Rising incidence of psychiatric disorders before diagnosis of immune-mediated inflammatory disease.

AIMS: After the diagnosis of immune-mediated inflammatory diseases (IMID) such as inflammatory bowel disease (IBD), multiple sclerosis (MS) and rheumatoid arthritis (RA), the incidence of psychiatric comorbidity 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 IMID as compared with the general population. METHODS: Using population-based administrative health data from the Canadian province of Manitoba, we identified all persons with incident IBD, MS and RA between 1989 and 2012, and cohorts from the general population matched 5 : 1 on year of birth, sex and region to each disease cohort. We identified members of these groups with at least 5 years of residency before and after the IMID diagnosis date. We applied validated algorithms for depression, anxiety disorders, bipolar disorder, schizophrenia, and any psychiatric disorder to determine the annual incidence of these conditions in the 5-year periods before and after the diagnosis year. RESULTS: We identified 12 141 incident cases of IMID (3766 IBD, 2190 MS, 6350 RA) and 65 424 matched individuals. 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 IMID cohort as compared with the matched cohort. Similar results were obtained for each of the IBD, MS and RA cohorts. The incidence of bipolar disorder was elevated beginning 3 years before IMID diagnosis (IRR 1.63; 95% CI 1.10-2.40). CONCLUSION: The incidence of psychiatric comorbidity is elevated in the IMID 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 IMID, a shared final common inflammatory pathway or other aetiology.

Efficacy and adverse events of oral isotretinoin for acne: a systematic review.

Despite many years of clinical use of isotretinoin, a comprehensive review of evidence for isotretinoin therapy in patients with acne is lacking. We searched MEDLINE, Embase, Cochrane Central, relevant web pages and bibliographies for randomized controlled trials in acne evaluating isotretinoin vs. control (placebo or other therapy). Data were extracted and summarized descriptively. Eleven trials were identified (total 760 patients randomized), containing mostly men. Mean treatment ages ranged from 18 to 47·9 years and participants generally had moderate-to-severe acne. Across all trials, isotretinoin therapy reduced acne lesion counts by a clinically relevant amount, and always by a greater amount than control, which was either placebo (two studies), oral antibiotics (seven studies) or other control (two studies). Across trials with an overall low risk of bias, two of three demonstrated statistically significant differences between isotretinoin and control. The frequency of adverse events was twice as high with isotretinoin (751 events) than with control (388 events). More than half of all adverse events were dermatological and related to dryness. Adverse events from isotretinoin causing participant withdrawal from trials (12 patients) included Stevens-Johnson syndrome, cheilitis, xerosis, acne flare, photophobia, elevated liver enzymes, decreased appetite, headaches and depressed mood. This review suggests that isotretinoin is effective in reducing acne lesion counts, but adverse events are common. This study was registered with PROSPERO number CRD42015025080.

Patterns of association of chronic medical conditions and major depression.

AIMS: Age and sex-related patterns of association between medical conditions and major depressive episodes (MDE) are important for understanding disease burden, anticipating clinical needs and for formulating etiological hypotheses. General population estimates are especially valuable because they are not distorted by help-seeking behaviours. However, even large population surveys often deliver inadequate precision to adequately describe such patterns. In this study, data from a set of national surveys were pooled to increase precision, supporting more precise characterisation of these associations. METHODS: The data were from a series of Canadian national surveys. These surveys used comparable sampling strategies and assessment methods for MDE. Chronic medical conditions were assessed using items asking about professionally diagnosed medical conditions. Individual-level meta-analysis methods were used to generate unadjusted, stratified and adjusted prevalence odds ratios for 11 chronic medical conditions. Random effects models were used in the meta-analysis. A procedure incorporating rescaled replicate bootstrap weights was used to produce 95% confidence intervals. RESULTS: Overall, conditions characterised by pain and inflammation tended to show stronger associations with MDE. The meta-analysis uncovered two previously undescribed patterns of association. Effect modification by age was observed in varying degrees for most conditions. This effect was most prominent for high blood pressure and cancer. Stronger associations were found in younger age categories. Migraine was an exception: the strength of association increased with age, especially in men. Second, especially for conditions predominantly affecting older age groups (arthritis, diabetes, back pain, cataracts, effects of stroke and heart disease) confounding by age was evident. For each condition, age adjustment resulted in strengthening of the associations. In addition to migraine, two conditions displayed distinctive patterns of association. Age adjusted odds ratios for thyroid disease reflected a weak association that was only significant in women. In epilepsy, a similar strength of association was found irrespective of age or sex. CONCLUSIONS: The prevalence of MDE is elevated in association with most chronic conditions, but especially those characterised by inflammation and pain. Effect modification by age may reflect greater challenges or difficulties encountered by young people attempting to cope with these conditions. This pattern, however, does not apply to migraine or epilepsy. Neurobiological changes associated with these conditions may offset coping-related effects, such that the association does not weaken with age. Prominent confounding by age for several conditions suggests that age adjustments are necessary in order to avoid underestimating the strength of these associations.

