Prevalence, symptoms, and treatment of depression suggest that major depressive disorders (MDD) present sex differences. Social stress-induced neurovascular pathology is associated with depressive ...symptoms in male mice; however, this association is unclear in females. Here, we report that chronic social and subchronic variable stress promotes blood-brain barrier (BBB) alterations in mood-related brain regions of female mice. Targeted disruption of the BBB in the female prefrontal cortex (PFC) induces anxiety- and depression-like behaviours. By comparing the endothelium cell-specific transcriptomic profiling of the mouse male and female PFC, we identify several pathways and genes involved in maladaptive stress responses and resilience to stress. Furthermore, we confirm that the BBB in the PFC of stressed female mice is leaky. Then, we identify circulating vascular biomarkers of chronic stress, such as soluble E-selectin. Similar changes in circulating soluble E-selectin, BBB gene expression and morphology can be found in blood serum and postmortem brain samples from women diagnosed with MDD. Altogether, we propose that BBB dysfunction plays an important role in modulating stress responses in female mice and possibly MDD.
ABSTRACTBACKGROUNDMultimorbidity and mental disorders are independently associated with frequent visits to the emergency department (≥ 3 visits/yr), but their interaction has been little studied. We ...aimed to measure the interaction between mental disorders and physical multimorbidity with respect to frequent visits to the emergency department.METHODSWe conducted a population-based cohort study of adults in Quebec from 2012 to 2016, using the Quebec Integrated Chronic Disease Surveillance System. We assessed multimorbidity as the number of physical illnesses and mental disorders as serious (psychotic or bipolar disorders), common or absent, using data from 2012 to 2014. We counted emergency department visits from 2014 to 2015. We used logistic regression to estimate interaction on frequent visits to the emergency department from 2 perspectives: of public health (additive scale as differences in risk) and of individual patients (multiplicative scale as odds ratios).RESULTSEach additional physical illness was associated with a greater increase in the absolute risk of frequent visits to the emergency department for people with mental disorders. Between 0 and ≥ 4 physical conditions, the absolute risk increased more for individuals with serious mental disorders (16.2%) than common (15.3%) or no disorders (11.4%). On the relative scale, for people with no mental disorders and ≥ 4 physical conditions, odds of frequent visits to the emergency department were 6.2 (95% confidence interval CI 6.08–6.35) times the odds for people with no physical conditions. For individuals with common and serious mental illnesses, corresponding odds ratios were 4.75 (95% CI 4.60–4.90) and 3.7 (95% CI 3.18–3.57), respectively.INTERPRETATIONMental disorders interact with physical multimorbidity to increase the odds of frequent visits to the emergency department. More research is needed on interventions that promote high-quality care for mental illness, especially in the context of physical multimorbidity.
Objectives
There is evidence that both low socioeconomic status (SES) and psychosocial stressors at work (PSW) increase risk of depression, but prospective studies on the contribution of PSW to the ...socioeconomic gradient of depression are still limited.
Methods
Using a prospective cohort of Quebec white-collar workers (n = 9188 participants, 50% women), we estimated randomized interventional analogues of the natural direct effect of SES indicators at baseline (education level, household income, occupation type and a combined measure) and of their natural indirect effects mediated through PSW (job strain and effort-reward imbalance (ERI) measured at the follow-up in 1999–2001) on incident physician-diagnosed depression.
Results
During 3 years of follow-up, we identified 469 new cases (women: 33.1 per 1000 person-years; men: 16.8). Mainly in men, low SES was a risk factor for depression education: hazard ratio 1.72 (1.08–2.73); family income: 1.67 (1.04–2.67); occupational type: 2.13 (1.08–4.19). In the entire population, exposure to psychosocial stressors at work was associated with increased risk of depression job strain: 1.42 (1.14–1.78); effort-reward imbalance (ERI) 1.73 (1.41–2.12). The estimated indirect effects of socioeconomic indicators on depression mediated through job strain ranged from 1.01 (0.99–1.03) to 1.04 (0.98–1.10), 4–15% of total effects, and for low reward from 1.02 (1.00–1.03) to 1.06 (1.01–1.11), 10–15% of total effects.
Discussion
Our study suggests that PSW only slightly mediate the socioeconomic gradient of depression, but that socioeconomic inequalities, especially among men, and PSW both increase the incidence of depression.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective:
There is substantial evidence suggesting that suicide aggregates in families. However, the extent of overlap between the liability to suicide and psychiatric disorders, particularly major ...depressive disorder, remains an important issue. Similarly, factors that account for the familial transmission of suicidal behavior remain unclear. Thus, through direct and blind assessment of first-degree relatives, the authors conducted a family study of suicide by examining three proband groups: probands who committed suicide in the context of major depressive disorder, living depressed probands with no history of suicidal behavior, and psychiatrically normal community comparison probands.
