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Background: Patients in the intensive care unit (ICU) are known to be at increased risk of developing delirium, but the risk of subsequent neuropsychiatric disorders is unclear. We therefore sought to examine the association between the presence of delirium in the ICU and incident neuropsychiatric disorders (including depressive, anxiety, trauma-and-stressor-related, and neurocognitive disorders) post-ICU stay among adult medical-surgical ICU patients., Methods: Retrospective cohort study utilizing clinical and administrative data from both inpatient and outpatient healthcare visits to identify the ICU cohort and diagnostic information 5 years prior to and 1 year post-ICU stay. Patients ≥ 18 years of age admitted to one of 14 medical-surgical ICUs across Alberta, Canada, January 1, 2014-June 30, 2016, and survived to hospital discharge were included. The main outcome of interest was a new diagnosis of any neuropsychiatric disorder 1 year post-ICU stay. The exposure variable was delirium during the ICU stay identified through any positive delirium screen by the Intensive Care Unit Delirium Screening Checklist (ICDSC) during the ICU stay., Results: Of 16,005 unique patients with at least one ICU admission, 4033 patients were included in the study of which 1792 (44%) experienced delirium during their ICU stay. The overall cumulative incidence of any neuropsychiatric disorder during the subsequent year was 19.7% for ICU patients. After adjusting for hospital characteristics using log-binomial regression, patients with delirium during the ICU stay had a risk ratio (RR) of 1.14 (95% confidence interval [CI] 0.98-1.33) of developing any neuropsychiatric disorder within 1 year post-ICU compared to those who did not experience delirium. Delirium was significantly associated with neurocognitive disorders (RR 1.59, 95% CI 1.08-2.35), but not depressive disorders (RR 1.16, 95% CI 0.92-1.45), anxiety (RR 1.16, 95% CI 0.92-1.47), and trauma-and-stressor-related (RR 0.82, 95% CI 0.53-1.28) disorders., Conclusions: The diagnosis of new onset of neurocognitive disorders is associated with ICU-acquired delirium. In this study, significant associations were not observed for depressive, anxiety, and trauma-and-stressor-related disorders.

Objective: Few studies have longitudinally followed trends in antidepressant prescribing for Canadian children following the Black Box warning issued in 2004. Using a national data source, we aim to describe trends in antidepressant recommendations for Canadian children ages 1-18 during 2012 to 2016. Methods: A database called the Canadian Disease and Therapeutic Index (CDTI), provided by IQVIA, was used to conduct analyses. The CDTI dataset collects a quarterly sample of pediatric antidepressant recommendations, projected using a weight procedure from a dynamic sample of 652 Canadian office-based physicians. The term "recommendations" is used because nonprescription drugs may be recommended and there is no confirmation in the database that the prescriptions were filled or medications taken. The data were collected from 2012 to 2016 and the sample population was projected by IQVIA to be representative of the entire Canadian pediatric population. Results: The total number of projected antidepressant recommendations for children increased from 2012 to 2016. Selective serotonin reuptake inhibitors were the most recommended class of antidepressants. Analysis indicated that fluoxetine was the most frequently recommended drug. Findings also suggest that recommendations for tricyclic antidepressants (TCAs) are increasing, but predominantly for reasons other than treatment of depression. Conclusions: Overall, antidepressant use in Canadian children increased over the study period. Unsurprisingly, fluoxetine was the most recommended antidepressant for Canadian children. However, the observed increase in TCA use for a pediatric population is unexpected. The data source is descriptive and lacks detailed measures supporting comprehensive explanation of the findings, therefore, further research is required.

Background: Because of symptom overlap, there is uncertainty about the validity of depression rating scales in neurologic populations. The objectives of this study were to evaluate the validity of the Patient Health Questionnaire-9 (PHQ-9) for detecting Diagnostic and Statistical Manual-defined major depressive episodes in people with neurologic conditions., Methods: Participants were recruited from outpatient clinics for multiple sclerosis, epilepsy, migraine, Parkinson disease, and stroke for this cross-sectional study. Participants were administered a questionnaire (this included the PHQ-9), chart review, and a follow-up telephone interview. The Structured Clinical Interview for Depression was used as the reference standard for psychiatric diagnoses. The performance of PHQ-9 was analyzed using sensitivity, specificity, diagnostic odds ratios (DORs), and receiver operator curve analysis., Results: All neurologic subpopulations had a specificity greater than 78% and sensitivity greater than 79% at a cut-point of 10. Using a random-effects model, the I-squared value was 13.7%, and Tau 2 was 0.05, showing homogeneity across the neurologic subpopulations. The pooled DOR was 25.3 (95% confidence interval [CI] 14.9-42.8). Meta-analytic analysis found that for sensitivity, the pooled estimate was 90% (95% CI 81-97), and for specificity, it was 85% (95% CI 79-90)., Conclusions: Despite theoretical concerns about its validity, the PHQ-9 performed well at its standard cut-point of 10. Consistent with the literature, being able to use a validated, brief tool that is available publicly should improve case finding of depression in neurologic populations. When considering clinical practicality along with the findings of this analyzed, this study confirmed that the PHQ-9 is valid in a general outpatient neurologic population., (© 2019 American Academy of Neurology.)

Objectives: Depression symptom questionnaires are not for diagnostic classification. Patient Health Questionnaire-9 (PHQ-9) scores ≥10 are nonetheless often used to estimate depression prevalence. We compared PHQ-9 ≥10 prevalence to Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (SCID) major depression prevalence and assessed whether an alternative PHQ-9 cutoff could more accurately estimate prevalence., Study Design and Setting: Individual participant data meta-analysis of datasets comparing PHQ-9 scores to SCID major depression status., Results: A total of 9,242 participants (1,389 SCID major depression cases) from 44 primary studies were included. Pooled PHQ-9 ≥10 prevalence was 24.6% (95% confidence interval [CI]: 20.8%, 28.9%); pooled SCID major depression prevalence was 12.1% (95% CI: 9.6%, 15.2%); and pooled difference was 11.9% (95% CI: 9.3%, 14.6%). The mean study-level PHQ-9 ≥10 to SCID-based prevalence ratio was 2.5 times. PHQ-9 ≥14 and the PHQ-9 diagnostic algorithm provided prevalence closest to SCID major depression prevalence, but study-level prevalence differed from SCID-based prevalence by an average absolute difference of 4.8% for PHQ-9 ≥14 (95% prediction interval: -13.6%, 14.5%) and 5.6% for the PHQ-9 diagnostic algorithm (95% prediction interval: -16.4%, 15.0%)., Conclusion: PHQ-9 ≥10 substantially overestimates depression prevalence. There is too much heterogeneity to correct statistically in individual studies., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Environments that promote use of active transport (walking, biking, and public transport use) are known as "active living environments" (ALE). Using a Canadian national sample, our aim was to determine if ALEs were associated with mental health outcomes, including depressive symptoms, and mood and anxiety disorders. Data from the Canadian Community Health Survey from 2015-2016 was used for demographic characteristics and mental health outcomes ( n ≈ 110,000). This data was linked to datasets from the Canadian Urban Environmental Health Research Consortium, reporting ALE and social and material deprivation. Depressive symptoms were evaluated using standard dichotomized scores of 5+ (mild) and 10+ (moderate/severe) from the Patient Health Questionnaire-9. Self-reported diagnosed mood and anxiety disorders were also included. Logistic regression was used to determine the association of mental health outcomes with four classes of ALE. The analysis included adjustments for social and material deprivation, age, sex, chronic conditions, marital status, education, employment, income, BMI, and immigrant status. No association between any mental health outcome and ALE were observed. While the benefits of ALE to physical health are known, these results do not support the hypothesis that more favorable ALE and increased use of active transport is associated with better mental health outcomes.

