ORIGINAL ARTICLE

Robust Association Between Inflammatory Bowel Disease and Generalized Anxiety Disorder: Findings from a Nationally Representative Canadian Study Esme Fuller-Thomson, PhD, Rusan Lateef, MSW, RSW, and Joanne Sulman, MSW, RSW

Background: Although the link between inflammatory bowel diseases (IBD) and depression is well accepted, less is known about the relationship between IBD and anxiety disorders and factors associated with anxiety among those with IBD.

Methods: Data were derived from the nationally representative 2012 Canadian Community Health Survey—Mental Health. The survey response rate was 68.9%. Two sets of analyses were undertaken. First, a series of logistic regression analyses were used to estimate the odd ratios of generalized anxiety disorder among those with IBD compared with those without (n ¼ 22,522). The fully adjusted model controlled for sociodemographics, depression, substance abuse/dependence, pain, and adverse childhood experiences. Second, among those with IBD (n ¼ 269), significant correlates of generalized anxiety disorder were identified using logistic regression. The presence of generalized anxiety disorder was determined using the WHOCIDI lifetime criteria, and IBD was assessed by a self-reported health professional diagnosis. Results: Individuals with IBD had over twice the odds of anxiety compared with those without IBD, even when controlling for a range of potential explanatory factors (odds ratio ¼ 2.18; 95% confidence interval, 1.50–3.16). Controlling for chronic pain and childhood adversities attenuate the relationship the most. Among those with IBD, a history of childhood sexual abuse, female gender, and chronic pain are the strongest correlates of anxiety. Those with Crohn’s and ulcerative colitis were equally vulnerable to generalized anxiety disorder. Conclusions: Our findings show that IBD is robustly related to generalized anxiety disorder. Health care professionals should be aware of the increased prevalence of generalized anxiety disorder among their patients with IBD, particularly women, those in chronic pain, and those with a history of childhood sexual abuse. (Inflamm Bowel Dis 2015;21:2341–2348) Key Words: Crohn’s disease, ulcerative colitis, mood disorders, generalized anxiety disorder, adverse childhood experiences

I

nflammatory bowel diseases (IBD) are a group of chronic inflammatory ailments of the gastrointestinal tract that are characterized by alternating periods of remission and relapses with symptoms and treatments that adversely affect quality of life.1 The 2 most clinically prevalent types of IBD are Crohn’s disease (CD) and ulcerative colitis (UC), which, together, affect approximately 1.4 million people in the United States.2 The Centers for Disease Control and Prevention reports that approximately $1.7 billion each year is spent on IBD-related health care costs in the United States, and that IBD results in more than 700,000 physician visits and 100,000 hospitalizations annually.2 Moreover, the number of people affected and their accompanying health care costs may be growing: recent

Received for publication April 21, 2015; Accepted May 20, 2015. From the Factor-Inwentash Faculty of Social Work, University of Toronto, Toronto, ON, Canada. E. Fuller-Thomson is supported by a Sandra Rotman Endowed Chair. The remaining authors have no conflict of interest to disclose. Reprints: Esme Fuller-Thomson, PhD, 246 Bloor Street, W Toronto, ON M5S 1A1, Canada (e-mail: [email protected]). Copyright © 2015 Crohn’s & Colitis Foundation of America, Inc. DOI 10.1097/MIB.0000000000000518 Published online 24 July 2015.

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data indicate that incidence and prevalence of IBD are increasing in several regions around the world including North America.3 IBD is commonly diagnosed in individuals between the ages of 15 and 30.2 This age group encompasses teenagers going through stages of identity formation, the college and university population, and young adults building their careers, starting families, and working towards personal and financial independence.4 At a time when individuals are trying to focus on making important life decisions, the symptoms of IBD can cause significant distress, sometimes leading to depression and anxiety disorders. A strong association between IBD and depression has been well established in clinical studies5,6 and in population-based surveys.4,7–9 Less research has focused on the link between IBD and anxiety disorders despite the fact that anxiety disorders are more common than depressive disorders in the general population with an estimated 15% of individuals in the United States experiencing such a disorder during their lifetime.10 Several population-based studies indicate that anxiety disorders are more prevalent among individuals with IBD compared with the general population.7,9,11 In one of these studies, the occurrence of anxiety among those with IBD was also found to be higher than among individuals with another serious medical www.ibdjournal.org |

