The burden of mental disorders, substance use disorders and self-harm among young people in Europe, 1990-2019: Findings from the Global Burden of Disease Study 2019.

Background: Mental health is a public health issue for European young people, with great heterogeneity in resource allocation. Representative population-based studies are needed. The Global Burden of Disease (GBD) Study 2019 provides internationally comparable information on trends in the health status of populations and changes in the leading causes of disease burden over time. Methods: Prevalence, incidence, Years Lived with Disability (YLDs) and Years of Life Lost (YLLs) from mental disorders (MDs), substance use disorders (SUDs) and self-harm were estimated for young people aged 10-24 years in 31 European countries. Rates per 100,000 population, percentage changes in 1990-2019, 95% Uncertainty Intervals (UIs), and correlations with Sociodemographic Index (SDI), were estimated. Findings: In 2019, rates per 100,000 population were 16,983 (95% UI 12,823 - 21,630) for MDs, 3,891 (3,020 - 4,905) for SUDs, and 89·1 (63·8 - 123·1) for self-harm. In terms of disability, anxiety contributed to 647·3 (432-912·3) YLDs, while in terms of premature death, self-harm contributed to 319·6 (248·9-412·8) YLLs, per 100,000 population. Over the 30 years studied, YLDs increased in eating disorders (14·9%;9·4-20·1) and drug use disorders (16·9%;8·9-26·3), and decreased in idiopathic developmental intellectual disability (-29·1%;23·8-38·5). YLLs decreased in self-harm (-27·9%;38·3-18·7). Variations were found by sex, age-group and country. The burden of SUDs and self-harm was higher in countries with lower SDI, MDs were associated with SUDs. Interpretation: Mental health conditions represent an important burden among young people living in Europe. National policies should strengthen mental health, with a specific focus on young people. Funding: The Bill and Melinda Gates Foundation.

Cross-disorder and disorder-specific deficits in social functioning among schizophrenia and alzheimer's disease patients.

BACKGROUND: Social functioning is often impaired in schizophrenia (SZ) and Alzheimer's disease (AD). However, commonalities and differences in social dysfunction among these patient groups remain elusive. MATERIALS AND METHODS: Using data from the PRISM study, behavioral (all subscales and total score of the Social Functioning Scale) and affective (perceived social disability and loneliness) indicators of social functioning were measured in patients with SZ (N = 56), probable AD (N = 50) and age-matched healthy controls groups (HC, N = 29 and N = 28). We examined to what extent social functioning differed between disease and age-matched HC groups, as well as between patient groups. Furthermore, we examined how severity of disease and mood were correlated with social functioning, irrespective of diagnosis. RESULTS: As compared to HC, both behavioral and affective social functioning seemed impaired in SZ patients (Cohen's d's 0.81-1.69), whereas AD patients mainly showed impaired behavioral social function (Cohen's d's 0.65-1.14). While behavioral indices of social functioning were similar across patient groups, SZ patients reported more perceived social disability than AD patients (Cohen's d's 0.65). Across patient groups, positive mood, lower depression and anxiety levels were strong determinants of better social functioning (p's <0.001), even more so than severity of disease. CONCLUSIONS: AD and SZ patients both exhibit poor social functioning in comparison to age- and sex matched HC participants. Social dysfunction in SZ patients may be more severe than in AD patients, though this may be due to underreporting by AD patients. Across patients, social functioning appeared as more influenced by mood states than by severity of disease.

The medium-term consequences of a COVID-19 lockdown on lifestyle among Spanish older people with hypertension, pulmonary disease, cardiovascular disease, musculoskeletal disease, depression, and cancer.