Background: Prevention and early detection of depression is a top public health priority. Accurate perception of depression risk may play an important role in health behavior change and prevention of depression. However, the way in which people in the community perceive their risk of developing depression is currently unknown., Methods: We analyzed the baseline data from a randomized controlled trial in 358 men and 356 women who are at high risk of having a major depressive episode (MDE). The predicted risk was assessed by sex-specific multivariable risk predictive algorithms for MDE. We compared participants' perceived risk and their predicted risk. Accurate risk perception was defined as perceived risk is in the range of predicted risk ± 10%., Results: In men, 29.7% perceived their risk accurately; 47.5% overestimated their risk; 22.8% underestimated their risk. In women, the proportions were 21.7%, 59.6% and 18.7%, respectively. Compared to men, women were more likely to overestimate their risk and less likely to be accurate. Regression modeling revealed that poor self-rated health and higher predicted depression risk were associated with inaccuracy of risk perception in men; a family history of MDE, higher psychological distress and lower predicted risk were associated with inaccuracy of risk perception in women., Conclusions: Individuals who are at high risk of developing depression tend to overestimate their risk, especially women. Inaccurate depression risk perception is related to people's health status. Educational interventions are needed to enhance the accuracy of risk perception to encourage positive behavior change and uptake of preventive strategies., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Neuropsychiatric Symptoms (NPS) are common in Mild Cognitive Impairment (MCI). The Neuropsychiatric Inventory (NPI) and its shorter version, the Neuropsychiatric Inventory Questionnaire (NPI-Q), are the most common measures to assess NPS. Our objective was to determine if NPI/NPI-Q ratings predict conversion from MCI to dementia., Methods: Empirical longitudinal studies published in English or Spanish, concerned with the role of NPS as a risk factor for conversion from MCI to dementia, with a diagnosis of MCI following clinical criteria, that reported NPI/NPI-Q total score in converters versus non-converters, were included. Random effects models were used, and heterogeneity was explored with stratification and a random-effects meta-regression. The overall conversion rate and the standardized mean difference (SMD) for evolution, as a function of NPI/NPI-Q scores, were calculated., Results: The overall conversion rate was 35 %. Mean NPI/NPI-Q ratings were higher in converters versus in non-converters, with the overall SMD approaching significance. Heterogeneity was observed in studies of more than two years of follow-up and in a study with a mean age of more than 80 years. This heterogeneity concerned the size, not the direction of the difference., Conclusions: Our results suggest that NPI/NPI-Q ratings are associated with conversion from MCI to dementia., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to report., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Suicide is a leading cause of death, particularly in younger persons, and this results in tremendous years of life lost., Objective: To compare the performance of recurrent neural networks, one-dimensional convolutional neural networks, and gradient boosted trees, with logistic regression and feedforward neural networks., Methods: The modeling dataset contained 3548 persons that died by suicide and 35,480 persons that did not die by suicide between 2000 and 2016. 101 predictors were selected, and these were assembled for each of the 40 quarters (10 years) prior to the quarter of death, resulting in 4040 predictors in total for each person. Model configurations were evaluated using 10-fold cross-validation., Results: The optimal recurrent neural network model configuration (AUC: 0.8407), one-dimensional convolutional neural network configuration (AUC: 0.8419), and XGB model configuration (AUC: 0.8493) all outperformed logistic regression (AUC: 0.8179). In addition to superior discrimination, the optimal XGB model configuration also achieved superior calibration., Conclusions: Although the models developed in this study showed promise, further research is needed to determine the performance limits of statistical and machine learning models that quantify suicide risk, and to develop prediction models optimized for implementation in clinical settings. It appears that the XGB model class is the most promising in terms of discrimination, calibration, and computational expense., Limitations: Many important predictors are not available in administrative data and this likely places a limit on how well prediction models developed with administrative data can perform., Competing Interests: Declaration of Competing Interest None, (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Suicide is a leading cause of death worldwide and results in a large number of person years of life lost. There is an opportunity to evaluate whether administrative health care system data and machine learning can quantify suicide risk in a clinical setting., Methods: The objective was to compare the performance of prediction models that quantify the risk of death by suicide within 90 days of an ED visit for parasuicide with predictors available in administrative health care system data.The modeling dataset was assembled from 5 administrative health care data systems. The data systems contained nearly all of the physician visits, ambulatory care visits, inpatient hospitalizations, and community pharmacy dispenses, of nearly the entire 4.07 million persons in Alberta, Canada. 101 predictors were selected, and these were assembled for each of the 8 quarters (2 years) prior to the quarter of death, resulting in 808 predictors in total for each person. Prediction model performance was validated with 10-fold cross-validation., Findings: The optimal gradient boosted trees prediction model achieved promising discrimination (AUC: 0.88) and calibration that could lead to clinical applications. The 5 most important predictors in the optimal gradient boosted trees model each came from a different administrative health care data system., Interpretation: The combination of predictors from multiple administrative data systems and the combination of personal and ecologic predictors resulted in promising prediction performance. Further research is needed to develop prediction models optimized for implementation in clinical settings., Funding: There was no funding for this study., Competing Interests: None., (© 2020 Published by Elsevier Ltd.)