Determinants and incidence of depression in multiple sclerosis: A prospective cohort study.

OBJECTIVE: To estimate the incidence and explore potential determinants of incidence of depression in MS. METHODS: A prospective cohort study used a sample of 192 patients from the southern Alberta MS clinic registry. Participants completed baseline risk factor assessment questionnaires using either online, mail or telephone surveys, and completed the Patient Health Questionnaire every 2weeks for 6months to assess depressive symptoms in real time. Risk factors assessed included biopsychosocial variables such as socioeconomic status, illness-related factors, childhood risk factors, psychosocial factors, and health behaviors. Cox proportional hazard models were fit to estimate predictors of incidence. RESULTS: 2-week incidence of depression for females was 0.019 (95% CI 0.013-0.029) and for males was 0.044 (0.026-0.074). Strongest predictor of depression incidence risk included fatigue impact, low mobility, resiliency, self-esteem, self-efficacy, and coping style. CONCLUSION: Depression in MS exhibits a risk factor profile similar to that of depression in the general population, with the additional impact of MS illness-related factors. Potentially modifiable risk factors, such as coping with stress and resiliency, present opportunities for focus of further research in depression in MS treatment and prevention efforts. Some differences in determinants of incidence were found compared to the prevalence risk factors, highlighting the danger of using cross-sectional data to make assumptions about risk. For example, the finding that depression incidence was higher for men is opposite to the higher depression prevalence estimates found for women as well as the consensus in the literature.

Seasonal variation in major depressive episode prevalence in Canada.

BACKGROUND: The purpose of this paper is to describe variation, over the months of the year, in major depressive episode (MDE) prevalence. This is an important aspect of the epidemiological description of MDE, and one that has received surprisingly little attention in the literature. Evidence of seasonal variation in MDE prevalence has been weak and contradictory. Most studies have sought to estimate the prevalence of seasonal affective disorder using cut-points applied to scales assessing mood seasonality rather than MDE. This approach does not align with modern classification in which seasonal depression is a diagnostic subtype of major depression rather than a distinct category. Also, some studies may have lacked power to detect seasonal differences. We addressed these limitations by examining the month-specific occurrence of conventionally defined MDE and by pooling data from large epidemiological surveys to enhance precision in the analysis. METHOD: Data from two national survey programmes (the National Population Health Survey and the Canadian Community Health Survey) were used, providing ten datasets collected between 1996 and 2013, together including over 500,000. These studies assessed MDE using a short form version of the Composite International Diagnostic Interview (CIDI) for major depression, with one exception being a 2012 survey that used a non-abbreviated version of the CIDI. The proportion of episodes occurring in each month was evaluated using items from the diagnostic modules and statistical methods addressing complex design features of these trials. Overall month-specific pooled estimates and associated confidence intervals were estimated using random effects meta-analysis and a gradient was assessed using a meta-regression model that included a quadratic term. RESULTS: There was considerable sampling variability when the month-specific proportions were estimated from individual survey datasets. However, across the various datasets, there was sufficient homogeneity to justify the pooling of these estimated proportions, producing large gains in precision. Seasonal variation was clearly evident in the pooled data. The highest proportion of episodes occurred in December, January and February and the lowest proportions occurred in June, July and August. The proportion of respondents reporting MDE in January was 70% higher than August, suggesting an association with implications for health policy. The pattern persisted with stratification for age group, sex and latitude. CONCLUSIONS: Seasonal effects in MDE may have been obscured by small sample sizes in prior studies. In Canada, MDE has clear seasonal variation, yet this is not addressed in the planning of services. These results suggest that availability of depression treatment should be higher in the winter than the summer months.

Under-diagnosis of mood disorders in Canada.

