Mental Health and Chronic Immune Diseases //
For the years 2014-2019 our group got a CIHR grant for $2.5 million to study psychiatric comorbidity in persons with chronic immune mediated diseases. The 3 diseases we focused on have been IBD, rheumatoid arthritis and multiple sclerosis. We enrolled approximately 1000 persons with any of IBD (we enrolled 254 persons), rheumatoid arthritis, multiple sclerosis or with depression and/or anxiety and no chronic immune diseases. We have been exploring the extent to which depression and/or anxiety affect persons with chronic immune disease; the types of treatment for depression and anxiety that have been studied specifically in persons with chronic immune diseases; the optimal survey tools to use to identify when depression and anxiety are present; the impact a diagnosis of depression or anxiety has on persons with a chronic immune disease. We have a large team including experts in neurology (Ruth Ann Marrie, MD, the nominated principle investigator), rheumatology (Carol Hitchon MD), psychiatry (Murray Enns, MD, Jitender Sareen, MD, James Bolton, MD, Scott Patten, MD), Clinical Psychology (Lesley Graff, PhD, John Walker, PhD, Renee El Gabalawy, PhD, John Fisk, PhD), Statistics (Lisa Lix, PhD, Randy Walld, PhD) and Family Practice (Alex Singer, MD, Alan Katz, MD).
Marrie RA, Walld R,Bolton JM, Sareen J, Walker JR, Patten SB, Singer A, Lix LM, Hitchon CA,El-Gabalawy R, Katz A, Fisk JD, Bernstein CN. Increased incidence of psychiatric disorders in immune-mediated inflammatory disease. Journal of Psychosomatic Research 2017;101:17-23.
We studied the incidence (number of new diagnoses) of psychiatric comorbidity in chronic immune mediated diseases. We used the administrative health data of Manitoba Health, the single provincial health provider, for the years of 1989-2012. We identified 19,572 incident cases of persons with chronic immune diseases including 6119 persons with IBD, 3514 persons with multiple sclerosis, 10,206 persons with RA, and 97,727 age-sex- and geographically-matched controls. The relative incidence of depression (incidence rate ratio [IRR] 1.71; 95%CI: 1.64-1.79), anxiety (IRR 1.34; 95%CI: 1.29-1.40), bipolar disorder (IRR 1.68; 95%CI: 1.52-1.85) and schizophrenia (IRR 1.32; 95%CI: 1.03-1.69) were elevated in the chronic immune diseases cohort. This means that persons with these chronic immune diseases were nearly twice as likely to have depression as persons without those diseases and 40% more likely to have an anxiety disorder. Depression and anxiety affected the multiple sclerosis population more often than the IBD and rheumatoid arthritis populations. This increased risk appears non-specific as it is seen for all three chronic immune diseases and for all psychiatric disorders studied, implying a common underlying biology for psychiatric diseases in those with chronic immune diseases.
Marrie RA, Walld R, Bolton JM, Sareen J, Walker JR, Patten SB, Singer A, Lix L, Hitchon C, El-Gabalawy R, Katz A, Fisk JD, Bernstein CN. Rising Incidence of Psychiatric Disorders Before Diagnosis of Immune-Mediated Inflammatory Diseases. Epidemiology and Psychiatric Sciences 2017; Nov 3:1-10.
We have shown that after the diagnosis of chronic immune-mediated inflammatory diseases such as IBD, multiple sclerosis and rheumatoid arthritis, the incidence of psychiatric diagnoses is increased relative to the general population. We aimed to determine whether the incidence of psychiatric disorders is increased in the 5 years before the diagnosis of having chronic immune-mediated inflammatory diseases as compared with the general population. Using administrative health data from Manitoba, we identified all persons with newly diagnosed IBD, multiple sclerosis and rheumatoid arthritis between 1989 and 2012, and matched controls from the general population. We identified 12 141 new cases of chronic immune diseases (3766 IBD, 2190 multiple sclerosis, 6350 rheumatoid arthritis). As early as 5 years before diagnosis, the incidence of depression [incidence rate ratio (IRR) 1.54; 95% CI 1.30-1.84) and anxiety disorders (IRR 1.30; 95% CI 1.12-1.51) were elevated in the chronic immune diseases cohort as compared with the controls. This means that for as long as 5 years prior to the diagnosis of their chronic immune disease these patients were 30-50% more likely to have depression or an anxiety disorder than members of the general population. Similar results were obtained for each of the IBD, multiple sclerosis and rheumatoid arthritis cohorts. We concluded that the incidence of psychiatric diagnoses is elevated in the chronic immune diseases population as compared with a matched population as early as 5 years before diagnosis. Future studies should elucidate whether this reflects shared risk factors for psychiatric disorders and chronic immune diseases, a shared final common inflammatory pathway or other etiology.