Objective: This study examined the association of anxiety alone, depression alone and the presence of both anxiety and depression with preterm birth (PTB) and further examined whether neighbourhood socioeconomic status (SES) modified this association., Design: Cohort study using individual-level data from two community-based prospective pregnancy cohort studies (All Our Families; AOF) and Alberta Pregnancy Outcomes and Nutrition (APrON) and neighbourhood SES data from the 2011 Canadian census., Setting: Calgary, Alberta, Canada., Participants: Overall, 5538 pregnant women who were <27 weeks of gestation and >15 years old were enrolled in the cohort studies between 2008 and 2012. 3341 women participated in the AOF study and 2187 women participated in the APrON study, with 231 women participated in both studies. Women who participated in both studies were only counted once., Primary and Secondary Outcome Measures: PTB was defined as delivery prior to 37 weeks of gestation. Depression was defined as an Edinburgh Postnatal Depression Scale (EPDS) score of ≥13, anxiety was defined as an EPDS-anxiety subscale score of ≥6, and the presence of both anxiety and depression was defined as meeting both anxiety and depression definitions., Results: Overall, 7.3% of women delivered preterm infants. The presence of both anxiety and depression, but neither of these conditions alone, was significantly associated with PTB (OR 1.6, 95% CI 1.1 to 2.3) and had significant interaction with neighbourhood deprivation (p=0.004). The predicted probability of PTB for women with both anxiety and depression was 10.0%, which increased to 15.7% if they lived in the most deprived neighbourhoods and decreased to 1.4% if they lived in the least deprived neighbourhoods., Conclusions: Effects of anxiety and depression on risk of PTB differ depending on where women live. This understanding may guide the identification of women at increased risk for PTB and allocation of resources for early identification and management of anxiety and depression., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Two previous individual participant data meta-analyses (IPDMAs) found that different diagnostic interviews classify different proportions of people as having major depression overall or by symptom levels. We compared the odds of major depression classification across diagnostic interviews among studies that administered the Depression subscale of the Hospital Anxiety and Depression Scale (HADS-D)., Methods: Data accrued for an IPDMA on HADS-D diagnostic accuracy were analysed. We fit binomial generalized linear mixed models to compare odds of major depression classification for the Structured Clinical Interview for DSM (SCID), Composite International Diagnostic Interview (CIDI), and Mini International Neuropsychiatric Interview (MINI), controlling for HADS-D scores and participant characteristics with and without an interaction term between interview and HADS-D scores., Results: There were 15,856 participants (1942 [12%] with major depression) from 73 studies, including 15,335 (97%) non-psychiatric medical patients, 164 (1%) partners of medical patients, and 357 (2%) healthy adults. The MINI (27 studies, 7345 participants, 1066 major depression cases) classified participants as having major depression more often than the CIDI (10 studies, 3023 participants, 269 cases) (adjusted odds ratio [aOR] = 1.70 (0.84, 3.43)) and the semi-structured SCID (36 studies, 5488 participants, 607 cases) (aOR = 1.52 (1.01, 2.30)). The odds ratio for major depression classification with the CIDI was less likely to increase as HADS-D scores increased than for the SCID (interaction aOR = 0.92 (0.88, 0.96))., Conclusion: Compared to the SCID, the MINI may diagnose more participants as having major depression, and the CIDI may be less responsive to symptom severity., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Depression varies with season in Canadian youth. However, the symptom profile of seasonal depression may differ from that of non-seasonal depression. Here we evaluate which specific symptoms vary by season., Methods: Using data from the 2015/2016 Canadian Community Health Survey, cross-sectional analysis was conducted. The Patient Health Questionnaire-9 (PHQ-9) was administered to respondents in 8 provinces/territories (n ≈ 53,000), with interviews conducted throughout the year. Seasonal effects were assessed using quadratic terms in a logistic regression model. Guided by previous literature and analysis, analyses were stratified by age into youth (age 12-24) and adult (age 25+) groups., Results: In the youth, 8 items of the PHQ-9 exhibited a significant season variation: lack of interest/pleasure, feeling depressed/down, hypersomnia/insomnia, lacking energy, poor appetite/overeating, feeling bad about yourself/ like a failure, being slow/fidgety, and trouble concentrating. In the adult group, only sleep and poor appetite/overeating exhibited a seasonal effect. Notably, symptoms of self-harm/suicide did not demonstrate seasonality in either group., Limitations: Due to use of cross-sectional data and a brief symptom rating scale, conventional criteria for Seasonal Affective Disorder or Major Depressive Disorder with seasonal variation could not be applied. Also, treatment status of respondents was not assessed in the survey, therefore possible confounding by this variable could not be assessed., Conclusions: A seasonal pattern was observed in most symptoms of depression in Canadian youth, whereas in adults, only symptoms related to sleep and appetite disturbance displayed seasonal variation., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: Immune-mediated inflammatory diseases (IMID) such as multiple sclerosis (MS), inflammatory bowel disease (IBD) and rheumatoid arthritis (RA) are associated with a high prevalence of psychiatric comorbidity but little is known about the prevalence of social phobia in IMID, or the factors associated with social phobia. We aimed to determine the prevalence of social phobia in MS, IBD and RA, and the factors associated with social phobia in these IMID., Methods: We obtained data from the enrollment visit of a cohort study in IMID of whom 654 participants were eligible for this analysis (MS: 254, IBD: 247, RA: 153). Each participant underwent a semi-structured psychiatric interview which identified depression and anxiety disorders including social phobia (lifetime and current), an assessment of disease activity, and reported sociodemographic information., Results: Overall, 12.8% of participants had a lifetime diagnosis of social phobia (MS: 10.2%, IBD: 13.0%, RA: 17.0%). Social phobia was associated with younger age (OR 0.98; 0.97-1.00), having a high school education or less (OR 1.78; 1.08-2.91), comorbid major depressive disorder (OR 2.79; 1.63-4.78) and comorbid generalized anxiety disorder (OR 2.56; 1.30-5.05). Persons with RA had increased odds of having social phobia as compared to persons with MS (OR 2.26; 1.14-4.48) but not IBD., Conclusion: Persons with IMIDs have a relatively high lifetime prevalence of social phobia, exceeding that reported for the Canadian general population. Strategies aimed at early detection, and effective clinical management of social phobia in IMID are warranted., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

We conducted a systematic review and a fixed-effects meta-analysis to determine whether incident adverse psychiatric events (APE) including depression, anxiety, psychosis, or suicide were associated with biologic therapy in IBD. Six randomized controlled trials and a cohort study met criteria, reporting an incidence of APE in 4,882 patients. The risk difference per 100 person-months of any APE with a biologic medication was 0.01 (95% confidence interval = 0.00-0.02). There was insufficient evidence available in randomized controlled trials to conclude that biologic therapy in IBD is associated with an increased incidence of APE., (© 2019 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)

Background: Screening for major depression with the Patient Health Questionnaire-9 (PHQ-9) can be done using a cutoff or the PHQ-9 diagnostic algorithm. Many primary studies publish results for only one approach, and previous meta-analyses of the algorithm approach included only a subset of primary studies that collected data and could have published results., Objective: To use an individual participant data meta-analysis to evaluate the accuracy of two PHQ-9 diagnostic algorithms for detecting major depression and compare accuracy between the algorithms and the standard PHQ-9 cutoff score of ≥10., Methods: Medline, Medline In-Process and Other Non-Indexed Citations, PsycINFO, Web of Science (January 1, 2000, to February 7, 2015). Eligible studies that classified current major depression status using a validated diagnostic interview., Results: Data were included for 54 of 72 identified eligible studies (n participants = 16,688, n cases = 2,091). Among studies that used a semi-structured interview, pooled sensitivity and specificity (95% confidence interval) were 0.57 (0.49, 0.64) and 0.95 (0.94, 0.97) for the original algorithm and 0.61 (0.54, 0.68) and 0.95 (0.93, 0.96) for a modified algorithm. Algorithm sensitivity was 0.22-0.24 lower compared to fully structured interviews and 0.06-0.07 lower compared to the Mini International Neuropsychiatric Interview. Specificity was similar across reference standards. For PHQ-9 cutoff of ≥10 compared to semi-structured interviews, sensitivity and specificity (95% confidence interval) were 0.88 (0.82-0.92) and 0.86 (0.82-0.88)., Conclusions: The cutoff score approach appears to be a better option than a PHQ-9 algorithm for detecting major depression., (© 2019 S. Karger AG, Basel.)

Objective: Recent reports express concerns about a mental health crisis among postsecondary students. These assertions, however, often arise from surveys conducted in postsecondary settings that lack the broader context of a referent group. The objectives of this study were (1) to assess the mental health status of postsecondary students 18 to 25 years old from 2011 to 2017 and (2) to compare the mental health status of postsecondary students to nonstudents., Methods: Prevalence was estimated for a set of mental health outcomes using seven annual iterations of the Canadian Community Health Survey (2011 to 2017). Logistic regression was used to derive odds ratio estimates comparing mental health status among postsecondary students and nonstudents, adjusting for age and sex. Random effects metaregression and meta-analyses techniques were used to evaluate trends in prevalence and odds ratio estimates over time., Results: Over the study period, the prevalence of perceived low mental health, diagnosed mood and anxiety disorders, and past-year mental health consultations increased among female students, whereas binge drinking decreased among male students. With the exception of perceived stress, the odds of experiencing each mental health outcome were lower among postsecondary students compared to nonstudents., Conclusions: These findings do not support the idea that postsecondary students have worse mental health than nonstudents of similar age. The perception of a crisis may arise from greater help-seeking behavior, diminishing stigma, or increasing mental health literacy. Regardless, the observance of these trends provide an opportunity to address a previously latent issue.

Background: To examine the association between electronic cigarette (e-cigarette) use and adverse mental health status., Methods: A cross-sectional analysis was conducted using data from the 2015 and 2016 Canadian Community Health Survey (n = 53,050). Sampling weights and associated bootstrap procedures were used to account for survey design effects. Multivariable logistic regression was employed to examine the association between e-cigarette use and the following mental health outcomes: depressive symptom ratings (using the Patient Health Questionnaire 9), self-reported professionally diagnosed mood and anxiety disorders, perceived mental health, suicidal thoughts/attempts, and binge drinking., Results: The overall prevalence of past 30-day e-cigarette use was 2.9% (95% CI: 2.6-3.1). 11.5% (95% CI: 10.4-12.7) of smokers reported also using e-cigarettes. Dual users had the highest prevalence of adverse mental health status. The association between e-cigarette use and mental health was found to be modified by smoking status and sex in most of the logistic models. E-cigarettes had less than multiplicative effects among smokers. Female e-cigarette users tended to have higher odds of adverse mental health than male users. Overall, in the multivariable modeling, e-cigarette use was consistently associated with poor mental health among non-smokers and women, a finding that persisted after adjustment for additional covariates., Conclusions: These results indicate that e-cigarette use is associated with adverse mental health status, particularly among the non-smoking general population and women., Limitations: The study relied on respondent self-report, and the cross-sectional nature of the study does not allow us to clarify the direction of this association., (Copyright © 2019. Published by Elsevier B.V.)