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condition: chronic liver disease.11 In a clinical study of patients with IBD, Porcelli et al12 found that anxiety is elevated primarily during times of active disease and subsequently reduced during periods of remission. Anxiety among persons with IBD is negatively associated with quality of life9 and may also affect medication adherence and health service use. For example, highly anxious adolescents with IBD were shown to be less likely to consistently adhere to their medication regime than their peers with IBD and no anxiety, even after adjustment for disease severity.13 Finally, a study comparing confirmed cases of IBD with matched controls from the general Canadian population found that those with IBD may have higher levels of traits relating to anxiety, such as distress and use of avoidant coping.14 As with any correlation, the possibility exists that the relationship between IBD and anxiety disorders may be caused by a hidden third variable that is closely related to both conditions and that when controlled for would reduce the relationship to nonsignificance. For this reason, it is important to adjust for known correlates of both anxiety disorders and IBD when assessing whether a significant association occurs. A review of the literature suggests that the following types of factors may be important to consider: sociodemographics, adverse childhood experiences (ACEs), mental health, and pain.

Sociodemographics Variations in IBD and anxiety prevalence by gender, race, age, socioeconomic status and marital status suggest that these factors should be taken into account. Starting with gender, research shows that CD is slightly more prevalent among women (although UC is a little more prevalent in men),2 and that anxiety disorders affect substantially more women than men.15 As for race, IBD is more common in the white populations than other ethnoracial groups,2 as are some types of anxiety disorders.16 The highest prevalence of both IBD4 and generalized anxiety disorder (GAD)17 is found among those who are in midlife. Regarding socioeconomic status, the prevalence of both IBD18 and GAD19 is lower among those with a university degree compared with those with less education. Although household income is not necessarily associated with IBD status,18 those with GAD are more likely to have lower family incomes than those without.17 Finally, although the literature on marital status and IBD is mixed,18 research shows that those with GAD are less likely to be living in a couple or family and are more likely to be living alone.19

Adverse Childhood Experiences Although only limited research has been undertaken on ACEs and IBD, there is some evidence of a relationship. For example, a clinical study by Drossman20 revealed that 37% of those with organic gastrointestinal diagnoses, including IBD, reported a history of sexual abuse. Exposure to early adversity, such as childhood sexual abuse (CSA), childhood physical abuse, and witnessing parental domestic violence, has been clearly associated with adult anxiety disorders.21,22

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Mental Health A number of mental health conditions could be comorbid with IBD and anxiety. The prevalence of depression is higher among those with IBD4,9 and among those with GAD.17 Substance abuse or dependence may also be related to both IBD and anxiety. There is some indication that those with CD have elevated rates of substance abuse compared with those without this condition.23 Individuals with IBD may also be more likely to use certain drugs, such as cannabis, which have been shown to be associated with a relief of symptoms, including abdominal pain, diarrhea, and reduced appetite.24,25 The relationship between substance abuse/ dependence and anxiety disorders is well established.26,27

Pain Chronic pain is commonly associated with both IBD28 and anxiety disorders.29 Active disease in patients with IBD is associated with more severe pain.28 Similarly, as the severity of anxiety symptoms increases, the likelihood of having highly disabling pain increases.29 Prior population-based research suggests that IBD and anxiety are associated,7,9,11 but multiple potentially confounding factors have not always been taken into consideration. The purpose of this study, thus, is to investigate the relationship between IBD and lifetime GAD in a nationally representative sample while controlling for a large range of potentially confounding factors, including sociodemographic variables, ACEs, mental health, and pain. To better understand those with comorbid IBD and anxiety, we also undertook an analysis to identify correlates of lifetime GAD among those with IBD.