AIMS: Under-diagnosis of mood disorders occurs worldwide. In this study, we characterized and compared Canadians with symptoms compatible with a mood disorder by diagnosis status; and described the associated health impacts, use of health services and perceived need for care. METHODS: Respondents to the 2012 Canadian Community Health Survey - Mental Health, a nationally representative sample of Canadians age ≥15 years were assessed for symptoms compatible with mood disorders based on a Canadian adaptation of the World Health Organization Composite International Diagnostic Interview (n = 23 504). Descriptive and multivariate regression analyses were performed. RESULTS: In 2012, an estimated 5.4% (1.5 million) Canadians aged 15 years and older reported symptoms compatible with a mood disorder, of which only half reported having been professionally diagnosed. The undiagnosed individuals were more likely to be younger (mean age: 36.2 v. 41.8), to be single (49.5 v. 32.7%), to have less than a post-secondary graduation (49.8 v. 41.1%) and to have no physical co-morbidities (56.4 v. 35.7%), and less likely to be part of the two lower income quintiles (49.6 v. 62.7%) compared with those with a previous diagnosis. Upon controlling for all socio-demographic and health characteristics, the associations with age and marital status disappeared. While those with a previous diagnosis reported significantly greater health impacts and were more likely to have consulted a health professional for their emotional and mental health problems in the previous 12 months compared with those undiagnosed (79.4 v. 31.0%), about a third of both groups reported that their health care needs were only partially met or not met at all. CONCLUSIONS: Mood disorders are prevalent and can profoundly impact the life of those affected, however, their diagnosis remains suboptimal and health care use falls short of apparent needs. Improvements in mental health literacy, help-seeking behaviours and diagnosis are needed. In light of the heterogeneity of mood disorders in terms of symptoms severity, impacts and prognosis, interventions must be tailored accordingly.

Systematic review and meta-analysis of interventions for depression and anxiety in persons with multiple sclerosis.

BACKGROUND: Depression and anxiety are common in persons with multiple sclerosis (MS), and adversely affect fatigue, medication adherence, and quality of life. Though effective treatments for depression and anxiety exist in the general population, their applicability in the MS population has not been definitively established. OBJECTIVE: To determine the overall effect of psychological and pharmacological treatments for depression or anxiety in persons with MS. METHODS: We searched the Medline, EMBASE, PsycINFO, PsycARTICLES Full Text, Cochrane Central Register of Controlled Trials, CINAHL, Web of Science, and Scopus databases using systematic review methodology from database inception until March 25, 2015. Two independent reviewers screened abstracts, extracted data, and assessed risk of bias and strength of evidence. We included controlled clinical trials reporting on the effect of pharmacological or psychological interventions for depression or anxiety in a sample of persons with MS. We calculated standardized mean differences (SMD) and pooled using random effects meta-analysis. RESULTS: Of 1753 abstracts screened, 21 articles reporting on 13 unique clinical trials met the inclusion criteria. Depression severity improved in nine psychological trials of depression treatment (N=307; SMD: -0.45 (95%CI: -0.74, -0.16)). The severity of depression also improved in three pharmacological trials of depression treatment (SMD: -0.63 (N=165; 95%CI: -1.07, -0.20)). For anxiety, only a single trial examined psychological therapy for injection phobia and reported no statistically significant improvement. CONCLUSION: Pharmacological and psychological treatments for depression were effective in reducing depressive symptoms in MS. The data are insufficient to determine the effectiveness of treatments for anxiety.

Childhood adversity and subsequent mental health status in adulthood: screening for associations using two linked surveys.

AIMS: Accumulating evidence links childhood adversity to negative health outcomes in adulthood. However, most of the available evidence is retrospective and subject to recall bias. Published reports have sometimes focused on specific childhood exposures (e.g. abuse) and/or specific outcomes (e.g. major depression). Other studies have linked childhood adversity to a large and diverse number of adult risk factors and health outcomes such as cardiovascular disease. To advance this literature, we undertook a broad examination of data from two linked surveys. The goal was to avoid retrospective distortion and to provide a descriptive overview of patterns of association. METHODS: A baseline interview for the Canadian National Longitudinal Study of Children and Youth collected information about childhood adversities affecting children aged 0-11 in 1994. The sampling procedures employed in a subsequent study called the National Population Health Survey (NPHS) made it possible to link n = 1977 of these respondents to follow-up data collected later when respondents were between the ages of 14 and 27. Outcomes included major depressive episodes (MDE), some risk factors and educational attainment. Cross-tabulations were used to examine these associations and adjusted estimates were made using the regression models. As the NPHS was a longitudinal study with multiple interviews, for most analyses generalized estimating equations (GEE) were used. As there were multiple exposures and outcomes, a statistical procedure to control the false discovery rate (Benjamini-Hochberg) was employed. RESULTS: Childhood adversities were consistently associated with a cluster of potentially related outcomes: MDE, psychotropic medication use and smoking. These outcomes may be related to one another since psychotropic medications are used in the treatment of major depression, and smoking is strongly associated with major depression. However, no consistent associations were observed for other outcomes examined: physical inactivity, excessive alcohol consumption, binge drinking or educational attainment. CONCLUSIONS: The conditions found to be the most strongly associated with childhood adversities were a cluster of outcomes that potentially share pathophysiological connections. Although prior literature has suggested that a very large number of adult outcomes, including physical inactivity and alcohol-related outcomes follow childhood adversity, this analysis suggests a degree of specificity with outcomes potentially related to depression. Some of the other reported adverse outcomes (e.g. those related to alcohol use, physical inactivity or more distal outcomes such as obesity and cardiovascular disease) may emerge later in life and in some cases may be secondary to depression, psychotropic medication use and smoking.