Objectives: A previous individual participant data meta-analysis (IPDMA) identified differences in major depression classification rates between different diagnostic interviews, controlling for depressive symptoms on the basis of the Patient Health Questionnaire-9. We aimed to determine whether similar results would be seen in a different population, using studies that administered the Edinburgh Postnatal Depression Scale (EPDS) in pregnancy or postpartum., Methods: Data accrued for an EPDS diagnostic accuracy IPDMA were analysed. Binomial generalised linear mixed models were fit to compare depression classification odds for the Mini International Neuropsychiatric Interview (MINI), Composite International Diagnostic Interview (CIDI), and Structured Clinical Interview for DSM (SCID), controlling for EPDS scores and participant characteristics., Results: Among fully structured interviews, the MINI (15 studies, 2,532 participants, 342 major depression cases) classified depression more often than the CIDI (3 studies, 2,948 participants, 194 major depression cases; adjusted odds ratio [aOR] = 3.72, 95% confidence interval [CI] [1.21, 11.43]). Compared with the semistructured SCID (28 studies, 7,403 participants, 1,027 major depression cases), odds with the CIDI (interaction aOR = 0.88, 95% CI [0.85, 0.92]) and MINI (interaction aOR = 0.95, 95% CI [0.92, 0.99]) increased less as EPDS scores increased., Conclusion: Different interviews may not classify major depression equivalently., (© 2019 The Authors. International Journal of Methods in Psychiatric Research published by John Wiley & Sons Ltd.)

Objective: The goal of this study was to characterize the frequency and trends of psychotropic drug prescribing in Canadian children from 2010 to 2016 and to compare these results with a previous study conducted between 2005 and 2009. Methods: Using a national physician panel survey database from IQVIA Canada, aggregated frequencies of written prescriptions and therapeutic indications for antipsychotics, attention-deficit/hyperactivity disorder (ADHD) medications (psychostimulants and nonstimulants), and antidepressants were analyzed in children. Changes in frequency of written prescriptions and therapeutic indications are presented using descriptive statistics. Results: Written prescriptions for antipsychotics decreased by 10% from 2010 to 2016, in contrast to a 114% increase in written prescriptions for antipsychotics observed between 2005 and 2009. Written prescriptions for psychostimulants and antidepressants rose by 35% and 27%, respectively, between 2012 and 2016, comparable with previous results. The most common reasons for recommending an antipsychotic were ADHD and conduct disorder, although there appears to be a downward trend for ADHD compared with other conditions. In contrast, the share of written prescriptions for antipsychotics for autism increased 34% over the study period. Within the second-generation antipsychotics, written prescriptions for aripiprazole increased. An increase in the use of guanfacine extended release for ADHD was also observed. Conclusion: Several factors may be involved in stabilization and small decrease in antipsychotic use in recent years, including physician and patient awareness of adverse effects related to antipsychotic use, knowledge implementation strategies advocating short-term and judicious use of antipsychotics in children, and the approval of guanfacine extended release for use in Canada for ADHD in 2013.

Objective: Arthroplasty requirements among patients with psoriatic arthritis (PsA) are not well known. This information is important to clinical and policy stakeholders for health-system planning and may serve as a surrogate for estimation of the efficacy of disease-modifying therapy., Methods: We utilized The Health Improvement Network (THIN), a large general practice medical records database in the UK, to assess rates of primary total arthroplasty among patients with PsA and the general population between the years 1995 and 2010. Linear regression was used to estimate arthroplasty rates for the 2 cohorts during the study period, and Poisson regression was used to determine age- and sex-adjusted incidence rate ratios (IRRs) between the PsA and general population cohorts., Results: We identified 5,619 patients with incident PsA and 5,090,814 eligible patients from the general population between 1995 and 2010. In total, 187 primary total arthroplasties were documented in patients with PsA, and 80,163 primary total arthroplasties were documented in the general population. A trend of increasing arthroplasty rates was observed for both the PsA (R 2 = 0.809; P < 0.0001) and general population (R 2 = 0.890; P < 0.0001) cohorts during the study period. After adjustment for age and sex, patients with PsA had a first arthroplasty incidence rate that was twice that of the general population (IRR 2.01 [95% confidence interval 1.73-2.34]; P < 0.0001), notably beyond the year 2003 when biologic therapies were introduced., Conclusion: Both the general population and patients with PsA have experienced increasing rates of first arthroplasty from 1995 to 2010, although the overall incidence rate was significantly higher for those with PsA., (© 2018, American College of Rheumatology.)

Background: Suicide is a leading cause of death worldwide. With the increasing volume of administrative health care data, there is an opportunity to evaluate whether machine learning models can improve upon statistical models for quantifying suicide risk., Objective: To compare the relative performance of logistic regression and single hidden layer feedforward neural network models that quantify suicide risk with predictors available in administrative health care system data., Methods: The modeling dataset contained 3548 persons that died by suicide and 35,480 persons that did not die by suicide between 2000 and 2016. 101 predictors were selected, and these were assembled for each of the 40 quarters (10 years) prior to the quarter of death, resulting in 4040 predictors in total for each person. Logistic regression and single hidden layer feedforward neural network model configurations were evaluated using 10-fold cross-validation., Results: The optimal feedforward neural network model configuration (AUC: 0.8352) outperformed logistic regression (AUC: 0.8179)., Limitations: Many important predictors are not available in administrative data and this likely places a limit on how well prediction models developed with administrative data can perform., Conclusions: Although the models developed in this study showed promise, further research is needed to determine the performance limits of statistical and machine learning models that quantify suicide risk, and to develop prediction models optimized for implementation in clinical settings., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Inflammatory bowel disease (IBD) 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., Methods: 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., Results: 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 more likely to have an undiagnosed depressive disorder (odds ratio [OR], 3.36; 95% confidence interval [CI], 1.28-8.85). Nonwhite participants were less likely to have an undiagnosed anxiety disorder (OR, 0.17; 95% CI, 0.042-0.72)., Conclusion: 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., (© 2019 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: We assessed the information needs of persons with any of three immune-mediated inflammatory diseases (multiple sclerosis [MS], inflammatory bowel disease [IBD] and rheumatoid arthritis [RA]) 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., Methods: We surveyed participants with MS, IBD and RA 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., Results: 328 participants provided complete responses (MS: 141, IBD: 114, RA: 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., Conclusions: Persons affected by MS, IBD and RA 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 MS, IBD and RA., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The association between antidepressant use during pregnancy and adverse perinatal outcomes is unclear. The association without taking into consideration the independent effect of depression leads to a confounding of the effects of antidepressants with those of the underlying reason for the use of those medications. Additionally, a history of depression and antidepressant use may also influence this association., Objective: This study examined the risks of adverse perinatal outcomes associated with antidepressant use during pregnancy., Methods: This retrospective cohort study used population-based data in Alberta, Canada, for women who delivered between 2012 and 2015 (n = 158486). Women with depression were identified using a validated case definition, and the receipt of antidepressants was identified using Anatomical Therapeutic Chemical codes. Adverse perinatal outcomes such as severe maternal/neonatal morbidity, preterm birth, and neonatal intensive care unit admission were assessed. Multivariable log-binomial regression was used to estimate the risk of adverse perinatal outcomes associated with antidepressants, adjusting for age and parity., Results: In total, 9.1% women had depression and 2.5% women received antidepressants during pregnancy. The relative risk of severe neonatal morbidity/mortality was 1.25 (95% confidence interval 1.17, 1.33) times higher for women with depression alone compared to women without depression. The risk of severe neonatal morbidity/mortality was 1.51 (95% confidence interval 1.36, 1.66) times higher for women who used antidepressants compared to women with depression alone-however, the risk differed between the women with and without a history of antidepressant use. A similar risk pattern was observed for preterm birth and neonatal intensive care unit admission., Conclusions: Both depression and antidepressant use were independently associated with the risk of adverse perinatal outcomes; however, the risk associated with antidepressants was higher over and above the risk associated with depression. This may reflect the biological effects of antidepressants, greater severity of depression in those treated, or both., (© 2019 John Wiley & Sons Ltd.)

