Showing papers in "JAMA Psychiatry in 2020"

Suicide Mortality and Coronavirus Disease 2019-A Perfect Storm?

Abstract: Suicide rates have been rising in the US over the last 2 decades. The latest data available (2018) show the highest age-adjusted suicide rate in the US since 1941.1 It is within this context that coronavirus disease 2019 (COVID-19) struck the US. Concerning disease models have led to historic and unprecedented public health actions to curb the spread of the virus. Remarkable social distancing interventions have been implemented to fundamentally reduce human contact. While these steps are expected to reduce the rate of new infections, the potential for adverse outcomes on suicide risk is high. Actions could be taken to mitigate potential unintended consequences on suicide prevention efforts, which also represent a national public health priority.

Schizophrenia-An Overview

Abstract: Importance Schizophrenia is a common, severe mental illness that most clinicians will encounter regularly during their practice. This report provides an overview of the clinical characteristics, epidemiology, genetics, neuroscience, and psychopharmacology of schizophrenia to provide a basis to understand the disorder and its treatment. This educational review is integrated with a clinical case to highlight how recent research findings can inform clinical understanding. Observations The first theme considered is the role of early-life environmental and genetic risk factors in altering neurodevelopmental trajectories to predispose an individual to the disorder and leading to the development of prodromal symptoms. The second theme is the role of cortical excitatory-inhibitory imbalance in the development of the cognitive and negative symptoms of the disorder. The third theme considers the role of psychosocial stressors, psychological factors, and subcortical dopamine dysfunction in the onset of the positive symptoms of the disorder. The final theme considers the mechanisms underlying treatment for schizophrenia and common adverse effects of treatment. Conclusions and Relevance Schizophrenia has a complex presentation with a multifactorial cause. Nevertheless, advances in neuroscience have identified roles for key circuits, particularly involving frontal, temporal, and mesostriatal brain regions, in the development of positive, negative, and cognitive symptoms. Current pharmacological treatments operate using the same mechanism, blockade of dopamine D2receptor, which contribute to their adverse effects. However, the circuit mechanisms discussed herein identify novel potential treatment targets that may be of particular benefit in symptom domains not well served by existing medications.

Establishment of Best Practices for Evidence for Prediction: A Review.

Abstract: Importance Great interest exists in identifying methods to predict neuropsychiatric disease states and treatment outcomes from high-dimensional data, including neuroimaging and genomics data. The goal of this review is to highlight several potential problems that can arise in studies that aim to establish prediction. Observations A number of neuroimaging studies have claimed to establish prediction while establishing only correlation, which is an inappropriate use of the statistical meaning of prediction. Statistical associations do not necessarily imply the ability to make predictions in a generalized manner; establishing evidence for prediction thus requires testing of the model on data separate from those used to estimate the model’s parameters. This article discusses various measures of predictive performance and the limitations of some commonly used measures, with a focus on the importance of using multiple measures when assessing performance. For classification, the area under the receiver operating characteristic curve is an appropriate measure; for regression analysis, correlation should be avoided, and median absolute error is preferred. Conclusions and Relevance To ensure accurate estimates of predictive validity, the recommended best practices for predictive modeling include the following: (1) in-sample model fit indices should not be reported as evidence for predictive accuracy, (2) the cross-validation procedure should encompass all operations applied to the data, (3) prediction analyses should not be performed with samples smaller than several hundred observations, (4) multiple measures of prediction accuracy should be examined and reported, (5) the coefficient of determination should be computed using the sums of squares formulation and not the correlation coefficient, and (6) k-fold cross-validation rather than leave-one-out cross-validation should be used.

Addressing the COVID-19 Pandemic in Populations With Serious Mental Illness.