OBJECTIVES: This study investigated the associations of chronic diseases with changes in lifestyle and health behaviours in older people following the coronavirus disease 2019 (COVID-19) lockdown in Spain and compared the differences in changes over time. METHODS: 1,092 participants (80.3±5.6 years; 66.5% female) from 2 Spanish cohorts were included. Telephone-based questionnaires were conducted to evaluate lifestyle and health risk behaviours at the end of lockdown and 7 months post-lockdown. Participants were classified as having physician-diagnosed chronic diseases based on self-reported data. Cox proportional models adjusted for major confounders were used. RESULTS: Compared to those without the corresponding chronic diseases, older people with hypertension were less likely to report increased alcohol consumption (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.55 to 0.99). Pulmonary diseases were associated with lower risks of increased sedentary time (HR, 0.58; 95% CI, 0.39 to 0.86) and worsened sleep quality (HR, 0.56; 95% CI, 0.36 to 0.87), while cardiovascular diseases were associated with a lower risk of decreased sedentary time (HR, 0.58; 95% CI, 0.38 to 0.88). Depression was linked to a higher likelihood of improved diet quality (HR, 1.53; 95% CI, 1.00 to 2.36). Cancer pacients were less likely to have worsened sleep quality (HR, 0.44; 95% CI, 0.22 to 0.89) but more likely to have reduced their frequency of social contact (HR, 2.05; 95% CI, 1.05 to 3.99). CONCLUSIONS: Older people with chronic diseases showed beneficial changes in lifestyle and health risk behaviours after the COVID-19 lockdown. In particular, older people with hypertension, pulmonary disease, and cancer tended to make beneficial lifestyle and health behaviour changes. However, older people with cardiovascular disease and depression engaged in more health risk behaviours.

The effect of loneliness and social support on the course of major depressive disorder among adults aged 50 years and older: A longitudinal study.

BACKGROUND: Previous research indicates that social support, loneliness, and major depressive disorder (MDD) are interrelated. Little is known about the potential pathways among these factors, in particular in the case of adults aged 50 years and older and suffering from MDD. The objective was to investigate whether loneliness mediates the association between low social support and recurrent episodes of MDD. METHODS: We used data from a cohort of the Spanish general population interviewed at three time-points over a 7-year period. We included 404 individuals aged 50+ suffering from MDD in the baseline assessment. A 12-month major depressive episode was assessed with the Composite International Diagnostic Interview (CIDI) at each interview. The University of California, Los Angeles Loneliness Scale was used to measure loneliness, whereas social support was assessed through the Oslo Social Support Scale. We tested cross-lagged and autoregressive longitudinal associations using structural equation modeling. RESULTS: We identified two significant longitudinal mediation patterns: lower social support predicted higher subsequent levels of loneliness (Coef. = -0.16; p < .05), which in turn predicted an increase in MDD recurrence (Coef. = 0.05; p < .05). CONCLUSIONS: Interventions focused on promoting social support among older adults suffering from MDD may decrease feelings of loneliness and prevent recurrent episodes of MDD.

A global field study of the international classification of diseases (ICD-11) mood disorders clinical descriptions and diagnostic guidelines.

BACKGROUND: We report results of an internet-based field study evaluating the diagnostic guidelines for ICD-11 mood disorders. Accuracy of clinicians' diagnostic judgments applying draft ICD-11 as compared to the ICD-10 guidelines to standardized case vignettes was assessed as well as perceived clinical utility. METHODS: 1357 clinician members of the World Health Organization's Global Clinical Practice Network completed the study in English, Spanish, Japanese or Russian. Participants were randomly assigned to apply ICD-11 or ICD-10 guidelines to one of eleven pairs of case vignettes. RESULTS: Clinicians using the ICD-11 and ICD-10 guidelines achieved similar levels of accuracy in diagnosing mood disorders depicted in vignettes. Those using the ICD-11 were more accurate in identifying depressive episode in recurrent depressive disorder. There were no statistically significant differences detected across classifications in the accuracy of identifying dysthymic or cyclothymic disorder. Circumscribed problems with the proposed ICD-11 guidelines were identified including difficulties differentiating bipolar type I from bipolar type II disorder and applying revised severity ratings to depressive episodes. Clinical utility of ICD-11 bipolar disorders was found to be significantly lower than for ICD-10 equivalent categories. LIMITATIONS: Standardized case vignettes were manipulated to evaluate specific changes. The degree of accuracy of clinicians' diagnostic judgments may not reflect clinical decision-making with patients. CONCLUSIONS: Alignment of the ICD-11 with current research appears to have been achieved without sacrificing diagnostic accuracy or clinical utility though specific training may be necessary as ICD-11 is implemented worldwide. Areas in which the ICD-11 guidelines did not perform as intended resulted in further revisions.

Genetic underpinnings of sociability in the general population.

