The assessment of transdiagnostic dimensions of emotional disorders: Validation of the Multidimensional Emotional Disorders Inventory (MEDI) in adolescents with subthreshold anxiety and depression.

BACKGROUND: The transdiagnostic approach to psychopathology has emerged as an alternative to traditional taxonomic approaches. The Multidimensional Emotional Disorders Inventory (MEDI) is a specifically designed self-report to measure the transdiagnostic dimensions proposed by Brown and Barlow (2009). This study aims to analyse the psychometric properties of the MEDI scores in adolescents with subthreshold anxiety and depression. METHOD: The sample consisted of a total of 476 students. The mean age was 13.77 years (SD = 1.43) (range 10 to 18 years), 73.9 % were females. Several questionnaires assessing positive affect, negative affect, mental health difficulties, and quality of life were used. RESULTS: The original 9-factor structure of the MEDI was confirmed with good fit indices. Satisfactory levels of internal consistency were observed in most of the MEDI scores using McDonald's Omega, ranging from 0.58 to 0.87. The MEDI dimensions were associated with psychopathology, positive affect, negative affect, and quality of life. LIMITATIONS: Reliance on self-reported data, a cross-sectional design limiting temporal assessment, and a 73.9 % female gender imbalance. CONCLUSION: The MEDI scores showed adequate psychometric properties among adolescents with subclinical emotional symptoms. The results found might have potential clinical implications for conceptualization, assessment, intervention, and prevention of emotional disorders at both clinical and research levels.

Social Media Use as a Predictor of Positive and Negative Affect: An Ecological Momentary Assessment Study of Adolescents with and without Clinical Depression.

Social media use is common in adolescents, with implications for psychosocial development and the emergence of depression. Yet, little is known about the time-linked connections between social media use and adolescents' affective experiences and how they may differ between depressed and non-depressed youth. We leveraged ecological momentary assessment in adolescents oversampled for current depression to examine (1) associations between social media use and concurrent and later positive and negative affect and (2) sex and presence of a depressive disorder as moderators of these associations. Adolescents aged 14-17 with (n = 48) and without (n = 97) clinical depression, as indicated via clinical interview, reported momentary social media use and positive and negative affect seven times per day for one week. Multilevel modeling indicated that social media use was associated with reduced positive affect both concurrently and at the next assessment. Further, among clinically depressed youth only, social media use was associated with reduced negative affect at the next assessment. Results suggest that social media use may reduce both positive and negative affect, highlighting the nuanced relation between adolescent social media use and emotional health and laying the groundwork for future research to address several open questions.

[Intended utilization of health care services in cases of mental illnesses with varying urgency]. / Intendierte Inanspruchnahme von Versorgungsangeboten bei psychischen Erkrankungen mit unterschiedlicher Dringlichkeit.

OBJECTIVE: To investigate variations in intended utilization in cases of an acute psychotic episode, an alcohol related or depressive disorder depending on different case characteristics. METHODS: A telephone survey with case vignettes was conducted (N=1,200). Vignettes varied in terms of urgency of symptoms, daytime, sex of the afflicted person and age/mental disorder. The respondents were asked to indicate whom they would contact first in the described case. RESULTS: Outpatient physicians were named most frequently as the first point of contact (61.1%) while only 6.5% of the respondents named emergency medicine including the medical on call service (8.1% in high urgency cases, i. e. emergencies that did not tolerate any delay). Intended utilization varied by urgency and age/mental illness. CONCLUSION: More Information about the need to seek medical help immediately in cases of mental illnesses with high urgency should be provided.

Determinants of patient-reported outcome trajectories and symptomatic recovery in Improving Access to Psychological Therapies (IAPT) services.

BACKGROUND: Despite evidence for the general effectiveness of psychological therapies, there exists substantial heterogeneity in patient outcomes. We aimed to identify factors associated with baseline severity of depression and anxiety symptoms, rate of symptomatic change over the course of therapy, and symptomatic recovery in a primary mental health care setting. METHODS: Using data from a service evaluation involving 35 527 patients in England's psychological and wellbeing [Improving Access to Psychological Therapies (IAPT)] services, we applied latent growth models to explore which routinely-collected sociodemographic, clinical, and therapeutic variables were associated with baseline symptom severity and rate of symptomatic change. We used a multilevel logit model to determine variables associated with symptomatic recovery. RESULTS: Being female, younger, more functionally impaired, and more socioeconomically disadvantaged was associated with higher baseline severity of both depression and anxiety symptoms. Being older, less functionally impaired, and having more severe baseline symptomatology was associated with more rapid improvement of both depression and anxiety symptoms (male gender and greater socioeconomic disadvantage were further associated with rate of change for depression only). Therapy intensity and appointment frequency seemed to have no correlation with rate of symptomatic improvement. Patients with lower baseline symptom severity, less functional impairment, and older age had a greater likelihood of achieving symptomatic recovery (as defined by IAPT criteria). CONCLUSIONS: We must continue to investigate how best to tailor psychotherapeutic interventions to fit patients' needs. Patients who begin therapy with more severe depression and/or anxiety symptoms and poorer functioning merit special attention, as these characteristics may negatively impact recovery.