Abstract: The coronavirus disease 2019 (COVID-19) pandemic will present an unprecedented stressor to patients and health care systems across the globe. Because there is currently no vaccine or treatment for the underlying infection, current health efforts are focused on providing prevention and screening, maintaining continuity of treatment for other chronic conditions, and ensuring access to appropriately intensive services for those with the most severe symptoms.1 Disasters disproportionately affect poor and vulnerable populations, and patients with serious mental illness may be among the hardest hit. High rates of smoking in this population may raise the risk of infection and confer a worse prognosis among those who develop the illness.2 Residential instability and homelessness can raise the risk of infection and make it harder to identify, follow up, and treat those who are infected.3 Individuals with serious mental illnesses who are employed may have challenges taking time off from work and may lack sufficient insurance coverage to cover testing or treatment. Small social networks may limit opportunities to obtain support from friends and family members should individuals with serious mental illness become ill. Taken together, these factors may lead to elevated infection rates and worse prognoses in this population. What strategies are available to mitigate the outcome of this epidemic among patients with serious mental illness? Federal preparedness policies developed in the wake of complex disasters have increasingly embraced the notion of whole community preparedness, which supports building and supporting structures at multiple levels to prepare and respond, particularly for vulnerable populations.4 Within the public mental health care system, this includes engagement with mental health service users, clinicians, and federal and state policies.

Association Between Recreational Marijuana Legalization in the United States and Changes in Marijuana Use and Cannabis Use Disorder From 2008 to 2016

Abstract: Importance Little is known about changes in marijuana use and cannabis use disorder (CUD) after recreational marijuana legalization (RML). Objectives To examine the associations between RML enactment and changes in marijuana use, frequent use, and CUD in the United States from 2008 to 2016. Design, Setting, and Participants This survey study used repeated cross-sectional survey data from the National Survey on Drug Use and Health (2008-2016) conducted in the United States among participants in the age groups of 12 to 17, 18 to 25, and 26 years or older. Interventions Multilevel logistic regression models were fit to obtain estimates of before-vs-after changes in marijuana use among respondents in states enacting RML compared to changes in other states. Main Outcomes and Measures Self-reported past-month marijuana use, past-month frequent marijuana use, past-month frequent use among past-month users, past-year CUD, and past-year CUD among past-year users. Results The study included 505 796 respondents consisting of 51.51% females and 77.24% participants 26 years or older. Among the total, 65.43% were white, 11.90% black, 15.36% Hispanic, and 7.31% of other race/ethnicity. Among respondents aged 12 to 17 years, past-year CUD increased from 2.18% to 2.72% after RML enactment, a 25% higher increase than that for the same age group in states that did not enact RML (odds ratio [OR], 1.25; 95% CI, 1.01-1.55). Among past-year marijuana users in this age group, CUD increased from 22.80% to 27.20% (OR, 1.27; 95% CI, 1.01-1.59). Unmeasured confounders would need to be more prevalent in RML states and increase the risk of cannabis use by 1.08 to 1.11 times to explain observed results, indicating results that are sensitive to omitted variables. No associations were found among the respondents aged 18 to 25 years. Among respondents 26 years or older, past-month marijuana use after RML enactment increased from 5.65% to 7.10% (OR, 1.28; 95% CI, 1.16-1.40), past-month frequent use from 2.13% to 2.62% (OR, 1.24; 95% CI, 1.08-1.41), and past-year CUD from 0.90% to 1.23% (OR, 1.36; 95% CI, 1.08-1.71); these results were more robust to unmeasured confounding. Among marijuana users in this age group, past-month frequent marijuana use and past-year CUD did not increase after RML enactment. Conclusions and Relevance This study’s findings suggest that although marijuana legalization advanced social justice goals, the small post-RML increase in risk for CUD among respondents aged 12 to 17 years and increased frequent use and CUD among adults 26 years or older in this study are a potential public health concern. To undertake prevention efforts, further studies are warranted to assess how these increases occur and to identify subpopulations that may be especially vulnerable.

