Poor Correlation Between Clinical Disease Activity and Mucosal Inflammation, and the Role of Psychological Comorbidity, in Inflammatory Bowel Disease
Abstract
OBJECTIVES: There is a move toward patient-reported outcome measures as end points in clinical trials of novel therapies for inflammatory bowel disease (IBD). However, the association between patient-reported symptoms and mucosal inflammation, and the influence of psychological factors, remains unclear. We examined this in a secondary care population. METHODS: Validated patient-reported disease activity indices were used to define clinically active disease in a cohort of 356 patients with ulcerative colitis (UC) or Crohn's disease (CD). A fecal calprotectin ≥250 μg/g was used to define active mucosal inflammation. The hospital anxiety and depression scale (HADS) and patient health questionnaire (PHQ)-15 were used to assess for anxiety, depression, or somatization, respectively. Logistic regression analysis was performed to determine the association between symptoms, mucosal inflammation, and psychological comorbidity. RESULTS: Clinical disease activity was associated with mucosal inflammation in UC (odds ratio (OR) 3.36; 95% confidence interval (CI) 1.34-8.47) but not in CD (OR 1.69; 95% CI 0.74-3.83). Depression in UC (OR 1.21 per 1-point increase in HADS; 95% CI 1.02-1.44) and somatization in UC (OR 1.17 per 1-point increase in PHQ-15; 95% CI 1.03-1.33) and CD (OR 1.31 per 1-point increase in PHQ-15; 95% CI 1.13-1.52) were associated with clinical disease activity. Overall, patient-reported symptoms yielded poor positive predictive values for mucosal inflammation in both CD and UC. CONCLUSIONS: Patient-reported symptoms and the Harvey-Bradshaw index were poor predictors of mucosal inflammation in CD. Psychological comorbidity was associated with gastrointestinal symptom-reporting. A shift in the focus of IBD management toward one addressing both psychological and physical well-being is required.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Some of the association may relate to patients with IBD with symptoms of a common mental disorder being more likely to report gastrointestinal symptoms, and therefore meet criteria for a flare of IBD.
“Some of this may relate to patients with IBD with symptoms of a common mental disorder being more likely to report gastrointestinal symptoms, and therefore meet criteria for a flare of IBD.[34]”
From Bidirectional brain-gut axis effects influence mood and prognosis in IBD: A systematic review and meta-analysis (2022) · cites this paper as [34]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
The Hospital Anxiety and Depression Scale
Zigmond, A. S., & Snaith, R. P. (1983) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.1983.tb09716.x · Cited by 47,139 · see citing works
Depression and quality of life in older persons: A review
Sivertsen, H., Bjørkløf, G. H., Engedal, K., Selbæk, G., & Helvik, A.-S. (2015) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000437299 · Cited by 14,152 · see citing works
Spitzer, R. L. (1999) · JAMA · doi:10.1001/jama.282.18.1737 · Cited by 9,802 · see citing works
Longstreth, G. F., Thompson, W. G., Chey, W. D., Houghton, L. A., Mearin, F., & Spiller, R. C. (2006) · Gastroenterology · doi:10.1053/j.gastro.2005.11.061 · Cited by 4,856 · see citing works
Molodecky, N. A., Soon, I. S., Rabi, D. M., Ghali, W. A., Ferris, M., Chernoff, G., Benchimol, E. I., Panaccione, R., Ghosh, S., Barkema, H. W., et al. (2012) · Gastroenterology · doi:10.1053/j.gastro.2011.10.001 · Cited by 4,833 · see citing works