Primary care-based screening and management of depression amongst heavy drinking patients: Interim secondary outcomes of a three-country quasi-experimental study in Latin America.

INTRODUCTION: Implementation of evidence-based care for heavy drinking and depression remains low in global health systems. We tested the impact of providing community support, training, and clinical packages of varied intensity on depression screening and management for heavy drinking patients in Latin American primary healthcare. MATERIALS AND METHODS: Quasi-experimental study involving 58 primary healthcare units in Colombia, Mexico and Peru randomized to receive: (1) usual care (control); (2) training using a brief clinical package; (3) community support plus training using a brief clinical package; (4) community support plus training using a standard clinical package. Outcomes were proportion of: (1) heavy drinking patients screened for depression; (2) screen-positive patients receiving appropriate support; (3) all consulting patients screened for depression, irrespective of drinking status. RESULTS: 550/615 identified heavy drinkers were screened for depression (89.4%). 147/230 patients screening positive for depression received appropriate support (64%). Amongst identified heavy drinkers, adjusting for country, sex, age and provider profession, provision of community support and training had no impact on depression activity rates. Intensity of clinical package also did not affect delivery rates, with comparable performance for brief and standard versions. However, amongst all consulting patients, training providers resulted in significantly higher rates of alcohol measurement and in turn higher depression screening rates; 2.7 times higher compared to those not trained. CONCLUSIONS: Training using a brief clinical package increased depression screening rates in Latin American primary healthcare. It is not possible to determine the effectiveness of community support on depression activity rates due to the impact of COVID-19.

Impact of Psychological Comorbidity on the Prognosis of Irritable Bowel Syndrome.

INTRODUCTION: Psychological comorbidities are associated with irritable bowel syndrome (IBS), but little is known about their cumulative effect on its prognosis. We examined this issue in a longitudinal 12-month follow-up study. METHODS: We collected complete demographic, symptom, and psychological comorbidity data (anxiety, depression, somatic symptom disorder, perceived stress, and gastrointestinal symptom-specific anxiety) at baseline from 807 adults who met Rome IV criteria for IBS. At 12 months, we collected data regarding IBS symptom severity and impact, consultation behavior, and treatments commenced from 452 individuals successfully followed up. We examined the cumulative effects of psychological comorbidities at baseline on subsequent IBS disease behavior. RESULTS: At baseline, among the 807 participants, 177 (21.9%) had 1, 139 (17.2%) 2, 103 (12.8%) 3, 89 (11.0%) 4, and 54 (6.7%) 5 psychological comorbidities. IBS symptom severity at baseline increased significantly with the number of psychological comorbidities (72.2% of those with 5 psychological comorbidities reported severe symptoms, vs 29.1% of those with none, P < 0.001). Among 452 (56.0%) participants followed up at 12 months, those with a higher number of psychological comorbidities at baseline were significantly more likely to have seen a gastroenterologist (33.3% of those with 5 psychological comorbidities, vs 21.4% of those with none, P = 0.001), cycle through more treatments (P < 0.0001), to report more severe IBS symptoms (66.7% with 5, vs 24.4% with none, P < 0.001) and continuous abdominal pain (22.1% with none, vs 61.9% with 5, P < 0.001), and to report that symptoms impacted on daily activities ≥50% of the time (90.5% with 5, vs 41.2% with none, P < 0.001). DISCUSSION: The prognosis of individuals with Rome IV-defined IBS worsens according to incremental increases in psychological comorbidity. This has important clinical and research implications.

A longitudinal assessment of depression and anxiety in the Republic of Ireland before and during the COVID-19 pandemic.

Few studies have examined changes in mental health before and after the outbreak of COVID-19. We examined changes in the prevalence of major depression and generalized anxiety disorder (GAD) between February 2019 and March-April 2020; if there were changes in major depression and GAD during six weeks of nationwide lockdown; and we identified factors that predicted major depression and GAD across the six-week lockdown period. Nationally representative samples of Irish adults were gathered using identical methods in February 2019 (N = 1020) and March-April 2020 (N = 1041). The latter was reassessed six weeks later. Significantly more people screened positive for depression in February 2019 (29.8% 95% CI = 27.0, 32.6) than in March-April 2020 (22.8% 95% CI = 20.2, 25.3), and there was no change in GAD. There were no significant changes in depression and GAD during the lockdown. Major depression was predicted by younger age, non-city dwelling, lower resilience, higher loneliness, and higher somatic problems. GAD was predicted by a broader set of variables including several COVID-19 specific variables. These findings indicate that the prevalence of major depression and GAD did not increase as a result of, or during the early phase of the COVID-19 pandemic in Ireland.