Levels of sociability are continuously distributed in the general population, and decreased sociability represents an early manifestation of several brain disorders. Here, we investigated the genetic underpinnings of sociability in the population. We performed a genome-wide association study (GWAS) of a sociability score based on four social functioning-related self-report questions from 342,461 adults in the UK Biobank. Subsequently we performed gene-wide and functional follow-up analyses. Robustness analyses were performed in the form of GWAS split-half validation analyses, as well as analyses excluding neuropsychiatric cases. Using genetic correlation analyses as well as polygenic risk score analyses we investigated genetic links of our sociability score to brain disorders and social behavior outcomes. Individuals with autism spectrum disorders, bipolar disorder, depression, and schizophrenia had a lower sociability score. The score was significantly heritable (SNP h2 of 6%). We identified 18 independent loci and 56 gene-wide significant genes, including genes like ARNTL, DRD2, and ELAVL2. Many associated variants are thought to have deleterious effects on gene products and our results were robust. The sociability score showed negative genetic correlations with autism spectrum, disorders, depression, schizophrenia, and two sociability-related traits-loneliness and social anxiety-but not with bipolar disorder or Alzheimer's disease. Polygenic risk scores of our sociability GWAS were associated with social behavior outcomes within individuals with bipolar disorder and with major depressive disorder. Variation in population sociability scores has a genetic component, which is relevant to several psychiatric disorders. Our findings provide clues towards biological pathways underlying sociability.

Effects of transient and chronic loneliness on major depression in older adults: A longitudinal study.

OBJECTIVES: The number of older adults is rapidly rising globally. Loneliness is a common problem that can deteriorate health. The aims of this work were to identify different types of loneliness (transient and chronic) and to assess their association with depression over time. METHODS: A nationally representative sample from the Spanish population comprising 1190 individuals aged 50+ years was interviewed on three evaluations over a 7-year period. The UCLA Loneliness Scale was used to measure loneliness. While chronic loneliness was defined as the presence of loneliness across all three waves, transient loneliness expressed the presence of loneliness in one wave only. A 12-month major depressive episode was assessed at each interview. After confirming the cross-sectional relationship, a multilevel mixed-effects model was used to examine the association between loneliness and depression. RESULTS: Almost a quarter of individuals felt lonely and one out of 10 presented depression at baseline. Of the sample, 22.78% showed transient loneliness, while 6.72% presented the chronic type. People experiencing chronic loneliness were at a higher risk of presenting major depression (OR = 6.11; 95% CI = 2.62, 14.22) than those presenting transient loneliness (OR = 2.22; 95% CI = 1.19, 4.14). This association varied over time and was stronger at the first follow-up than at the second one. CONCLUSIONS: Focusing on loneliness prevention could reduce the risk of depression. Chronic loneliness is a public health problem that should be addressed through the full participation of the political, social, and medical sectors.

Diagnostic classification of irritability and oppositionality in youth: a global field study comparing ICD-11 with ICD-10 and DSM-5.

BACKGROUND: Severe irritability has become an important topic in child and adolescent mental health. Based on the available evidence and on public health considerations, WHO classified chronic irritability within oppositional defiant disorder (ODD) in ICD-11, a solution markedly different from DSM-5's (i.e. the new childhood mood diagnosis, disruptive mood dysregulation disorder [DMDD]) and from ICD-10's (i.e. ODD as one of several conduct disorders without attention to irritability). In this study, we tested the accuracy with which a global, multilingual, multidisciplinary sample of clinicians were able to use the ICD-11 classification of chronic irritability and oppositionality as compared to the ICD-10 and DSM-5 approaches. METHODS: Clinicians (N = 196) from 48 countries participated in an Internet-based field study in English, Spanish, or Japanese and were randomized to review and use one of the three diagnostic systems. Through experimental manipulation of validated clinical vignettes, we evaluated how well clinicians in each condition could identify chronic irritability versus nonirritable oppositionality, episodic bipolar disorder, dysthymic depression, and normative irritability. RESULTS: Compared to ICD-10 and DSM-5, ICD-11 led to more accurate identification of severe irritability and better differentiation from boundary presentations. Participants using DSM-5 largely failed to apply the DMDD diagnosis when it was appropriate, and they more often applied psychopathological diagnoses to developmentally normative irritability. CONCLUSIONS: The formulation of irritability and oppositionality put forth in ICD-11 shows evidence of clinical utility, supporting accurate diagnosis. Global mental health clinicians can readily identify ODD both with and without chronic irritability.

