiftung Bamberg, 96049 Bamberg, Germany
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25
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Hirten RP, Danieletto M, Scheel R, Shervey M, Ji J, Hu L, Sauk J, Chang L, Arnrich B, Bӧttinger E, Dudley J, Keefer L, Sands BE. Longitudinal Autonomic Nervous System Measures Correlate With Stress and Ulcerative Colitis Disease Activity and Predict Flare. Inflamm Bowel Dis 2021; 27:1576-1584. [PMID: 33382065 DOI: 10.1093/ibd/izaa323] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2020] [Indexed: 12/29/2022]
Abstract
BACKGROUND Differences in autonomic nervous system function, measured by heart rate variability (HRV), have been observed between patients with inflammatory bowel disease and healthy control patients and have been associated in cross-sectional studies with systemic inflammation. High HRV has been associated with low stress. METHODS Patients with ulcerative colitis (UC) were followed for 9 months. Their HRV was measured every 4 weeks using the VitalPatch, and blood was collected at baseline and every 12 weeks assessing cortisol, adrenocorticotropin hormone, interleukin-1β, interleukin-6, tumor necrosis factor-α, and C-reactive protein (CRP). Stool was collected at enrollment and every 6 weeks for fecal calprotectin. Surveys assessing symptoms, stress, resilience, quality of life, anxiety, and depression were longitudinally collected. RESULTS Longitudinally evaluated perceived stress was significantly associated with systemic inflammation (CRP, P = 0.03) and UC symptoms (P = 0.02). There was a significant association between HRV and stress (low-frequency to high-frequency power [LFHF], P = 0.04; root mean square of successive differences [RMSSD], P = 0.04). The HRV was associated with UC symptoms (LFHF, P = 0.03), CRP (high frequency, P < 0.001; low frequency, P < 0.001; RMSSD, P < 0.001), and fecal calprotectin (high frequency, P < 0.001; low frequency, P < 0.001; RMSSD, P < 0.001; LFHF, P < 0.001). Significant changes in HRV indices from baseline developed before the identification of a symptomatic or inflammatory flare (P < 0.001). CONCLUSIONS Longitudinally evaluated HRV was associated with UC symptoms, inflammation, and perceived and physiological measures of stress. Significant changes in HRV were observed before the development of symptomatic or inflammatory flare.
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Affiliation(s)
- Robert P Hirten
- The Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Matteo Danieletto
- Hasso Plattner Institute for Digital Health at Mount Sinai, Icahn School of Medicine at Mount Sinai, New York, New York, USA.,Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Robert Scheel
- The Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Mark Shervey
- Hasso Plattner Institute for Digital Health at Mount Sinai, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Jiayi Ji
- Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Liangyuan Hu
- Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Jenny Sauk
- Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
| | - Lin Chang
- Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
| | - Bert Arnrich
- Hasso Plattner Institute for Digital Health at Mount Sinai, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Erwin Bӧttinger
- Hasso Plattner Institute for Digital Health at Mount Sinai, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Joel Dudley
- Hasso Plattner Institute for Digital Health at Mount Sinai, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Laurie Keefer
- The Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Bruce E Sands
- The Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
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26
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Moradi S, Zobeiri M, Feizi A, Clark CCT, Entezari MH. The effects of spirulina (Arthrospira platensis) supplementation on anthropometric indices, blood pressure, sleep quality, mental health, fatigue status and quality of life in patients with ulcerative colitis: A randomised, double-blinded, placebo-controlled trial. Int J Clin Pract 2021; 75:e14472. [PMID: 34107141 DOI: 10.1111/ijcp.14472] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2021] [Revised: 05/12/2021] [Accepted: 06/06/2021] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND An emerging body of evidence has highlighted the protective role of spirulina in human health. Thus, we conducted a randomised controlled trial to discern the effects of spirulina supplementation on anthropometric indices, blood pressure, sleep quality, mood, fatigue status and quality of life among ulcerative colitis patients. METHODS Eighty participants with ulcerative colitis were randomly allocated to receive, either, 1 g/day (two 500 mg capsules) spirulina (n = 40) or placebo (n = 40), in a clinical trial for eight weeks. Dietary intake, physical activity, sleep quality, mental health, fatigue status and quality of life were assessed for each participant at baseline and trial cessation. Anthropometric indices and blood pressure were also assessed. RESULTS Seventy-three participants completed the intervention. Our results revealed that spirulina supplementation significantly reduced sleep disturbances (P = .03), while no significant changes occurred in the sleep quality score or other sleep parameters, vs the placebo group (P > .05). Furthermore, a significant reduction in stress score (P = .04) and increase in quality of life (P = .03) was detected; but not anxiety, depression or fatigue scores (P > .05). Additionally, anthropometric indices and blood pressure did not significantly change (P > .05). CONCLUSION An improved quality of life was observed among ulcerative colitis patients following spirulina supplementation, which could be attributed to improved sleep disturbance and stress status. Further clinical studies, with longer duration interventions and suitably powered sample sizes, are necessary to elucidate the veracity of our findings.
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Affiliation(s)
- Sajjad Moradi
- Department of Clinical Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mehdi Zobeiri
- Department of Internal Medicine, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Awat Feizi
- Department of Biostatistics and Epidemiology, School of Health, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Cain C T Clark
- Centre for Intelligent Healthcare, Coventry University, Coventry, UK
| | - Mohammad Hassan Entezari
- Department of Clinical Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
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Dubinsky MC, Dotan I, Rubin DT, Bernauer M, Patel D, Cheung R, Modesto I, Latymer M, Keefer L. Burden of comorbid anxiety and depression in patients with inflammatory bowel disease: a systematic literature review. Expert Rev Gastroenterol Hepatol 2021; 15:985-997. [PMID: 34130572 DOI: 10.1080/17474124.2021.1911644] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
INTRODUCTION Patients with inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, often have comorbid anxiety and depression that affects their quality of life (QoL) and management of their IBD. AREAS COVERED A systematic literature review (SLR) was conducted to identify articles and conference abstracts on comorbid anxiety and depression in IBD patients using MEDLINE® and Embase® (January 2003 - June 2018). The impact of these psychological comorbidities on QoL and economic burden was examined. Non-pharmacologic interventions and disease-specific unmet clinical needs associated with these comorbidities were also evaluated. EXPERT OPINION There is evidence that individual and group-based cognitive behavioral therapy can reduce rates of anxiety and depression in adults and adolescents with IBD. Patients with IBD and anxiety or depression had an increased risk of hospitalization, emergency department visits, readmission, and used outpatient services more often than people without these conditions. Several disease-specific unmet clinical needs for IBD patients were identified. These included lack of reimbursement for mental-health care, inconsistent screening for psychological comorbidities and patients not consulting mental-health professionals when needed. IBD patients may benefit from integrated medical and psychological treatment, and should be considered for behavioral treatment.Plain Language Summary. BACKGROUND People with IBD may have mental-health conditions, such as anxiety and depression. These conditions can affect people's quality of life and how they manage their IBD. WHAT DID THIS REVIEW LOOK AT? We found 79 publications on anxiety or depression in people with IBD, published between January 2003 and June 2018. In people with IBD and anxiety or depression, researchers looked at: the impact on health-related quality of life and healthcare utilization, including access to and reimbursement for mental-health services how effective interventions that do not involve the use of medicines were (known as non-pharmacologic therapy). WHAT WERE THE MAIN FINDINGS FROM THIS REVIEW? People with IBD and anxiety or depression were more likely to be admitted to hospital and visit emergency departments than people without these conditions. Access to mental-health care varied and some people with IBD were not screened for depression.Individual and group-based talking therapy (known as cognitive behavioral therapy) reduced rates of anxiety and depression in some people with IBD. WHAT WERE THE MAIN CONCLUSIONS FROM THIS REVIEW? We found evidence that people with IBD and anxiety or depression may benefit from certain non-pharmacologic interventions. However, many people with IBD and anxiety or depression did not have access to mental-health services. Healthcare professionals should address gaps in patient care to improve outcomes in people with IBD and anxiety or depression.See Additional file 1 for an infographic plain language summary.
