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Symptoms of Depression and Anxiety Are Independently Associated With Clinical Recurrence of Inflammatory Bowel Disease

Published:January 25, 2016DOI:https://doi.org/10.1016/j.cgh.2015.12.045

      Background & Aims

      We examined the relationship between symptoms of depression and anxiety and clinical recurrence of inflammatory bowel disease (IBD) in a large patient cohort. We considered the progression of depression and anxiety over time.

      Methods

      We collected clinical and treatment data on 2007 adult participants of the Swiss IBD study (56% with Crohn’s disease [CD], 48% male) performed in Switzerland from 2006 through 2015. Depression and anxiety symptoms were quantified by using the Hospital Anxiety and Depression Scale. The relationship between depression and anxiety scores and clinical recurrence was analyzed by using survival-time techniques.

      Results

      We found a significant association between symptoms of depression and clinical recurrence over time (for all patients with IBD, P = .000001; for subjects with CD, P = .0007; for subjects with ulcerative colitis, P = .005). There was also a significant relationship between symptoms of anxiety and clinical recurrence over time in all subjects with IBD (P = .0014) and in subjects with CD (P = .031) but not ulcerative colitis (P = .066).

      Conclusions

      In an analysis of a large cohort of subjects with IBD, we found a significant association between symptoms of depression or anxiety and clinical recurrence. Patients with IBD should therefore be screened for clinically relevant levels of depression and anxiety and referred to psychologists or psychiatrists for further evaluation and treatment.

      Keywords

      Abbreviations used in this paper:

      CD (Crohn’s disease), CDAI (Crohn’s Disease Activity Index), HADS (Hospital Anxiety and Depression Scale), IBD (inflammatory bowel disease), MTWAI (Modified Truelove and Witts Severity Index), SIBDC (Swiss IBD cohort), UC (ulcerative colitis)
      Inflammatory bowel disease (IBD), of which Crohn’s disease (CD), ulcerative colitis (UC), and indeterminate colitis are subtypes, is a chronic relapsing gastrointestinal condition with etiology involving a deregulated immune response to intestinal microbiome, triggered by environmental factors, in those with a genetic susceptibility. There are more than 2.2 million people living with IBD in Europe,
      • Loftus Jr., E.V.
      Clinical epidemiology of inflammatory bowel disease: incidence, prevalence, and environmental influences.
      12,000 in Switzerland alone,
      • Pittet V.
      • Juillerat P.
      • Mottet C.
      • et al.
      Cohort profile: the Swiss Inflammatory Bowel Disease Cohort Study (SIBDCS).
      and its incidence is on the rise.
      • Burisch J.
      • Jess T.
      • Martinato M.
      • et al.
      The burden of inflammatory bowel disease in Europe.
      The overall annual cost of IBD to European healthcare systems is estimated to be 4.6–5.6 billion euros.
      • Burisch J.
      • Jess T.
      • Martinato M.
      • et al.
      The burden of inflammatory bowel disease in Europe.
      IBD is associated with a clinically highly relevant and significant psychosocial burden.
      • Panara A.J.
      • Yarur A.J.
      • Rieders B.
      • et al.
      The incidence and risk factors for developing depression after being diagnosed with inflammatory bowel disease: a cohort study.
      • Graff L.A.
      • Walker J.R.
      • Lix L.
      • et al.
      The relationship of inflammatory bowel disease type and activity to psychological functioning and quality of life.
      • Hauser W.
      • Janke K.H.
      • Klump B.
      • et al.
      Anxiety and depression in patients with inflammatory bowel disease: comparisons with chronic liver disease patients and the general population.
      • Nahon S.
      • Lahmek P.
      • Durance C.
      • et al.
      Risk factors of anxiety and depression in inflammatory bowel disease.
      • Mittermaier C.
      • Dejaco C.
      • Waldhoer T.
      • et al.
      Impact of depressive mood on relapse in patients with inflammatory bowel disease: a prospective 18-month follow-up study.
      • Fuller-Thomson E.
      • Sulman J.
      Depression and inflammatory bowel disease: findings from two nationally representative Canadian surveys.
      A large Canadian population-based study reported the rates of depression in IBD patients to be 3 times higher than in the healthy population.
      • Fuller-Thomson E.
      • Sulman J.
      Depression and inflammatory bowel disease: findings from two nationally representative Canadian surveys.
      Symptoms of depression and anxiety have been linked to more severe IBD symptoms and more frequent IBD flares,
      • Mittermaier C.
      • Dejaco C.
      • Waldhoer T.
      • et al.
      Impact of depressive mood on relapse in patients with inflammatory bowel disease: a prospective 18-month follow-up study.
      increased hospitalization rates,
      • van Langenberg D.R.
      • Lange K.
      • Hetzel D.J.
      • et al.
      Adverse clinical phenotype in inflammatory bowel disease: a cross sectional study identifying factors potentially amenable to change.
      and lower compliance with treatment.
      • Nigro G.
      • Angelini G.
      • Grosso S.B.
      • et al.
      Psychiatric predictors of noncompliance in inflammatory bowel disease: psychiatry and compliance.
      However, the relationship of depression and anxiety with disease activity in IBD has been controversial,
      • Mikocka-Walus A.
      • Turnbull D.A.
      • Moulding N.T.
      • et al.
      Controversies surrounding the comorbidity of depression and anxiety in inflammatory bowel disease patients: a literature review.
      with no causal link established to date. Although some reviews have been published on the relationship between psychological factors and disease activity,
      • Maunder R.G.
      Evidence that stress contributes to inflammatory bowel disease: evaluation, synthesis, and future directions.
      • Graff L.A.
      • Walker J.R.
      • Bernstein C.N.
      Depression and anxiety in inflammatory bowel disease: a review of comorbidity and management.
      • Maunder R.G.
      • Levenstein S.
      The role of stress in the development and clinical course of inflammatory bowel disease: epidemiological evidence.
      none to date has been systematic.
      Our recent search of MEDLINE, Embase, CINAHL, PsychINFO, and Web of Science for the purpose of this study identified 12 prospective studies on depression and anxiety in IBD (studies on stress only were excluded), with samples varying from 18 to 388
      • Mittermaier C.
      • Dejaco C.
      • Waldhoer T.
      • et al.
      Impact of depressive mood on relapse in patients with inflammatory bowel disease: a prospective 18-month follow-up study.
      • Andrews H.
      • Barczak P.
      • Allan R.N.
      Psychiatric illness in patients with inflammatory bowel disease.
      • Bitton A.
      • Sewitch M.J.
      • Peppercorn M.A.
      • et al.
      Psychosocial determinants of relapse in ulcerative colitis: a longitudinal study.
      • Lima F.D.
      • Ribeiro T.C.
      • Chebli L.A.
      • et al.
      Mood swings in patients with Crohn's disease: incidence and associated factors.
      • Lix L.M.
      • Graff L.A.
      • Walker J.R.