MATERIALS AND METHODS Sample For this study, we analyzed data from the 2012 Canadian Community Health Survey—Mental Health (CCHS-MH). The CCHS-MH is a cross-sectional survey that collects data on the factors, influences, and processes that contribute to mental health through a multidisciplinary approach focusing on health, social, and economic determinants.30 The CCHS covers the population of individuals aged 15 years and older living in the 10 provinces. Excluded from the survey are residents of the 3 territories, those living on reserves or other Aboriginal settlements, full-time members of the armed forces, and the institutionalized population, who, altogether, represent less than 3% of the target population.30 The sample for the CCHS-MH was selected using a 3-stage design. First, individuals were selected from geographical areas. Next, households were selected within each geographical area. Last, from all eligible respondents, one individual per household was randomly chosen according to varying selection probabilities.30 Out of all selected units, 36,443 were in scope for the survey and, of these, 29,088 households agreed to participate yielding an overall household-level response rate of 79.8%. From responding households, 25,113 out of 29,088 persons selected to

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participate provided a valid questionnaire, producing an overall person-level response rate of 86.3%. At the national level, these figures combine to produce an overall response rate of 68.9%.30 For this study, we analyzed 2 subsamples of the full CCHSMH. The first subsample is made up of those with complete data on IBD and lifetime anxiety, as well as each of the independent measures included in the final analysis (n ¼ 22,522). Note that our sample only contains respondents aged 18 years and older because younger respondents were not asked questions about ACEs. In a second subsample, we restricted the analysis to only those respondents who reported they had been diagnosed with IBD (n ¼ 269).

Measures Inflammatory Bowel Disease Respondents were asked if they had any “conditions diagnosed by a health professional” which are “expected to last or have already lasted 6 months or more.” Included in the list of potential health problems was IBD, which was assessed as follows: do you have a bowel disorder such as CD, UC, irritable bowel syndrome or bowel incontinence? A follow-up question determined the type of IBD that the respondent had. We created a variable that compared those with Crohn’s or UC versus all others. For the analysis of the second subsample that was restricted to the 269 respondents with IBD, a variable identified if they had Crohn’s disease or UC.

Generalized Anxiety Disorder Individuals were coded as having an anxiety disorder if they met the WHO-CIDI lifetime criteria for GAD. For more details, please see Statistics Canada.30

IBD and Generalized Anxiety Disorder

each other or another adult” aged 18 years or older in their home. 2. CSA: CSA was measured by the question “How many times did an adult force you or attempt to force you into any unwanted sexual activity, by threatening you, holding you down, or hurting you in some way?” This variable was coded never versus ever. 3. Childhood Physical Abuse: Individuals were ascertained as having been physically abused if they reported that before they reached the age of 16, an adult had at least once kicked, bit, punch, choked, burned, or physically attacked them. A sum representing the total number of ACEs experienced by the respondent was included in the first series of analyses described in the Statistical Analyses section testing the relationship between IBD and anxiety, whereas each ACE was included separately in the second model investigating correlates of anxiety among those with IBD.

Depression Individuals were coded as having a depressive disorder if they met the WHO-CIDI lifetime criteria for Major Depressive Episode. For more details please see Statistics Canada.30

Chronic Pain Chronic pain was determined using a question from a section of the survey on pain and discomfort beginning with the statement: “The next set of questions asks about the level of pain or discomfort you usually experience. They are not about illnesses like colds that affect people for short periods of time.” Respondents were coded as being regularly in pain if they responded negatively to the question “Are you usually free of pain or discomfort?”

Substance Abuse/Dependence Sociodemographic Variables Sociodemographic Variables include gender, self-identified race/ethnicity (non-Aboriginal white versus visible minority, and/ or Aboriginal) and age (in decades). Socioeconomic Status was measured by the highest level of achieved education (less than postsecondary diploma or university degree versus postsecondary degree or higher) and household income. The latter was determined based on Statistics Canada’s measure of household income as a ratio related to the national low-income cutoff divided into deciles. This variable takes into account the number of people in the household and the size of the community. Marital status was measured according to the following categories: Married, common-law, formally married, single/never married.