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Affiliation(s)
- Marla C Dubinsky
- Susan and Leonard Feinstein IBD Clinical Center, Icahn School of Medicine, Mount Sinai, New York City, USA
| | - Iris Dotan
- Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel and the Sackler Faculty of Medicine Tel Aviv University, Israel
| | - David T Rubin
- University of Chicago Medicine Inflammatory Bowel Disease Center, USA
| | | | | | | | | | | | - Laurie Keefer
- Susan and Leonard Feinstein IBD Clinical Center, Icahn School of Medicine, Mount Sinai, New York City, USA
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Dolovich C, Bernstein CN, Singh H, Nugent Z, Tennakoon A, Shafer LA, Marrie RA, Sareen J, Targownik LE. Anxiety and Depression Leads to Anti-Tumor Necrosis Factor Discontinuation in Inflammatory Bowel Disease. Clin Gastroenterol Hepatol 2021; 19:1200-1208.e1. [PMID: 32668341 DOI: 10.1016/j.cgh.2020.07.013] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2019] [Revised: 07/03/2020] [Accepted: 07/08/2020] [Indexed: 12/26/2022]
Abstract
BACKGROUND & AIMS Anxiety and mood disorders (AMDs) are common among persons with inflammatory bowel diseases (IBD) and are associated with increased health care use and lower quality of life. We assessed the effects of AMDs on persistence on anti-tumor necrosis factor (anti-TNF) therapy in patients with IBD, and risk of IBD-related adverse outcomes after therapy initiation. METHODS We identified all persons with IBD in Manitoba, Canada who were dispensed an anti-TNF agent from 2001 through 2016 and then identified those with a validated administrative definition of AMD in the 2 years before initiation of therapy. Survival analysis was used to assess the association between active AMDs and anti-TNF discontinuation and the first occurrence of an IBD-related adverse outcome (defined as IBD-related hospitalization or surgery, new or recurrent corticosteroid use, switching to an alternative anti-TNF, or death). We used Cox proportional hazards multivariable regression models to adjust for demographic and clinical factors associated with outcomes. RESULTS We identified 1135 persons with IBD who began anti-TNF therapy; 178 of these patients (15.7%) met the diagnostic criteria for an AMD. AMDs significantly increased risk of discontinuation of anti-TNF therapy (adjusted hazard ratio, 1.28; 95% CI, 1.03-1.59) and discontinuation in the 1 year following anti-TNF initiation (hazard ratio, 1.50; 95% CI, 1.15-1.94). There was no association between AMDs and subsequent risk of IBD-related adverse events. CONCLUSIONS Patients with IBD and an AMD within 2 years before starting anti-TNF therapy are at increased risk of discontinuing therapy, compared to patients with IBD without AMD. Studies are needed to determine if treatment of AMDs increases compliance with treatment.
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Affiliation(s)
- Casandra Dolovich
- Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Charles N Bernstein
- Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada; University of Manitoba IBD Clinical and Research Centre, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Harminder Singh
- Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada; University of Manitoba IBD Clinical and Research Centre, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Zoann Nugent
- University of Manitoba IBD Clinical and Research Centre, University of Manitoba, Winnipeg, Manitoba, Canada; CancerCare Manitoba, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Aruni Tennakoon
- University of Manitoba IBD Clinical and Research Centre, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Leigh Ann Shafer
- Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Ruth Ann Marrie
- Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Jitender Sareen
- Department of Psychiatry, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Laura E Targownik
- Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada; University of Manitoba IBD Clinical and Research Centre, University of Manitoba, Winnipeg, Manitoba, Canada; Division of Gastroenterology, Department of Medicine, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
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Cushman GK, Shih S, Stolz MG, Hinrichs RC, Jovanovic T, Lee JL, Kugathasan S, Reed B. Stressful life events, depression, and the moderating role of psychophysiological reactivity in patients with pediatric inflammatory bowel disease. J Psychosom Res 2021; 141:110323. [PMID: 33321262 PMCID: PMC7855667 DOI: 10.1016/j.jpsychores.2020.110323] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2020] [Revised: 11/23/2020] [Accepted: 11/27/2020] [Indexed: 12/17/2022]
Abstract
OBJECTIVE The development of depressive symptoms in youth with IBD is a concerning disease complication, as higher levels of depressive symptoms have been associated with poorer quality of life and lower medication adherence. Previous research has examined the association between disease activity and depression, but few studies have examined individual differences in experience of stressful life events in relation to depressive symptoms. The purpose of the current study is to examine the relation between stressful life events and depression within pediatric IBD and to determine whether individual differences in stress response moderates this association. METHODS 56 youth ages 8-17 years old diagnosed with IBD completed questionnaires about their depressive symptoms and history of stressful life events. We assessed skin conductance reactivity (SCR) to a stressful task as an index of psychophysiological reactivity. RESULTS Stressful life events (r = 0.36, p = .007) were positively related to depressive symptoms. Youth who demonstrated a greater maximum SC level during the IBD-specific stress trial compared to baseline (n = 32) reported greater depressive symptoms. For these same participants, the relationship between stressful life events and depressive symptoms depended on SCR F(3, 28) = 4.23, p = .01, such that at moderate and high levels of SCR, a positive relationship between stressful life events and depressive symptoms was observed. CONCLUSIONS The relationship between stressful life events and depressive symptoms in youth with IBD may depend on individual differences in processing stress, such that risk may increase with greater psychophysiological reactivity.
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Affiliation(s)
| | | | | | | | | | | | | | - Bonney Reed
- Emory/Children's Pediatric Institute, United States of America.
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30
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Peppas S, Pansieri C, Piovani D, Danese S, Peyrin-Biroulet L, Tsantes AG, Brunetta E, Tsantes AE, Bonovas S. The Brain-Gut Axis: Psychological Functioning and Inflammatory Bowel Diseases. J Clin Med 2021; 10:377. [PMID: 33498197 PMCID: PMC7863941 DOI: 10.3390/jcm10030377] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Revised: 01/11/2021] [Accepted: 01/18/2021] [Indexed: 02/07/2023] Open
Abstract
The brain-gut axis represents a complex bi-directional system comprising multiple interconnections between the neuroendocrine pathways, the autonomous nervous system and the gastrointestinal tract. Inflammatory bowel disease (IBD), comprising Crohn's disease and ulcerative colitis, is a chronic, relapsing-remitting inflammatory disorder of the gastrointestinal tract with a multifactorial etiology. Depression and anxiety are prevalent among patients with chronic disorders characterized by a strong immune component, such as diabetes mellitus, cancer, multiple sclerosis, rheumatoid arthritis and IBD. Although psychological problems are an important aspect of morbidity and of impaired quality of life in patients with IBD, depression and anxiety continue to be under-diagnosed. There is lack of evidence regarding the exact mechanisms by which depression, anxiety and cognitive dysfunction may occur in these patients, and whether psychological disorders are the result of disease activity or determinants of the IBD occurrence. In this comprehensive review, we summarize the role of the brain-gut axis in the psychological functioning of patients with IBD, and discuss current preclinical and clinical data on the topic and therapeutic strategies potentially useful for the clinical management of these patients. Personalized pathways of psychological supports are needed to improve the quality of life in patients with IBD.
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Affiliation(s)
- Spyros Peppas
- Department of Gastroenterology, Athens Naval Hospital, 11521 Athens, Greece;
| | - Claudia Pansieri
- Department of Biomedical Sciences, Humanitas University, 20090 Milan, Italy; (C.P.); (S.D.); (E.B.)
- Humanitas Clinical and Research Center–IRCCS, 20089 Milan, Italy
| | - Daniele Piovani
- Department of Biomedical Sciences, Humanitas University, 20090 Milan, Italy; (C.P.); (S.D.); (E.B.)
- Humanitas Clinical and Research Center–IRCCS, 20089 Milan, Italy
| | - Silvio Danese
- Department of Biomedical Sciences, Humanitas University, 20090 Milan, Italy; (C.P.); (S.D.); (E.B.)
- Humanitas Clinical and Research Center–IRCCS, 20089 Milan, Italy
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology, Inserm U1256 NGERE, Nancy University Hospital, Lorraine University, 54500 Vandoeuvre-les-Nancy, France;
| | - Andreas G. Tsantes
- Attiko Hospital, School of Medicine, National and Kapodistrian University of Athens, 12462 Athens, Greece; (A.G.T.); (A.E.T.)
| | - Enrico Brunetta
- Department of Biomedical Sciences, Humanitas University, 20090 Milan, Italy; (C.P.); (S.D.); (E.B.)