Objective: Depression is associated with IBD, but the effect of antidepressants on IBD has been sparsely studied. We assessed the impact of depression and antidepressant therapies on the development of IBD., Design: The Health Improvement Network (THIN) was used to identify a cohort of patients with new-onset depression from 1986 to 2012. THIN patients who did not meet the defining criteria for depression were part of the referent group. The outcome was incident Crohn's disease (CD) or ulcerative colitis (UC). Cox proportional hazards modelling was performed to evaluate the rate of Crohn's disease or UC development among patients with an exposure of depression after controlling for age, sex, socioeconomic status, comorbid conditions, smoking, anxiety and antidepressant use including atypical antidepressants, mirtazapine, monoamine oxidase inhibitors (MAOI), serotonin norepinephrine reuptake inhibitors (SNRI), selective serotonin reuptake inhibitors (SSRI), serotonin modulators; and tricyclic antidepressants (TCA)., Results: We identified 403 665 (7.05%) patients with incident depression. Individuals with depression had a significantly greater risk of developing CD (adjusted HR=2.11, 95% CI 1.65 to 2.70) and UC (adjusted HR=2.23, 95% CI 1.92 to 2.60) after controlling for demographic and clinical covariates. SSRI and TCA were protective against CD, whereas mirtazapine, SNRI, SSRI, serotonin modulators and TCA were protective for UC., Conclusion: Patients with a history of depression were more likely to be diagnosed with IBD. In contrast, antidepressant treatments were selectively protective for Crohn's disease and UC. These results may impact counselling and management of depression and IBD., Competing Interests: Competing interests: MGS, AAS and GGK share a patent: TREATMENT OF INFLAMMATORY DISORDERS, AUTOIMMUNE DISEASE, AND PBC. UTI Limited Partnership, assignee. Patent 62/555,397. 7 September 2017. GGK has served as a speaker for Janssen, AbbVie and Pfizer, and has received research support from Janssen, AbbVie, GlaxoSmithKline and Shire., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: There is no consensus as to whether depressive symptoms vary by season. Using data from the Canadian Community Health Survey (CCHS), the purpose of this study was to evaluate seasonal variation in depressive symptoms in the Canadian household population., Methods: A cross-sectional analysis of data from the CCHS in 2015 and 2016 was used. Mean Patient Health Questionnaire-9 (PHQ-9) scores, and categories defined by 5+ or 10+ cut-points were used for analysis. Seasonal effects were assessed using quadratic terms in regression models, generalized linear models were used for this purpose. Models were stratified by youth ages 12-24 (rounded n ≈ 8000) and adults ages 25+ (rounded n ≈ 45,000)., Results: Significant seasonal variation was observed for youth (age 12-24) for mean PHQ-9 scores and proportion with scores of 5+. There was evidence of effect modification by age. The youth group had stronger seasonal effects compared to respondents age 25+. Seasonal effect was highly significant for mean PHQ-9 scores (p = 0.009) and 5+ (p = 0.001), but not for 10+ (p = 0.481)., Limitations: Use of cross-sectional data limits the capacity to generalize results to the classic definition of Seasonal Affective Disorder. Data surrounding respondent's anti-depressant use was unavailable., Conclusions: Seasonal variation in depressive symptoms is evident in the Canadian population. Higher levels of symptoms were reported in winter months compared to summer months. The seasonal trend is most pronounced in youth specifically those who reported at least mild depressive symptoms, but not in respondents reporting moderate to severe symptoms., (Copyright © 2019. Published by Elsevier B.V.)

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.

Purpose of Review: Rheumatoid arthritis (RA) is associated with negative changes in mental health. This is generally attributed to symptoms of inflammation and the adverse impact of RA on quality of life and functioning. Until recently, causal pathways in the opposite direction have not been fully appreciated. This review examines the recent literature on the risk of RA associated with depression., Recent Findings: Current literature links depression with an increased risk of RA and with a more detrimental disease course. These effects are likely to be partially mediated by negative effects of depression on coping with RA and on factors such as medication adherence, both of which lead to poorer disease outcomes. Growing evidence also suggests that inflammation is central both to depression and RA and may account for some of the complex interplay between these conditions., Summary: Awareness of a bidirectional relationship between depression and RA through a biopsychosocial framework may assist clinicians in maintaining an appropriate index of suspicion about the co-occurrence of these conditions. This review also suggests an important need for integration of rheumatologic and mental health services and generates hypotheses for future research towards a better understanding of both depression and RA.

Background: Vitiligo patients often report their mental health has an effect on their skin. However, it is unknown as to whether a common mental disorder, such as major depressive disorder (MDD), can also precipitate the onset of vitiligo., Objective: Evaluate a bidirectional relationship between MDD and vitiligo using The Health Improvement Network database., Methods: Incident MDD and referent cohorts were followed until the development of vitiligo. Also, incident vitiligo and referent cohorts were followed until the development of MDD. Cox proportional hazards models were used, and numerous covariates were adjusted for., Results: In adjusted models, MDD patients (n = 405,397) were at a 64% increased risk for vitiligo (hazard ratio 1.64, 95% confidence interval [CI] 1.43-1.87, P < .0001) compared with the referent cohort (n = 5,739,048). This risk was decreased in patients using antidepressants. Compared with the referent cohort (n = 6,137,696), patients with vitiligo (n = 7104) that were <30 years of age at diagnosis had a higher risk of developing MDD than patients ≥30 years of age (hazard ratio 1.31, 95% CI 1.14-1.50, P < .0001 vs 1.22, 95% CI 1.08-1.37, P = .001, respectively)., Limitations: This study did not evaluate the severity of MDD or vitiligo on outcome development., Conclusion: These results highlight the burden of depression in patients with vitiligo and support the possible existence of pathophysiological connections between these 2 conditions., (Copyright © 2018 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: In persons with migraine, severity of migraine is an important determinant of several health outcomes (e.g., patient quality of life and health care resource utilization). This study investigated how migraine patients rate the severity of their disease and how these ratings correlate with their socio-demographic, clinical, and psycho-social characteristics., Methods: This is a cohort of 263 adult migraine patients consecutively enrolled in the Neurological Disease and Depression Study (NEEDs). We obtained a broad range of clinical and patient-reported measures (e.g., patients' ratings of migraine severity using the Global Assessment of Migraine Severity (GAMS), and migraine-related disability, as measured by the Migraine Disability Scale (MIDAS)). Depression was measured using the 9-item Patient Health Questionnaire (PHQ-9) and the 14-item Hospital Anxiety and Depression Scale (HADS). Median regression analysis was used to examine the predictors of patient ratings of migraine severity., Results: The mean age for the patients was 42.5 years (SD = 13.2). While 209 (79.4%) patients were females, 177 (67.4%) participants reported "moderately severe" to "extremely severe" migraine on the GAMS, and 100 (31.6%) patients had chronic migraine. Patients' report of severity on the GAMS was strongly correlated with patients' ratings of MIDAS global severity question, overall MIDAS score, migraine type, PHQ-9 score, and frequency of migraine attacks. Mediation analyses revealed that MIDAS mediated the effect of depression on patient ratings of migraine severity, accounting for about 32% of the total effect of depression. Overall, migraine subtype, frequency of migraine, employment status, depression, and migraine-related disability were statistically significant predictors of patient-ratings of migraine severity., Conclusions: This study highlights the impact of clinical and psychosocial determinants of patient-ratings of migraine severity. GAMS is a brief and valid tool that can be used to assess migraine severity in busy clinical settings.