Silverberg, M. S., Satsangi, J., Ahmad, T., Arnott, I. D., Bernstein, C. N., Brant, S. R., Caprilli, R., Colombel, J., Gasché, C., Geboes, K., et al. (2005) · Canadian Journal of Gastroenterology · doi:10.1155/2005/269076 · Cited by 3,408 · see citing works
Infliximab, Azathioprine, or Combination Therapy for Crohn's Disease
Colombel, J., Sandborn, W. J., Reinisch, W., Mantzaris, G. J., Kornbluth, A. A., Rachmilewitz, D., Lichtiger, S., D’Haens, G., Diamond, R. H., Broussard, D. L., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa0904492 · Cited by 3,140 · see citing works
A SIMPLE INDEX OF CROHN'S-DISEASE ACTIVITY
Harvey, R. F., & Bradshaw, J. M. (1980) · The Lancet · doi:10.1016/s0140-6736(80)92767-1 · Cited by 2,974 · see citing works
Peyrin‐Biroulet, L., Sandborn, W. J., Sands, B. E., Reinisch, W., Bemelman, W. A., Bryant, R. V., D’Haens, G., Dotan, I., Dubinsky, M. C., Feagan, B. G., et al. (2015) · The American Journal of Gastroenterology · doi:10.1038/ajg.2015.233 · Cited by 1,843 · see citing works
A simple clinical colitis activity index
Walmsley, R. S., Ayres, R., Pounder, R. E., & Allan, R. N. (1998) · Gut · doi:10.1136/gut.43.1.29 · Cited by 1,320 · see citing works
Kappelman, M. D., Rifas‐Shiman, S. L., KLEINMAN, K. P., Ollendorf, D., Bousvaros, A., Grand, R. J., & Finkelstein, J. A. (2007) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2007.07.012 · Cited by 931 · see citing works
Spitzer, R. L., Williams, J. B. W., Kroenke, K., Hornyak, R., & McMurray, J. (2000) · American Journal of Obstetrics and Gynecology · doi:10.1067/mob.2000.106580 · Cited by 847 · see citing works
Fecal calprotectin is a surrogate marker for endoscopic lesions in inflammatory bowel disease
D’Haens, G., Ferrante, M., Vermeire, S., Baert, F., Noman, M., Moortgat, L., Geens, P., Iwens, D., Aerden, I., Assche, G. V., et al. (2012) · Inflammatory Bowel Diseases · doi:10.1002/ibd.22917 · Cited by 816 · see citing works
Halpin, S. J., & Ford, A. C. (2012) · American Journal of Gastroenterology · doi:10.1038/ajg.2012.260 · Cited by 607 · see citing works
Self-citationSchoepfer, A. M., Beglinger, C., Straumann, A., Trummler, M., Vavricka, S. R., Bruegger, L. E., & Seibold, F. (2009) · The American Journal of Gastroenterology · doi:10.1038/ajg.2009.545 · Cited by 566 · see citing works
Sipponen, T. M., Savilahti, E., Kolho, K., Nuutinen, H. U., Turunen, U., & Färkkilä, M. A. (2007) · Inflammatory Bowel Diseases · doi:10.1002/ibd.20312 · Cited by 480 · see citing works
Walker, J. R., Ediger, J. P., Graff, L. A., Greenfeld, J. M., Clara, I., Lix, L., Rawsthorne, P., Miller, N., Rogala, L., McPhail, C. M., et al. (2008) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2008.01980.x · Cited by 437 · see citing works
Jones, J., Loftus, E. V., Panaccione, R., Chen, L., Peterson, S. E., McConnell, J. P., Baudhuin, L. M., Hanson, K., Feagan, B. G., Harmsen, S. W., et al. (2008) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2008.06.010 · Cited by 414 · see citing works
Vermeire, S., Schreiber, S., Sandborn, W. J., Dubois, C., & Rutgeerts, P. J. (2010) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2010.01.001 · Cited by 403 · see citing works
The Prevalence of Symptoms in Medical Outpatients and the Adequacy of Therapy
Arrington, M. E. (1990) · Archives of Internal Medicine · doi:10.1001/archinte.1990.00040031685016 · Cited by 367 · see citing works
Vivinus-Nébot, M., Frin-Mathy, G., Bzioueche, H., Dainese, R., Bernard, G., Anty, R., Filippi, J., Saint‐Paul, M., Tulić, M. K., Verhasselt, V., et al. (2013) · Gut · doi:10.1136/gutjnl-2012-304066 · Cited by 365 · see citing works
Lin, J., Chen, J., Zuo, J., Yu, A., Xiao, Z.-J., Deng, F., Nie, B., & Jiang, B. (2014) · Inflammatory Bowel Diseases · doi:10.1097/mib.0000000000000057 · Cited by 295 · see citing works
