Depressive Symptoms Predict Clinical Recurrence of Inflammatory Bowel Disease
Authors: Jordi Sebastian Bruno Ulrich , Lang Brian Matthew , Auschra Bianca , von Känel Roland , Biedermann Luc , Greuter Thomas , Schreiner Philipp , Rogler Gerhard , Krupka Niklas , Sulz Michael Christian , Misselwitz Benjamin , Begré Stefan ,   Swiss IBD Cohort Study Group, Anderegg Claudia , Bauerfeind Peter , Beglinger Christoph , Begré Stefan , Belli Dominique , Bengoa José M , Biedermann Luc , Bigler Beat , Binek Janek , Blattmann Mirjam , Boehm Stephan , Borovicka Jan , Braegger Christian P , Brunner Nora , Bühr Patrick , Burnand Bernard , Burri Emanuel , Buyse Sophie , Cremer Matthias , Criblez Dominique H , de Saussure Philippe , Degen Lukas , Delarive Joakim , Doerig Christopher , Dora Barbara , Dorta Gian , Egger Mara , Ehmann Tobias , El-Wafa Ali , Engelmann Matthias , Ezri Jessica , Felley Christian , Fliegner Markus , Fournier Nicolas , Fraga Montserrat , Frei Pascal , Frei Remus , Fried Michael , Froehlich Florian , Funk Christian , Furlano Raoul Ivano , Gallot-Lavallée Suzanne , Geyer Martin , Girardin Marc , Golay Delphine , Grandinetti Tanja , Gysi Beat , Haack Horst , Haarer Johannes , Helbling Beat , Hengstler Peter , Herzog Denise , Hess Cyrill , Heyland Klaas , Hinterleitner Thomas , Hiroz Philippe , Hirschi Claudia , Hruz Petr , Iwata Rika , Jost Res , Juillerat Pascal , Brondolo Vera Kessler , Knellwolf Christina , Knoblauch Christoph , Köhler Henrik , Koller Rebekka , Krieger-Grübel Claudia , Kullak-Ublick Gerd , Künzler Patrizia , Landolt Markus , Lange Rupprecht , Lehmann Frank Serge , Macpherson Andrew , Maerten Philippe , Maillard Michel H , Manser Christine , Manz Michael , Marbet Urs , Marx George , Matter Christoph , McLin Valérie , Meier Rémy , Mendanova Martina , Meyenberger Christa , Michetti Pierre , Misselwitz Benjamin , Moradpour Darius , Morell Bernhard , Mosler Patrick , Mottet Christian , Müller Christoph , Müller Pascal , Müllhaupt Beat , Münger-Beyeler Claudia , Musso Leilla , Nagy Andreas , Neagu Michaela , Nichita Cristina , Niess Jan , Noël Natacha , Nydegger Andreas , Obialo Nicole , Oneta Carl , Oropesa Cassandra , Peter Ueli , Peternac Daniel , Petit Laetitia Marie , Piccoli-Gfeller Franziska , Pilz Julia Beatrice , Pittet Valérie , Raschle Nadia , Rentsch Ronald , Restellini Sophie , Richterich Jean-Pierre , Rihs Sylvia , Ritz Marc Alain , Roduit Jocelyn , Rogler Daniela , Rogler Gerhard , Rossel Jean-Benoît , Sagmeister Markus , Saner Gaby , Sauter Bernhard , Sawatzki Mikael , Schäppi Michela , Scharl Michael , Schelling Martin , Schibli Susanne , Schlauri Hugo , Uebelhart Sybille Schmid , Schnegg Jean-François , Schoepfer Alain , Seibold Frank , Seirafi Mariam , Semadeni Gian-Marco , Semela David , Senning Arne , Sidler Marc , Sokollik Christiane , Spalinger Johannes , Spangenberger Holger , Stadler Philippe , Steuerwald Michael , Straumann Alex , Straumann-Funk Bigna , Sulz Michael , Thorens Joël , Tiedemann Sarah , Tutuian Radu , Vavricka Stephan , Viani Francesco , Vögtlin Jürg , von Känel Roland , Vonlaufen Alain , Vouillamoz Dominique , Vulliamy Rachel , Wermuth Jürg , Werner Helene , Wiesel Paul , Wiest Reiner , Wylie Tina , Zeitz Jonas , Zimmermann Dorothee 
Published: June 2021

Abstract

Background
Inflammatory bowel disease (IBD) patients are at high risk for depression, and depression has been shown to affect disease course. We examined interrelations between depression, genetic risk factors for depression, and IBD flares.

Method
In 1973 patients (1137 Crohn’s disease, 836 ulcerative colitis) of the Swiss IBD Cohort Study (SIBDCS), depressive status (hospital anxiety and depression subscale for depression, HADS-D ≥11) was assessed on a yearly basis. We investigated the impact of depression on IBD-relevant clinical outcomes in Cox proportional hazards models. We used active disease (CDAI ≥150 or MTWAI ≥10) and 2 published composite flare definitions—FNCE (physician-reported flare, nonresponse to therapy, new complication, or extraintestinal manifestation) and AFFSST (active disease, physician-reported flare, fistula, stenosis, and new systemic therapy)—as clinical end points. Additionally, 62 preselected single nucleotide polymorphisms (SNPs) were screened for cross-sectional associations with depression, and if present, their predictive value for future depression and clinical deterioration was assessed.

Results
Depression was a strong risk factor for disease-related end points, including active disease (adjusted hazard ratio [aHR], 3.55; P &lt; 0.001), AFFSST (aHR, 1.62; P &lt; 0.001), and FNCE (aHR, 1.35; P = 0.019). The SNP rs2522833 was significantly associated with depression at enrollment (q = 0.059). The TC allele of rs588765 was negatively associated with the presence of depression at enrollment (q = 0.050) and after enrollment (aHR, 0.67; P = 0.035) and with fewer active disease states (aHR, 0.72; P = 0.045) during follow-up.

Conclusion
In IBD, depressive symptoms and inflammatory activity are intimately related. Depressive symptoms were a strong predictor of clinical deterioration, and genetic markers may play a role in this relationship.