Affect fluctuations examined with ecological momentary assessment in patients with current or remitted depression and anxiety disorders.

BACKGROUND: There is increasing interest in day-to-day affect fluctuations of patients with depressive and anxiety disorders. Few studies have compared repeated assessments of positive affect (PA) and negative affect (NA) across diagnostic groups, and fluctuation patterns were not uniformly defined. The aim of this study is to compare affect fluctuations in patients with a current episode of depressive or anxiety disorder, in remitted patients and in controls, using affect instability as a core concept but also describing other measures of variability and adjusting for possible confounders. METHODS: Ecological momentary assessment (EMA) data were obtained from 365 participants of the Netherlands Study of Depression and Anxiety with current (n = 95), remitted (n = 178) or no (n = 92) DSM-IV defined depression/anxiety disorder. For 2 weeks, five times per day, participants filled-out items on PA and NA. Affect instability was calculated as the root mean square of successive differences (RMSSD). Tests on group differences in RMSSD, within-person variance, and autocorrelation were performed, controlling for mean affect levels. RESULTS: Current depression/anxiety patients had the highest affect instability in both PA and NA, followed by remitters and then controls. Instability differences between groups remained significant when controlling for mean affect levels, but differences between current and remitted were no longer significant. CONCLUSIONS: Patients with a current disorder have higher instability of NA and PA than remitted patients and controls. Especially with regard to NA, this could be interpreted as patients with a current disorder being more sensitive to internal and external stressors and having suboptimal affect regulation.

Mental illness is associated with increased risk of suicidal ideation among cancer surgical patients.

BACKGROUND: Mental illness and depression can be associated with increased risk of suicidal ideation (SI). We sought to determine the association between mental illness and SI among cancer surgical patients. METHODS: Medicare beneficiaries who underwent resection of lung, esophageal, pancreatic, colon, or rectal cancer were analyzed. Patients were categorized as no mental illness, anxiety and/or depression disorders or bipolar/schizophrenic disorders. RESULTS: Among 211,092 Medicare beneficiaries who underwent surgery for cancer, the rate of suicidal ideation was 270/100,000 patients. Antecedent mental health diagnosis resulted in a marked increased SI. On multivariable analysis, patients with anxiety alone (OR 1.49, 95%CI 1.04-2.14), depression alone (OR 2.60, 95%CI 1.92-3.38), anxiety + depression (OR 4.50, 95%CI 3.48-5.86), and bipolar/schizophrenia (OR 7.30, 95%CI 5.27-10.30) had increased odds of SI. CONCLUSIONS: Roughly 1 in 370 Medicare beneficiaries with cancer who underwent a wide range of surgical procedures had SI. An antecedent mental health diagnosis was a strong risk factor for SI.

The burden of loneliness: Implications of the social determinants of health during COVID-19.

This study sought to examine if mental health issues, namely depression and anxiety symptoms, and loneliness were experienced differently according to various demographic groups during the COVID-19 pandemic (i.e., a societal stressor). An online survey, comprising demographic questions and questionnaires on depression, anxiety and loneliness symptoms, was distributed in Canada during the height of social distancing restrictions during the COVID-19 pandemic. Respondents (N=661) from lower income households experienced greater anxiety, depression and loneliness. Specifically, loneliness was greater in those with an annual income <$50,000/yr versus higher income brackets. Younger females (18-29yr) displayed greater anxiety, depressive symptoms and loneliness than their male counterparts; this difference did not exist among the other age groups (30-64yr, >65yr). Moreover, loneliness scores increased with increasing depression and anxiety symptom severity category. The relationship between loneliness and depression symptoms was moderated by gender, such that females experienced higher depressive symptoms when encountering greater loneliness. These data identify younger females, individuals with lower income, and those living alone as experiencing greater loneliness and mental health challenges during the height of the pandemic in Canada. We highlight the strong relationship between loneliness, depression and anxiety, and emphasize increased vulnerability among certain cohorts.

Can Trans-Syndromal Prototypes ("Types") Improve Depiction of Complex Psychiatric Cases?: An Alternative Way to Consider Concordant Comorbid Psychiatric Disorders and Their Contexts as Coherent Units for Research, Assessment, and Treatment Planning.