Method:
Participants were 718 first-degree relatives from 120 families: 296 relatives of 51 depressed probands who committed suicide, 185 relatives of 34 nonsuicidal depressed probands, and 237 relatives of 35 community comparison subjects. Psychopathology, suicidal behavior, and behavioral measures were assessed via interviews.
Results:
The relatives of probands who committed suicide had higher levels of suicidal behavior (10.8%) than the relatives of nonsuicidal depressed probands (6.5%) and community comparison probands (3.4%). Testing cluster B traits as intermediate phenotypes of suicide showed that the relatives of depressed probands who committed suicide had elevated levels of cluster B traits; familial predisposition to suicide was associated with increased levels of cluster B traits; cluster B traits demonstrated familial aggregation and were associated with suicide attempts among relatives; and cluster B traits mediated, at least in part, the relationship between familial predisposition and suicide attempts among relatives. Analyses were repeated for severity of attempts, where cluster B traits also met criteria for endophenotypes of suicide.
Conclusions:
Familial transmission of suicide and major depression, while partially overlapping, are distinct. Cluster B traits and impulsive-aggressive behavior represent intermediate phenotypes of suicide.
Suicide is a major public health concern. In 2017, the suicide rate in Canada was 11 per 100,000 inhabitants. According to literature, 1 in 5 people have experienced a death by suicide during their ...lifetime. The aim of this study was to describe the met and unmet needs of suicide-bereaved survivors and to provide postvention recommendations.
Further to an exploratory mixed-method audit of 39 suicides that occurred in Montreal (Canada) in 2016, suicide-bereaved survivors (n = 29) participated in semi-structured interviews and completed instruments to discuss and assess potential pathological grief, depression (PHQ-9), and anxiety (GAD-7), as well as health and social services utilization. A panel then reviewed each case and provided recommendations. The mean age of participants was 57.7 years and 23 were women.
Although help was offered initially, in most cases by a health professional or service provider (16/29), 22 survivors would have liked to be contacted by telephone in the first 2 months post suicide. Four categories of individual unmet needs (medical/pharmacological, information, support, and outreach) and one collective unmet need (suicide pre/postvention training and delivery) emerged.
Although Quebec provincial services have been developed and offered to suicide-bereaved survivors in the past decade, many dwindled over time and none has been applied systematically. Recommendations for different stakeholders (Ministry of Health and Social Services, coroners, NGOs, and representatives of suicide-bereaved survivors) outlined in this study could be an interesting first step to help develop a suicide pre/postvention strategy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Generic instruments are of interest in measuring global health-related quality of life (GHRQoL). Their applicability to all patients, regardless of their health profile, allows program comparisons of ...whether the patients share the same disease or not. In this setting, quality-adjusted life-year (QALY) instruments must consider GHRQoL to allow the best programs to emerge for more efficiency in health resource utilization. However, many differences may be perceived among the existing generic instruments relative to their composition, where dimensions related to physical aspects of health are generally depicted more often than dimensions related to mental or social aspects. The objective of this study was to develop a generic instrument that would be complete in its covered meta-dimensions and reflect, in a balanced way, the important aspects of GHRQoL. To this end, a Delphi procedure was held in four rounds, gathering 18 participants, including seven patients, six caregivers, and five citizens. The structure of the instrument derived from the Delphi procedure was submitted to psychometric tests using data from an online survey involving the general population of Quebec, Canada (
n
= 2,273). The resulting questionnaire, the 13-MD, showed satisfying psychometric properties. It comprises 33 items or dimensions, with five to seven levels each. The 13-MD reflects, in a balanced form, the essential aspects of GHRQoL by including five meta-dimensions for physical health, four meta-dimensions for mental health, three meta-dimensions for social health, and one meta-dimension for sexuality and intimacy. The next step will involve the development of a value set for the 13-MD to allow QALY calculation.
Purpose National initiatives, such as the UK Improving Access to Psychological Therapies program (IAPT), demonstrate the feasibility of conducting empirical mental health assessments on a large ...scale, and similar initiatives exist in other countries. However, there is a lack of international consensus on which outcome domains are most salient to monitor treatment progress and how they should be measured. The aim of this project was to propose (1) an essential set of outcome domains relevant across countries and cultures, (2) a set of easily accessible patientreported instruments, and (3) a psychometric approach to make scores from different instruments comparable. Methods Twenty-four experts, including ten health outcomes researchers, ten clinical experts from all continents, two patient advocates, and two ICHOM coordinators worked for seven months in a consensus building exercise to develop recommendations based on existing evidence using a structured consensus-driven modified Delphi technique. Results The group proposes to combine an assessment of potential outcome predictors at baseline (47 items: demographics, functional, clinical status, etc.), with repeated assessments of disease-specific symptoms during the treatment process (19 items: symptoms, side effects, etc.), and a comprehensive annual assessment of broader treatment outcomes (45 items: remission, absenteeism, etc.). Further, it is suggested reporting disease-specific symptoms for depression and anxiety on a standardized metric to increase comparability with other legacy instruments. All recommended instruments are provided online (www.ichom.org). Conclusion An international standard of health outcomes assessment has the potential to improve clinical decision making, enhance health care for the benefit of patients, and facilitate scientific knowledge.