- Humanitas Clinical and Research Center–IRCCS, 20089 Milan, Italy
| | - Argirios E. Tsantes
- Attiko Hospital, School of Medicine, National and Kapodistrian University of Athens, 12462 Athens, Greece; (A.G.T.); (A.E.T.)
| | - Stefanos Bonovas
- Department of Biomedical Sciences, Humanitas University, 20090 Milan, Italy; (C.P.); (S.D.); (E.B.)
- Humanitas Clinical and Research Center–IRCCS, 20089 Milan, Italy
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Hmar EBL, Paul S, Boruah N, Sarkar P, Borah S, Sharma HK. Apprehending Ulcerative Colitis Management With Springing Up Therapeutic Approaches: Can Nanotechnology Play a Nascent Role? CURRENT PATHOBIOLOGY REPORTS 2021. [DOI: 10.1007/s40139-020-00218-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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Marrie RA, Graff LA, Fisk JD, Patten SB, Bernstein CN. The Relationship Between Symptoms of Depression and Anxiety and Disease Activity in IBD Over Time. Inflamm Bowel Dis 2021; 27:1285-1293. [PMID: 33393632 PMCID: PMC8314114 DOI: 10.1093/ibd/izaa349] [Citation(s) in RCA: 80] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Indexed: 02/06/2023]
Abstract
BRACKGROUND We aimed to examine associations between elevated symptoms of depression and anxiety and disease activity in inflammatory bowel disease (IBD). Previous findings have been inconsistent and have not accounted for variability in the courses of these conditions over time. METHODS We followed 247 participants with IBD (153 Crohn's disease [CD], 94 ulcerative colitis [UC]) for 3 years. Annually, participants underwent an abdominal examination, reported therapies used for IBD, and completed the Hospital Anxiety and Depression Scale (HADS) questionnaire. We evaluated associations of elevated symptoms (scores ≥11) of anxiety (HADS-A) and depression (HADS-D) with the presence of active IBD as measured using the Powell Tuck Index for UC and the Harvey-Bradshaw Disease Activity Index for CD. We employed logistic regression with generalized estimating equations, simultaneously estimating between-person and within-person effects. RESULTS Of 247 participants, 15 (6.1%) had elevated symptoms of depression (HADS-D ≥11) at enrollment, 41 (16.6%) had elevated symptoms of anxiety (HADS-A ≥11), and 101 (40.9%) had active IBD. On average, individuals with elevated symptoms of depression (odds ratio [OR], 6.27; 95% CI, 1.39-28.2) and anxiety (OR, 2.17; 95% CI, 1.01-4.66) had increased odds of active IBD. Within individuals, elevations in symptoms of depression over time were associated with increased odds of active IBD (OR, 2.70; 95% CI, 1.15-6.34), but elevated symptoms of anxiety were not. After adjustment for covariates (including disease activity), elevated symptoms of depression were also associated with increased odds of biologic therapy use (OR, 2.02; 95% CI, 1.02-4.00). CONCLUSION Symptoms of depression and anxiety are associated with disease activity in IBD over time. Reducing these symptoms should be incorporated into the management of IBD.
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Affiliation(s)
- Ruth Ann Marrie
- Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, CANADA,Department of Community Health Sciences, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, CANADA,University of Manitoba IBD Clinical and Research Centre, Winnipeg, Manitoba, CANADA
| | - Lesley A Graff
- University of Manitoba IBD Clinical and Research Centre, Winnipeg, Manitoba, CANADA,Department of Clinical Health Psychology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, CANADA
| | - John D Fisk
- Departments of Psychiatry, Psychology & Neuroscience, and Medicine, Dalhousie University, Halifax, Nova Scotia, CANADA
| | - Scott B Patten
- Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, CANADA
| | - Charles N Bernstein
- Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, CANADA,University of Manitoba IBD Clinical and Research Centre, Winnipeg, Manitoba, CANADA,Address correspondence to: Charles N. Bernstein, MD, 804F-715 McDermot Avenue, University of Manitoba, Winnipeg, Manitoba, Canada R3E3P4. E-mail:
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33
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Zingone F, Siniscalchi M, Savarino EV, Barberio B, Cingolani L, D'Incà R, De Filippo FR, Camera S, Ciacci C. Perception of the COVID-19 Pandemic Among Patients With Inflammatory Bowel Disease in the Time of Telemedicine: Cross-Sectional Questionnaire Study. J Med Internet Res 2020; 22:e19574. [PMID: 33006945 PMCID: PMC7654503 DOI: 10.2196/19574] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Revised: 07/07/2020] [Accepted: 09/14/2020] [Indexed: 01/08/2023] Open
Abstract
Background After the COVID-19 outbreak, the Italian Government stopped most regular health care activity. As a result, patients with inflammatory bowel disease (IBD) had limited access to outpatient clinics and hospitals. Objective This study aimed to analyze the perception of the COVID-19 emergency among patients with IBD during the early weeks of the lockdown. Methods We invited adult patients with IBD from the University of Salerno (Campania, South Italy) and the University of Padua (Veneto, North Italy) by email to answer an ad hoc anonymous survey about COVID-19. We also collected data on demographic and disease characteristics. Results In total, 167 patients with IBD from Padua and 83 patients from Salerno answered the survey (age: mean 39.7 years, SD 13.9 years; female: n=116, 46.4%). We found that patients with IBD were particularly worried about the COVID-19 pandemic (enough: 77/250, 30.8%; much/very much: 140/250, 56.0%), as they felt more vulnerable to COVID-19 due to their condition (enough: 70/250, 28.0%; much/very much: 109/250, 43.6%). Patients with IBD from the red zone of Veneto were more worried than patients from Campania (P=.001), and men felt more susceptible to the virus than women (P=.05). Additionally, remote medicine was appreciated more by younger patients than older patients (P=.04). Conclusions The results of our survey demonstrate that the lockdown had a significant impact on the psychological aspects of patients with IBD and suggest the need for increasing communication with patients with IBD (eg, through telemedicine) to ensure patients receive adequate health care, correct information, and proper psychological support.
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Affiliation(s)
- Fabiana Zingone
- Inflammatory Bowel Disease Center, Department of Surgery, Oncology, and Gastroenterology, University of Padua, Padua, Italy
| | - Monica Siniscalchi
- Inflammatory Bowel Disease Center, Department of Medicine, Surgery, Dentistry, Scuola Medica Salernitana, University of Salerno, University Hospital San Giovanni di Dio e Ruggi d'Aragona, Salerno, Italy
| | - Edoardo Vincenzo Savarino
- Inflammatory Bowel Disease Center, Department of Surgery, Oncology, and Gastroenterology, University of Padua, Padua, Italy
| | - Brigida Barberio
- Inflammatory Bowel Disease Center, Department of Surgery, Oncology, and Gastroenterology, University of Padua, Padua, Italy
| | - Linda Cingolani
- Inflammatory Bowel Disease Center, Department of Surgery, Oncology, and Gastroenterology, University of Padua, Padua, Italy
| | - Renata D'Incà
- Inflammatory Bowel Disease Center, Department of Surgery, Oncology, and Gastroenterology, University of Padua, Padua, Italy
| | - Francesca Romana De Filippo
- Inflammatory Bowel Disease Center, Department of Medicine, Surgery, Dentistry, Scuola Medica Salernitana, University of Salerno, University Hospital San Giovanni di Dio e Ruggi d'Aragona, Salerno, Italy
| | - Silvia Camera
- Inflammatory Bowel Disease Center, Department of Medicine, Surgery, Dentistry, Scuola Medica Salernitana, University of Salerno, University Hospital San Giovanni di Dio e Ruggi d'Aragona, Salerno, Italy
| | - Carolina Ciacci
- Inflammatory Bowel Disease Center, Department of Medicine, Surgery, Dentistry, Scuola Medica Salernitana, University of Salerno, University Hospital San Giovanni di Dio e Ruggi d'Aragona, Salerno, Italy
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Schoultz M, Beattie M, Gorely T, Leung J. Assessment of causal link between psychological factors and symptom exacerbation in inflammatory bowel disease: a systematic review utilising Bradford Hill criteria and meta-analysis of prospective cohort studies. Syst Rev 2020; 9:169. [PMID: 32738908 PMCID: PMC7395978 DOI: 10.1186/s13643-020-01426-2] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2019] [Accepted: 07/10/2020] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Psychological stress is a prevalent factor in inflammatory bowel disease (IBD) with detrimental effects on patients' quality of life and possibly disease course. Although the aetiology of symptom exacerbation in IBD has been explored, determining any causation between psychological stress and symptom worsening remains challenging and requires a methodologically rigorous approach. AIM The aim of this systematic review with meta-analysis was to determine a causal relationship between psychological stress and symptom exacerbation in IBD, subsequently utilising Bradford Hill's criteria (approach never used in this topic area before) to evaluate the likelihood of causal associations. METHODS Medline, EMBASE, CINAHL and PsycInfo were searched for relevant studies up to July 20, 2019. Data extraction and quality appraisal were performed by two independent reviewers. Results of all retained papers were presented as a narrative synthesis. A random-effect meta-analysis was conducted on studies meeting the criteria for meta-analysis. Bradford Hill criteria were applied to assess the causality of the relationship between all psychological factors and symptom exacerbation. RESULTS The searches yielded 2472 potential articles. Nineteen clinical prospective cohort studies were eligible for the narrative review with five suitable for the meta-analysis. Meta-analysis showed depression, anxiety and perceived stress did not have a statistically significant association with an increased risk of symptom exacerbation. Four of the Bradford Hill criteria were met which indicates that there is weak to moderate evidence of a causal association between all the psychological factors and disease activity. Inconsistent results and a dearth of studies using the same tools for measuring psychological factors suggest the need for more research to be done to facilitate more conclusive findings. CONCLUSIONS This original review utilising Bradford Hill criteria in addition to meta-analysis to evaluate the causality of relationship between psychological factors and symptom exacerbation in IBD provides evidence that psychological factors have a weak to moderate causal involvement in IBD symptom exacerbation. However, when combining this finding with the outcomes of the meta-analysis, we can say that the results were inconclusive. Interventions to reduce the associated psychological impact should be part of the treatment plan for patients with IBD. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42012003143.