Patient-reported outcomes as primary end points in clinical trials of inflammatory bowel disease
Williet, N., Sandborn, W. J., & Peyrin–Biroulet, L. (2014) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2014.02.016 · Cited by 260 · see citing works
Khanna, R., Zou, G., D’Haens, G., Feagan, B. G., Sandborn, W. J., Vandervoort, M. K., Rolleri, R. L., Bortey, E. B., Paterson, C. A., Forbes, W. P., et al. (2014) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.13001 · Cited by 243 · see citing works
Goodhand, J. R., Wahed, M., Mawdsley, J. E., Farmer, A. D., Aziz, Q., & Rampton, D. S. (2012) · Inflammatory Bowel Diseases · doi:10.1002/ibd.22916 · Cited by 234 · see citing works
Validation of the Rome III Criteria for the Diagnosis of Irritable Bowel Syndrome in Secondary Care
Ford, A. C., Berčík, P., Morgan, D. G., Bolino, C., Pinto-Sánchez, M. I., & Moayyedi, P. (2013) · Gastroenterology · doi:10.1053/j.gastro.2013.08.048 · Cited by 204 · see citing works
Self-citationJairath, V., Khanna, R., Zou, G., et al. (2015) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.13408 · Cited by 178 · see citing works
Kappelman, M. D., Long, M. D., Martin, C., DeWalt, D. A., Kinneer, P. M., Chen, W., Lewis, J. D., & Sandler, R. S. (2014) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2013.10.019 · Cited by 178 · see citing works
Targownik, L. E., Sexton, K. A., Bernstein, M. T., Beatie, B., Sargent, M., Walker, J. R., & Graff, L. A. (2015) · American Journal of Gastroenterology · doi:10.1038/ajg.2015.147 · Cited by 157 · see citing works
Disease Activity Assessment in IBD
Falvey, J. D., Hoskin, T. S., Meijer, B., Ashcroft, A., Walmsley, R. S., Day, A. S., & Gearry, R. B. (2015) · Inflammatory Bowel Diseases · doi:10.1097/mib.0000000000000341 · Cited by 153 · see citing works
af Björkesten, C.-G., Nieminen, U., Turunen, U., Arkkila, P. E. T., Sipponen, T. M., & Färkkilä, M. A. (2012) · Scandinavian Journal of Gastroenterology · doi:10.3109/00365521.2012.660542 · Cited by 153 · see citing works
Defining Relapse of Ulcerative Colitis Using a Symptom-based Activity Index
Jowett, S. L., & Jowett, S. L. (2003) · Scandinavian Journal of Gastroenterology · doi:10.1080/00365520310000654 · Cited by 134 · see citing works
Antidepressants and inflammatory bowel disease: a systematic review.
Mikocka‐Walus, A. A., Turnbull, D. A., Moulding, N., Wilson, I. G., Andrews, J. M., & Holtmann, G. (2006) · Clinical Practice and Epidemiology in Mental Health · doi:10.1186/1745-0179-2-24 · Cited by 120 · see citing works
Small Bowel Capsule Endoscopy in the Management of Established Crohnʼs Disease
Kopylov, U., Németh, A., Koulaouzidis, A., et al. (2014) · Inflammatory Bowel Diseases · doi:10.1097/mib.0000000000000255 · Cited by 119 · see citing works
Prevalence of, and predictors of, bile acid malabsorption in outpatients with chronic diarrhea
Gracie, D. J., Kane, J. S., Mumtaz, S., Scarsbrook, A. F., Chowdhury, F. U., & Ford, A. C. (2012) · Neurogastroenterology & Motility · doi:10.1111/j.1365-2982.2012.01953.x · Cited by 102 · see citing works
Self-citationMcCombie, A., Gearry, R., Andrews, J., Mulder, R., & Mikocka-Walus, A. (2016) · Inflammatory Bowel Diseases · doi:10.1097/mib.0000000000000567 · Cited by 100 · see citing works
Bryant, R. V., van Langenberg, D. R., Holtmann, G., & Andrews, J. M. (2011) · Journal of Gastroenterology and Hepatology · doi:10.1111/j.1440-1746.2011.06624.x · Cited by 87 · see citing works
Mikocka-Walus, A., Bampton, P., Hetzel, D., Hughes, P., Esterman, A., & Andrews, J. M. (2015) · BMC Gastroenterology · doi:10.1186/s12876-015-0278-2 · Cited by 86 · see citing works