Bernstein CN. The brain-gut axis and stress in inflammatory bowel disease. Gastroenterology Clinics in North America 2017; 46(4):839-846.
This review article discusses the important connection between the brain and the gut in IBD and how stress may impact on outcomes in IBD.
Marrie RA, Graff LA, Walker JR Fisk JD, Patten SB, Walld R, Hitchon C, Lix L, Bolton JM, Sareen J, Singer A, Lix L, Katz A, Berrigan LI, Marriott JM, Singer A, El-Gabalawy R, Peschken CA, Zarychanski R, Bernstein CN. Effects of Psychiatric Comorbidity in Immune-Mediated Inflammatory Disease: Protocol for a Prospective Study. JMIR Research Protocols 2018; Jan 17;7(1):e15.
In this paper we reported the research protocol we have pursued in studying psychiatric comorbidity (having a concurrent mental health diagnosis) in persons with a chronic immune disease (any of IBD, multiple sclerosis or rheumatoid arthritis). We described how participants were recruited and how we interviewed participants on an annual basis. We also described the aspects of the research program that did involve direct patient contact. This included using administrative health data (insurance data from Manitoba Health) to understand how common it was in the general population to have both a mental health diagnosis and one of the chronic immune disease diagnoses; and also how likely it was that these mental health disorders occurred long before the onset of the chronic immune disease. Another aspect of our research program was to undertake systematic reviews of the medical research to understand the degree to which research has been undertaken exploring treatment of mental health diseases in these chronic immune diseases and what the outcomes of that research were.
Litster B, Bernstein CN, Graff LA, Walker JR, Fisk JD, Patten SB, Bolton JM, Sareen J, El-Gabalawy R, Marrie RA. Validation of the PHQ-9 for suicidal ideation in persons with inflammatory bowel disease. Inflammatory Bowel Diseases 2018; 24: 1641-8.
Suicide is a leading cause of death worldwide. Transition from suicidal ideation (SI) to suicide attempt is high within a year of SI onset. The risk of suicide and SI is elevated in persons with IBD versus the general population. We aimed to validate the Patient Heath Questionnaire (PHQ)-9 as a screening tool for SI in IBD and to determine factors associated with SI in IBD. IBD participants in our research program exploring psychiatric comorbidity in chronic immune diseases completed the PHQ-9 and participated in the Structured Clinical Interview for DSM-IV (SCID). We determined the sensitivity, specificity, and positive and negative predictive value (PPV and NPV) of the PHQ-9 in identifying SI as compared to the SCID. In other words, we determined how robust a tool the PHQ-9 was at predicting SI. SI was endorsed by 24 (9.7%) participants on the PHQ-9 and 5 (2.0%) based on the SCID. The PHQ-9 had good sensitivity (100%), specificity (92.2%), and NPV (100%) but low PPV (20.8%) for SI. Factors strongly associated with SI were depression (OR 13.1; 95%CI: 4.46, 40.5), anxiety (OR 11.3; 95%CI: 4.46, 28.6), and active disease (OR 3.87; 95%CI: 1.54, 9.71). On multivariable analysis, the only factors that predicted SI were depression (OR 5.54; 95%CI: 1.67, 18.4) and pain (OR 1.14; 95%CI: 1.03, 1.25). People with depression were more than 5 times as likely to have SI than people without depression.) We concluded that overall the PHQ-9 is a valid screening tool for SI in IBD patients, and routine implementation of this tool would support screening for depression and SI effectively and efficiently in clinical practice.
Marrie RA, Fisk J, Walker JR, Patten S, Lix L, El Gabalawy R, Hitchon CA, Walld R, Katz A, Bernstein CN. Physical Comorbidities Increase the Risk of Psychiatric Comorbidity in Immune-Mediated Inflammatory Disease. General Hospital Psychiatry; 2018; 51: 71-78.