Pain rates in general population for the period 1991-2015 and 10-years prediction: results from a multi-continent age-period-cohort analysis.

BACKGROUND: Pain is a common symptom, often associated with neurological and musculoskeletal conditions, and experienced especially by females and by older people. The aims of this study are to evaluate the temporal variations of pain rates among general populations for the period 1991-2015 and to project 10-year pain rates. METHODS: We used the harmonized dataset of ATHLOS project, which included 660,028 valid observations in the period 1990-2015 and we applied Bayesian age-period-cohort modeling to perform projections up to 2025. The harmonized Pain variable covers the content "self-reported pain experienced at the time of the interview", with a dichotomous (yes or no) modality. RESULTS: Pain rates were higher among females, older subjects, in recent periods, and among observations referred to cohorts of subjects born between the 20s and the 60s. The 10-year projections indicate a noteworthy increase in pain rates in both genders and particularly among subjects aged 66 or over, for whom a 10-20% increase in pain rate is foreseen; among females only, a 10-15% increase in pain rates is foreseen for those aged 36-50. CONCLUSIONS: Projected increase in pain rates will require specific interventions by health and welfare systems, as pain is responsible for limited quality of subjective well-being, reduced employment rates and hampered work performance. Worksite and lifestyle interventions will therefore be needed to limit the impact of projected higher pain rates.

Cross-cultural comparison of symptom networks in late-life major depressive disorder: Yoruba Africans and the Spanish Population.

BACKGROUND: The concept of European psychologisation of depression versus somatisation in non-European populations has been the basis of several studies of cultural psychopathology in the general population. Little is currently known about cross-cultural differences and similarities in late-life depression symptom reporting. We cross-culturally compared symptom reporting in the context of Major Depressive Disorder (MDD) among community-dwelling older adults from Spain and Nigeria. METHODS: We relied on data from two household multistage probability samples comprising 3,715 persons aged 65 years or older in the Spanish and Nigerian populations. All participants underwent assessments for MDD using the World Mental Health Survey version of the Composite International Diagnostic Interview. Cross-cultural comparison of broad somatic and psychological categories as well as relationship and influence of individual symptoms were analysed using the Symptom Network Analysis approach. RESULTS: Current MDD was diagnosed in 232 and 195 older persons from Spain and Nigeria, respectively. The symptom network of the two samples were invariant in terms of global strength, S(GSPAIN , GNIGERIA ) = 7.56, P = .06, with psychological and somatic symptoms demonstrating centrality in both countries. However, country-specific relationships and influence of individual symptoms were found in the network structure of both samples, M(GSPAIN , GNIGERIA ) = 2.95, P < .01. CONCLUSION: Broad somatic and psychological symptoms categories contributed to the structural network of older Africans and their peers from the Spanish population. Variations in the relationship and influence of individual symptoms suggests that the functional and "communicative" role of individual symptoms may be differentiated by context specific imperatives. J Am Geriatr Soc 68:-, 2020.

Predictors of pain in general ageing populations: results from a multi-country analysis based on ATHLOS harmonized database.

BACKGROUND: Pain is a common symptom, often associated with neurological and musculoskeletal conditions, and experienced especially by females and by older people, and with increasing trends in general populations. Different risk factors for pain have been identified, but generally from studies with limited samples and a limited number of candidate predictors. The aim of this study is to evaluate the predictors of pain from a large set of variables and respondents. METHODS: We used part of the harmonized dataset of ATHLOS project, selecting studies and waves with a longitudinal course, and in which pain was absent at baseline and with no missing at follow-up. Predictors were selected based on missing distribution and univariable association with pain, and were selected from the following domains: Socio-demographic and economic characteristics, Lifestyle and health behaviours, Health status and functional limitations, Diseases, Physical measures, Cognition, personality and other psychological measures, and Social environment. Hierarchical logistic regression models were then applied to identify significant predictors. RESULTS: A total of 13,545 subjects were included of whom 5348 (39.5%) developed pain between baseline and the average 5.2 years' follow-up. Baseline risk factors for pain were female gender (OR 1.34), engaging in vigorous exercise (OR 2.51), being obese (OR 1.36) and suffering from the loss of a close person (OR 1.88) whereas follow-up risk factors were low energy levels/fatigue (1.93), difficulties with walking (1.69), self-rated health referred as poor (OR 2.20) or average to moderate (OR 1.57) and presence of sleep problems (1.80). CONCLUSIONS: Our results showed that 39.5% of respondents developed pain over a five-year follow-up period, that there are proximal and distal risk factors for pain, and that part of them are directly modifiable. Actions aimed at improving sleep, reducing weight among obese people and treating fatigue would positively impact on pain onset, and avoiding vigorous exercise should be advised to people aged 60 or over, in particular if female or obese.