BACKGROUND AND AIMS: In many psychiatric settings, patients with complex cases are the rule rather than the exception. These cases are characterized by multidiagnostic conditions, often complicated with distressed social contexts, for which few if any evidence-based practice guidelines exist. The aim of this hypothesis-generating article is to consider whether and how these cases might comprise trans-syndromal prototypes ("types"), coherent units that could serve as the basis for further study, assessment, and treatment planning. METHODS: For context, psychiatric and medical visit diagnoses and problem lists noted among principle visit diagnoses and "snapshot" portions of electronic medical records were tabulated for 293 psychiatric outpatients seen consecutively during a 1-week period at a university psychiatric clinic. By considering resulting comorbidity patterns in these records from the perspectives of clinicians caring for these patients, several commonly encountered diagnostic-problem sets emerged as candidate types. RESULTS: Of 293 patients, only 18% had a single diagnosis, 43% had two, 29% had three, and 7% had four or more noted. Occurring in assorted combinations, specific diagnostic areas noted included depressive disorders (68%, the large majority major depressive disorder recurrent), anxiety disorders (60%, the large majority generalized anxiety disorder, with or without panic disorder and/or social anxiety disorder), posttraumatic stress disorder (22%), attention deficit hyperactivity disorder (ADHD) (17%), alcohol and substance abuse disorders (16%), personality disorders (11%), and bipolar disorders (18%). Several illustrative candidate types emerging from this population are described including major anxious depressive disorder, anxiety disorder secondary to ADHD, complex emotional instability disorder, multi-impulsive eating disorder, substance-dependent impoverished personality disorder, painful mood disorder, and complex personal and cultural trauma disorder. Other potential types are identified as well. CONCLUSIONS AND IMPLICATIONS: The types described here are but a small selection, because other settings including community mental health centers, private practices, public and private hospitals, and forensic facilities see a variety of other types as well. The study of types might provide important findings about pathogenesis, course, outcome, and treatment to augment information obtained from examination of individual diagnostic components.

Depression and Impulsivity Self-Assessment Tools to Identify Dopamine Agonist Side Effects in Patients With Pituitary Adenomas.

Background: Dopamine agonists (DA) are the first line therapy for prolactinoma and symptomatic hyperprolactinemia; use as an adjuvant treatment for acromegaly and Cushing's disease is rare. Some patients develop de novo psychiatric symptoms or have exacerbation of pre-existing conditions during DA therapy. A practical, clinically sensitive depression and impulse control disorders (ICD; particularly hypersexuality and gambling disorders) detection tool is important for identifying at risk patients. The Barratt Impulsivity Scale (BIS-11) and the 9-item Patient Health Questionnaire (PHQ-9) are sensitive in identifying impulsivity and depression. Objective: Detail use of the BIS-11 and PHQ-9 as screening tools for depression and ICD in patients with pituitary disease at a high-volume academic pituitary center. Methods: DA-treated and naïve patients with pituitary disease were included. Patients with a known history of depression or psychiatric disorder were excluded. PHQ-9 standardized interpretation criteria were utilized to classify depression severity. For BIS-11, threshold was established based on previous studies. Statistical analysis was with SPSS version 25. Results: Seventy-six DA-treated and 27 naïve patients were included. Moderate and moderately severe depression were more prevalent in DA-treated patients; severe depression only found in DA-treated patients. A normal BIS-11 score was noted in 76.69%; higher scores (not significant) were noted in DA-treated patients. There was a positive correlation between higher BIS-11 and PHQ-9 scores; higher in DA-treated patients (r = 0.52, p < 0.001) than DA-naïve patients. Patients with BIS-11 scores ≥60 were younger and received lower cumulative DA doses compared to patients with BIS scores <60. There was no association between male sex and BIS-11 ≥60 and male sex did not increase the odds of increased scores (OR = 0.66, CI95% 0.25-1.76, p = 0.41). No significant difference was found for macroadenoma, prolactin levels, testosterone levels, hypogonadism, testosterone replacement in men, and increased impulsivity or depression scores. Conclusion: Use of PHQ-9 and BIS-11 is practical for routine screening of depression and ICD during outpatient pituitary clinic visits for patients with pituitary disease both naïve to treatment and during DA therapy. We recommend close follow-up after initiation of DA therapy for younger patients, regardless of dose.

Socioeconomic status and well-being during COVID-19: A resource-based examination.