As part of our research program exploring psychiatric comorbidity in chronic immune diseases we tested the association between physical comorbidity and incident depression, anxiety disorder and bipolar disorder in IBD), multiple sclerosis and rheumatoid arthritis compared to matched controls. Using population-based administrative data we identified 6119 persons with IBD, 3514 persons with MS, 10,206 persons with RA and 97,727 matched controls. We identified incident cases of depression, anxiety disorder and bipolar disorder in these populations. The risk of incident depression, anxiety disorders and bipolar disorder was higher in each chronic immune disease cohort compared with controls. The risk of newly diagnosed mental health disorders increased with an increasing number of physical comorbidities for each mental health disorder evaluated, across all 3 immune diseases. In conclusion within each chronic immune disease cohort physical comorbidity increases the risk of psychiatric comorbidity.
Bernstein CN, Zhang L, Lix LM, Graff LA, Walker JR, Fisk JD, Patten SB, Hitchon CA, Bolton JM, Sareen J, El-Gabalawy R, Marriott J, Marrie RA. The validity and reliability of screening measures for depression and anxiety disorders in inflammatory bowel disease. Inflammatory Bowel Diseases 2018; in press.
We evaluated the validity and reliability of multiple symptom scales for depression and anxiety for persons with IBD. IBD participants in a cohort study completed a Structured Clinical Interview for DSM-IV-TR Axis I Disorders (SCID) and completed the Patient Health Questionnaire (PHQ-9), Hospital Anxiety and Depression Scale (HADS), Kessler-6 Distress Scale, PROMIS Emotional Distress Depression Short-Form 8a (PROMIS Depression) and Anxiety Short-Form 8a (PROMIS Anxiety), Generalized Anxiety Disorder 7-item Scale, and Overall Anxiety and Severity Impairment Scale. The SCID diagnoses was the reference standard. Of 242 participants, the SCID classified 8.7% as having major depression and 17.8% as having anxiety disorders. Among the depression scales, the PHQ-9 had the highest sensitivity (95%). Specificity was generally higher than sensitivity and was highest for the HADS-D (cut-point of 11; 97%). The area under the ROC curve (AUC) did not differ significantly among depression scales. Among the anxiety scales, sensitivity was highest for the PROMIS (79%). Specificity ranged from 82% to 88% for all tools except the HADS-A (cut-point of 8; 65%). The AUC did not differ between depression and anxiety tools. We concluded that overall, the symptom scales for depression and anxiety were similar in their psychometric properties. The anxiety scales did not perform as well as the depression scales. Alternate cut-points may be more relevant when these scales are used in an IBD sample.
Enns M, Bernstein CN, Kroeker K, Graff LA, Walker JR, Lix LM, Hitchon CA, El-Gabalawy R, Fisk JD, Marrie RA. The association of fatigue, pain, depression and anxiety with work and activity impairment 2 in immune mediated inflammatory diseases. PLOS One 2018; Jun 7;13(6):e0198975.
Impairment in work function is a frequent outcome in patients with chronic conditions such as immune-mediated inflammatory diseases (IMID), depression and anxiety disorders. The personal and economic costs of work impairment in these disorders are immense. Symptoms of pain, fatigue, depression and anxiety are potentially remediable forms of distress that may contribute to work impairment in chronic health conditions such as IMID. The present study evaluated the association between pain [Medical Outcomes Study Pain Effects Scale], fatigue [Daily Fatigue Impact Scale], depression and anxiety [Hospital Anxiety and Depression Scale] and work impairment [Work Productivity and Activity Impairment Scale] in four patient populations: multiple sclerosis (n = 255), IBD (n = 248, rheumatoid arthritis (n = 154) and a depression and anxiety group (n = 307), using quantile regression, controlling for the effects of sociodemographic factors, physical disability, and cognitive deficits. Each of pain, depression symptoms, anxiety symptoms, and fatigue individually showed significant associations with work absenteeism, presenteeism, and general activity impairment. When the distress variables were entered concurrently into the regression models, fatigue was a significant predictor of work and activity impairment in all models (quantile regression standardized estimates ranging from 0.2 to 0.5). These findings have important clinical implications for understanding the determinants of work impairment and for improving work-related outcomes in chronic disease.
Marrie RA, Walld R, Bolton J, Sareen J, Patten S, Singer A, Lix L, Hitchon C, El-Gabalawy R, Katz A, Fisk J, Bernstein CN. Psychiatric comorbidity increases mortality in immune-mediated inflammatory diseases. General Hospital Psychiatry 2018; 53:65-72.