Effective methods for knowledge transfer to strengthen mental health systems in low- and middle-income countries.

BACKGROUND: The Emerald project's focus is on how to strengthen mental health systems in six low- and middle-income countries (LMICs) (Ethiopia, India, Nepal, Nigeria, South Africa and Uganda). This was done by generating evidence and capacity to enhance health system performance in delivering mental healthcare.A common problem in scaling-up interventions and strengthening mental health programmes in LMICs is how to transfer research evidence, such as the data collected in the Emerald project, into practice. AIMS: To describe how core elements of Emerald were implemented and aligned with the ultimate goal of strengthening mental health systems, as well as their short-term impact on practices, policies and programmes in the six partner countries. METHOD: We focused on the involvement of policy planners, managers, patients and carers. RESULTS: Over 5 years of collaboration, the Emerald consortium has provided evidence and tools for the improvement of mental healthcare in the six LMICs involved in the project. We found that the knowledge transfer efforts had an impact on mental health service delivery and policy planning at the sites and countries involved in the project. CONCLUSIONS: This approach may be valid beyond the mental health context, and may be effective for any initiative that aims at implementing evidence-based health policies for health system strengthening.

Strengthening mental health systems in low- and middle-income countries: recommendations from the Emerald programme.

BACKGROUND: There is a large treatment gap for mental, neurological or substance use (MNS) disorders. The 'Emerging mental health systems in low- and middle-income countries (LMICs)' (Emerald) research programme attempted to identify strategies to work towards reducing this gap through the strengthening of mental health systems. AIMS: To provide a set of proposed recommendations for mental health system strengthening in LMICs. METHOD: The Emerald programme was implemented in six LMICs in Africa and Asia (Ethiopia, India, Nepal, Nigeria, South Africa and Uganda) over a 5-year period (2012-2017), and aimed to improve mental health outcomes in the six countries by building capacity and generating evidence to enhance health system strengthening. RESULTS: The proposed recommendations align closely with the World Health Organization's key health system strengthening 'building blocks' of governance, financing, human resource development, service provision and information systems; knowledge transfer is included as an additional cross-cutting component. Specific recommendations are made in the paper for each of these building blocks based on the body of data that were collected and analysed during Emerald. CONCLUSIONS: These recommendations are relevant not only to the six countries in which their evidential basis was generated, but to other LMICs as well; they may also be generalisable to other non-communicable diseases beyond MNS disorders. DECLARATION OF INTEREST: None.

Innovations and changes in the ICD-11 classification of mental, behavioural and neurodevelopmental disorders.

Following approval of the ICD-11 by the World Health Assembly in May 2019, World Health Organization (WHO) member states will transition from the ICD-10 to the ICD-11, with reporting of health statistics based on the new system to begin on January 1, 2022. The WHO Department of Mental Health and Substance Abuse will publish Clinical Descriptions and Diagnostic Guidelines (CDDG) for ICD-11 Mental, Behavioural and Neurodevelopmental Disorders following ICD-11's approval. The development of the ICD-11 CDDG over the past decade, based on the principles of clinical utility and global applicability, has been the most broadly international, multilingual, multidisciplinary and participative revision process ever implemented for a classification of mental disorders. Innovations in the ICD-11 include the provision of consistent and systematically characterized information, the adoption of a lifespan approach, and culture-related guidance for each disorder. Dimensional approaches have been incorporated into the classification, particularly for personality disorders and primary psychotic disorders, in ways that are consistent with current evidence, are more compatible with recovery-based approaches, eliminate artificial comorbidity, and more effectively capture changes over time. Here we describe major changes to the structure of the ICD-11 classification of mental disorders as compared to the ICD-10, and the development of two new ICD-11 chapters relevant to mental health practice. We illustrate a set of new categories that have been added to the ICD-11 and present the rationale for their inclusion. Finally, we provide a description of the important changes that have been made in each ICD-11 disorder grouping. This information is intended to be useful for both clinicians and researchers in orienting themselves to the ICD-11 and in preparing for implementation in their own professional contexts.

