Symptoms of anxiety/depression is associated with more aggressive inflammatory bowel disease

Studies have demonstrated that inflammatory bowel disease (IBD) patients are at an increased risk of developing anxiety and/or depression. IBD patients with depression/anxiety have higher rates of hospitalization and increased disease severity than those without. So far, there is a paucity of data concerning the impact of anxiety/depression on Chinese IBD patients. The aim of this study was to find out the prevalence of symptoms of anxiety/depression in Chinese IBD population and its impact on IBD-related features. This is a cross-sectional study from the southwest China IBD referral center. Eligible participants were divided into those with symptoms of anxiety/depression and those without based on the Hospital Anxiety and Depression Scale (HADS). Demographic data and disease duration, IBD-related surgery, tobacco use, extra-intestinal manifestations, disease activity scores, endoscopic evaluation, laboratory data and current medication use were compared between two groups. A total of 341 IBD patients [221 Crohn’s disease (CD) and 120 ulcerative colitis (UC)] were included. The prevalence of symptoms of anxiety/depression in IBD was 33.1%. CD patients with symptoms of anxiety/depression tended to have higher scores of simple endoscopic scores for Crohn’s disease (SES-CD) (p = 0.0005). UC patients with symptoms of anxiety/depression had a significantly higher Mayo score (p = 0.0017) and ulcerative colitis endoscopic index of severity (UCEIS) (p < 0.0001) than their non-anxiety/depression counterparts. CD-related surgery (p = 0.012) and Crohn's disease activity index (CDAI) (p < 0.0001) were identified as independent risk factors for symptoms of anxiety/depression in CD, while corticosteroid use (p = 0.036) as an independent risk factor for symptoms of anxiety/depression in UC. This study helps our understanding of the prevalence of symptoms of anxiety/depression in IBD patients and its impact on IBD course and reminds us to pay more attention on IBD management with anxiety/depression.


Statement of ethics. This study was approved by the Ethics Committee of West China Hospital of Sichuan
University and carried out in accordance with the Helsinki Declaration. The purpose and methods of the study were explained to all participants. Written informed consent was obtained from each participant prior to enrollment.
Different markers predicted symptoms of anxiety/depression in IBD patients. As shown by multivariable logistic regression, CD-related surgery and CDAI were independently associated with symptoms of anxiety/depression in CD patients, while corticosteroid use was a predictor of symptoms of anxiety/depression in UC patients. (Tables 4 and 5).

Discussion
IBD is a relapsing and disabling disease, and its prevalence is increasing worldwide [17][18][19][20] . Disease-related stress, financial burden, and some other unrecognized factors may lead to the significantly higher prevalence of symptoms of anxiety/depression in IBD patients compared with that of the general population 9,21-25 . A cohort study found that 40.1% IBD participants met the criteria for diagnosis of depression and 30.6% met criteria for anxiety. However, one-third of participants with depression and two-thirds with anxiety were undiagnosed, especially males 26 . The effects of an untreated mental illness can be devastating and can worsen the disease course of IBD 27 . So, it's important to timely recognize the mental disorders in the IBD population. To the best of our knowledge, the present study unveiled the state of suffering from symptoms of anxiety/depression in the Chinese IBD population with the largest sample size so far.
Some studies have reported discrepancies as to the prevalence of anxiety and depression and their impact upon IBD subtypes. In a prospective cohort study, depression was associated with an increased risk of CD, but  20 . Another review showed that fatigue was reportedly prevalent in 41-48% of patients with IBD in remission and 86% of those in active stage 21 . CD patients with impaired sleep had a twofold increase in risk of active disease at 6 months 22 . However, most of these studies were based on populations from western countries, and the relationship between the above factors were also obscure. The present study was representative of the Chinese IBD population since it was conducted in the largest IBD center of southwest China. In our study, IBD patients with symptoms of anxiety/depression were predisposed to have decreased quality of life and sleep compared with their non-anxiety/ depression counterparts. Dysfunction of autonomic nerve and fatigue were more common in participants with symptoms of anxiety/depression. Moreover, we also found that patients with symptoms of anxiety/depression were older, and had lower levels of ALB, which disaccorded to Navabi's study on USA IBD patients 4 .
We identified history of surgery and CDAI as independent predictors of symptoms of anxiety/depression in Chinese CD patients. In contrast, Navabi et al. demonstrated immunomodulator use, history of extra-intestinal manifestations and history of tobacco use as predictors of anxiety/depression in CD, which was inconsistent with our findings 4 . Another study found that anxiety was significantly correlated with female sex, history of perianal disease and perianal surgery in CD patients 28 , which was partly in agreement with our results. These discrepancies may be attributed either to the heterogeneity of participants including races, regions, social cultures, economic www.nature.com/scientificreports/ conditions, or to the methodology of studies such as standards and protocols. In addition, endoscopic score was found to be the independent risk factors for the symptoms of anxiety/depression. Further studies are needed to define the role of endoscopic score in predicating anxiety/depression for CD. When it comes to UC patients, corticosteroid use was found to be a predictor of symptoms of anxiety/ depression in our study. This is also inconsistent with Navabi's study which revealed that disease duration and immunomodulator use to be predictors of anxiety/depression in UC 4 . Previous research found that initial medical management of IBD was different among countries. For instance, UC patients were more likely to receive immunomodulators in United States 29 . In contrast, moderate-to-severe UC patients in China were often given corticosteroid as the first-line therapy 30 . The fact that most of our participants were moderate-to-severe UC patients may explain that corticosteroid rather than immunomodulator use was an independent predictor. In addition, colectomy is used as the rescue therapy which brings better quality of life for UC 12 , but might be a  www.nature.com/scientificreports/ fuse for severe complications in CD, such as fistula, stricture and short bowel syndrome 31 . This may also explain that the surgery being an independent predictor for symptoms of anxiety/depression in CD rather than in UC. There are limitations in the present study. Firstly, participants were limited to hospitalized patients, who had worsened disease course compared with outpatients. A study encompassing IBD outpatients showed that the prevalence of depression was 25%, which could not be neglected in the management of IBD 32 . Secondly, this is a cross-sectional, single-center study, despite the largest IBD referral center of the southwest China. Therefore, longitudinal multi-center studies are needed in the future to further strengthen our findings.
In conclusion, this study delineated the impact of symptoms of anxiety/depression on Chinese IBD population and necessitated special attention paid on mental disorders in IBD patients by physicians. Moreover, timely recognition and even psychiatric treatment are very important to improve the prognosis of IBD.
Received: 10 September 2020; Accepted: 4 January 2021 Table 5. Predictors of symptoms of anxiety and depression in UC patients. UC ulcerative colitis, UCEIS ulcerative colitis endoscopic index of severity, OR odds ratio.