Jharap, B., Sandborn, W. J., Reinisch, W., D’Haens, G., Robinson, A. M., Wang, W., Huang, B., Lazar, A., Thakkar, R. B., & Colombel, J. (2015) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.13387 · Cited by 81 · see citing works
Robust Association Between Inflammatory Bowel Disease and Generalized Anxiety Disorder
Fuller‐Thomson, E., Lateef, R., & Sulman, J. (2015) · Inflammatory Bowel Diseases · doi:10.1097/mib.0000000000000518 · Cited by 77 · see citing works
van Hoboken, E. A., Thijssen, A. Y., Verhaaren, R., van der Veek, P. P. J., Prins, F. A., Verspaget, H. W., & Masclee, A. (2011) · Scandinavian Journal of Gastroenterology · doi:10.3109/00365521.2011.579156 · Cited by 68 · see citing works
Fecal Calprotectin in Ileal Crohnʼs Disease
Cerrillo, E., Beltrán, B., Pous, S., Echarri, A., Ojea, J. C. G., Iborra, M., Pamies, J., & Nos, P. (2015) · Inflammatory Bowel Diseases · doi:10.1097/mib.0000000000000404 · Cited by 64 · see citing works
Stawczyk‐Eder, K., Eder, P., Łykowska‐Szuber, L., Krela‐Kaźmierczak, I., Klimczak, K., Szymczak‐Tomczak, A., Szachta, P., Katulska, K., & Linke, K. (2015) · Archives of Medical Science · doi:10.5114/aoms.2014.43672 · Cited by 56 · see citing works
Rogler, G., Aldeguer, X., Kruis, W., Lasson, A., Mittmann, U., Nally, K., Peyrin‐Biroulet, L., Schoepfer, A. M., Vatn, M., Vavricka, S. R., et al. (2013) · Journal of Crohn s and Colitis · doi:10.1016/j.crohns.2013.02.014 · Cited by 56 · see citing works
Childhood Maltreatment Is Associated with Ulcerative Colitis but Not Crohnʼs Disease
Fuller‐Thomson, E., West, K. J., Sulman, J., & Baird, S. L. (2015) · Inflammatory Bowel Diseases · doi:10.1097/mib.0000000000000551 · Cited by 49 · see citing works
Greco, A., Caviglia, G. P., Brignolo, P., et al. (2015) · Scandinavian Journal of Gastroenterology · doi:10.3109/00365521.2015.1050691 · Cited by 46 · see citing works
Hyphantis, T. N., Tomenson, B., Bai, M., Tsianos, E. V., Mavreas, V. G., & Creed, F. H. (2009) · Digestive Diseases and Sciences · doi:10.1007/s10620-009-0762-z · Cited by 40 · see citing works
Prevalence of mental health disorders in inflammatory bowel disease: an Australian outpatient cohort
Knowles, S. R., Tribbick, D., Salzberg, M. R., Ftanou, M., Connell, W. R., Macrae, F., Kamm, M. A., Bates, G. W., Cunningham, G., & Austin, D. (2015) · Clinical and Experimental Gastroenterology · doi:10.2147/ceg.s77567 · Cited by 39 · see citing works
A case of a stomach gastrointestinal stromal tumor with extremely predominant cystic formation
Okano, H., Tochio, T., Suga, D., et al. (2015) · Clinical Journal of Gastroenterology · doi:10.1007/s12328-015-0577-8 · Cited by 24 · see citing works
T1282 Comparison of Two Commercially Available Serologic Kits for the Detection of Fecal Calprotecin
Loitsch, S. M., Berger, C., Hartmann, F., et al. (2010) · Gastroenterology · doi:10.1016/s0016-5085(10)62436-5 · Cited by 2 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Lamb, C. A., Kennedy, N. A., Raine, T., Hendy, P. A., Smith, P. J., Limdi, J. K., Hayee, B., Lomer, M. C. E., Parkes, G. C., Selinger, C., et al. (2019) · Gut · doi:10.1136/gutjnl-2019-318484 · Cited by 2,346 · see citing works
Barberio, B., Zamani, M., Black, C. J., Savarino, E. V., & Ford, A. C. (2021) · The Lancet Gastroenterology & Hepatology · doi:10.1016/s2468-1253(21)00014-5 · Cited by 758 · see citing works
Self-citationBi-directionality of brain–gut interactions in patients with inflammatory bowel disease
Gracie, D. J., Guthrie, E. A., Hamlin, P. J., & Ford, A. C. (2018) · Gastroenterology · doi:10.1053/j.gastro.2018.01.027 · Cited by 408 · see citing works