Adverse Childhood Experiences ACES included the following:

1. Witnessing Parental Domestic Violence: Individuals were determined as having been exposed to intimate partner violence if they reported they had seen or heard 11 or more times one of their “parents, step-parents, or guardians hit

Substance abuse/dependence was based on the WHO-CIDI using a combination of the derived variables created by Statistics Canada “Drug Abuse or Dependence (including Cannabis)” and “Alcohol Abuse or Dependence.” Both were derived using the lifetime algorithm. For more information, please see Statistics Canada.30

Statistical Analyses Two series of logistic regression analyses were conducted. In the first series, the outcome was anxiety and the key exposure variable was IBD. The first model and each subsequent model controlled for age, gender, race, income, education, and marital status. The second model adjusted for the number of early adversities (witnessing parental domestic violence, being physically abused, and being sexually abused as a child). The third and fourth models took into account substance abuse/dependence and depression, respectively. The fifth model controlled for chronic pain. The sixth and final model controlled for all the above named factors simultaneously. A second series of logistic regression analyses was completed using the subsample of those diagnosed with IBD www.ibdjournal.org |

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1.00 1.24 (1.09–1.41) 0.95 (0.80–1.12) 0.64 (0.44–0.92) 1.00 1.29 (1.14–1.46) 0.73 (0.62–0.85) 0.32 (0.22–0.45) 1.00 1.44 (1.26–1.63) 1.04 (0.89–1.23) 0.63 (0.44–0.90) 1.00 1.36 (1.20–1.53) 0.89 (0.77–1.04) 0.44 (0.31–0.63) 1.00 1.50 (1.33–1.69) 0.90 (0.77–1.05) 0.39 (0.28–0.56)

1.00 1.51 (1.34–1.70) 0.98 (0.84–1.14) 0.47 (0.33–0.67)

1.00 1.73 (1.49–2.00) 1.00 1.97 (1.72–2.27) 1.00 1.75 (1.52–2.02) 1.00 2.09 (1.82–2.39) 1.00 2.07 (1.81–2.37)

1.00 1.84 (1.61–2.11)

2.28 (1.61–3.21) 1.00 2.91 (2.02–4.19) 1.00 2.72 (1.94–3.83) 1.00 2.33 (1.64–3.30) 1.00 2.83 (2.03–3.95) 1.00

IBD Yes No (Ref) Demographics Race Not white (Ref) Only white Age, yr ,40 (Ref) 40–59 60–79 $80

Model 2 Demographics and SES + ACEs Model 1 Demographics, and SES

DISCUSSION In our population-based study of Canadian adults, the OR of GAD were found to be over twice as high for those with IBD versus those without IBD, even after controlling for sociodemographics, ACEs, depression, substance abuse/dependence, and pain. This finding coincides with the results of other populationbased research suggesting that rates of anxiety are higher among those with IBD than the general population.9,11 We note, however, that prior research has tended not to control for a wide range of potential explanatory factors and, thus, this study provides novel evidence of an independent relationship between IBD and anxiety disorders.

TABLE 1. Logistic Regression of Lifetime Anxiety Among Those with IBD (n ¼ 22,522)

RESULTS One out of 100 Canadians (0.9%) in our population-based sample reported that they had been diagnosed by a health professional with UC or CD (together referred to as IBD from herein). Our results from the first set of analyses investigating the relationship between IBD and anxiety are presented in Table 1. In all the models, the odds of anxiety are over twice as high for those with IBD versus those without. The odds ratios (ORs) span from 2.83 in model 1, which controls for sociodemographics only, to 2.18 in the fully adjusted model. Unexpectedly, the odds of anxiety are highest in model 4, controlling for sociodemographics and depression (OR ¼ 2.91), suggesting that rather than helping to explain the association between IBD and anxiety, controlling for depression makes the association slightly stronger. Of all the factors, controlling for pain seems to attenuate the IBD-anxiety relationship the most (ORmodel1 ¼ 2.83 versus ORmodel5 ¼ 2.28), followed by the 3 ACES (ORmodel1 ¼ 2.83 versus ORmodel5 ¼ 2.33). Results for the second series of analyses investigating independent correlates of anxiety among those with IBD are presented in Table 2. The strongest predictor of anxiety was a history of sexual abuse (OR ¼ 6.83), followed by female gender (OR ¼ 4.13) and chronic pain (OR ¼ 2.43). Increasing age was marginally associated with lower odds of anxiety (OR ¼ 0.97, p ¼ 0.06), but none of the other factors were significantly related to anxiety. It is worth noting that there was no statistical difference in the odds of anxiety disorders between those with UC and CD. In fact, the odds ratio in the fully adjusted model was remarkably close to 1 (p ¼ 0.93).