We determined the association between any common mental disorder (depression, anxiety disorder, bipolar disorder) and mortality and suicide in three immune-mediated inflammatory diseases (IMID), inflammatory bowel disease (IBD), multiple sclerosis and rheumatoid arthritis, versus age-, sex- and geographically-matched controls. Using administrative data, we identified 28,384 IMID cases (IBD: 8695; Multiple sclerosis: 5496; rheumatoid arthritis: 14,503) and 141,672 matched controls. We determined annual rates of mortality, suicide and suicide attempts. We evaluated the association of any common mental disorder with all-cause mortality and suicide using multivariable Cox regression models. In the IMID cohort, any common mental disorder was associated with increased mortality. We observed a greater than additive interaction between depression and IMID status (attributable proportion 5.2%), but a less than additive interaction with anxiety (attributable proportion -13%). Findings were similar for multiple sclerosis and rheumatoid arthritis. In IBD, a less than additive interaction existed with depression and anxiety on mortality risk. The IMID cohort with any common mental disorder had an increased suicide risk versus the matched cohort without common mental disorder. We concluded that common mental disorders are associated with increased mortality and suicide risk in IMID. In multiple sclerosis and rheumatoid arthritis, the effects of depression on mortality risk are greater than associations of these IMID and depression alone.
Bernstein CN, Hitchon CA, Walld R, Bolton JM, Sareen J, Walker JR, Graff LA, Pattem SB, Singer A, Lix LM, El-Gabalawy R, Katz A Fisk JD, Marrie RA. Increased burden of psychiatric disorders in inflammatory bowel disease. Inflammatory Bowel Disease 2019 Jan 10;25(2): 352-359.
Psychiatric comorbidity in inflammatory bowel disease (IBD) is well known; however, data from a truly representative sample are sparse. We aimed to estimate the incidence and prevalence of psychiatric disorders in an IBD cohort compared with a matched cohort without IBD. Using the population-based University of Manitoba IBD Epidemiology Database, we identified all persons with incident IBD from 1989 to 2012 and a general population matched cohort (5:1). We applied validated algorithms for IBD, depression, anxiety disorders, bipolar disorder, and schizophrenia to determine the annual incidence of these conditions post-IBD diagnosis and their lifetime and current prevalence. There were 6119 incident cases of IBD and 30,573 matched individuals. After adjustment for age, sex, socioeconomic status, region of residence, and year, there was a 60% higher incidence in the IBD cohort compared with controls for depression (incidence rate ratio [IRR], 1.58; 95% confidence interval [CI], 1.41-1.76), 40% for anxiety disorder (IRR, 1.39; 95% CI, 1.26-1.53), 80% for bipolar disorder (IRR, 1.82; 95% CI, 1.44-2.30), and 65% for schizophrenia (IRR, 1.64; 95% CI, 0.95-2.84). Incidence rate ratios were similar for Crohn's disease and ulcerative colitis and between males and females and were stable over time. However, within the IBD cohort, the incidence rates of depression, anxiety, and bipolar disorders were higher among females, those aged 18-24 years vs those older than 44 years, urbanites, and those of lower socioeconomic status. The lifetime and current prevalence rates of psychiatric disorders were also higher in the IBD than the matched cohort. We concluded that the incidence and prevalence of psychiatric disorders are elevated in the IBD population.
Whitehouse CE, Fisk JD, Bernstein CN, Berrigan LI, Bolton JM, Graff LA, Hitchon CA, Marriott JA, Peschken CA, Sareen JA, Walker JR, Stewart SH, Marrie RA for the CIHR Team in Defining the Burden and Managing the Effects of Psychiatric Comorbidity in Chronic Immunoinflammatory Disease. Comorbid anxiety, depression and cognition in MS and other immune-mediated disorders. Neurology 2018; in press.