Comparison of the estimated prevalence of mood and/or anxiety disorders in Canada between self-report and administrative data.

BACKGROUND: To compare trends in the estimated prevalence of mood and/or anxiety disorders identified from two data sources (self-report and administrative). Reviewing, synthesising and interpreting data from these two sources will help identify potential factors that underlie the observed estimates and inform public health action. METHOD: We used self-reported, diagnosed mood and/or anxiety disorder cases from the Canadian Community Health Survey (CCHS) across a 5-year span (from 2003 to 2009) to estimate the prevalence among the Canadian population aged ≥15 years. We also estimated the prevalence of mood and/or anxiety disorders using the Canadian Chronic Disease Surveillance System (CCDSS), which identified cases using ICD-9/-10-CA codes from physician billing claims and hospital discharge records during the same time period. The prevalence rates for mood and/or anxiety disorders were compared across the CCHS and CCDSS by age and sex for all available years of data from 2003 to 2009. Summary rates were age-standardised to the Canadian population as of 1 October 1991. RESULTS: In 2009, the prevalence of mood and/or anxiety disorders was 9.4% using self-reported data v. 11.3% using administrative data. Prevalence rates obtained from administrative data were consistently higher than those from self-report for both men and women. However, due to an increase in the prevalence of self-reported cases, these differences decreased over time (rate ratios for both sexes: 1.6-1.2). Prevalence estimates were consistently higher among females compared with males irrespective of data source. While differences in the prevalence estimates between the two data sources were evident across all age groups, the reduction of these differences was greater among adolescent, young and middle-aged adults compared with those 70 years and older. CONCLUSIONS: The overall narrowing of differences over time reflects a convergence of information regarding the prevalence of mood and/or anxiety disorders trends between self-report and administrative data sources. While the administrative data-based prevalences remained relatively stable, the self-reported prevalences increased over time. These observations may reflect positive societal changes in the perceptions of mental health (declining stigma) and/or increasing mental health literacy. Additional research using non-ecological data is required to further our understanding of the observed findings and trends, including a data linkage exercise permitting a comparison of prevalence estimates and population characteristics from these two data sources both separately and merged.

Comorbidity is associated with pain-related activity limitations in multiple sclerosis.

BACKGROUND: Comorbidities are common in multiple sclerosis (MS). The high prevalence of pain in MS is well-established but the influence of comorbidities on pain, specifically, pain-related interference in activity is not. OBJECTIVE: To examine the relationship between comorbidity and pain in MS. METHODS: We recruited 949 consecutive patients with definite MS from four Canadian centres. Participants completed the Health Utilities Index (HUI-Mark III) and a validated comorbidity questionnaire at 3 visits over 2 years. The HUI's pain scale was dichotomized into two groups: those with/without pain that disrupts normal activities. We used logistic regression to assess the association of pain with each comorbidity individually at baseline and over time. RESULTS: The incidence of disruptive pain over two years was 31.1 per 100 persons. Fibromyalgia, rheumatoid arthritis, irritable bowel syndrome, migraine, chronic lung disease, depression, anxiety, hypertension, and hypercholesterolemia were associated with disruptive pain (p<0.006). Individual-level effects on the presence of worsening pain were seen for chronic obstructive pulmonary disease (odds ratio [OR]: 1.50 95% CI: 1.08-2.09), anxiety (OR: 1.49 95% CI: 1.07-2.08), and autoimmune thyroid disease (OR: 1.40 95% CI: 1.00-1.97). CONCLUSION: Comorbidity is associated with pain in persons with MS. Closer examination of these associations may provide guidance for better management of this disabling symptom in MS.

Major depressive disorder: reification and (maybe) rheostasis.

