Increased psychological distress and somatization in patients with irritable bowel syndrome compared with functional diarrhea or functional constipation, based on Rome IV criteria

The Rome IV criteria for disorders of gut‐brain interaction define irritable bowel syndrome (IBS) as a functional bowel disorder associated with frequent abdominal pain of at least 1 day per week. In contrast, functional diarrhea (FD) and functional constipation (FC) are relatively painless. We compared differences in mood and somatization between Rome IV IBS and FC/FD.


| INTRODUC TI ON
Functional bowel disorders belong to the spectrum of disorders of gut-brain interaction. 1 They are defined as chronic lower gastrointestinal symptoms that occur in the absence of organic disease to explain the symptoms. 1 Recent large-scale epidemiological studies report functional bowel disorders to affect 1-in-4 adults, in whom the vast majority are represented by either irritable bowel syndrome (IBS), functional constipation (FC), or functional diarrhea (FD). 2 The Rome Foundation has, over the last 30 years, provided clinicians and researchers with symptom-based criteria to aid toward the recognition of functional gastrointestinal disorders. 3 As of May 2016, the Rome IV criteria was released which differs markedly from the previous Rome III iteration with regards to the diagnosis of IBS. 4

,5 The
Rome IV criteria defines IBS as a functional bowel disorder associated with frequent abdominal pain of at least 1 day per week, which contrasts to the relatively lax Rome III criteria where a diagnosis of IBS was based on abdominal pain or discomfort at least 2-3 day per month. 4,5 This change in criteria has reduced the prevalence of IBS by almost half, going from 9.0% under Rome III to 4.6% under Rome IV. 2 Those individuals no longer satisfying a diagnosis of IBS under Rome IV are instead re-classified as having another functional bowel disorder, such as the relatively painless FD and FC. Indeed, following the change in criteria from Rome III to Rome IV, the prevalence of FD has subsequently risen from 0.9% to 4.4% and FC has risen from 5.6% to 7.8%. 2 The relevance of this update in criteria to Rome IV, which in essence differentiates IBS from FC or FD on the basis of frequent abdominal pain, is unclear with regards to the role of psychological distress, an important factor associated with disorders of gut-brain interaction. 1,3 While functional abdominal pain has historically been linked with mood disturbances, 6 a recent study comprising 100 patients found no difference in psychosomatic symptoms between patients with IBS-D and FD based on the Rome IV criteria. 7 9,10 whereas others have recruited online participants self-reporting IBS without verifying the diagnosis. 11 Moreover, those subjects deemed unlikely to have Rome IV IBS have not been distinctly defined as having FD or FC, but rather pooled under the spectrum of any other functional bowel disorder, thereby limiting our understanding of their particular disease subtype. [8][9][10][11] We therefore undertook a study to compare levels of psychological distress and somatization between IBS and FC/FD based on the Rome IV criteria. We hypothesized that Rome IV IBS, a bowel disorder characterized by frequent abdominal pain, will be strongly associated with mood disturbances and high levels of somatization, compared with the relatively painless FD or FC.

| Study design and participants
This prospective observational study took place at Sheffield Teaching Hospitals, United Kingdom, during the course of 2019.
All English-speaking adults, aged 18 years and over, referred at the clinical discretion of their GI physician for an out-patient colonoscopy (excluding those as part of the national bowel cancer screening program) were eligible to participate. Individuals were invited to self-complete a baseline questionnaire collecting demographic and symptom-based data followed by undergoing a colonoscopy.

K E Y W O R D S
functional constipation, functional diarrhea, HADS, IBS, PHQ-12, Rome IV, Somatization

Key points
• Based on Rome IV criteria, IBS is associated with increased levels of psychological distress and somatization compared with FD or FC.
• The frequency of abdominal pain correlates positively with psychological distress and somatic co-morbidity.
• Patients with functional bowel disorders, and in particular those who report abdominal pain, should be routinely and comprehensively screened for extra-intestinal ill-health.
• Future research studies should consider evaluating the role of psychological therapies early in the disease course for IBS, whilst evaluating both bowel-and mental-health related end points.

| Baseline questionnaire
The following items were collected prior to colonoscopy: a. Demographic data-participants entered their age, sex, and Subjects were asked to rate how much they had been troubled by these twelve symptoms over the last four weeks as 0 ("not bothered at all"), 1 ("bothered a little"), or 2 ("bothered a lot").
e. The Rome IV bowel disorder questionnaire 14 -this validated tool was used to identify patients who had symptoms compatible with one of the following functional bowel disorders; IBS and its sub-

| Colonoscopy
The endoscopists performing the colonoscopies were blinded to the baseline questionnaire data. A normal colonoscopy was defined as no endoscopic and histological evidence of colon cancer, inflammatory bowel disease, or microscopic colitis. We did not take diverticulosis into consideration and, moreover, any association with functional bowel disorders is controversial. 15