      • et al.
      Longitudinal study of quality of life and psychological functioning for active, fluctuating, and inactive disease patterns in inflammatory bowel disease.
      • Mardini H.E.
      • Kip K.E.
      • Wilson J.W.
      Crohn's disease: a two-year prospective study of the association between psychological distress and disease activity.
      • Maunder R.G.
      • Lancee W.J.
      • Hunter J.J.
      • et al.
      Attachment insecurity moderates the relationship between disease activity and depressive symptoms in ulcerative colitis.
      • Mikocka-Walus A.A.
      • Turnbull D.A.
      • Moulding N.T.
      • et al.
      Does psychological status influence clinical outcomes in patients with inflammatory bowel disease (IBD) and other chronic gastroenterological diseases: an observational cohort prospective study.
      • Persoons P.
      • Vermeire S.
      • Demyttenaere K.
      • et al.
      The impact of major depressive disorder on the short- and long-term outcome of Crohn's disease treatment with infliximab.
      • Porcelli P.
      • Leoci C.
      • Guerra V.
      A prospective study of the relationship between disease activity and psychologic distress in patients with inflammatory bowel disease.
      • Riley S.A.
      • Mani V.
      • Goodman M.J.
      • et al.
      Why do patients with ulcerative colitis relapse?.
      • Langhorst J.
      • Hofstetter A.
      • Wolfe F.
      • et al.
      Short-term stress, but not mucosal healing nor depression was predictive for the risk of relapse in patients with ulcerative colitis: a prospective 12-month follow-up study.
      and an observation period of up to 37 months. Seven of these studies (n = 978) observed a significant positive relationship between symptoms of depression and anxiety and disease activity,
      • Mittermaier C.
      • Dejaco C.
      • Waldhoer T.
      • et al.
      Impact of depressive mood on relapse in patients with inflammatory bowel disease: a prospective 18-month follow-up study.
      • Andrews H.
      • Barczak P.
      • Allan R.N.
      Psychiatric illness in patients with inflammatory bowel disease.
      • Lix L.M.
      • Graff L.A.
      • Walker J.R.
      • et al.
      Longitudinal study of quality of life and psychological functioning for active, fluctuating, and inactive disease patterns in inflammatory bowel disease.
      • Mardini H.E.
      • Kip K.E.
      • Wilson J.W.
      Crohn's disease: a two-year prospective study of the association between psychological distress and disease activity.
      • Maunder R.G.
      • Lancee W.J.
      • Hunter J.J.
      • et al.
      Attachment insecurity moderates the relationship between disease activity and depressive symptoms in ulcerative colitis.
      • Persoons P.
      • Vermeire S.
      • Demyttenaere K.
      • et al.
      The impact of major depressive disorder on the short- and long-term outcome of Crohn's disease treatment with infliximab.
      • Porcelli P.
      • Leoci C.
      • Guerra V.
      A prospective study of the relationship between disease activity and psychologic distress in patients with inflammatory bowel disease.
      whereas 5 (n = 336) did not make this observation.
      • Bitton A.
      • Sewitch M.J.
      • Peppercorn M.A.
      • et al.
      Psychosocial determinants of relapse in ulcerative colitis: a longitudinal study.
      • Lima F.D.
      • Ribeiro T.C.
      • Chebli L.A.
      • et al.
      Mood swings in patients with Crohn's disease: incidence and associated factors.
      • Mikocka-Walus A.A.
      • Turnbull D.A.
      • Moulding N.T.
      • et al.
      Does psychological status influence clinical outcomes in patients with inflammatory bowel disease (IBD) and other chronic gastroenterological diseases: an observational cohort prospective study.
      • Riley S.A.
      • Mani V.
      • Goodman M.J.
      • et al.
      Why do patients with ulcerative colitis relapse?.
      • Langhorst J.
      • Hofstetter A.
      • Wolfe F.
      • et al.
      Short-term stress, but not mucosal healing nor depression was predictive for the risk of relapse in patients with ulcerative colitis: a prospective 12-month follow-up study.
      The conflicting evidence in these studies may result from the observation periods that were too short (only in 5 studies the follow-up exceeded 1 year) and small and unrepresentative samples (6 studies with n <100) but also from different definitions and measures of depression and anxiety (only 1 study
      • Andrews H.
      • Barczak P.
      • Allan R.N.
      Psychiatric illness in patients with inflammatory bowel disease.
      used clinical interviews and thus provided data on the diagnosis of depression and anxiety rather than symptoms only) and measures of disease activity. Studies addressing these limitations of the previous literature are needed to inform current research and practice in IBD.
      The Swiss IBD cohort (SIBDC) (Appendix) offers an ideal setting for conducting a comprehensive study on a large IBD sample during a long period of time, allowing for an observation of the natural course of IBD. The present study thus aimed to examine the relationship between symptoms of depression and anxiety and clinical recurrence in a large IBD cohort by taking into account the progression of depression and anxiety over time. The study examined the following hypothesis: There is a significant relationship between depression and anxiety symptoms and clinical recurrence over time. Because of the inconclusive results across previous studies, we did not specify the direction of this relationship.