The authors assess levels and within-person changes in psychological well-being (i.e., depressive symptoms and life satisfaction) from before to during the COVID-19 pandemic for individuals in the United States, in general and by socioeconomic status (SES). The data is from 2 surveys of 1,143 adults from RAND Corporation's nationally representative American Life Panel, the first administered between April-June, 2019 and the second during the initial peak of the pandemic in the United States in April, 2020. Depressive symptoms during the pandemic were higher than population norms before the pandemic. Depressive symptoms increased from before to during COVID-19 and life satisfaction decreased. Individuals with higher education experienced a greater increase in depressive symptoms and a greater decrease in life satisfaction from before to during COVID-19 in comparison to those with lower education. Supplemental analysis illustrates that income had a curvilinear relationship with changes in well-being, such that individuals at the highest levels of income experienced a greater decrease in life satisfaction from before to during COVID-19 than individuals with lower levels of income. We draw on conservation of resources theory and the theory of fundamental social causes to examine four key mechanisms (perceived financial resources, perceived control, interpersonal resources, and COVID-19-related knowledge/news consumption) underlying the relationship between SES and well-being during COVID-19. These resources explained changes in well-being for the sample as a whole but did not provide insight into why individuals of higher education experienced a greater decline in well-being from before to during COVID-19. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Reassessing evidence-based content in popular smartphone apps for depression and anxiety: Developing and applying user-adjusted analyses.

OBJECTIVE: To assess the dissemination of evidence-based content within smartphone apps for depression and anxiety by developing and applying user-adjusted analysis-a method for weighting app content based on each app's number of active users. METHOD: We searched the Apple App Store and Google Play Store and identified 27 apps within the top search hits, which real-world users are most likely to encounter. We developed a codebook of evidence-based treatment elements by reviewing past research on empirically supported treatments. We coded the apps to develop an initial tally of the frequency of treatment elements within the mental health (MH) apps. We then developed and applied user-adjusted analysis to refine the tallies based on each app's number of monthly active users. RESULTS: The 2 most popular apps were responsible for 90% of monthly active users, and user-adjusted analysis markedly altered conclusions of prior reports based on tallies alone. For example, mindfulness was present in 37% of apps but reached 96% of monthly active users, cognitive restructuring was present in 22% but reached only 2%, and exposure was present in 7% but reached only 0.0004%. CONCLUSIONS: The potential impact of MH apps on mental health may be best evaluated via assessment that combines tallies of evidence-based content with data on the content users are actually accessing. Given wide variation in the popularity of MH apps, findings weighted by usage data may differ markedly from findings based on raw tallies alone. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Excess mortality and shortened life expectancy in people with major mental illnesses in Taiwan.

AIMS: Given the concerns of health inequality associated with mental illnesses, we aimed to reveal the extent of which general mortality and life expectancy at birth in people with schizophrenia, bipolar disorder and depressive disorder varied in the 2005 and 2010 nationally representative cohorts in Taiwan. METHODS: Two nationally representative samples of individuals with schizophrenia, bipolar disorder and depressive disorder were identified from Taiwan's national health insurance database in 2005 and 2010, respectively, and followed-up for consecutive 3 years. The database was linked to nationwide mortality registry to identify causes and date of death. Age-, gender- and cause-specific mortality rates were generated, with the average follow-up period of each age- and gender-band applied as 'weighting' for the calculation of expected number of deaths. Age- and gender-standardised mortality ratios (SMRs) were calculated for these 3-year observation periods with Taiwanese general population in 2011/2012 as the standard population. The SMR calculations were then stratified by natural/unnatural causes and major groups of death. Corresponding life expectancies at birth were also calculated by gender, diagnosis of mental disorders and year of cohorts for further elucidation. RESULTS: The general differential in mortality rates for people with schizophrenia and bipolar disorder remained wide, revealing an SMR of 3.65 (95% confidence interval (CI): 3.55-3.76) for cohort 2005 and 3.27 (3.18-3.36) for cohort 2010 in schizophrenia, and 2.65 (95% CI: 2.55-2.76) for cohort 2005 and 2.39 (2.31-2.48) for cohort 2010 in bipolar disorder, respectively. The SMRs in people with depression were 1.83 (95% CI: 1.81-1.86) for cohort 2005 and 1.59 (1.57-1.61) for cohort 2010. SMRs due to unnatural causes tended to decrease in people with major mental illnesses over the years, but those due to natural causes remained relatively stable. The life expectancies at birth for schizophrenia, bipolar disorder and depression were all significantly lower than the national norms, specifically showing 14.97-15.50 years of life lost for men and 15.15-15.48 years for women in people with schizophrenia. CONCLUSIONS: Compared to general population, the differential in mortality rates for people with major mental illnesses persisted substantial. The differential in mortality for unnatural causes of death seemed decreasing over the years, but that due to natural causes remained relatively steady. Regardless of gender, people with schizophrenia, bipolar disorder and depression were shown to have shortened life expectancies compared to general population.

Association of End Point Definition and Randomized Clinical Trial Duration in Clinical Trials of Schizophrenia Medications.