Model 3 Demographics and Model 4 Demographics and SES + Addictions SES + Depression

Model 5 Demographics and SES + Pain

Model 6 Fully Adjusted

(n ¼ 269) to determine predictors of anxiety. We included the following factors in the model: age, gender, race, education, income, marital status, 3 ACEs, substance abuse/dependence, and chronic pain. Finally, because there is uncertainty regarding whether anxiety is more prevalent in CD or UC,31 we also included IBD type (i.e., CD versus UC). Data from all the analyses were weighted to adjust for the probability of selection and nonresponse. Sample sizes are reported in their unweighted form.

2.18 (1.50–3.16) 1.00

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Sex Male (Ref) Female Marital status Married (Ref) Common-law Formerly married Single/never married SES Education ,Postsecondary (Ref) $Postsecondary Household income Decile of household incomea Substance abuse/ dependence Neither (Ref) Drug and/or alcohol Lifetime depression Never (Ref) Yes Pain No or mild pain (Ref) Moderate or severe pain ACEs (Sum) Nagelkerke R-square 22 Log likelihood

Model 1 Demographics, and SES

Model 2 Demographics and SES + ACEs

Model 3 Demographics and Model 4 Demographics and SES + Addictions SES + Depression

Model 5 Demographics and SES + Pain

Model 6 Fully Adjusted

1.00 1.91 (1.73–2.11)

1.00 1.90 (1.72–2.10)

1.00 1.67 (1.51–1.86)

1.00 1.68 (1.51–1.86)

1.00 1.85 (1.68–2.05)

1.00 1.87 (1.67–2.09)

1.00 1.42 (1.22–1.65) 1.55 (1.35–1.78) 1.33 (1.16–1.52)

1.00 1.32 (1.13–1.53) 1.47 (1.28–1.69) 1.29 (1.12–1.47)

1.00 1.31 (1.13–1.52) 1.48 (1.29–1.70) 1.22 (1.06–1.40)

1.00 1.32 (1.13–1.55) 1.32 (1.14–1.53) 1.20 (1.04–1.38)

1.00 1.38 (1.19–1.61) 1.51 (1.31–1.73) 1.32 (1.15–1.51)

1.00 1.20 (1.02–1.41) 1.26 (1.08–1.46) 1.14 (0.99–1.33)

1.00 0.94 (0.85–1.04)

1.00 0.97 (0.88–1.07)

1.00 0.98 (0.89–1.09)

1.00 0.92 (0.82–1.02)

1.00 0.97 (0.88–1.08)

1.00 0.99 (0.89–1.10)

0.94 (0.93–0.96)

0.96 (0.94–0.98)

0.94 (0.92–0.96)

0.96 (0.94–0.98)

0.96 (0.95–0.98)

0.98 (0.97–1.00)

— —

— —

1.00 2.45 (2.20–2.73)

— —

— —

1.00 1.63 (1.45–1.84)

— —

— —

— —

1.00 8.75 (7.89–9.71)

— —

1.00 6.97 (6.26–7.77)

— — — 0.054 12,933.5

— — 1.91 (1.79–2.04) 0.087 12,589.6

— — — 0.078 12,678.1

— — — 0.197 11,398.6

1.00 3.23 (2.89–3.60) — 0.092 12,531.8

1.00 2.25 (1.99–2.53) 1.45 (1.35–1.57) 0.233 10,989.5

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IBD and Generalized Anxiety Disorder

a Decile of household income is derived from total household income taking into account low-income cutoff according to number of individuals in the household and community size. SES, socioeconomic status.