      Materials and Methods

       Design and Setting

      This is a prospective cohort study that used data from participants who had been included in the SIBDC between 2006 and 2015.
      • Pittet V.
      • Juillerat P.
      • Mottet C.
      • et al.
      Cohort profile: the Swiss Inflammatory Bowel Disease Cohort Study (SIBDCS).
      Participants were included through their treating gastroenterologists, who were located in Swiss university hospitals, regional hospitals, and private practices. Clinical and treatment data were collected during the enrollment and yearly follow-up medical visits; in addition, participants were receiving self-administered questionnaires (at enrollment and on a yearly basis) comprising sociodemographic and psychosocial data to be completed at home. The study reporting followed the STROBE statement.

       Selection Criteria

      All adult patients who were enrolled in the SIBDC (to be included, patients must have a diagnosis established at least 4 months before inclusion or have had at least 1 recurrence of symptoms), who completed the baseline patient self-reported questionnaire and the 1-year follow-up medical visit, were included. Pregnant patients and those with missing data on depression and anxiety scores were excluded.

       Measures

      To minimize the assessment bias and optimize data quality of the registry, gastroenterologists and study nurses were asked to clarify inconclusive data for information collected from patient charts (clinical and treatment characteristics).
      Depression and anxiety symptoms were measured by using the Hospital Anxiety and Depression Scale (HADS). The HADS is a self-assessment mood scale developed for medical outpatients
      • Zigmond A.S.
      • Snaith R.P.
      The hospital anxiety and depression scale.
      containing 14 questions graded on a 4-point Likert scale with subscales of anxiety and depression, with a sum score ranging from 0 to 21 for each and a cutoff value of >7 on either of the 2 subscales. The scores of 0–7 are considered normal, 8–10 are indicative of mild anxiety/depression symptoms, 11–14 are indicative of moderate anxiety/depression symptoms, and 15–21 are indicative of severe anxiety/depression symptoms.
      Disease activity measures included the widely used Crohn’s Disease Activity Index (CDAI)
      • Best W.R.
      • Becktel J.M.
      • Singleton J.W.
      • et al.
      Development of a Crohn's disease activity index: National Cooperative Crohn's Disease Study.
      and the Modified Truelove and Witts Severity Index (MTWAI),
      • Truelove S.C.
      • Witts L.J.
      Cortisone in ulcerative colitis: preliminary report on a therapeutic trial.
      • Truelove S.C.
      • Witts L.J.
      Cortisone in ulcerative colitis: final report on a therapeutic trial.
      as appropriate. These were collected by the clinicians.

       Outcome Measure

      We were interested in the relationship between the symptoms of depression and anxiety and a clinical recurrence as a measure of outcome. The outcome was constructed by taking account of the following variables: disease activity, flare events or worsening of the disease (established by physicians as part of their assessment of the patient’s overall disease activity), fistulas and stenosis, anal fissure, abscess, IBD surgery (including any type of resection, colectomy, ileostomy, colostomy), and intake of steroids or biologics. The end point was reached when any of these events occurred. Each participant started with a value of 0 at baseline, and this value became 1 when an event occurred. If a participant had already experienced the outcome (eg, a fistula) at baseline, we were then interested in the appearance of the next event. We were interested in the time of the first appearance of a clinical recurrence event after enrollment. For each participant, we defined a time interval (tn, tn+1] where tn corresponded to the time of the nth visit. In this situation, we knew that no relevant event had occurred before tn, but at least 1 clinical recurrence event from the list above occurred between tn and tn+1.