Importance: Levetiracetam is a commonly used antiepileptic drug, yet psychiatric adverse effects are common and may lead to treatment discontinuation., Objective: To derive prediction models to estimate the risk of psychiatric adverse effects from levetiracetam use., Design, Setting, and Participants: Retrospective open cohort study. All patients meeting the case definition for epilepsy after the Acceptable Mortality Reporting date in The Health Improvement Network (THIN) database based in the United Kingdom (inclusive January 1, 2000, to May 31, 2012) who received a first-ever prescription for levetiracetam were included. Of 11 194 182 patients registered in THIN, this study identified 7400 presumed incident cases (66.1 cases per 100 000 persons) over a maximum of 12 years' follow-up. The index date was when patients received their first prescription code for levetiracetam, and follow-up lasted 2 years or until an event, loss to follow-up, or censoring. The analyses were performed on April 22, 2018., Exposure: A presumed first-ever prescription for levetiracetam., Main Outcomes and Measures: The outcome of interest was a Read code for any psychiatric sign, symptom, or disorder as reached through consensus by 2 authors. This study used regression techniques to derive 2 prediction models, one for the overall population and one for those without a history of a psychiatric sign, symptom, or disorder during the study period., Results: Among 1173 patients with epilepsy receiving levetiracetam, the overall median age was 39 (interquartile range, 25-56) years, and 590 (50.3%) were female. A total of 14.1% (165 of 1173) experienced a psychiatric symptom or disorder within 2 years of index prescription. The odds of reporting a psychiatric symptom were significantly elevated for women (odds ratio [OR], 1.41; 95% CI, 0.99-2.01; P = .05) and those with a preexposure history of higher social deprivation (OR, 1.15; 95% CI, 1.01-1.31; P = .03), depression (OR, 2.20; 95% CI, 1.49-3.24; P < .001), anxiety (OR, 1.74; 95% CI, 1.11-2.72; P = .02), or recreational drug use (OR, 2.02; 95% CI, 1.20-3.37; P = .008). The model performed well after stratified k = 5-fold cross-validation (area under the curve [AUC], 0.68; 95% CI, 0.58-0.79). There was a gradient in risk, with probabilities increasing from 8% for 0 risk factors to 11% to 17% for 1, 17% to 31% for 2, 30% to 42% for 3, and 49% when all risk factors were present. For those free of a preexposure psychiatric code, a second model performed comparably well after k = 5-fold cross-validation (AUC, 0.72; 95% CI, 0.54-0.90). Specificity was maximized using threshold cutoffs of 0.10 (full model) and 0.14 (second model); a score below these thresholds indicates safety of prescription., Conclusions and Relevance: This study derived 2 simple models that predict the risk of a psychiatric adverse effect from levetiracetam. These algorithms can be used to guide prescription in clinical practice.

Importance: Alopecia areata (AA) is an autoimmune disease characterized by hair loss that can impose a substantial psychological burden on patients, including major depressive disorder (MDD), yet many patients report mental health symptoms prior to the onset of AA. As such, there may be an association between MDD and AA that acts in both directions., Objective: To assess the bidirectional association between MDD and AA., Design, Setting, and Participants: This population-based retrospective cohort study included patients 10 to 90 years of age registered with The Health Improvement Network in general practices in the United Kingdom between January 1, 1986, and May 16, 2012. Statistical analysis was conducted from August 17, 2017, to April 23, 2018. To assess the risk of AA, the following 2 cohorts were defined: patients with an incident diagnosis of MDD (exposure) and a reference general population cohort. To assess the risk of MDD, the following 2 cohorts were defined: patients with an incident diagnosis of AA (exposure) and a reference general population cohort. Person-time was partitioned into unexposed and exposed time in the exposure cohorts., Main Outcomes and Measures: In the analysis of the risk of AA, development of incident AA during follow-up was considered the main outcome measure. In the analysis of the risk of MDD, development of incident MDD during follow-up was considered the primary outcome measure., Results: In the analysis of the risk of AA, 405 339 patients who developed MDD (263 916 women and 141 423 men; median age, 36.7 years [interquartile range, 26.6-50.5 years]) and 5 738 596 patients who did not develop MDD (2 912 201 women and 2 826 395 men; median age, 35.8 years [interquartile range, 25.3-52.6 years]) were followed up for 26 years. After adjustment for covariates, MDD was found to increase the risk of subsequently developing AA by 90% (hazard ratio, 1.90; 95% CI, 1.67-2.15; P < .001). Antidepressants demonstrated a protective effect on the risk of AA (hazard ratio, 0.57; 95% CI, 0.53-0.62; P < .001). In the analysis of the risk of MDD, 6861 patients who developed AA (3846 women and 3015 men; median age, 31.5 years [interquartile range, 18.2 years]) and 6 137 342 patients who did not develop AA (3 172 371 women and 2 964 971 men; median age, 35.9 years [interquartile range, 27.0 years]) were followed up for 26 years. After adjustment for covariates, AA was found to increase the risk of subsequently developing MDD by 34% (hazard ratio, 1.34; 95% CI, 1.23-1.46; P < .001)., Conclusions and Relevance: These temporal analyses suggest that, while patients with AA are at risk for subsequently developing MDD, having MDD also appears to be a significant risk factor for development of AA, with antidepressant use confounding this risk.

Objective: To develop a detailed profile of individuals living with migraine in Canada. Such a profile is important for planning and administration of services., Methods: The 2011-2012 Survey of Living with Neurological Conditions in Canada (SLNCC), a cross-sectional community-based survey, was used to examine a representative sample of migraineurs (N = 949) aged 15 years and older. Several health-related variables were examined (e.g., general health, health utility index (HUI) [a measure of health status and health-related quality of life, where dead = 0.00 and perfect health = 1.00], stigma, depression, and social support). Respondents were further stratified by sex, age, and age of migraine onset. Weighted overall and stratified prevalence estimates and odds ratios, both with 95% CIs, were used to estimate associations., Results: Overall, males had poorer health status compared with females (e.g., mean HUI was 0.67 in males vs. 0.82 in females; men had over two times the odds of their migraine limiting educational and job opportunities compared with females). Poorer health-related variables were seen in the older age groups (35-64 years/≥65 years) compared with the 15-34-year age group. There were no differences between those whose migraine symptoms began before versus after the age of 20 years., Conclusions: In this Canadian sample, migraine was associated with worse health-related variables in men compared with women. However, both men and women were significantly affected by migraine across various health-related variables. Thus, it is important to improve clinical and public health interventions addressing the impact of migraine across individuals of all ages, sexes, and sociodemographic backgrounds.

Objective: Pregnant women are often concerned about the impact of medication use on their pregnancy, such as congenital abnormalities. This study examined the rate of adherence to and persistence with antidepressant medications during pregnancy based on the class of antidepressants prescribed., Methods: Women who gave birth between 2012 and 2015 in Alberta, Canada; had ≥1 diagnosis of depression within 1 year of preconception in outpatient physician claims, emergency department, or hospitalization administrative data; and were adherent (medication possession ratio ≥80%) to ≥2 consecutive antidepressant prescriptions during the preconception year ( n = 1865) were included in this retrospective cohort study. The rates of adherence and persistence (prescription refill gap ≤30 days) were calculated by antidepressant class and were compared using chi-square tests., Results: During pregnancy, 834 (44.7%; 95% CI, 42.4% to 47.0%) women discontinued antidepressants. Among those continuing antidepressants, the overall rate of adherence was 62.6% (95% CI, 59.4% to 65.7%). The rate differed significantly by medication class ( P < 0.0001), with a rate of 75.1% (95% CI, 68.3% to 80.9%) for serotonin-norepinephrine inhibitors, 60.9% (95% CI, 57.2% to 64.5%) for selective serotonin reuptake inhibitors, 42.8% (95% CI, 19.9% to 69.3%) for nonselective monoamine reuptake inhibitors, and 37.5% (95% CI, 22.5% to 55.4%) for atypical antidepressants. Only, 40.7% (95% CI, 37.5 to 44.1) of women were persistent with antidepressants for the full pregnancy period-the rate differed significantly by medication class ( P < 0.0001)., Conclusions: Adherence to and persistence with antidepressants is low during pregnancy and varies by medication class. Low adherence and persistence can interfere with a therapeutic effect of antidepressants, which may contribute to the worsening of depression symptoms.