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Affiliation(s)
- Mariyana Schoultz
- School of Health and Society, University of Salford, Manchester, UK.
| | - Michelle Beattie
- Centre for Health Sciences, University of Highlands and Islands, Inverness, Scotland, UK
| | - Trish Gorely
- Centre for Health Sciences, University of Highlands and Islands, Inverness, Scotland, UK
| | - Janni Leung
- Faculty of Health and Behavioural Sciences, The University of Queensland, Brisbane, Australia
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Abstract
Various lifestyle factors including physical activity and obesity, stress, sleep, and smoking may modify the risk of developing inflammatory bowel diseases (IBDs). In patients with established IBD, these lifestyle factors may significantly impact the natural history and clinical outcomes. Recreational exercise decreases the risk of flare and fatigue in patients with IBD. In contrast, obesity increases the risk of relapse and is associated with higher anxiety, depression, fatigue, and pain and higher health care utilization. Obesity also modifies pharmacokinetics of biologic agents unfavorably and is associated with a higher risk of treatment failure. Sleep disturbance is highly prevalent in patients with IBD, independent of disease activity, and increases the risk of relapse and chronic fatigue. Similarly, stress, particularly perceived stress rather than major life events, may trigger symptomatic flare in patients with IBD, although its impact on inflammation is unclear. Cigarette smoking is associated with unfavorable outcomes including the risk of corticosteroid dependence, surgery, and disease progression in patients with Crohn's disease; in contrast, smoking does not significantly impact outcomes in patients with ulcerative colitis, although some studies suggest that it may be associated with a lower risk of flare. The effect of alcohol and cannabis use in patients with IBD is inconsistent, with some studies suggesting that cannabis may decrease chronic pain in patients with IBD, without a significant effect of biological remission. Although these lifestyle factors are potentially modifiable, only a few interventional studies have been conducted. Trials of structured exercise and psychological therapy including mindfulness-based therapies such as meditation and yoga and gut-directed hypnotherapy have not consistently demonstrated benefit in clinical and/or endoscopic disease activity in IBD, although may improve overall quality of life.
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Araki M, Shinzaki S, Yamada T, Arimitsu S, Komori M, Shibukawa N, Mukai A, Nakajima S, Kinoshita K, Kitamura S, Murayama Y, Ogawa H, Yasunaga Y, Oshita M, Fukui H, Masuda E, Tsujii M, Kawai S, Hiyama S, Inoue T, Tanimukai H, Iijima H, Takehara T. Psychologic stress and disease activity in patients with inflammatory bowel disease: A multicenter cross-sectional study. PLoS One 2020; 15:e0233365. [PMID: 32453762 PMCID: PMC7250441 DOI: 10.1371/journal.pone.0233365] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2019] [Accepted: 05/04/2020] [Indexed: 12/13/2022] Open
Abstract
Background and aims Psychologic stress can affect the pathogenesis of inflammatory bowel disease (IBD), but the precise contribution of psychologic stress to IBD remains unclear. We investigated the association of psychologic stress with disease activity in patients with IBD, especially in terms of mental state and sleep condition. Methods This was a multi-center observational study comprising 20 institutions. Data were collected using survey forms for doctors and questionnaires for patients, and the association of psychologic stress with clinical parameters was investigated. Mental state was evaluated using the Center for Epidemiologic Studies Depression (CES-D) scale, and sleep condition was evaluated by querying patients about the severity of insomnia symptoms. Results A total of 1078 IBD patients were enrolled, including 303 patients with Crohn’s disease and 775 patients with ulcerative colitis. Seventy-five percent of IBD patients believed that psychologic stress triggered an exacerbation of their disease (PSTE group) and 25% did not (non-PSTE group). The CES-D scores were significantly higher for patients with clinically active disease than for those in remission in the PSTE group (median (interquartile range) = 7 (4–9.5) vs. 5 (3–7), p < .0001), but not in the non-PSTE group (5 (2–8) vs. 4 (3–7), p = 0.78). Female sex and disease exacerbation by factors other than psychologic stress were independent factors of psychologic stress-triggered disease exacerbation. Also, patients with insomnia had higher disease activity than those without insomnia, especially in the PSTE group. Conclusions A worsened mental state correlates with disease activity in IBD patients, especially those who believe that their disease is exacerbated by psychologic stress.
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Affiliation(s)
- Manabu Araki
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Shinichiro Shinzaki
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Takuya Yamada
- Department of Gastroenterology, National Hospital Organization Osaka National Hospital, Osaka, Japan
| | | | - Masato Komori
- Department of Gastroenterology, Osaka Rosai Hospital, Sakai, Osaka, Japan
| | | | - Akira Mukai
- Department of Gastroenterology, Sumitomo Hospital, Osaka, Japan
| | - Sachiko Nakajima
- Department of Gastroenterology, Toyonaka Municipal Hospital, Toyonaka, Osaka, Japan
| | - Kazuo Kinoshita
- Department of Gastroenterology, Otemae Hospital, Osaka, Japan
| | - Shinji Kitamura
- Department of Gastroenterology, Sakai City Medical Center, Sakai, Osaka, Japan
| | - Yoko Murayama
- Department of Gastroenterology and Hepatology, Itami City Hospital, Itami, Hyogo, Japan
| | - Hiroyuki Ogawa
- Department of Gastroenterology, Nishinomiya Municipal Central Hospital, Nishinomiya, Hyogo, Japan
| | - Yuichi Yasunaga
- Department of Gastroenterology, Hyogo Prefectural Nishinomiya Hospital, Nishinomiya, Hyogo, Japan
| | - Masahide Oshita
- Department of Internal Medicine, Osaka Police Hospital, Osaka, Japan
| | - Hiroyuki Fukui
- Department of Gastroenterology, Yao Municipal Hospital, Yao, Osaka, Japan
| | - Eiji Masuda
- Department of Gastroenterology, National Hospital Organization Osaka-minami National Hospital, Kawachinagano, Osaka, Japan
| | - Masahiko Tsujii
- Department of Gastroenterology, Higashiosaka City Medical Center, Higashiosaka, Osaka, Japan
| | - Shoichiro Kawai
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Satoshi Hiyama
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Takahiro Inoue
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Hitoshi Tanimukai
- Faculty of Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Hideki Iijima
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
- * E-mail:
| | - Tetsuo Takehara
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
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Koch AK, Schöls M, Langhorst J, Dobos G, Cramer H. Perceived stress mediates the effect of yoga on quality of life and disease activity in ulcerative colitis. Secondary analysis of a randomized controlled trial. J Psychosom Res 2020; 130:109917. [PMID: 31927346 DOI: 10.1016/j.jpsychores.2019.109917] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2019] [Revised: 12/23/2019] [Accepted: 12/31/2019] [Indexed: 01/25/2023]
Abstract
OBJECTIVE Yoga positively affects health-related quality of life and disease activity in ulcerative colitis. The underlying modes of action remain unclear. Within the present study we hypothesized that patients´ perceived stress mediates the effects of yoga on health-related quality of life and disease activity. METHODS This is a secondary analysis of a randomized controlled trial comparing the effects of yoga to written self-care advice in patients with inactive ulcerative colitis and impaired quality of life. Perceived stress was assessed using the Perceived Stress Questionnaire, health-related quality of life using the Inflammatory Bowel Disease Questionnaire and disease activity using the Clinical Activity Index. Outcomes were assessed at weeks 0, 12 and 24. RESULTS Seventy-seven patients participated. Thirty-nine patients attended the 12 supervised weekly yoga sessions (71.8% women; 45.0 ± 13.3 years) and 38 patients written self-care advice (78.9% women; 46.1 ± 10.4 years). Perceived stress correlated significantly with health-related quality of life and disease activity at week 24. Perceived stress at week 12 fully mediated the effects of yoga on health-related quality of life (B = 16.23; 95% Confidence interval [6.73; 28.40]) and disease activity (B = -0.28; 95% Confidence interval [-0.56; -0.06]) at week 24. CONCLUSION Our findings confirm the importance of perceived stress in reducing disease activity and increasing health-related quality of life in patients with ulcerative colitis and impaired quality of life. Practitioners should keep psychosocial risk in mind as a risk factor for disease exacerbation, and consider yoga as an adjunct intervention for highly stressed patients with ulcerative colitis. CLINICALTRIALS. GOV REGISTRATION NUMBER The trial was registered at clinicaltrials.gov prior to patient recruitment (registration number NCT02043600).