Self-citationGracie, D. J., Irvine, A. J., Sood, R., Mikocka-Walus, A., Hamlin, P. J., & Ford, A. C. (2017) · The Lancet Gastroenterology & Hepatology · doi:10.1016/s2468-1253(16)30206-0 · Cited by 271 · see citing works
Self-citationFairbrass, K. M., Lovatt, J., Barberio, B., Yuan, Y., Gracie, D. J., & Ford, A. C. (2022) · Gut · doi:10.1136/gutjnl-2021-325985 · Cited by 225 · see citing works
Self-citationInfluences and impact of anxiety and depression in the setting of inflammatory bowel disease
Navabi, S., Gorrepati, V. S., Yadav, S., Chintanaboina, J., Maher, S., Demuth, P., Stern, B., Stuart, A., Tinsley, A., Clarke, K., et al. (2018) · Inflammatory Bowel Diseases · doi:10.1093/ibd/izy143 · Cited by 172 · see citing works
Psychological comorbidity in gastrointestinal diseases: Update on the brain-gut-microbiome axis
Person, H., & Keefer, L. (2021) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2020.110209 · Cited by 158 · see citing works
Sexton, K. A., Walker, J. R., Graff, L. A., Bernstein, M. T., Beatie, B., Miller, N., Sargent, M., & Targownik, L. E. (2017) · Inflammatory Bowel Diseases · doi:10.1097/mib.0000000000001040 · Cited by 79 · see citing works
Alexakis, C., Kumar, S., Saxena, S., & Pollok, R. (2017) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.14171 · Cited by 69 · see citing works
Anxiety but not depression predicts poor outcomes in inflammatory bowel disease
Narula, N., Pinto-Sanchez, M. I., Calo, N. C., Ford, A. C., Bercik, P., Reinisch, W., & Moayyedi, P. (2019) · Inflammatory Bowel Diseases · doi:10.1093/ibd/izy385 · Cited by 52 · see citing works
Self-citationFairbrass, K. M., Gracie, D. J., & Ford, A. C. (2021) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.16454 · Cited by 31 · see citing works
Self-citationRiggott, C., Fairbrass, K. M., Black, C. J., Gracie, D. J., & Ford, A. C. (2023) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.17735 · Cited by 14 · see citing works
Self-citationLing, F., Tu, L., Li, J., Chen, Y., Xu, M., & Zhu, L. (2021) · Scandinavian Journal of Gastroenterology · doi:10.1080/00365521.2021.1966093 · Cited by 10 · see citing works
Tse, C. S., Singh, S., & Sandborn, W. J. (2022) · Inflammatory Bowel Diseases · doi:10.1093/ibd/izab153 · Cited by 3 · see citing works
- Authors
- Gracie, D. J., Williams, C. J. M., Sood, R., Mumtaz, S., Bholah, H. M., Hamlin, J. P., & Ford, A. C.
- Affiliations
- University of Leeds (GB)
- St James's University Hospital (GB)
- Corresponding author
- Gracie, David J
- Venue
- American Journal of Gastroenterology
- Published
- 2016-04
- Volume
- 111
- Issue
- 4
- Pages
- 541-551
- ISSN
- 0002-9270 (ISSN-L)
- OpenAlex
- W2318470257
- Cited by
- 173
- References
- 50
- Citations by year
- 2026: 7 · 2025: 18 · 2024: 17 · 2023: 16 · 2022: 20 · 2021: 23 · 2020: 20 · 2019: 10 · 2018: 17 · 2017: 13 · 2016: 10
- FWCI
- 13.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The American Journal of Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
- Health Sciences › Medicine › Epidemiology › Microscopic Colitis
- Keywords
- inflammatory bowel disease, ulcerative colitis, Crohn's disease, mucosal inflammation, fecal calprotectin, clinical disease activity, patient-reported outcomes, Harvey-Bradshaw Index, depression, anxiety, somatization, psychological comorbidity, disease activity index
- MeSH terms
- Patient Reported Outcome Measures, Mental Disorders, Cross-Sectional Studies, Female, Humans, Male, Middle Aged, Psychiatric Status Rating Scales, Severity of Illness Index, Inflammatory Bowel Diseases, Biomarkers, Comorbidity, Leukocyte L1 Antigen Complex
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