       Data Analysis

      The composite outcome measure (clinical recurrence) was a 0/1 variable, which was analyzed by using survival-time techniques. For each participant, the time between 0 and tn+1 was split into several smaller subintervals according to their depression and anxiety levels. In each subinterval, depression and anxiety were assumed to be constant. The non-parametric approach of Kaplan-Meier curves with standard survival techniques, where events occurred exactly at tn+1, was applied. The obtained survival curves were compared by using the log-rank test to quantify differences in survival probability (event-free probability) between participants with and without depression and anxiety. Missing or invalid information on the variables of interest resulted in exclusion of the respective case from analysis.

       Ethical Considerations

      The ethical committees of all Cantons where participants were included approved the SIBDC study, and all the participants were enrolled after providing written informed consent.

      Results

       Descriptive Statistics

      Of the 2886 participants registered in the SIBDC, 879 did not meet the inclusion criteria for the present study and were excluded. In particular, after excluding pregnant patients, 2870 cases (99.4%) remained in the study. After excluding those who did not answer the questionnaire, 2321 cases (80.4%) remained in the study. After excluding patients for whom depression and anxiety levels were unknown, 2289 (79.3%) remained in the study, and finally, after excluding participants who were lost to follow-up (participants are considered lost to follow-up if they did not come for a medical visit/did not reply to a patient questionnaire for ≥18 months) after the enrollment, 2007 (69.5%) remained in the study, and these 2007 participants were thus included in the analysis.
      Overall, 55.9% participants had CD, and 48.3% were men (CD, 45.6%; UC, 51.8%). At baseline, median age was 40.5 years, median disease duration was 7.2 years, and 20.2% of participants had a depression score and 37.5% had an anxiety score above the cutoff value (>7) (Table 1). There was no difference between the sexes in depression at baseline (200 men, 20.6% versus 205 women, 19.8%; P = .635). However, there was a significant difference in anxiety at baseline between the sexes, with 304 male participants (31.3%) versus 448 female participants (43.2%) who were anxious (P < .001). There was no significant association between the CDAI score, anxiety or depression at baseline (P = .221 and P = .266, respectively). Similarly, there was no association between the MTWAI score, anxiety, or depression (P = .167 and P = .288, respectively).
      Table 1Characteristics of the Sample at Baseline
      CDUC or ICTotal
      Total no. of patients (%)1122 (55.9)885 (44.1)2007
      Age (y)
       Median, q25–q75, minimum–maximum40.2, 28.5–52.6, 15.8–87.541.0, 30.9–52.1, 16.5–82.840.5, 29.7–52.4, 15.8–87.5
       Male (%)512 (45.6)458 (51.8)970 (48.3)
      Disease duration (y)
       Median, q25–q75, minimum–maximum8.17, 2.5–17.2, 0.03–52.56.2, 2.0–13.4, 0.03–46.27.2, 2.2–15.5, 0.03–52.5
      CD location at baseline
       L1 (ileal)252 (22.5)
       L2 (colonic)245 (21.8)
       L3 (ileocolonic)516 (46.0)
       L4 (upper GI only)9 (0.8)
       Unclear/unknown100 (8.9)
      UC/IC location at baseline
       Proctitis329 (37.2)
       Left-sided colitis293 (33.1)
       Pancolitis170 (19.2)
       Unclear/unknown93 (10.5)
      CDAI at baseline
       Median, q25–q75, minimum–maximum36.5, 14–81, 0–450
      MTWAI at baseline
       Median, q25–q75, minimum–maximum3, 1–5, 0–19
      Anxiety symptoms at baseline
       None679 (60.5)576 (65.1)1255 (62.5)
       Mild241 (21.5)183 (20.7)424 (21.1)
       Moderate157 (14.0)98 (11.1)255 (12.7)
       Severe45 (4.0)28 (3.2)73 (3.6)
      Depression symptoms at baseline
       None881 (78.5)721 (81.5)1602 (79.8)
       Mild142 (12.7)111 (12.5)253 (12.6)
       Moderate78 (7.0)40 (4.5)118 (5.9)
       Severe21 (1.9)13 (1.5)34 (1.7)
      IC, indeterminate colitis.