In this report we aimed to determine whether anxiety and depression were associated with cognition in multiple sclerosis, and whether these associations were similar in other immune-mediated inflammatory diseases like IBD, and rheumatoid arthritis, and in anxious/depressed individuals without a chronic immune mediated disease. There were 255 persons with multiple sclerosis, 247 persons with IBD, 154 persons with rheumatoid arthritis and 308 persons with anxiety and/or depression. All persons completed a structured psychiatric interview (SCID), the Hospital Anxiety and Depression Scale (HADS), and cognitive testing, including the Symbol Digit Modalities Test (SDMT), the California Verbal Learning Test (CVLT-II), and Letter Number Sequencing (LNS). All cohorts exhibited higher rates of cognitive impairment in the domains of processing speed, verbal learning, and delayed recall memory relative to general population norms. Higher levels of anxiety symptoms were associated with slower processing speed, lower verbal learning, and lower working memory performance (all p < 0.001); higher levels of depression symptoms were associated with slower processing speed. These associations did not differ across cohorts.
We concluded that anxiety and depression were associated with lower cognitive function in multiple sclerosis with a similar pattern observed in persons with other IBD and rheumatoid arthritis, and persons without a a chronic immune disease. Managing symptoms of anxiety and of depression in chronic immune diseases is important to mitigate their effect on cognition.
Bernstein CN. Addressing mental health in persons with IBD. Journal of Canadian Association of Gastroenterology 2018;1:97-98.
This editorial discusses the importance of addressing mental health issues in patients with IBD.
Marrie RA, Walker JR, Graff LA, Patten SB, Bolton JM, Marriott JJ, Fisk JD, Hitchon C, Bernstein CN for the CIHR Team in Defining the Burden and Managing the Effects of Immune-mediated Inflammatory Disease. Gender differences in information needs and preferences regarding depression among individuals with multiple sclerosis, inflammatory bowel disease and rheumatoid arthritis. Patient and Education Counseling 2019; in press.
We assessed the information needs of persons with any of three immune-mediated inflammatory diseases (multiple sclerosis, inflammatory bowel disease and rheumatoid arthritis) regarding depression, as a first step toward developing patient-relevant information resources, ultimately to facilitate self-management and appropriate care. We also compared information needs across genders. We surveyed participants with multiple sclerosis, IBD and rheumatoid arthritis regarding depression-related information needs including types of treatments, effectiveness, risks, benefits, and perceived helpfulness of treatments. We compared responses between groups using multivariate regression. 328 participants provided complete responses (Multiple sclerosis: 141, IBD: 114, rheumatoid arthritis: 73). Most of the topics queried were perceived as very important, and similarly important for all groups. Women placed higher importance than men on most topics. The most popular formats for receiving information were discussion with a counselor (very preferred: 67.4%) and written information (very preferred: 65.5%); this did not differ between groups. We concluded that persons affected by multiple sclerosis, IBD and rheumatoid arthritis are interested in receiving information about multiple topics related to depression treatment, from multiple sources. Women desire more information than men. PRACTICE IMPLICATIONS: These findings can be used to design information resources to meet information needs regarding depression in multiple sclerosis, IBD and rheumatoid arthritis.
Lewis K, Marrie RA, Bernstein CN, Graff LA, Patten SB, Sareen J, Fisk JD, Bolton JM; CIHR Team in Defining the Burden and Managing the Effects of Immune-Mediated Inflammatory Disease. The prevalence and risk factors of undiagnosed depression and anxiety disorders among patients with inflammatory bowel disease. Inflammatory Bowel Diseases 2019; in press
Inflammatory bowel disease is associated with a high prevalence of comorbid depressive and anxiety disorders. A significant proportion of IBD patients with comorbid psychiatric disorders remain undiagnosed and untreated, but factors associated with diagnosis are unknown. We evaluated the prevalence of undiagnosed depression and anxiety in an IBD cohort, along with the associated demographic and clinical characteristics. We obtained data from the enrollment visit of a cohort study of psychiatric comorbidity in immune-mediated diseases including IBD. Each participant underwent a Structured Clinical Interview for DSM-IV-TR Axis I Disorders (SCID) to identify participants who met lifetime criteria for a diagnosis of depression or anxiety. Those with a SCID-based diagnosis were classified as diagnosed or undiagnosed based on participant report of a physician diagnosis. Of 242 eligible participants, 97 (40.1%) met SCID criteria for depression, and 74 (30.6%) met criteria for anxiety. One-third of participants with depression and two-thirds with anxiety were undiagnosed. Males were nearly 3.5x more likely to have an undiagnosed depressive disorder. Nonwhite participants were 80% less likely to have an undiagnosed anxiety disorder. Our findings highlight the importance of screening for depression and anxiety in patients with IBD, with particular attention to those of male sex and with a lower education level.