Working definitions, subjective and objective assessments and experimental paradigms in a study exploring social withdrawal in schizophrenia and Alzheimer's disease.

Social withdrawal is one of the first and common signs of early social dysfunction in a number of important neuropsychiatric disorders, likely because of the enormous amount and complexity of brain processes required to initiate and maintain social relationships (Adolphs, 2009). The Psychiatric Ratings using Intermediate Stratified Markers (PRISM) project focusses on the shared and unique neurobiological basis of social withdrawal in schizophrenia, Alzheimer and depression. In this paper, we discuss the working definition of social withdrawal for this study and the selection of objective and subjective rating scales to assess social withdrawal chosen or adapted for this project. We also discuss the MRI and EEG paradigms selected to study the systems and neural circuitry thought to underlie social functioning and more particularly to be involved in social withdrawal in humans, such as the social perception and the social affiliation networks. A number of behavioral paradigms were selected to assess complementary aspects of social cognition. Also, a digital phenotyping method (a smartphone application) was chosen to obtain real-life data.

Understanding the direct and indirect costs of a first episode of psychosis program: Insights from PAFIP of Cantabria, Spain, during the first year of intervention.

AIM: Early intervention psychiatric services for patients with psychosis aim to limit the most damaging outcomes and reduce the patient's risk of social drift, decreasing illness severity and thus containing healthcare costs. There is a scarcity of studies that focus on first-episode psychosis (FEP), and those few that have been published only looked at direct health costs, but not at indirect costs, which make up the bulk of the budget. Our study aims to explore the short-term (1-year follow-up) economic cost of a FEP Program, including both direct and indirect costs. METHODS: Data were collected retrospectively from the clinical records of 157 patients included in the Programa Atención Fases Iniciales de Psicosis, from Marqués de Valdecilla University Hospital, Santander. Our data collection sheet collated data from direct and indirect costs associated with the illness. Data were also extracted from the Cantabria Health Service Records. STATA 15.0 was used for statistical analysis. RESULTS: On average, the total costs during the first year were €48 353.51 per patient, with direct healthcare costs being €13 729.47 (28.39%), direct non-medical costs €108.6 (0.22%), and indirect costs €34 515.44 (71.39%). We found that hospitalization costs were higher in males (p = 0.081) and in cannabis users (p = 0.032). The number of relapses increased both, hospitalization and treatment costs (r = 0.40 p = 0.000; r = 0.24 p = 0.067, respectively). CONCLUSIONS: Intensive Early Intervention in Psychosis Services may result in cost savings by decreasing hospitalization, premature mortality, disability, unemployment, and legal problems; however, the first year after diagnosis would represent the one with the highest costs.

Research Recommendations for Improving Measurement of Treatment Effectiveness in Depression.

Background: Despite the steadily escalating psychological and economic burden of depression, there is a lack of evidence for the effectiveness of available interventions on functioning areas beyond symptomatology. Therefore, the main objective of this study was to give an insight into the current measurement of treatment effectiveness in depression and to provide recommendations for its improvement. Materials and Methods: The study was based on a multi-informant approach, comparing data from a systematic literature review, an expert survey with representatives from clinical practice (130), and qualitative interviews with patients (11) experiencing depression. Results: Current literature places emphasis on symptomatic outcomes and neglects other domains of functioning, whereas clinicians and depressed patients highlight the importance of both. Interpersonal relationships, recreation and daily activities, communication, social participation, work difficulties were identified as being crucial for recovery. Personal factors, neglected by the literature, such as self-efficacy were introduced by experts and patients. Furthermore, clinicians and patients identified a number of differences regarding the areas improved by psychotherapeutic or pharmacological interventions that were not addressed by the pertinent literature. Conclusion: Creation of a new cross-nationally applicable measure of psychosocial functioning, broader remission criteria, report of domain-specific information, and a personalized approach in treatment decision-making are the first crucial steps needed for the improvement of the measurement of treatment effectiveness in depression. A better measurement will facilitate the clinical decision making and answer the escalating burden of depression.