       Symptoms of Depression and Anxiety and Clinical Recurrence Over Time

      Figures 1 and 2 present the Kaplan-Meier curves of the association between depression symptoms, anxiety symptoms, and clinical recurrence. There was a strong and statistically significant relationship between depression and clinical recurrence over time (all IBD, P = .000001; CD, P = .0007; UC, P = .005). However, this relationship was less obvious for anxiety symptoms. The relationship between anxiety and clinical recurrence over time was observable in the whole sample (P = .0014) and in the CD participants alone (P = .031) but not in the UC participants (P = .066). These results indicated that those IBD participants who reported clinically relevant symptoms of depression or anxiety (HADS score >7) had shorter time to a clinical recurrence event than the participants without depression or anxiety symptoms. When sex was factored in the Kaplan-Meier curves and a comparison was conducted by using a log-rank test, no significant difference was detected (P > .05), indicating that the relationship between depression and clinical recurrence or anxiety and clinical recurrence is not influenced by sex.
      Figure thumbnail gr1
      Figure 1Depression symptoms and disease activity over time. CI, confidence interval.
      Figure thumbnail gr2
      Figure 2Anxiety symptoms and disease activity over time. CI, confidence interval.
      When we explored particular components of the composite outcome responsible for the effect by using the Kaplan-Meier curves, we observed that there was a statistically significant relationship between depression and fistula in CD patients (P = .009), between anxiety and flares in CD and UC (P = .070 and P = .044, respectively) and between depression and flares in UC (P = .013), depression and surgery in CD (P = .007), anxiety and biologics use and depression and biologics use in CD (P < .001 and P = .016, respectively), depression and steroids use in CD (P = .035), and anxiety and steroids use in UC (P = .013).