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Affiliation(s)
- Anna K Koch
- Department of Internal and Integrative Medicine, Kliniken Essen-Mitte, Faculty of Medicine, University of Duisburg-Essen, Essen, Germany.
| | - Margarita Schöls
- Department of Internal and Integrative Medicine, Kliniken Essen-Mitte, Faculty of Medicine, University of Duisburg-Essen, Essen, Germany
| | - Jost Langhorst
- Department of Internal and Integrative Medicine, Klinikum Bamberg, Bamberg, Germany.
| | - Gustav Dobos
- Department of Internal and Integrative Medicine, Kliniken Essen-Mitte, Faculty of Medicine, University of Duisburg-Essen, Essen, Germany.
| | - Holger Cramer
- Department of Internal and Integrative Medicine, Kliniken Essen-Mitte, Faculty of Medicine, University of Duisburg-Essen, Essen, Germany.
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Labanski A, Langhorst J, Engler H, Elsenbruch S. Stress and the brain-gut axis in functional and chronic-inflammatory gastrointestinal diseases: A transdisciplinary challenge. Psychoneuroendocrinology 2020; 111:104501. [PMID: 31715444 DOI: 10.1016/j.psyneuen.2019.104501] [Citation(s) in RCA: 113] [Impact Index Per Article: 22.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2019] [Revised: 10/17/2019] [Accepted: 10/29/2019] [Indexed: 12/18/2022]
Abstract
The broad role of stress in the brain-gut axis is widely acknowledged, with implications for multiple prevalent health conditions that are characterized by chronic gastrointestinal symptoms. These include the functional gastrointestinal disorders (FGID), such as irritable bowel syndrome and functional dyspepsia, as well as inflammatory bowel diseases (IBD) like ulcerative colitis and Crohn's disease. Although the afferent and efferent pathways linking the gut and the brain are modulated by stress, the fields of neurogastroenterology and psychoneuroendocrinology (PNE)/ psychoneuroimmunology (PNI) remain only loosely connected. We aim to contribute to bringing these fields closer together by drawing attention to a fascinating, evolving research area, targeting an audience with a strong interest in the role of stress in health and disease. To this end, this review introduces the concept of the brain-gut axis and its major pathways, and provides a brief introduction to epidemiological and clinical aspects of FGIDs and IBD. From an interdisciplinary PNE/PNI perspective, we then detail current knowledge regarding the role of chronic and acute stress in the pathophysiology of FGID and IBD. We provide an overview of evidence regarding non-pharmacological treatment approaches that target central or peripheral stress mechanisms, and conclude with future directions, particularly those arising from recent advances in the neurosciences and discoveries surrounding the gut microbiota.
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Affiliation(s)
- Alexandra Labanski
- Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Jost Langhorst
- Chair for Integrative Medicine, University of Duisburg-Essen, Essen, Germany; Clinic for Internal and Integrative Medicine, Klinikum Bamberg, Bamberg, Germany
| | - Harald Engler
- Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Sigrid Elsenbruch
- Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
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Mackner LM, Hatzakis E, Allen JM, Davies RH, Kim SC, Maltz RM, Bailey MT. Fecal microbiota and metabolites are distinct in a pilot study of pediatric Crohn's disease patients with higher levels of perceived stress. Psychoneuroendocrinology 2020; 111:104469. [PMID: 31654986 PMCID: PMC6956257 DOI: 10.1016/j.psyneuen.2019.104469] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2019] [Revised: 08/14/2019] [Accepted: 09/30/2019] [Indexed: 12/14/2022]
Abstract
Stress is associated with increased Crohn's Disease (CD) activity. This pilot study tested whether pediatric patients with CD reporting higher levels of perceived stress exhibited differences in the fecal microbiome and metabolome. The perceived stress scale (PSS) questionnaire was administered within 2 days of collecting a stool sample for microbiome (using 16S rRNA gene sequencing) and metabolome (using NMR metabolomics) analyses. Higher levels of perceived stress were correlated with increased disease activity on the short Pediatric Crohn's Disease Activity Index (sPCDAI). Patients with High PSS scores vs. Low PSS scores based on a median split had significantly lower relative abundances of Firmicutes and Anaerostipes, as well as higher relative abundances of Parabacteroides. Fecal alanine and nicotinate were also significantly different in patients with High vs. Low PSS Scores. This pilot study suggests that the fecal microbiome and metabolome differs in pediatric patients with CD and high perceived stress.
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Affiliation(s)
- Laura M. Mackner
- Center for Biobehavioral Health, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43205,Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH 43210
| | - Emmanuel Hatzakis
- Department of Food Science, The Ohio State University, Columbus, OH 43205
| | - Jacob M. Allen
- Center for Microbial Pathogenesis, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43205
| | - Ronald H. Davies
- Center for Microbial Pathogenesis, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43205
| | - Sandra C. Kim
- Gastroenterology, Hepatology, and Nutrition; UPMC Children’s Hospital of Pittsburgh and the University of Pittsburgh School of Medicine, Pittsburgh, PA 1522
| | - Ross M. Maltz
- Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH 43210.,Center for Microbial Pathogenesis, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43205.,Gastroenterology, Hepatology and Nutrition, Nationwide Children’s Hospital, Columbus, OH 43205.,Oral and GI Research Affinity Group, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43205
| | - Michael T. Bailey
- Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH 43210.,Center for Microbial Pathogenesis, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43205.,Oral and GI Research Affinity Group, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43205
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40
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The Role of Distress and Pain Catastrophizing on the Health-related Quality of Life of Children With Inflammatory Bowel Disease. J Pediatr Gastroenterol Nutr 2019; 69:e99-e104. [PMID: 31335840 DOI: 10.1097/mpg.0000000000002447] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVES Inflammatory bowel disease (IBD) can be particularly challenging during the pediatric age with a relevant impact on patient's health-related quality of life (HRQoL). Disease activity accounts for only a small part of the variability in HRQoL, and psychological factors can play a significant role. We aimed to evaluate the impact of patient's distress and pain catastrophizing on children and adolescents with IBD. METHODS We prospectively recruited children aged 8 to 18 with IBD and recorded demographic and disease characteristics. Patients answered questionnaires on HRQoL (IMPACT III), distress (distress thermometer [DT]), and pain catastrophizing (Pain Catastrophizing Scale-Children [PCS-C]). Univariate and multivariate regression models analysis were used to evaluate correlations between patients' characteristics, disease activity, distress, pain catastrophizing, and HRQoL. RESULTS Seventy-one patients were enrolled (median age 13.6, 49.3% Crohn disease, 50.7% ulcerative colitis). Median HRQoL, DT, and PCS-C scores were 78.6 (interquartile range 68.0-87.1), 3.0 (1.0-5.0), and 12.0 (4.0-23.0), respectively. Patient's distress and pain catastrophizing levels significantly correlated with HRQoL. Pain catastrophizing had the strongest impact on HRQoL (Spearman correlation coefficient, ρ = 0.73), followed by distress (ρ = 0.67), and ulcerative colitis severity (ρ = 0.67). The DT and the PCS-C scores were significantly associated (ρ = 0.46). CONCLUSIONS Distress and pain catastrophizing have a significative impact on HRQoL in young patients with IBD. Physicians should recognize the role of these psychological factors and consider cognitive-behavioral therapy to optimize the patient's health.