Importance: Facilitating the development of safe and effective medications for schizophrenia is a public health imperative. Objectives: To evaluate the association of shortening randomized clinical trial (RCT) duration with the modification of the Positive and Negative Syndrome Scale (PANSS) for the design of RCTs of medications for schizophrenia and to offer perspective on an alternative regulatory pathway to the historically accepted trial duration and response assessment. Data Sources: A database was created consisting of clinical trial data from 32 placebo-controlled RCTs of 8 atypical antipsychotic drugs approved by the US Food and Drug Administration (FDA) between January 1, 2001, and December 31, 2015. The database included information on total and individual PANSS item ratings, demographic characteristics, disposition, and adverse events (AEs). Study Selection: All clinical trials submitted to 8 new drug applications of atypical antipsychotic drugs were selected. Data Extraction and Synthesis: Quality control checks were performed to ensure that the collected data were consistent with the reported results of each trial. Data were collected from March 15, 2015, to September 30, 2015. Data analysis was conducted from October 1, 2015, to June 20, 2016. Main Outcomes and Measures: The following analyses were performed: (1) longitudinal assessment of mean change from baseline in total PANSS score, (2) correlation analyses between change from baseline in total PANSS score at week 6 and earlier time points, (3) concordance analyses of outcomes across trials between week 6 and earlier time points using total PANSS and modified PANSS, and (4) analyses of time course of treatment-emergent AEs. Results: The final database contained data from 14 219 participants enrolled in 32 drug trials; 9805 of 14 219 participants (69.0%) were male and were either white (7183 [50.5%]) or black (4346 [30.6%]) individuals. The mean (SD) age during treatment was 38.9 (10.9) years, and the mean (SD) age at schizophrenia diagnosis was 25 (8.5) years. Statistically significant separation between treatment response and placebo response was observed after 1 week of treatment. The overall concordance rate across treatment groups steadily increased from week 1 to week 4 (68.0% for week 1, 74.0% for week 2, 83.0% for week 3, and 93.0% for week 4). Trends in AE occurrence were evident by week 1 and percentage of AEs were similar across weeks 3, 4, and 6. The overall concordance rate between change from baseline in the modified PANSS score and change from baseline in the total PANSS score was 93.0% (80 of 86 treatment groups) at week 4 and 97.7% (84 of 86 treatment groups) at week 6. Shortening the trial duration to 4 weeks increased the required sample size to 502 participants. Using the modified PANSS as the end point, the sample size for a 4-week trial was 402 participants and 296 participants for a 6-week trial. Conclusions and Relevance: Findings from this analysis suggest that there is the potential to streamline the design of schizophrenia drug clinical trials. Trial sponsors may consider incorporating these strategies and are encouraged to consult with the FDA early in the drug development process.

Is trade a blessing or a curse? A panel data analysis of the determinants of depressive disorders.

OBJECTIVES: Given the speculation of the market economy causing an epidemic of depression, this study aimed to examine the influence of international trade on the prevalence of depressive disorders. METHODS: We used panel data from 1993 to 2015 covering 170 countries (n = 3787) and applied fixed effects regression models. We modeled the prevalence of depressive disorders as a function of international trade, adjusting for economic development, economic growth, and population size. Regime types, media freedom, and capital-labor ratio were included as moderators. RESULTS: A 100% point increase in the value of international trade indicated a 0.09% point decrease in the prevalence of depressive disorders (- 0.09, confidence interval [CI] - 0.01 to - 0.18). However, this effect existed only for democratic countries (- 0.15, CI - 0.03 to - 0.28). The effect was more prevalent when the governments allowed the media more freedom (score of 100, - 0.31, CI - 0.17 to - 0.45) or when a country's capital-labor ratio of endowments was high (50,000, - 0.22, CI - 0.08 to - 0.35). CONCLUSIONS: Trade brings about positive mental health outcomes in democracies, countries having free media, or capital-abundant economies.

Association of Symptoms of Depression With Cardiovascular Disease and Mortality in Low-, Middle-, and High-Income Countries.