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TABLE 1 (Continued)

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TABLE 2. Independent Correlates of IBD Among Those with Generalized Anxiety Disorder (n ¼ 269) OR (95% Confidence Interval) Types of IBD UC CD (Ref) Demographics Race Not white (Ref) White Age By decade Sex Male (Ref) Female ACEs Witnessed parental domestic violence .10 times #10 times Physical abuse Yes No Sexual abuse Yes No Socioeconomic status Education ,Postsecondary (Ref) $Postsecondary Household income Decile of household incomea Marital status Single/never married Married/common-law/formerly married (Ref) Drug abuse/dependence Neither drug nor alcohol (Ref) Drug and/or alcohol Pain No or mild pain (Ref) Moderate or severe pain

0.97 (0.45–2.09) 1.00

1.00 1.17 (0.36–3.79) 0.98 (0.95–1.00) 1.00 4.13 (1.84–9.26)

0.64 (0.18–2.30) 1.00 2.15 (0.79–5.83) 1.00 6.83 (2.33–19.99) 1.00

1.00 0.95 (0.42–2.15) 0.98 (0.85–1.14) 0.78 (0.25–2.46) 1.00

1.00 0.94 (0.40–2.20) 1.00 2.43 (1.14–5.18)

a Decile of household income is based on total household income based on low-income cutoff according to number of individuals in the household and community. Bolded odds ratios are significantly different from 1.

Of all the factors that were controlled for in our analyses, pain seemed to attenuate the relationship between IBD and GAD the most, followed by a history of ACEs. Chronic pain is commonly associated with both anxiety disorders29 and IBD,28 with the severity of symptoms in both conditions being positively

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associated with more severe pain.28,29 There are a number of interconnections between pain, anxiety, and IBD, which may help explain this finding. Anxiety and pain have similar pathophysiological pathways with the same areas of the brain playing a role in both anxiety disorders and the modulation of the pain response.32,33 The stress that is experienced by individuals with anxiety may increase the production of proinflammatory cytokines34 that have the potential to elicit pain.35 Also, at elevated levels, proinflammatory cytokines may disrupt the intestinal immune system and stimulate intestinal inflammation,36,37 one of the mechanisms through which pain is experienced among individuals with IBD.36 Concentrations of proinflammatory cytokines are found to be elevated in individuals with IBD.37 We speculate that similar mechanisms by which anxiety produces stress that increases the concentrations of proinflammatory cytokines, leading to pain and pain-causing intestinal inflammation apparent in IBD, may be instigated by a history of childhood adversities. This may help explain why controlling for the number ACEs leads to the second largest attenuation of the relationship between IBD and anxiety. Unexpectedly, the odds of GAD were the highest when sociodemographics and depression were taken into account meaning that controlling for depression made the IBD-anxiety association slightly stronger. This was unexpected because anxiety and depression are highly comorbid38 and IBD and depression are strongly associated,4–9 and so, it would seem reasonable that depression would help explain the relationship between IBD and anxiety to an extent. Future research could investigate this unexpected finding more closely. An important finding of this study is that a strong relationship between IBD and GAD persists even after controlling for potential explanatory factors, such as pain and ACEs. What, then, might explain the link between these 2 conditions? Two lines of research help elucidate this finding. The first has to do with micronutrient deficiencies associated with both IBD and anxiety. More specifically, IBD is associated with magnesium and zinc deficiency,39–41 possibly resulting from factors, such as reduced dietary intake, malabsorption, or chronic diarrhea.41 Anxiety, in turn, has been related to low levels of magnesium and, possibly, zinc.42,43 Second, recent advances in understanding of the microbiome suggest that it may play a role in the pathogenesis of anxiety, and that IBD may contribute to individuals’ susceptibility to anxiety disorders through the alterations in gut microbiota composition characteristic of IBD (e.g., reduction in proportion of Firmicutes).44 Future research is needed that can further investigate biological pathways linking IBD and anxiety relating to micronutrient deficiencies and alterations in gut microbiota. The second series of analyses investigating the correlates of anxiety among those with IBD found that the strongest predictors of anxiety among those with IBD were a history of sexual abuse, followed by female gender and then chronic pain. A history of CSA was associated with almost 7 times the odds of anxiety disorders in those with IBD, making it more strongly related to anxiety in this subpopulation than better known anxiety