| Definitions of functional bowel disorders
We have recently used this dataset to report on the diagnostic outcomes of colonoscopy in patients with symptoms compatible with a Rome IV functional bowel disorder. 16

| Statistical analysis
The primary analysis compared differences in mood and somatization scores between Rome IV IBS and FC/FD, and the relative influence of abdominal pain frequency on these extra-intestinal symptoms. However, prior to undertaking this main analysis, we compared difference in mood and somatization scores between those patients with and without a Rome IV functional bowel disorder. The secondary analysis evaluated differences across individual IBS subtypes, and also between FC and FD.
Statistical analysis was carried out using SPSS version 25.0 software, with significance set at a p-value of <0.05. Categorical variables were summarized by descriptive statistics, including total numbers and percentages, with comparisons between groups performed using the chi-square test or Fisher exact test, and adjusted odds ratios (AOR) with 95% confidence intervals (95% CI) presented when appropriate. Continuous variables were summarized by mean and standard deviation, with difference between two independent groups performed using the unpaired Student t test, and between multiple groups using 1-way analysis of variance. Correlations were assessed using Spearman's test.

| Ethics
The study commenced following ethical approval by Sheffield Teaching Hospital (protocol number: STH20572) and the Health Research Authority (IRAS project ID: 253210). The study was conducted in accordance with the STROBE statement. Patients who returned their questionnaire consented for their data to be used for analysis.

| Study participants
We sent out 3000 questionnaires of which 1329 were returned with complete dataset and underwent colonoscopy. Of these, 567 pa-

| Comparison in demographic and symptom scores between subjects with and without a Rome IV functional bowel disorder
Patients with a Rome IV functional bowel disorder-compared to those without-were significantly younger (mean age 56 vs. 59 years, p < 0.001), had a higher female representation (62% vs. 48%, p < 0.001), and reported greater levels of psychological distress and somatization (

| Comparison in demographic and symptom scores between Rome IV IBS and FC/FD
As outlined in Table 2, patients with IBS were significantly younger than those with FD/FC (mean age 51 years vs. 61 years, p < 0.001) and had a higher female predominance (62% vs. 52%, p < 0.001).
They also had a significantly higher mean PHQ-12 somatization score

| Comparison between IBS-D and FD, and between IBS-C and FC
Patients with IBS-D were younger, had a greater female representation, experienced more psychosomatic distress, and reported increased stool urgency than those with FD ( We found no statistical differences in mood and somatization symptom scores between FC and FD, and nor between individual IBS subtypes (supplementary tables B/C).  Our study had limitations. Firstly, all included patients completed the questionnaire prior to colonoscopy, and it is therefore conceivable that levels of psychological distress may have been heightened due to the presence of alarm features, severe symptoms, and the concern regarding the potential endoscopic diagnosis. However, this is unlikely to explain the difference in psychological distress and somatization seen between those subsequently diagnosed with and without a functional bowel disorder, and between Rome IV IBS compared with FD or FC. Secondly, despite population-based studies having previously demonstrated high levels of psychosomatic disorders in community subjects with IBS, 6,17,18 our results should not be generalized to patients managed in the primary-or secondary-care out-patient clinic setting, many of whom will be a younger cohort with mild symptoms and no red flags to warrant a colonoscopy.

| Correlation between the frequency of abdominal pain and psychosomatic symptoms
Thirdly, while a colonoscopy excluded organic disease within the colon, it is possible that subjects with diarrhea may have had coeliac disease or primary bile acid diarrhea which can account for roughly 4% and 25% of cases, respectively, although testing for the latter is not routine international practice. [30][31][32] For those with symptoms of constipation, we did not mandate testing for dysenergic defecatory disorders, although its presence would not alter the diagnosis of IBS-C or FC. Finally, this was a cross-sectional observational study, and the association noted between IBS and psychosomatic distress cannot be evaluated further to identify the direction of causality.
Previous studies have shown that in one-third of individuals a mood disorder precedes gut symptoms, but in two-thirds gut symptoms precede the mood disorder. 33 In conclusion, IBS is associated with increased levels of psychological distress and somatization compared with FD or FC, based on the Rome IV criteria. Patients with functional bowel disorders, and in particular those who report abdominal pain, should be routinely and comprehensively screened for extra-intestinal ill-health. Future research studies should consider evaluating the role of psychological therapies early in the disease course for IBS, while evaluating both bowel-and mental health-related end points.

CO N FLI C T O F I NTE R E S T
Nothing to declare.

AUTH O R CO NTR I B UTI O N S
IA designed the study and its conduct. All authors collected data. IA, MGS and ZA analyzed the data and wrote the initial manuscript. All authors revised the manuscript and approved the final version of the article. IA is guarantor of the article.