Importance: Depression is associated with incidence of and premature death from cardiovascular disease (CVD) and cancer in high-income countries, but it is not known whether this is true in low- and middle-income countries and in urban areas, where most people with depression now live. Objective: To identify any associations between depressive symptoms and incident CVD and all-cause mortality in countries at different levels of economic development and in urban and rural areas. Design, Setting, and Participants: This multicenter, population-based cohort study was conducted between January 2005 and June 2019 (median follow-up, 9.3 years) and included 370 urban and 314 rural communities from 21 economically diverse countries on 5 continents. Eligible participants aged 35 to 70 years were enrolled. Analysis began February 2018 and ended September 2019. Exposures: Four or more self-reported depressive symptoms from the Short-Form Composite International Diagnostic Interview. Main Outcomes and Measures: Incident CVD, all-cause mortality, and a combined measure of either incident CVD or all-cause mortality. Results: Of 145 862 participants, 61 235 (58%) were male and the mean (SD) age was 50.05 (9.7) years. Of those, 15 983 (11%) reported 4 or more depressive symptoms at baseline. Depression was associated with incident CVD (hazard ratio [HR], 1.14; 95% CI, 1.05-1.24), all-cause mortality (HR, 1.17; 95% CI, 1.11-1.25), the combined CVD/mortality outcome (HR, 1.18; 95% CI, 1.11-1.24), myocardial infarction (HR, 1.23; 95% CI, 1.10-1.37), and noncardiovascular death (HR, 1.21; 95% CI, 1.13-1.31) in multivariable models. The risk of the combined outcome increased progressively with number of symptoms, being highest in those with 7 symptoms (HR, 1.24; 95% CI, 1.12-1.37) and lowest with 1 symptom (HR, 1.05; 95% CI, 0.92 -1.19; P for trend < .001). The associations between having 4 or more depressive symptoms and the combined outcome were similar in 7 different geographical regions and in countries at all economic levels but were stronger in urban (HR, 1.23; 95% CI, 1.13-1.34) compared with rural (HR, 1.10; 95% CI, 1.02-1.19) communities (P for interaction = .001) and in men (HR, 1.27; 95% CI, 1.13-1.38) compared with women (HR, 1.14; 95% CI, 1.06-1.23; P for interaction < .001). Conclusions and Relevance: In this large, population-based cohort study, adults with depressive symptoms were associated with having increased risk of incident CVD and mortality in economically diverse settings, especially in urban areas. Improving understanding and awareness of these physical health risks should be prioritized as part of a comprehensive strategy to reduce the burden of noncommunicable diseases worldwide.

Cognitive behavioural therapy for adults with dissociative seizures (CODES): a pragmatic, multicentre, randomised controlled trial.