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correlates, such as gender and pain. CSA is a well-known risk factor for anxiety disorders,45 with some research showing that CSA may be more commonly associated with anxiety disorders than other forms of abuse,46 and that a history of CSA may be more prevalent among those with anxiety disorders than those with depressive disorders.47 As CSA is predictive of anxiety disorders in the general population, it makes sense that it would also relate to anxiety among individuals with IBD. We note that this study is the first we are aware of that has explored the relationship between ACEs and anxiety among those with IBD. Keeping with previous literature that has found an increased prevalence of anxiety disorders among women in the general population,15 this study found that females with IBD had 4 times the odds of having an anxiety disorder in comparison with males with IBD. Women with IBD have reported higher levels of IBD symptom severity and greater concerns than men regarding a number of specific issues, such as attractiveness, feeling alone, and intimacy.48 Greater IBD symptom severity has been associated with elevated anxiety,12 so it is not surprising that female gender was strongly related to anxiety among individuals with IBD. Another robust correlate of anxiety among those with IBD was chronic pain. The mechanisms, described above, by which chronic pain may attenuate the relationship between IBD and anxiety could be used to explain this finding. Interestingly, our analysis showed that there was no statistical difference in the odds of anxiety disorders between those with UC and CD. One of the controversies surrounding the comorbidity of anxiety and IBD has been whether the cooccurrence of anxiety is specific to CD or UC.31 Some studies have found that anxiety occurred more commonly in CD compared with UC (e.g., Nordin et al49), whereas other studies have shown that both CD and UC patients were equally as likely to have a comorbid anxiety disorder (e.g., Huser et al11). Our population-based findings support the latter findings. There also is a possibility that psychological disorders interact differently with type of IBD depending on level of physical illness,50 which may lead to inconsistencies across studies investigating prevalence between the 2 types of IBD. Future research, therefore, should control for illness severity when assessing relationship between IBD type and anxiety, if possible. There are several limitations to this research. First, the cross-sectional nature of our study prohibited our ability to examine the timing of onset of IBD and the onset of the anxiety disorder. One of the main controversies regarding the comorbidity of IBD and anxiety is whether psychological disorders precede and/or follow the onset of IBD.31 Further research is needed in this area to settle the differing findings that exist. A second limitation is that IBD was self-reported. However, 2 recent studies of those with IBD comparing self-report with medical records51 or physician reports52 indicate 97% accuracy in individuals’ selfreport of IBD status52 and of type of IBD (Crohn’s versus UC).51,52 Related is that we were not able to assess the stage of IBD (i.e., active disease, remission, postsurgery) in our sample. Research shows that co-occurrence of anxiety varies during

IBD and Generalized Anxiety Disorder

different stages of IBD.12 Third, several researchers have shown an anxiety-inducing effect of medications commonly administered to patients with IBD (e.g., Fardet et al53); however, we did not have information on whether individuals in the study were taking these potentially anxiety-inducing medications. So, it is possible that the association between IBD and anxiety could be partially due to the effects of the medications commonly administered to patients with IBD. Finally, the ACEs were assessed retrospectively and, thus, may have been subject to recall bias. That being said, evidence from longitudinal research suggests that if early adversities are misrecalled, they tend to be underreported rather than overreported.54 This would have the effect of rendering our results more conservative. Future research using different methods to ascertain a positive history of childhood adversity among those with IBD is recommended. In conclusion, this study found that individuals with IBD had over twice the odds of anxiety compared with those without IBD, even when controlling for a range of potential explanatory factors. Among these, chronic pain and ACEs attenuated the relationship the most, whereas a history of CSA, female gender, and chronic pain most strongly predicted anxiety among those with IBD. These findings suggest that better management of pain and psychological treatment for ACEs among patients with IBD may help mitigate the association between IBD and anxiety.

ACKNOWLEDGMENTS The analysis presented in this article was conducted at the Toronto RDC, which is part of the Canadian Research Data Center Network (CRDCN). The services and activities provided by the Toronto RDC are made possible by the financial or in-kind support of the SSHRC, the CIHR, the CFI, Statistics Canada, and University of Toronto. The views expressed in this article do not necessarily represent the CRDCN or that of its partners. The authors would like to thank Anastasiya Slyepchenko and Keri West for their help with manuscript preparation.

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Robust Association Between Inflammatory Bowel Disease and Generalized Anxiety Disorder: Findings from a Nationally Representative Canadian Study.

Although the link between inflammatory bowel diseases (IBD) and depression is well accepted, less is known about the relationship between IBD and anxi...
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