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Asscher VER, Lee-Kong FVY, Kort ED, van Deudekom FJ, Mooijaart SP, Maljaars PWJ. Systematic Review: Components of a Comprehensive Geriatric Assessment in Inflammatory Bowel Disease-A Potentially Promising but Often Neglected Risk Stratification. J Crohns Colitis 2019; 13:1418-1432. [PMID: 31002331 PMCID: PMC6821240 DOI: 10.1093/ecco-jcc/jjz082] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND The population of older patients with inflammatory bowel disease [IBD] is increasing. Patient age does not fully account for poor outcomes and its clinical utility for risk stratification is limited. Comprehensive geriatric assessment [CGA], comprising a somatic, functional, mental, and social assessment or frailty, could be a predictor tool. AIMS To systematically review literature on the kind of components of a CGA being used in adult IBD patients and the association of these components with adverse health outcomes. METHODS An electronic literature search was performed on January 16, 2018, using PubMed, Embase, Web of Science, the Cochrane Library, CENTRAL, Emcare, and PsycINFO. Longitudinal studies relating somatic, functional, mental, and social assessment or frailty to adverse health outcomes during follow-up in IBD patients were included. The Newcastle-Ottawa scale was used to assess individual study quality. RESULTS Of 4080 identified citations, 27 studies were included, reporting 169 associations. Median sample size was 108 patients (interquartile range [IQR] 60-704). No studies performed subgroup analyses on older patients, and the highest mean age reported was 52.7 years. Somatic and functional assessments were used in three studies, mental in 24, and social in five. No study assessed cognitive status, functional performance, or frailty. In 62 associations [36.7%], components of a CGA were significantly associated with adverse health outcome measurements. CONCLUSIONS Components of a CGA were associated with adverse health outcomes in IBD patients, but older patients were under-represented. More studies among older patients with IBD are warranted to further establish the clinical impact of a CGA.
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Affiliation(s)
- Vera E R Asscher
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands,Corresponding author: Vera E. R. Asscher, MD, Department of Gastroenterology and Hepatology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden. Tel.: +31 71 526 3507; Fax: +31 71 524 8115;
| | - Felicia V Y Lee-Kong
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands
| | - Esther D Kort
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands
| | - Floor J van Deudekom
- Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands
| | - Simon P Mooijaart
- Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands,Institute for Evidence-Based Medicine in Old Age [IEMO], Leiden, The Netherlands
| | - P W Jeroen Maljaars
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands
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Wang SL, Shao BZ, Zhao SB, Chang X, Wang P, Miao CY, Li ZS, Bai Y. Intestinal autophagy links psychosocial stress with gut microbiota to promote inflammatory bowel disease. Cell Death Dis 2019; 10:391. [PMID: 31564717 PMCID: PMC6766473 DOI: 10.1038/s41419-019-1634-x] [Citation(s) in RCA: 69] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2019] [Revised: 04/14/2019] [Accepted: 05/07/2019] [Indexed: 12/14/2022]
Abstract
Psychosocial stress is a critical inducing factor of inflammatory bowel diseases (IBD), while autophagy is a novel central issue of IBD development. The present study investigated the potential role of autophagy in stress-related IBD in patients and animal model. The correlation between psychosocial stress and intestinal autophagy was determined in 23 patients with IBD. Corticotropin-releasing hormone (CRH), a well-established inducer of psychosocial stress, was administrated in dextran sulfate sodium (DSS)-induced IBD mice and lipopolysaccharide (LPS)-stimulated bone marrow-derived macrophages (BMDM). In IBD patients, the autophagy markers beclin-1, LC3-II/I ratio, Atg16L1, and Atg4B were significantly enhanced. The psychosocial stress score was positively associated with the levels of beclin-1 and the LC3II/I ratio in intestinal biopsy specimens. In IBD mouse model, CRH significantly aggravated intestinal inflammation, increased Paneth cell metaplasia, and enhanced intestinal autophagy (beclin-1, Atg16L1, PIK3R4, and Atg4B upregulation; GAA, CTSD, and PPKAA1 downregulation). Additionally, the CRH-induced gut microbial dysbiosis was evidenced by a marked increase in the number of detrimental bacteria. In LPS-stimulated BMDM, CRH substantially increased M1/M2 polarization and thus promoted inflammation. In both IBD mice and LPS-treated BMDM, blockade of autophagy by chloroquine abrogated the unbeneficial effects of CRH, whereas autophagy inducer rapamycin resulted in a pronounced protective effect against IBD lesion. Our data demonstrate that psychosocial stress may link the enhanced intestinal autophagy by modulating gut microbiota and inflammation to aggravate IBD. These data indicate autophagy as a promising therapeutic target for psychosocial stress-related IBD.
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Affiliation(s)
- Shu-Ling Wang
- Department of Gastroenterology, Changhai Hospital, Second Military Medical University/Naval Medical University, Shanghai, China
| | - Bo-Zong Shao
- General Hospital of the Chinese People's Liberation Army, Beijing, China
| | - Sheng-Bing Zhao
- Department of Gastroenterology, Changhai Hospital, Second Military Medical University/Naval Medical University, Shanghai, China
| | - Xin Chang
- Department of Gastroenterology, Changhai Hospital, Second Military Medical University/Naval Medical University, Shanghai, China
| | - Pei Wang
- Department of Pharmacology, Second Military Medical University/Naval Medical University, Shanghai, China
| | - Chao-Yu Miao
- Department of Pharmacology, Second Military Medical University/Naval Medical University, Shanghai, China.
| | - Zhao-Shen Li
- Department of Gastroenterology, Changhai Hospital, Second Military Medical University/Naval Medical University, Shanghai, China.
| | - Yu Bai
- Department of Gastroenterology, Changhai Hospital, Second Military Medical University/Naval Medical University, Shanghai, China.
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Bakkum L, Willemen AM, Zoetebier L, Bouts AH. A longitudinal study on the effects of psychological stress on proteinuria in childhood steroid-sensitive nephrotic syndrome. J Psychosom Res 2019; 121:8-13. [PMID: 30739735 PMCID: PMC6543065 DOI: 10.1016/j.jpsychores.2019.01.011] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2018] [Revised: 01/16/2019] [Accepted: 01/16/2019] [Indexed: 02/05/2023]
Abstract
OBJECTIVE Steroid-sensitive nephrotic syndrome (SSNS) in children is often complicated by one or more relapses, as manifested by the appearance of proteinuria. Besides health-related triggers, psychological stress might be related to relapse. This longitudinal study examined the link between perceived stress, emotional valence (feeling happy vs. unhappy) and daily reported proteinuria, and investigated the temporal relation between stressful events and proteinuria. METHOD Sixteen children (4-13 years) diagnosed with SSNS were included. Patients kept an online diary for an average of 124 days, wherein they reported proteinuria (n = 1985 urine samples), perceived stress, emotional valence, medication use and health complaints. Stressful days were determined at the start of the study. Using multilevel analysis, the following associations were tested: (1) the relation between perceived stress, emotional valence and proteinuria, and (2) the temporal relation between stressful days and proteinuria. RESULTS Appearance of proteinuria was reported in 410/1985 urine samples. Perceived stress and not emotional valence significantly predicted proteinuria (95% CI [0.11, 0.27]), even five days later. There was a significant temporal association between stressful days and proteinuria (95% CI [0.22, 1.14]). The effect sizes of these associations were small, f = 0.04 and f = 0.12, respectively. CONCLUSIONS Our findings suggest that psychological stress may trigger proteinuria in children with SSNS. Future research in larger samples is needed to support our findings.