      Discussion

      This study is the largest to date prospective design on the relationship between depression and anxiety and clinical recurrence in IBD. Although previous prospective studies on the topic exist, because of small samples, short observation periods, and inconsistencies in measuring depression/anxiety and disease activity, the relationship between depression, anxiety, and disease activity in IBD has been controversial.
      Examining the longitudinal data of more than 2000 Swiss IBD participants, we found that symptoms of depression are associated with clinical recurrence, with those depressed having a significantly shorter time to a clinical recurrence event. The link between depressive symptoms and clinical recurrence appears stronger in participants with CD, which has been previously reported in several much smaller studies.
      • Mikocka-Walus A.
      • Turnbull D.A.
      • Moulding N.T.
      • et al.
      Controversies surrounding the comorbidity of depression and anxiety in inflammatory bowel disease patients: a literature review.
      Our study’s results are consistent with the results of 7 of 12 previous prospective studies,
      • Mittermaier C.
      • Dejaco C.
      • Waldhoer T.
      • et al.
      Impact of depressive mood on relapse in patients with inflammatory bowel disease: a prospective 18-month follow-up study.
      • Andrews H.
      • Barczak P.
      • Allan R.N.
      Psychiatric illness in patients with inflammatory bowel disease.
      • Lix L.M.
      • Graff L.A.
      • Walker J.R.
      • et al.
      Longitudinal study of quality of life and psychological functioning for active, fluctuating, and inactive disease patterns in inflammatory bowel disease.
      • Mardini H.E.
      • Kip K.E.
      • Wilson J.W.
      Crohn's disease: a two-year prospective study of the association between psychological distress and disease activity.
      • Maunder R.G.
      • Lancee W.J.
      • Hunter J.J.
      • et al.
      Attachment insecurity moderates the relationship between disease activity and depressive symptoms in ulcerative colitis.
      • Persoons P.
      • Vermeire S.
      • Demyttenaere K.
      • et al.
      The impact of major depressive disorder on the short- and long-term outcome of Crohn's disease treatment with infliximab.
      • Porcelli P.
      • Leoci C.
      • Guerra V.
      A prospective study of the relationship between disease activity and psychologic distress in patients with inflammatory bowel disease.
      offering, however, a significantly larger sample and the observations conducted from 2006 until 2015 and thus the longest to date. In addition, our approach to defining clinical recurrence was different from the previous studies because we used a composite outcome measure, whereas the majority of studies relied solely on a single disease activity measure such as the CDAI, which can be highly subjective. Opting to rely on physician-reported flare events, fistulas and stenosis (for CD only), IBD surgery, and steroids or biologics intake has allowed us to provide a more robust and likely less biased measure of clinical recurrence than relying on a single disease activity measure.
      Although anxiety is a more prevalent mental disorder than depression (its 12-month prevalence in IBD is 17.9% as compared with 10.5% for mood disorders
      • Walker J.R.
      • Ediger J.P.
      • Graff L.A.
      • et al.
      The Manitoba IBD cohort study: a population-based study of the prevalence of lifetime and 12-month anxiety and mood disorders.
      ), the role played by anxiety in terms of its negative influence on IBD activity seems less pronounced than that of depression. Anxiety frequently coexists with depression, and together with psychological stress, which is best examined of the three in the context of IBD, they impact inflammation.
      • Sexton K.A.
      • Bernstein C.N.
      Stress, distress and IBD.
      Stress has also been linked to disease activity in 13 of 18 prospective studies systematically reviewed by Camara et al.
      • Camara R.J.
      • Ziegler R.
      • Begre S.
      • et al.
      The role of psychological stress in inflammatory bowel disease: quality assessment of methods of 18 prospective studies and suggestions for future research.
      Nevertheless, because there is a lack of research differentiating between depression and anxiety in terms of their specific impact on inflammation in IBD, it is unknown whether pathophysiology of either disorder can explain a stronger relationship of depression to clinical recurrence in IBD in the present study. However, it is clear that symptoms of depression such as loss of interest in daily activities may lead to noncompliance with IBD treatment,
      • Nigro G.
      • Angelini G.
      • Grosso S.B.
      • et al.
      Psychiatric predictors of noncompliance in inflammatory bowel disease: psychiatry and compliance.
      which, in turn, can lead to a flare. In addition, anxiety is often not a constant symptom in IBD participants but rather related to a situation; for example, it can rise when patients have no easy access to a toilet but then drops to a normal level when the patient returns home. It is thus possible that an ongoing character of depressive symptoms is responsible for its strong relationship with clinical recurrence.
      Finally, this study unavoidably has limitations. One of them is reliance on patient self-report in psychological measures. A psychological diagnostic interview would likely provide more accurate rates of depression and anxiety than the HADS, which is a screening measure unable to provide a diagnosis. Furthermore, there is an ongoing controversy on the usefulness of the HADS. Some studies show it to be equally good in detecting anxiety and depression as the widely used Brief-PHQ
      • Hahn D.
      • Reuter K.
      • Harter M.
      Screening for affective and anxiety disorders in medical patients: comparison of HADS, GHQ-12 and Brief-PHQ.
      and better than another widely used scale, the General Health Questionnaire.
      • Hahn D.
      • Reuter K.
      • Harter M.
      Screening for affective and anxiety disorders in medical patients: comparison of HADS, GHQ-12 and Brief-PHQ.
      • Harter M.
      • Woll S.
      • Wunsch A.
      • et al.
      Screening for mental disorders in cancer, cardiovascular and musculoskeletal diseases: comparison of HADS and GHQ-12.
      The 2002 update to a literature review on the HADS’ validity, including 747 research articles, concluded that it performs well in assessing symptom severity and caseness of anxiety and depression in somatic, psychiatric, and primary care patients and in the general population.
      • Bjelland I.
      • Dahl A.A.
      • Haug T.T.
      • et al.
      The validity of the Hospital Anxiety and Depression Scale: an updated literature review.
      On the other hand, the recent psychometric systematic reviews showed the HADS to be a measure of a state of general psychological distress rather than unique mood states.
      • Norton S.
      • Cosco T.
      • Doyle F.
      • et al.
      The Hospital Anxiety and Depression Scale: a meta confirmatory factor analysis.
      • Cosco T.D.
      • Doyle F.
      • Ward M.
      • et al.
      Latent structure of the Hospital Anxiety And Depression Scale: a 10-year systematic review.
      Other measures may potentially more accurately report on these symptoms; however, it is as yet unclear which questionnaire is best for depression and anxiety screening in IBD.
      • Hahn D.
      • Reuter K.
      • Harter M.
      Screening for affective and anxiety disorders in medical patients: comparison of HADS, GHQ-12 and Brief-PHQ.
      To date, it is the HADS that has been used most commonly in the studies on IBD,
      • Mikocka-Walus A.
      • Knowles S.R.
      • Keefer L.
      • et al.
      Controversies revisited: a systematic review of the comorbidity of depression and anxiety with inflammatory bowel diseases.
      and thus it is the scale that facilitates comparisons with previous studies. In any case, the controversy around the HADS’ performance had been unknown at the time the cohort was set up. Another limitation is annual intervals between each follow-up, which, although practical in a study of this size, may lead to underreporting of clinical recurrence events. In addition, patients themselves may underreport disease events to doctors, leading to further underreporting of disease activity. Although it is large, the cohort is not population-based, and thus the study results may not be necessarily generalizable to the whole IBD population.