BACKGROUND: Dissociative seizures are paroxysmal events resembling epilepsy or syncope with characteristic features that allow them to be distinguished from other medical conditions. We aimed to compare the effectiveness of cognitive behavioural therapy (CBT) plus standardised medical care with standardised medical care alone for the reduction of dissociative seizure frequency. METHODS: In this pragmatic, parallel-arm, multicentre randomised controlled trial, we initially recruited participants at 27 neurology or epilepsy services in England, Scotland, and Wales. Adults (≥18 years) who had dissociative seizures in the previous 8 weeks and no epileptic seizures in the previous 12 months were subsequently randomly assigned (1:1) from 17 liaison or neuropsychiatry services following psychiatric assessment, to receive standardised medical care or CBT plus standardised medical care, using a web-based system. Randomisation was stratified by neuropsychiatry or liaison psychiatry recruitment site. The trial manager, chief investigator, all treating clinicians, and patients were aware of treatment allocation, but outcome data collectors and trial statisticians were unaware of treatment allocation. Patients were followed up 6 months and 12 months after randomisation. The primary outcome was monthly dissociative seizure frequency (ie, frequency in the previous 4 weeks) assessed at 12 months. Secondary outcomes assessed at 12 months were: seizure severity (intensity) and bothersomeness; longest period of seizure freedom in the previous 6 months; complete seizure freedom in the previous 3 months; a greater than 50% reduction in seizure frequency relative to baseline; changes in dissociative seizures (rated by others); health-related quality of life; psychosocial functioning; psychiatric symptoms, psychological distress, and somatic symptom burden; and clinical impression of improvement and satisfaction. p values and statistical significance for outcomes were reported without correction for multiple comparisons as per our protocol. Primary and secondary outcomes were assessed in the intention-to-treat population with multiple imputation for missing observations. This trial is registered with the International Standard Randomised Controlled Trial registry, ISRCTN05681227, and ClinicalTrials.gov, NCT02325544. FINDINGS: Between Jan 16, 2015, and May 31, 2017, we randomly assigned 368 patients to receive CBT plus standardised medical care (n=186) or standardised medical care alone (n=182); of whom 313 had primary outcome data at 12 months (156 [84%] of 186 patients in the CBT plus standardised medical care group and 157 [86%] of 182 patients in the standardised medical care group). At 12 months, no significant difference in monthly dissociative seizure frequency was identified between the groups (median 4 seizures [IQR 0-20] in the CBT plus standardised medical care group vs 7 seizures [1-35] in the standardised medical care group; estimated incidence rate ratio [IRR] 0·78 [95% CI 0·56-1·09]; p=0·144). Dissociative seizures were rated as less bothersome in the CBT plus standardised medical care group than the standardised medical care group (estimated mean difference -0·53 [95% CI -0·97 to -0·08]; p=0·020). The CBT plus standardised medical care group had a longer period of dissociative seizure freedom in the previous 6 months (estimated IRR 1·64 [95% CI 1·22 to 2·20]; p=0·001), reported better health-related quality of life on the EuroQoL-5 Dimensions-5 Level Health Today visual analogue scale (estimated mean difference 6·16 [95% CI 1·48 to 10·84]; p=0·010), less impairment in psychosocial functioning on the Work and Social Adjustment Scale (estimated mean difference -4·12 [95% CI -6·35 to -1·89]; p<0·001), less overall psychological distress than the standardised medical care group on the Clinical Outcomes in Routine Evaluation-10 scale (estimated mean difference -1·65 [95% CI -2·96 to -0·35]; p=0·013), and fewer somatic symptoms on the modified Patient Health Questionnaire-15 scale (estimated mean difference -1·67 [95% CI -2·90 to -0·44]; p=0·008). Clinical improvement at 12 months was greater in the CBT plus standardised medical care group than the standardised medical care alone group as reported by patients (estimated mean difference 0·66 [95% CI 0·26 to 1·04]; p=0·001) and by clinicians (estimated mean difference 0·47 [95% CI 0·21 to 0·73]; p<0·001), and the CBT plus standardised medical care group had greater satisfaction with treatment than did the standardised medical care group (estimated mean difference 0·90 [95% CI 0·48 to 1·31]; p<0·001). No significant differences in patient-reported seizure severity (estimated mean difference -0·11 [95% CI -0·50 to 0·29]; p=0·593) or seizure freedom in the last 3 months of the study (estimated odds ratio [OR] 1·77 [95% CI 0·93 to 3·37]; p=0·083) were identified between the groups. Furthermore, no significant differences were identified in the proportion of patients who had a more than 50% reduction in dissociative seizure frequency compared with baseline (OR 1·27 [95% CI 0·80 to 2·02]; p=0·313). Additionally, the 12-item Short Form survey-version 2 scores (estimated mean difference for the Physical Component Summary score 1·78 [95% CI -0·37 to 3·92]; p=0·105; estimated mean difference for the Mental Component Summary score 2·22 [95% CI -0·30 to 4·75]; p=0·084), the Generalised Anxiety Disorder-7 scale score (estimated mean difference -1·09 [95% CI -2·27 to 0·09]; p=0·069), and the Patient Health Questionnaire-9 scale depression score (estimated mean difference -1·10 [95% CI -2·41 to 0·21]; p=0·099) did not differ significantly between groups. Changes in dissociative seizures (rated by others) could not be assessed due to insufficient data. During the 12-month period, the number of adverse events was similar between the groups: 57 (31%) of 186 participants in the CBT plus standardised medical care group reported 97 adverse events and 53 (29%) of 182 participants in the standardised medical care group reported 79 adverse events. INTERPRETATION: CBT plus standardised medical care had no statistically significant advantage compared with standardised medical care alone for the reduction of monthly seizures. However, improvements were observed in a number of clinically relevant secondary outcomes following CBT plus standardised medical care when compared with standardised medical care alone. Thus, adults with dissociative seizures might benefit from the addition of dissociative seizure-specific CBT to specialist care from neurologists and psychiatrists. Future work is needed to identify patients who would benefit most from a dissociative seizure-specific CBT approach. FUNDING: National Institute for Health Research, Health Technology Assessment programme.

Exploring health state utility values of parents of children with a serious illness.

PURPOSE: In cost-utility analysis, outcomes are usually measured in terms of quality-adjusted life years, where length of life is adjusted by levels of health-related quality of life (HRQoL) using a single value, known as a health state utility value (HSUV). This study explores the HSUVs of parents of children with a serious illness admitted within three hospital departments (cardiology, oncology and paediatric intensive care) across four time points, compares HSUVs with Australian population norms and examines predictors of parental HSUVs. METHODS: Data were obtained from the Take a Breath study, where parental HSUVs were measured using the Assessment of Quality of Life-8 Dimensions (AQoL-8D). Descriptive statistics and t-tests compared the AQoL-8D scores with population norms, while repeated measures ANOVA was used to compare parental HSUVs of children treated across illness groups over time. Regression analysis was performed to determine predictors of parental HSUVs. RESULTS: Parental HSUVs were not significantly different from the general Australian population norms (p = 0.939), as measured by the AQoL-8D. However, statistically significant differences were observed in the psychosocial super-dimension (p < 0.01) and in all eight AQoL-8D dimensions, except for senses and self-worth. No significant differences were observed across illness groups. Parental HSUVs were associated with psychosocial risk factors of trait anxiety (p < 0.001), depression (p < 0.001) and family beliefs (p = 0.024). CONCLUSION: Having a child with a severe illness has an impact on the psychosocial aspects of parental HRQoL regardless of the type of illness. Psychosocial health factors of trait anxiety, depression and family beliefs were important predictors of parental HSUV.