Background: An understanding of the risk factors contributing to disease burden is critical for determining research priorities and informing national health policy. We aimed to identify the risk factor trends in Canada., Methods: As part of the Global Burden of Disease (GBD) study (1990-2016), we conducted an analysis of country-level estimates for Canada to assess the burden of diseases and injuries attributable to risk factors. For both 1990 and 2016, metabolic, environmental and behavioural risk factors were ranked according to their contribution to disability-adjusted life years (healthy years of life lost), total deaths and years lived with disability., Results: In 2016, the risk factors accounting for the largest percentage of disability-adjusted life years in Canada were (1) tobacco, (2) diet, (3) high body mass index, (4) high fasting plasma glucose, (5) high systolic blood pressure, (6) alcohol and drug use, (7) occupational risks, (8) high total cholesterol, (9) impaired kidney function and (10) air pollution. Risk factor rankings remained similar from 1990 to 2016 despite some substantial declines in burden, including a 47% (± 3%) decline in the age-standardized disability-adjusted life years rate attributable to tobacco since 1990. Risk factors with an increasing contribution to disability-adjusted life years rates from 1990 to 2016 included high body mass index, high fasting plasma glucose and alcohol and drug use., Interpretation: Metabolic and behavioural risk factors, including modifiable factors such as tobacco use and diet, remain the leading risk factors contributing to the burden of diseases and injuries in Canada. This work identifies priorities and targets for reducing premature death and disability burden in Canada., Competing Interests: Competing interests: Aaron Drucker reports grants and personal fees from Sanofi and Regeneron for activities outside the work reported here. No other competing interests were declared., (Copyright 2019, Joule Inc. or its licensors.)

Objective: This study developed and internally validated a predictive model for preterm birth (PTB) to examine the ability of neighbourhood socioeconomic status (SES) to predict PTB., Design: Cohort study using individual-level data from two community-based prospective pregnancy cohort studies (All Our Families (AOF) and Alberta Pregnancy Outcomes and Nutrition (APrON)) and neighbourhood SES data from the 2011 Canadian census., Setting: Calgary, Alberta, Canada., Participants: Pregnant women who were <24 weeks of gestation and >15 years old were enrolled in the cohort studies between 2008 and 2012. Overall, 5297 women participated in at least one of these cohorts: 3341 women participated in the AOF study, 2187 women participated in the APrON study and 231 women participated in both studies. Women who participated in both studies were only counted once., Primary and Secondary Outcome Measures: PTB (delivery prior to 37 weeks of gestation)., Results: The rates of PTB in the least and most deprived neighbourhoods were 7.54% and 10.64%, respectively. Neighbourhood variation in PTB was 0.20, with an intra-class correlation of 5.72%. Neighbourhood SES, combined with individual-level predictors, predicted PTB with an area under the receiver-operating characteristic curve (AUC) of 0.75. The sensitivity was 91.80% at a low-risk threshold, with a high false-positive rate (71.50%), and the sensitivity was 5.70% at a highest risk threshold, with a low false-positive rate (0.90%). An agreement between the predicted and observed PTB demonstrated modest model calibration. Individual-level predictors alone predicted PTB with an AUC of 0.60., Conclusion: Although neighbourhood SES combined with individual-level predictors improved the overall prediction of PTB compared with individual-level predictors alone, the detection rate was insufficient for application in clinical or public health practice. A prediction model with better predictive ability is required to effectively find women at high risk of preterm delivery., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: 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., Methods: Using population-based administrative health data from Manitoba, Canada, 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., Results: 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 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), anxiety disorder (IRR, 1.39; 95% CI, 1.26-1.53), bipolar disorder (IRR, 1.82; 95% CI, 1.44-2.30), and schizophrenia (IRR, 1.64; 95% CI, 0.95-2.84). Incidence rate ratios were similar for Crohn's disease and ulcerative colitis 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., Conclusions: The incidence and prevalence of psychiatric disorders are elevated in the IBD population.

A variety of neuropsychiatric problems can occur in people with multiple sclerosis (MS) and these are often among the most important determinants of their quality of life. Taken together, a high prevalence of depression, anxiety, fatigue, and cognitive problems means that most people with MS end up struggling with one or more of these neuropsychiatric difficulties. Although these problems manifest across a broad range of severity, this is often a burdensome struggle. Pharmacologic treatments are an important domain of therapeutic intervention. Unfortunately, the use of these medications is supported by a very limited literature. Clinicians often must make clinical decisions about the use of psychopharmacologic treatments in the absence of guidance from high quality evidence. This requires synthesizing clinical information about MS with more general principles of psychiatric and psychopharmacologic care. This chapter provides such a synthesis of available evidence as it pertains to the most important neuropsychiatric syndromes in MS. The goal is to help facilitate effective psychopharmacologic treatment, which, in turn, can translate into better quality of life for people with MS., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: To explore the association between major depressive episodes (MDE) and subsequent mortality in a representative sample of the general household population, with adjustment for other determinants of mortality., Method: The analysis used four datasets from the Canadian Community Health Survey (CCHS); the CCHS 1.1 (conducted in 2000 and 2001), the CCHS 1.2 (conducted in 2002), the CCHS 2.1 (conducted in 2003 and 2004) and the CCHS 3.1 (conducted in 2005 and 2006). Each survey included an assessment of past-year major depressive episodes (MDEs) and was linked to mortality data from the Canadian Mortality Database for January 1, 2000 to December 31, 2011. The hazard ratio (HR) for all-cause mortality was estimated in each survey sample. Random effects, individual-level meta-analysis was used to pool estimates from the four survey data sets. Estimates were adjusted for other determinants of mortality prior to pooling in order to help quantify the independent contribution of MDE to all-cause mortality., Results: The unadjusted HR was 0.77 (95% CI 0.63-0.95). A naïve interpretation of this HR suggests a protective effect of MDE, but the estimate was found to be strongly confounded by age (age adjusted HR for MDE: 1.61, 95% CI 1. 34-1.93) and by sex (sex adjusted HR for MDE: 1.15, 95% CI 0.75-1.77). The age and sex adjusted HR was: 1.70 (95% CI 1.45-2.00). No evidence of effect modification by any determinant of mortality was found, including sex. After adjustment for a set of mortality risk factors, the pooled HR was weakened, but remained statistically significant, HR = 1.29 (I-squared = < 1%, tau-squared < 0.001, 95% CI 1.10-1.51). Smoking was the strongest single confounding variable., Conclusions: MDE is associated with elevated mortality. The elevated risk is partially attributable to psychosocial, behavioral and health-related determinants. Since MDE itself may have caused changes to these variables, these estimates cannot fully quantify the independent contribution of MDE to mortality. However, these results suggest that clinical and public health efforts to counteract the effect of MDE on mortality may benefit from attention to a broad set of mortality risk factors e.g. smoking, physical activity, management of medical conditions., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: The objective of this study was to develop and validate a short form of the Patient Health Questionnaire-9 (PHQ-9), a self-report questionnaire for assessing depressive symptomatology, using objective criteria., Methods: Responses on the PHQ-9 were obtained from 7,850 English-speaking participants enrolled in 20 primary diagnostic test accuracy studies. PHQ unidimensionality was verified using confirmatory factor analysis, and an item response theory model was fit. Optimal test assembly (OTA) methods identified a maximally precise short form for each possible length between one and eight items, including and excluding the ninth item. The final short form was selected based on prespecified validity, reliability, and diagnostic accuracy criteria., Results: A four-item short form of the PHQ (PHQ-Dep-4) was selected. The PHQ-Dep-4 had a Cronbach's alpha of 0.805. Sensitivity and specificity of the PHQ-Dep-4 were 0.788 and 0.837, respectively, and were statistically equivalent to the PHQ-9 (sensitivity = 0.761, specificity = 0.866). The correlation of total scores with the full PHQ-9 was high (r = 0.919)., Conclusion: The PHQ-Dep-4 is a valid short form with minimal loss of information of scores when compared to the full-length PHQ-9. Although OTA methods have been used to shorten patient-reported outcome measures based on objective, prespecified criteria, further studies are required to validate this general procedure for broader use in health research. Furthermore, due to unexamined heterogeneity, there is a need to replicate the results of this study in different patient populations., (© 2018 Wiley Periodicals, Inc.)

