Retrospective Cohort Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 14, 2020; 26(42): 6626-6637
Published online Nov 14, 2020. doi: 10.3748/wjg.v26.i42.6626
Attention deficit hyperactivity disorder and gastrointestinal morbidity in a large cohort of young adults
Sivan Kedem, Shlomit Yust-Katz, Dan Carter, Zohar Levi, Ron Kedem, Adi Dickstein, Salah Daher, Lior H Katz
Sivan Kedem, Ron Kedem, Adi Dickstein, Salah Daher, Lior H Katz, Medical Corps, Israeli Defense Forces, Ramat-Gan 52621, Israel
Sivan Kedem, Medical School, Hebrew University - Hadassah Medical Center, Jerusalem 91120, Israel
Shlomit Yust-Katz, Dan Carter, Zohar Levi, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 77096, Israel
Shlomit Yust-Katz, Neuro-Oncology Unit, Davidoff Cancer Center, Rabin Medical Center, Petach Tikva 49100, Israel
Dan Carter, Department of Gastroenterology, Sheba Medical Center, Ramat-Gan 52361, Israel
Zohar Levi, Department of Gastroenterology, Beilinson Hospital, Rabin Medical Center, Petach Tikva 49100, Israel
Salah Daher, Lior H Katz, Department of Gastroenterology and Hepatology, Hebrew University - Hadassah Medical Center, Jerusalem 91120, Israel
Author contributions: Kedem S was involved in data curation, investigation and analysis, and wrote the original draft; Yust-Katz S, Cater D was involved in the conceptualization and supervision of the study, and writing, review and editing of the manuscript; Levi Z was involved in data analysis, and writing, review and editing of the manuscript; Kedem R was involved in the investigation, data analysis and statistics, and writing, review and editing of the manuscript; Dickstein A was involved in data curation and investigation; Daher S was involved in project administration and supervision; Katz LH performed the conceptualization, was involved in data curation, investigation and analysis, project administration, and writing, review and editing of the manuscript; All authors have read and approve the final manuscript.
Institutional review board statement: The study was reviewed and approved for publication by our Institutional Reviewer.
Conflict-of-interest statement: All the authors have no conflicts of interest related to the manuscript.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE statement and the manuscript was prepared and revised according to the STROBE statement.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Lior H Katz, MD, Chairman, Doctor, Department of Gastroenterology and Hepatology, Hebrew University - Hadassah Medical Center, Ein-Kerem, Jerusalem 91120, Israel.
Received: April 6, 2020
Peer-review started: April 6, 2020
First decision: April 26, 2020
Revised: July 3, 2020
Accepted: September 28, 2020
Article in press: September 28, 2020
Published online: November 14, 2020
Research background

Attention deficit hyperactivity disorder (ADHD) is a very common chronic condition of inappropriate levels of inattention and/or hyperactivity that interferes with the quality of social, academic, or occupational functioning. Although ADHD is associated with some gastrointestinal (GI) symptoms in children, the association of ADHD to GI disorders in adults is not well characterized.

Research motivation

The motivation for the research came from the clinical observation that many young adults attending the GI clinic with functional gastrointestinal disorders (FGID) mention ADHD as a chronic condition they suffer from. Therefore, we decided to conduct a study to confirm this association. Finding an association between ADHD and GI-related functional morbidity might affect clinical decisions and treatment; in such patients who have both ADHD and FGID, treatment should be taken by an integrative approach combined of a multidisciplinary team of primary care physician, GI specialist, and psychiatrist, and centrally acting neuromodulators should be considered in the treatment plan.

Research objectives

The aim of this study was to investigate the prevalence and types of GI comorbidities in young adults with ADHD and their burden on the healthcare system. Indeed, we found an association between ADHD and FGID, such as irritable bowel syndrome (IBS), dyspepsia, and chronic constipation. ADHD was not associated with IBD or celiac disease.

Research methods

This was a retrospective cohort study, consisting of all young adults of both sexes recruited to the Israeli Defense Forces (IDF) between January 2007 and February 2013 and assigned to active duty. This population accounts for about 50% of the entire Israeli young adult population. Several sources were used to accurately identify ADHD patients as well as to use only well-established diagnoses of IBS, dyspepsia, and constipation. The following sociodemographic data were collected: year of birth; age at the time of examination; country of birth; education; and socioeconomic status. Outcome measures were diagnosis of IBS, dyspepsia, constipation, IBD, and celiac disease, as well as GI symptoms as the reason for a primary care clinic visit, referral to a GI specialist, and recurrent GI complaints.

Research results

The cohort included 389032 recruits, 41.3% female, aged 17-35 years, of whom 33380 (8.6%) had ADHD. Most ADHD patients (n = 23138, 69.3%) had mild ADHD, and only 3980 subjects (11.9%) received anti-ADHD drugs during the study period. Compared to controls, the ADHD group had a higher rate of dyspepsia, constipation, IBS and FGID. There was no between-group difference in the rate of diagnosis of IBD and celiac disease. The effect of ADHD on the rate of dyspepsia, constipation, IBS and FGID was larger in females, although still significant in males as well. Among participants with ADHD, methylphenidate prescription was associated with an increased risk of dyspepsia and constipation, but not of IBS, IBD, and celiac disease. Compared to controls, the subjects with ADHD were referred more often to a GI specialist, examined more frequently by a primary care physician for GI symptoms, and had more episodes of recurrent GI symptoms. Participants with ADHD suffered more from recurrent heartburn and gastroesophageal reflux disease, nausea and vomiting, abdominal pain, and diarrhea.

The study contributes to the research in the field since this is the first study to focus on young adults and it is a large size population-based study.

Research conclusions

The present study of a large cohort of young adults with ADHD showed that ADHD is associated with an increased rate of comorbid FGID (IBS, constipation, and dyspepsia) but not with somatic immune-mediated GI conditions, such as IBD and celiac disease. In addition, the ADHD group had a significantly increased rate of primary care visits for GI symptoms, referrals to GI specialists, and recurrent GI symptoms than the control group, pointing to the high burden of GI morbidity in individuals with ADHD on healthcare resources. These associations were not related to the use of methylphenidate; although, those who received methylphenidate had a higher relative risk of all the measured outcomes, except IBS. The association between ADHD and GI-related functional morbidity may affect clinical decisions and treatment. Attention should be addressed to GI problems in patients with known ADHD, including a careful medical history focused on GI-related morbidity, so as not to miss some of the common GI problems. The presence of ADHD in a patient with GI symptoms, normal laboratory results and no red flags may by itself support the diagnosis of a functional GI disorder. Since FGIDs are now considered disorders of gut-brain interaction and centrally acting neuromodulators are amongst the mainstays of refractory FGIDs, these drugs may be considered in treating patients suffering from both FGID and ADHD.

Research perspectives

ADHD is associated with FGID and a high need for GI-related health services. This study emphasizes the complex interaction between mind and body. Further research is needed to explore the possible combination of treatment of FGID with the neuropsychological therapeutic modalities for ADHD, and to determine if the presence of ADHD can assist in the diagnosis of FGID.