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Affiliation(s)
- Lianne Bakkum
- Department of Public Health and Primary Care, Primary Care Unit, University of Cambridge, Cambridge, United Kingdom; Department of Clinical Child and Family Studies and Amsterdam Public Health, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
| | - Agnes Maresa Willemen
- Department of Clinical Child and Family Studies and Amsterdam Public Health, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | | | - Antonia H Bouts
- Department of Pediatric Nephrology, Emma Children's Hospital, AMC, Amsterdam, The Netherlands
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Gracie DJ, Hamlin PJ, Ford AC. The influence of the brain-gut axis in inflammatory bowel disease and possible implications for treatment. Lancet Gastroenterol Hepatol 2019; 4:632-642. [PMID: 31122802 DOI: 10.1016/s2468-1253(19)30089-5] [Citation(s) in RCA: 206] [Impact Index Per Article: 34.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2019] [Revised: 03/05/2019] [Accepted: 03/06/2019] [Indexed: 12/11/2022]
Abstract
Brain-gut interactions affect psychological wellbeing and symptom reporting in functional gastrointestinal disorders; the presence of anxiety or depression is associated with the development of new-onset gastrointestinal symptoms, and the presence of gastrointestinal symptoms is associated with the development of psychological disorders de novo. In inflammatory bowel diseases (IBD), the reporting of irritable bowel syndrome (IBS)-type symptoms by patients with quiescent disease is common, and is associated with psychological disorders, impaired quality of life, and increased health-care use. In IBD, data from observational studies suggest that psychological disorders might be associated with relapse of disease activity, and that inflammatory activity is associated with the development of new psychological disorders, as has been described for functional gastrointestinal disorders such as IBS and functional dyspepsia. The brain-gut axis provides the physiological link between the CNS and gastrointestinal tract that might facilitate these relationships. In IBS, treatments targeting disordered brain-gut axis activity, including psychological therapies and antidepressants, might lead to improved symptoms and quality of life. However, in IBD, the benefit of these treatments is less certain because of a scarcity of interventional studies. Despite the scarcity of trials, observational data suggest that the effect of disordered brain-gut axis activity in IBD is substantial, and scope remains for further well designed trials of psychological therapies and antidepressants, particularly in the subset of patients who have coexistent psychological disorders, or in those who report IBS-type symptoms. Integrating these treatments into a biopsychosocial model of care has the potential to improve both psychological wellbeing and quality of life in some patients with IBD, reducing health-care use and altering the natural history of disease.
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Affiliation(s)
- David J Gracie
- Leeds Gastroenterology Institute, St James's University Hospital, Leeds Teaching Hospitals National Health Service Trust, Leeds, UK.
| | - P John Hamlin
- Leeds Gastroenterology Institute, St James's University Hospital, Leeds Teaching Hospitals National Health Service Trust, Leeds, UK
| | - Alexander C Ford
- Leeds Gastroenterology Institute, St James's University Hospital, Leeds Teaching Hospitals National Health Service Trust, Leeds, UK; Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK
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Wintjens DSJ, de Jong MJ, van der Meulen-de Jong AE, Romberg-Camps MJ, Becx MC, Maljaars JP, van Bodegraven AA, Mahmmod N, Markus T, Haans J, Masclee AAM, Winkens B, Jonkers DMAE, Pierik MJ. Novel Perceived Stress and Life Events Precede Flares of Inflammatory Bowel Disease: A Prospective 12-Month Follow-Up Study. J Crohns Colitis 2019; 13:410-416. [PMID: 30371776 DOI: 10.1093/ecco-jcc/jjy177] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Inflammatory bowel disease [IBD] is characterized by recurrent disease flares. The impact of psychosocial wellbeing on the occurrence of flares is unclear. In this prospective study, we aimed to evaluate the association between patient-reported psychosocial wellbeing and disease flares using continuous monitoring. METHODS Consecutive IBD patients were recruited from the myIBDcoach telemedicine study cohort. Over 12 months, participants reported on disease activity together with anxiety, depression, fatigue, perceived stress and life events every 1-3 months. Flares were defined using a combination of clinical disease activity and additional measurements. Generalized estimating equation models were used to assess associations between psychosocial wellbeing and flares over time. The influences of both the presence of psychosocial symptoms in general as well as novel psychosocial symptoms were analysed. RESULTS In total, 417 patients were included. Forty-nine patients [11.8%] experienced a flare during the study period. The occurrence of life events in the preceding 3 months was positively associated with flares (odds ratio [OR] = 1.81; 95% confidence interval [CI] = 1.04-3.17), while the presence of anxiety, depression, fatigue and perceived stress in general was not. However, novel perceived stress [OR = 2.92; 95% CI = 1.44-5.90] was associated with flares. CONCLUSIONS The occurrence of life events and novel perceived stress are associated with disease flares in the next 3 months, while the presence of perceived stress in general is not. These findings underline the importance of continuous personalized monitoring of IBD patients and may contribute to the prevention of disease flares.
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Affiliation(s)
- Dion S J Wintjens
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Centre, Maastricht, The Netherlands.,NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre, Maastricht, The Netherlands
| | - Marin J de Jong
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Centre, Maastricht, The Netherlands
| | | | - Mariëlle J Romberg-Camps
- Department of Gastroenterology and Hepatology, Zuyderland Medical Centre, Sittard-Geleen, The Netherlands
| | - Marco C Becx
- Department of Gastroenterology and Hepatology, St. Antonius Hospital, Nieuwegein, The Netherlands
| | - Jeroen P Maljaars
- Department of Gastroenterology and Hepatology, Leiden University Medical Centre, Leiden, The Netherlands
| | - Ad A van Bodegraven
- Department of Gastroenterology and Hepatology, Zuyderland Medical Centre, Sittard-Geleen, The Netherlands
| | - Nofel Mahmmod
- Department of Gastroenterology and Hepatology, St. Antonius Hospital, Nieuwegein, The Netherlands
| | - Tineke Markus
- CCUVN, Dutch IBD Patients Organization, Woerden, The Netherlands
| | - Jeoffrey Haans
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Centre, Maastricht, The Netherlands
| | - Ad A M Masclee
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Centre, Maastricht, The Netherlands.,NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre, Maastricht, The Netherlands
| | - Bjorn Winkens
- Department of Methodology and Statistics, Care and Public Health Research Institute (CAPHRI), Maastricht, The Netherlands
| | - Daisy M A E Jonkers
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Centre, Maastricht, The Netherlands.,NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre, Maastricht, The Netherlands
| | - Marie J Pierik
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Centre, Maastricht, The Netherlands.,NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre, Maastricht, The Netherlands
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Gut-brain actions underlying comorbid anxiety and depression associated with inflammatory bowel disease. Acta Neuropsychiatr 2018; 30:275-296. [PMID: 28270247 DOI: 10.1017/neu.2017.3] [Citation(s) in RCA: 118] [Impact Index Per Article: 16.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
UNLABELLED IntroductionInflammatory bowel disease (IBD) is a chronic relapsing and remitting disorder characterised by inflammation of the gastrointestinal tract. There is a growing consensus that IBD is associated with anxiety- and depression-related symptoms. Psychological symptoms appear to be more prevalent during active disease states with no difference in prevalence between Crohn's disease and ulcerative colitis. Behavioural disturbances including anxiety- and depression-like symptoms have also been observed in animal models of IBD. RESULTS The likely mechanisms underlying the association are discussed with particular reference to communication between the gut and brain. The close bidirectional relationship known as the gut-brain axis includes neural, hormonal and immune communication links. Evidence is provided for a number of interacting factors including activation of the inflammatory response system in the brain, the hypothalamic-pituitary-adrenal axis, and brain areas implicated in altered behaviours, changes in blood brain barrier integrity, and an emerging role for gut microbiota and response to probiotics in IBD.DiscussionThe impact of psychological stress in models of IBD remains somewhat conflicted, however, it is weighted in favour of stress or early stressful life events as risk factors in the development of IBD, stress-induced exacerbation of inflammation and relapse. CONCLUSION It is recommended that patients with IBD be screened for psychological disturbance and treated accordingly as intervention can improve quality of life and may reduce relapse rates.