The heterogeneity of clinical syndromes subsumed by diagnostic criteria for major depressive disorder (MDD) is regarded by some as a reason to abandon or modify the criteria. However, heterogeneity may be unavoidable because of the biopsychosocial complexity of depression. MDD may be characterised by complexities that cannot be distilled down to any brief set of diagnostic criteria. Psychiatrists and psychiatric epidemiologists may need to revise their expectations of this diagnosis in order to avoid over-estimating its ability to guide the selection of treatments and prediction of prognosis. An opposing perspective is that of reification, in which the diagnosis is viewed as being more real than it really is. The concept of rheostasis may help to explain some features of this condition, such as why major depressive episodes sometimes seem understandable or even adaptive (e.g. in the context of bereavement) whereas at other times such episodes are inexplicable and maladaptive.

Medical models and metaphors for depression.

BACKGROUND: The aetiology of depression is not fully understood, which allows many different perspectives on aetiology to be adopted. Researchers and clinicians may be attracted to concepts of aetiology that parallel other diagnoses with which they are familiar. Such parallels may assume the role of informal models or metaphors for depressive disorders. They may even function as informal scientific theories of aetiology, energising research activities by guiding hypothesis generation and organising new knowledge. Parallels between different types of disease may ultimately prove valuable as frameworks supporting the emergence and maturation of new knowledge. However, such models may be counterproductive if their basis, which is likely to lay at least partially in analogy, is unacknowledged or overlooked. This could cause such models to appear more compelling than they really are. Listing examples of situations in which models of depression may arise from, or be strengthened by, parallels to other familiar conditions may increase the accessibility of such models either to criticism or support. However, such a list has not yet appeared in the literature. The present paper was written with the modest goal of stating several examples of models or metaphors for depression. METHOD: This paper adopted narrative review methods. The intention was not to produce a comprehensive list of such ideas, but rather to identify prominent examples of ways of thinking about depression that may have been invigorated as a result parallels with other types of disease. RESULTS: Eight possible models are identified: depressive disorders as chemical imbalances (e.g., a presumed or theoretical imbalance of normally balanced neurotransmission in the brain), degenerative conditions (e.g., a brain disease characterised by atrophy of specified brain structures), toxicological syndromes (a result of exposure to a noxious psychological environment), injuries (e.g., externally induced brain damage related to stress), deficiency states (e.g., a serotonin deficiency), an obsolete category (e.g., similar to obsolete terms such as 'consumption' or 'dropsy'), medical mysteries (e.g., a condition poised for a paradigm-shifting breakthrough) or evolutionary vestiges (residual components of once adaptive mechanisms have become maladaptive in modern environments). CONCLUSIONS: Conceptualisation of depressive disorders may be partially shaped by familiar disease concepts. Analogies of this sort may ultimately be productive (e.g., through generating hypotheses by analogy) or destructive (e.g., by structuring knowledge in incorrect, but intellectually seductive, ways).

Retrospective and prospectively assessed childhood adversity in association with major depression, alcohol consumption and painful conditions.

BACKGROUND: Considerable evidence now links childhood adversity to a variety of adult health problems. Unfortunately, almost all of these studies have relied upon retrospective assessment of childhood events, creating a vulnerability to bias. In this study, we sought to examine three associations using data sources that allowed for both prospective and retrospective assessment of childhood events. METHODS: A 1994 national survey of children between the ages of 0 and 11 collected data from a 'person most knowledgeable' (usually the mother) about a child. It was possible to link data for n = 1977 of these respondents to data collected from the same people in a subsequent adult study. The latter survey included retrospective reports of childhood adversity. We examined three adult health outcomes in relation to prospectively and retrospectively assessed childhood adversity: major depressive episodes, excessive alcohol consumption and painful conditions. RESULTS: A strong association between childhood adversities (as assessed by both retrospective and prospective methods) and major depression was identified although the association with retrospective assessment was stronger. Weaker associations were found for painful conditions, but these did not depend on the method of assessment. Associations were not found for excessive alcohol consumption irrespective of the method of assessment. CONCLUSIONS: These findings help to allay concerns that associations between childhood adversities and health outcomes during adulthood are merely artefacts of recall bias. In this study, retrospective and prospective assessment strategies produced similar results.

Antidepressant dose and the risk of deliberate self-harm.

Although the mechanism by which antidepressants (ADs) may increase the risk of suicide-related outcomes is unknown, it has been hypothesised that some adverse effects, including akathisia, insomnia and panic attacks, as well as an early energising effect that might allow patients with depression to act on suicidal impulses, may have a key role. Considering that these adverse effects are dose-related, it might be hypothesised that the risk of suicidal behaviour is similarly related to the AD dose. This research question has recently been addressed by a propensity score-matched observational cohort study that involved 162 625 patients aged 10-64 years with a depression diagnosis who initiated therapy with citalopram, sertraline or fluoxetine. In this commentary, we discuss the main findings of this study in view of its methodological strengths and limitations, and we suggest possible implications for day-to-day clinical practice.