Background: Depression often occurs in association with stressful events. However, people with depressive disorders may experience episodes in response to minor stressors or "out of the blue." Similar episodes can occur in people who do not have a disorder in response to severe events. This plurality of symptom patterns, occurring as it does in the absence of precise demarcation from normality has led to controversy over how depressive disorders should be defined, how common they are, and when treatment should be offered. Much of the controversy, however, may be illusory, arising from a tendency to view depressive disorders as defects or disease processes (the "clincian's illusion"). Avoiding the illusion involves understanding depression as a defense rather than a defect and requires consideration of aspects of signal detection theory and the associated "smoke detector" principle. This perspective may help to understand aspects of depressive disorders that are otherwise puzzling and controversial., Methods: In this paper, implications of signal detection theory and the "smoke detector principle" are explored: (1) conceptually, (2) using calculations performed in a spreadsheet and (3) using an agent-based model. Depressive episodes are conceptualized or represented as all-or-nothing phenomena activated in response to stressful life events. These events occur in an environment that also includes variable levels of baseline stress, creating a signal detection problem. The agent-based framework allows interaction with the environment as agents attempt to achieve an ideal level of adaptation., Results: The smoke detector principle, if valid, may explain otherwise puzzling and controversial features of the depressive disorders, such as their lack of precise demarcation from normality, the role of life events and stressors and their patterns of prevalence., Conclusions: Signal detection concepts help to avoid the "clinician's illusion" in which aspects of functioning of the body's defenses are mistaken for a disease entity or defect. These principles emphasize inevitable difficulties that are encountered in attempts to conceptualize depressive disorders without reference to the environment in which they occur, and without addressing possible stochastic (randomly varying) elements. Because of the "clinicians illusion", current research priorities, as well as diagnosis and treatment strategies, may be flawed.

Introduction: The 30-item Geriatric Depression Scale (GDS-30) and the shorter GDS-15, GDS-5 and GDS-4 are recommended as depression screening tools for elderly individuals. Existing meta-analyses on the diagnostic accuracy of the GDS have not been able to conduct subgroup analyses, have included patients already identified as depressed who would not be screened in practice and have not accounted for possible bias due to selective reporting of results from only better-performing cut-offs in primary studies. Individual participant data meta-analysis (IPDMA), which involves a standard systematic review, then a synthesis of individual participant data, rather than summary results, could address these limitations. The objective of our IPDMA is to generate accuracy estimates to detect major depression for all possible cut-offs of each version of the GDS among studies using different reference standards, separately and among participant subgroups based on age, sex, dementia diagnosis and care settings. In addition, we will use a modelling approach to generate individual participant probabilities for major depression based on GDS scores (rather than a dichotomous cut-off) and participant characteristics (eg, sex, age, dementia status, care setting)., Methods and Analysis: Individual participant data comparing GDS scores to a major depression diagnosis based on a validated structured or semistructured diagnostic interview will be sought via a systematic review. Data sources will include Medline, Medline In-Process & Other Non-Indexed Citations, PsycINFO and Web of Science. Bivariate random-effects models will be used to estimate diagnostic accuracy parameters for each cut-off of the different versions of the GDS. Prespecified subgroup analyses will be conducted. Risk of bias will be assessed with the Quality Assessment of Diagnostic Accuracy Studies-2 tool., Ethics and Dissemination: The findings of this study will be of interest to stakeholders involved in research, clinical practice and policy., Prospero Registration Number: CRD42018104329., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The Global Burden of Disease Study represents a large and systematic effort to describe the burden of diseases and injuries over the past 3 decades. We aimed to summarize the Canadian data on burden of diseases and injuries., Methods: We summarized data from the 2016 iteration of the Global Burden of Disease Study to provide current (2016) and historical estimates for all-cause and cause-specific diseases and injuries using mortality, years of life lost, years lived with disability and disability-adjusted life years in Canada. We also compared changes in life expectancy and health-adjusted life expectancy between Canada and 21 countries with a high sociodemographic index., Results: In 2016, leading causes of all-age disability-adjusted life years were neoplasms, cardiovascular diseases, musculoskeletal diseases, and mental and substance use disorders, which together accounted for about 56% of disability-adjusted life years. Between 2006 and 2016, the rate of all-cause age-standardized years of life lost declined by 12%, while the rate of all-cause age-standardized years lived with disability remained relatively stable (+1%), and the rate of all-cause age-standardized disability-adjusted life year declined by 5%. In 2016, Canada aligned with countries that have a similar high sociodemographic index in terms of life expectancy (82 yr) and health-adjusted life expectancy (71 yr)., Interpretation: The patterns of mortality and morbidity in Canada reflect an aging population and improving patterns of population health. If current trends continue, Canada will continue to face challenges of increasing population morbidity and disability alongside decreasing premature mortality., Competing Interests: Competing interests: Aaron Drucker reports grants and personal fees from Sanofi and Regeneron for activities outside the work reported here. No other competing interests were declared., (© 2018 Joule Inc. or its licensors.)

Background: Psychiatric comorbidity is prevalent in persons with multiple sclerosis (MS). Few studies have assessed whether second-generation disease-modifying therapies (DMT) are associated with adverse psychiatric effects., Objective: We aimed to systematically review the literature regarding the APEs associated with natalizumab, fingolimod, dimethyl fumarate, teriflunomide and alemtuzumab in MS. As a secondary objective, we evaluated changes in anxiety or depression scores following treatment with the aforementioned DMTs., Methods: We searched MEDLINE, EMBASE, International Pharmaceutical Abstracts, PsychINFO, Central Register of Controlled Trials & Cochrane database of systematic reviews for published studies, and clinicaltrials.gov and regulatory documents from the US and Canada for unpublished studies. Data sources were searched from inception to September 2017. Studies reporting adverse psychiatric effects involving any DMT of interest were included. We report the incidence proportions of the adverse psychiatric effects and, where applicable, risk differences between DMT-exposed and unexposed individuals along with the corresponding 95% confidence intervals. We calculated the standardized mean differences (SMD) of changes in anxiety and depression scores if reported as study outcomes, and pooled the data using random effects meta-analysis., Results: Of 4389 abstracts screened, 78 met the inclusion criteria, including 48 clinical trials, 28 observational studies and 2 case reports. Depression was the most commonly reported adverse psychiatric effect. Incidence proportions for all adverse psychiatric effects ranged from 0 to 24.7%. None of the DMT studied were associated with a statistically significant increased risk of any adverse psychiatric effect (range of risk difference: -7.69% [95%CI: -16.06%, 5.56%] to 6.67 [-8.56, 15.59]). Eighteen studies examined changes in depression or anxiety following fingolimod, natalizumab or dimethyl fumarate treatment; depression symptoms improved in fingolimod-treated groups (SMD [95%CI]: 1.18 [0.17, 2.19]). We did not identify studies examining changes in these outcomes following treatment with any of the other DMTs., Conclusion: The DMTs reviewed were not associated with an increased risk of adverse psychiatric effect in MS, and some may reduce the incidence of depressive symptoms. This may reflect either a positive direct effect (e.g. immune modulation) or an indirect effect arising due to a positive impact on disease activity or course., (Copyright © 2018. Published by Elsevier B.V.)