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Dobos GJ. [Not Available]. MMW Fortschr Med 2018; 160:22-24. [PMID: 30259455 DOI: 10.1007/s15006-018-0917-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/08/2023]
Affiliation(s)
- Gustav J Dobos
- Kliniken Essen-Mitte, Klinik für Naturheilkunde und Integrative Medizin, Am Deimelsberg 34a, D-45276, Essen, Deutschland.
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Sharif K, Watad A, Coplan L, Lichtbroun B, Krosser A, Lichtbroun M, Bragazzi NL, Amital H, Afek A, Shoenfeld Y. The role of stress in the mosaic of autoimmunity: An overlooked association. Autoimmun Rev 2018; 17:967-983. [PMID: 30118900 DOI: 10.1016/j.autrev.2018.04.005] [Citation(s) in RCA: 61] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2018] [Accepted: 04/04/2018] [Indexed: 12/22/2022]
Abstract
Stress is defined as the pscyophysiological reaction in which the steady state is disturbed or threatened. Stress is not always perceived as a negative response. Stress results when environmental demands exceed an individuals' adaptive capacities. Autoimmune diseases are heterogeneous group of chronic diseases which occur secondary to loss of self antigen tolerance. The etiopathogenesis of autoimmune disease is uncertain. Genetic factors as well as environmental factors appear to interplay, leading to a cascade of events resulting in disease onset. Stress has been postulated to play a role in disease onset in the genetically susceptible patients. During the stress response, catecholamines and glucocorticoids are released from locus coeruleus and adrenal gland. These biomolecules exert control over various immune cells in the innate and adaptive arms of the immune system, thereby altering the cytokine profile released. The increase of IL-4 promotes T-helper 2 (Th2) cell differentiation, while the decrease in IL-12 and the increased IL-10 production reduce the number of T-helper 1 (Th1) cells. The relationship between stress and autoimmune diseases is intricate. Stress has been shown to be associated with disease onset, and disease exacerbations in rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, multiple sclerosis, Graves' disease as well as other autoimmune conditions. In certain conditions such as psoriasis, stress has been implicated in delaying lesion clearance upon the application of standard treatment regimes. Finally, psychological therapy and cognitive behavioral therapy aimed to reduce stress levels was shown to be effective in influencing better outcomes in many autoimmune diseases. The purpose of this paper is to closer inspect the clinical evidence regarding the role of stress on influencing the various aspects of disease entities.
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Affiliation(s)
- Kassem Sharif
- Department of Medicine 'B', Israel; Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Abdulla Watad
- Department of Medicine 'B', Israel; Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Louis Coplan
- Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | | | - Alec Krosser
- Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | | | - Nicola Luigi Bragazzi
- School of Public Health, Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy
| | - Howard Amital
- Department of Medicine 'B', Israel; Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Arnon Afek
- Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Yehuda Shoenfeld
- Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel; Incumbent of the Laura Schwarz-Kipp Chair for Research of Autoimmune Diseases, Tel-Aviv University, Head of The Mosaic of Autoimmunity Project, Saint Petersburg State University, Israel; Head of The Mosaic of Autoimmunity Project, Saint Petersburg State University, Russia.
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Gracie DJ, Guthrie EA, Hamlin PJ, Ford AC. Bi-directionality of Brain-Gut Interactions in Patients With Inflammatory Bowel Disease. Gastroenterology 2018; 154:1635-1646.e3. [PMID: 29366841 DOI: 10.1053/j.gastro.2018.01.027] [Citation(s) in RCA: 281] [Impact Index Per Article: 40.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2017] [Revised: 01/11/2018] [Accepted: 01/13/2018] [Indexed: 12/16/2022]
Abstract
BACKGROUND & AIMS Inflammatory bowel diseases (IBD) are associated with mood disorders, such as anxiety or depression, but it is not clear whether one contributes to development of the other, or if the interaction is bi-directional (anxiety or depression contributes to the progression of IBD, and IBD affects psychological health). We performed a 2-year longitudinal prospective study of patients in secondary to care investigate the bi-directionality of IBD and mood disorders. METHODS We collected data from 405 adult patients with a diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) from November 2012 through June 2017. Demographic features, subtypes of IBD, treatments, symptoms, somatization, and fecal level of calprotectin were recorded at baseline. IBD activity was determined at baseline and after the follow-up period (2 years or more) using the Harvey-Bradshaw Index for CD and the Simple Clinical Colitis Activity Index for UC (scores ≥5 used to define disease activity). Anxiety and depression data were collected using the Hospital Anxiety and Depression Scale (HADS), at baseline and after the follow-up period. Objective markers of disease activity, including glucocorticosteroid prescription or flare of disease activity, escalation of therapy, hospitalization secondary to IBD activity, and intestinal resection during follow-up were assessed via case note review. A brain-gut direction of disease activity was defined as development of new IBD activity in patients with quiescent IBD and abnormal HADS scores at baseline. A gut-brain direction of disease activity was defined by subsequent development of abnormal HADS scores in patients with active IBD and normal HADS scores at baseline. We performed multivariate Cox regression controlling for patient characteristics and follow-up duration. RESULTS Baseline CD or UC disease activity were associated with an almost 6-fold increase in risk for a later abnormal anxiety score (hazard ratio [HR], 5.77; 95% CI, 1.89-17.7). In patients with quiescent IBD at baseline, baseline abnormal anxiety scores were associated with later need for glucocorticosteroid prescription or flare of IBD activity (HR, 2.08; 95% CI, 1.31-3.30) and escalation of therapy (HR, 1.82; 95% CI, 1.19-2.80). These associations persisted when normal IBD activity index scores and fecal level of calprotectin <250 μg/g were used to define quiescent disease at baseline. CONCLUSIONS In a 2-year study of patients with CD or UC, we found evidence for bi-directional effects of IBD activity and psychological disorders. Patients with IBD should be monitored for psychological well-being.
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Affiliation(s)
- David J Gracie
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, United Kingdom; Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds, United Kingdom.
| | - Elspeth A Guthrie
- Leeds Institute of Health Sciences, University of Leeds, Leeds, United Kingdom
| | - P John Hamlin
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, United Kingdom; Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds, United Kingdom
| | - Alexander C Ford
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, United Kingdom; Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds, United Kingdom
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50
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Reed-Knight B, van Tilburg MAL, Levy RL, Langer SL, Romano JM, Murphy TB, DuPen MM, Feld AD. Maladaptive Coping and Depressive Symptoms Partially Explain the Association Between Family Stress and Pain-Related Distress in Youth With IBD. J Pediatr Psychol 2018; 43:94-103. [PMID: 28541526 PMCID: PMC5896627 DOI: 10.1093/jpepsy/jsx082] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2016] [Revised: 04/24/2017] [Accepted: 04/29/2017] [Indexed: 12/31/2022] Open
Abstract
Objective To extend existing research on the pain burden experienced by youth with inflammatory bowel disease (IBD) by examining the complexity of psychosocial factors involved in pain-related distress. Methods Parents completed measures of family stress and their child's pain-related expressions of distress and coping. Youth with IBD rated their depressive symptoms (n = 183 dyads). Mediation analyses were performed using regression-based techniques and bootstrapping. Results Greater family stress was positively related to children's pain-related expressions of distress and passive coping. Significant indirect effects were found in the relationship between family stress and expressed pain-related distress through parent-reported passive coping, depressive symptoms, and both passive coping and depressive symptoms sequentially. Conclusions Results suggest that family stress can place children at risk for greater expressed pain-related distress through effects on coping and depressive symptoms. Addressing psychosocial difficulties is important for closing the gap between disability and health in youth with IBD.
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Affiliation(s)
- Bonney Reed-Knight
- Children’s Healthcare of Atlanta
- Division of Gastroenterology, Hepatology, & Nutrition, Emory University School of Medicine
- GI Care for Kids
| | | | - Rona L Levy
- School of Social Work, University of Washington
| | - Shelby L Langer
- Center for Health Promotion and Disease Prevention, College of Nursing and Health Innovation, Arizona State University
| | - Joan M Romano
- Department of Psychiatry & Behavioral Sciences, Psychiatry & Behavioral Sciences, University of Washington
| | | | | | - Andrew D Feld
- Gastroenterology Kaiser Permanente, Washington
- Clinical Professor of Medicine, University of Washington
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