Abstract
Background
Administrative data have several advantages over questionnaire and interview data to identify cases of depression: they are usually inexpensive, available for a long period of ...time and are less subject to recall bias and differential classification errors. However, the validity of administrative data in the correct identification of depression has not yet been studied in general populations. The present study aimed to 1) evaluate the sensitivity and specificity of administrative cases of depression using the validated Composite International Diagnostic Interview – Short Form (CIDI-SF) as reference standard and 2) compare the known-groups validity between administrative and CIDI-SF cases of depression.
Methods
The 5487 participants seen at the last wave (2015–2018) of the PROQ cohort had CIDI-SF questionnaire data linked to hospitalization and medical reimbursement data provided by the provincial universal healthcare provider and coded using the International Classification of Disease. We analyzed the sensitivity and specificity of several case definitions of depression from this administrative data. Their association with known predictors of depression was estimated using robust Poisson regression models.
Results
Administrative cases of depression showed high specificity (≥ 96%), low sensitivity (19–32%), and rather low agreement (Cohen’s kappa of 0.21–0.25) compared with the CIDI-SF. These results were consistent over strata of sex, age and education level and with varying case definitions. In known-groups analysis, the administrative cases of depression were comparable to that of CIDI-SF cases (RR for sex: 1.80 vs 2.03 respectively, age: 1.53 vs 1.40, education: 1.52 vs 1.28, psychological distress: 2.21 vs 2.65).
Conclusion
The results obtained in this large sample of a general population suggest that the dimensions of depression captured by administrative data and by the CIDI-SF are partially distinct. However, their known-groups validity in relation to risk factors for depression was similar to that of CIDI-SF cases. We suggest that neither of these data sources is superior to the other in the context of large epidemiological studies aiming to identify and quantify risk factors for depression.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Suicide is a complex, multidimensional event, and a significant challenge for prevention globally. Artificial intelligence (AI) and machine learning (ML) have emerged to harness large-scale datasets ...to enhance risk detection. In order to trust and act upon the predictions made with ML, more intuitive user interfaces must be validated. Thus, Interpretable AI is one of the crucial directions which could allow policy and decision makers to make reasonable and data-driven decisions that can ultimately lead to better mental health services planning and suicide prevention. This research aimed to develop sex-specific ML models for predicting the population risk of suicide and to interpret the models. Data were from the Quebec Integrated Chronic Disease Surveillance System (QICDSS), covering up to 98% of the population in the province of Quebec and containing data for over 20,000 suicides between 2002 and 2019. We employed a case-control study design. Individuals were considered cases if they were aged 15+ and had died from suicide between January 1st, 2002, and December 31st, 2019 (n = 18339). Controls were a random sample of 1% of the Quebec population aged 15+ of each year, who were alive on December 31st of each year, from 2002 to 2019 (n = 1,307,370). We included 103 features, including individual, programmatic, systemic, and community factors, measured up to five years prior to the suicide events. We trained and then validated the sex-specific predictive risk model using supervised ML algorithms, including Logistic Regression (LR), Random Forest (RF), Extreme Gradient Boosting (XGBoost) and Multilayer perceptron (MLP). We computed operating characteristics, including sensitivity, specificity, and Positive Predictive Value (PPV). We then generated receiver operating characteristic (ROC) curves to predict suicides and calibration measures. For interpretability, Shapley Additive Explanations (SHAP) was used with the global explanation to determine how much the input features contribute to the models' output and the largest absolute coefficients. The best sensitivity was 0.38 with logistic regression for males and 0.47 with MLP for females; the XGBoost Classifier with 0.25 for males and 0.19 for females had the best precision (PPV). This study demonstrated the useful potential of explainable AI models as tools for decision-making and population-level suicide prevention actions. The ML models included individual, programmatic, systemic, and community levels variables available routinely to decision makers and planners in a public managed care system. Caution shall be exercised in the interpretation of variables associated in a predictive model since they are not causal, and other designs are required to establish the value of individual treatments. The next steps are to produce an intuitive user interface for decision makers, planners and other stakeholders like clinicians or representatives of families and people with live experience of suicidal behaviors or death by suicide. For example, how variations in the quality of local area primary care programs for depression or substance use disorders or increased in regional mental health and addiction budgets would lower suicide rates.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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