      Conclusion

      Depression (and to some degree anxiety as well) is strongly associated with clinical recurrence over time. Thus it seems prudent to recommend that screening for common mental disorders and referring for psychological/psychiatric treatment should be included in standard IBD care. Whether this improves patient outcomes and is cost-effective remain to be established. Studies in other populations do not always support the value of routine screening particularly in primary care,
      • Thombs B.D.
      • Arthurs E.
      • Coronado-Montoya S.
      • et al.
      Depression screening and patient outcomes in pregnancy or postpartum: a systematic review.
      although populations with chronic conditions or with a history of depression or other mental health problems may benefit from such screening.
      • Goldberg D.
      The value of screening in patient populations with high prevalence of a disorder.
      Because occurrence of depression appears to shorten the time to a clinical recurrence event, resulting in flares and complications and thus, consequently, a more aggressive treatment, prevention and early detection of depression could potentially reduce not only individual patient’s suffering but also healthcare costs. Stepped care or collaborative care models might facilitate this,
      • Mikocka-Walus A.A.
      • Andrews J.M.
      • von Kanel R.
      • et al.
      What are the implications of changing treatment delivery models for patients with inflammatory bowel disease: a discussion paper.
      and their efficacy has been investigated in the context of IBD, with encouraging results.
      • Mikocka-Walus A.A.
      • Turnbull D.
      • Holtmann G.
      • et al.
      An integrated model of care for inflammatory bowel disease sufferers in Australia: development and the effects of its implementation.
      • Phan V.A.
      • van Langenberg D.R.
      • Grafton R.
      • et al.
      A dedicated inflammatory bowel disease service quantitatively and qualitatively improves outcomes in less than 18 months: a prospective cohort study in a large metropolitan centre.
      • Sack C.
      • Phan V.A.
      • Grafton R.
      • et al.
      A chronic care model significantly decreases costs and healthcare utilisation in patients with inflammatory bowel disease.

      Acknowledgments

      The first author would like to acknowledge the Brocher Foundation for awarding her a monthly residency fellowship in Geneva to enable the work on this paper. The authors thank all the patients for their collaboration and are grateful to the SIBDCS Scientific Committee for granting approval for this study.

      Appendix

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

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