Prevention of Psychosis: Advances in Detection, Prognosis, and Intervention

Abstract: Importance Detection, prognosis, and indicated interventions in individuals at clinical high risk for psychosis (CHR-P) are key components of preventive psychiatry. Objective To provide a comprehensive, evidence-based systematic appraisal of the advancements and limitations of detection, prognosis, and interventions for CHR-P individuals and to formulate updated recommendations. Evidence Review Web of Science, Cochrane Central Register of Reviews, and Ovid/PsychINFO were searched for articles published from January 1, 2013, to June 30, 2019, to identify meta-analyses conducted in CHR-P individuals. MEDLINE was used to search the reference lists of retrieved articles. Data obtained from each article included first author, year of publication, topic investigated, type of publication, study design and number, sample size of CHR-P population and comparison group, type of comparison group, age and sex of CHR-P individuals, type of prognostic assessment, interventions, quality assessment (using AMSTAR [Assessing the Methodological Quality of Systematic Reviews]), and key findings with their effect sizes. Findings In total, 42 meta-analyses published in the past 6 years and encompassing 81 outcomes were included. For the detection component, CHR-P individuals were young (mean [SD] age, 20.6 [3.2] years), were more frequently male (58%), and predominantly presented with attenuated psychotic symptoms lasting for more than 1 year before their presentation at specialized services. CHR-P individuals accumulated several sociodemographic risk factors compared with control participants. Substance use (33% tobacco use and 27% cannabis use), comorbid mental disorders (41% with depressive disorders and 15% with anxiety disorders), suicidal ideation (66%), and self-harm (49%) were also frequently seen in CHR-P individuals. CHR-P individuals showed impairments in work (Cohend = 0.57) or educational functioning (Cohend = 0.21), social functioning (Cohend = 1.25), and quality of life (Cohend = 1.75). Several neurobiological and neurocognitive alterations were confirmed in this study. For the prognosis component, the prognostic accuracy of CHR-P instruments was good, provided they were used in clinical samples. Overall, risk of psychosis was 22% at 3 years, and the risk was the highest in the brief and limited intermittent psychotic symptoms subgroup (38%). Baseline severity of attenuated psychotic (Cohend = 0.35) and negative symptoms (Cohend = 0.39) as well as low functioning (Cohend = 0.29) were associated with an increased risk of psychosis. Controlling risk enrichment and implementing sequential risk assessments can optimize prognostic accuracy. For the intervention component, no robust evidence yet exists to favor any indicated intervention over another (including needs-based interventions and control conditions) for preventing psychosis or ameliorating any other outcome in CHR-P individuals. However, because the uncertainty of this evidence is high, needs-based and psychological interventions should still be offered. Conclusions and Relevance This review confirmed recent substantial advancements in the detection and prognosis of CHR-P individuals while suggesting that effective indicated interventions need to be identified. This evidence suggests a need for specialized services to detect CHR-P individuals in primary and secondary care settings, to formulate a prognosis with validated psychometric instruments, and to offer needs-based and psychological interventions.

Incidence Rates and Cumulative Incidences of the Full Spectrum of Diagnosed Mental Disorders in Childhood and Adolescence.

Abstract: Importance Knowledge about the epidemiology of mental disorders in children and adolescents is essential for research and planning of health services. Surveys can provide prevalence rates, whereas population-based registers are instrumental to obtain precise estimates of incidence rates and risks. Objective To estimate age- and sex-specific incidence rates and risks of being diagnosed with any mental disorder during childhood and adolescence. Design This cohort study included all individuals born in Denmark from January 1, 1995, through December 31, 2016 (1.3 million), and followed up from birth until December 31, 2016, or the date of death, emigration, disappearance, or diagnosis of 1 of the mental disorders examined (14.4 million person-years of follow-up). Data were analyzed from September 14, 2018, through June 11, 2019. Exposures Age and sex. Main Outcomes and Measures Incidence rates and cumulative incidences of all mental disorders according to theICD-10 Classification of Mental and Behavioral Disorders: Diagnostic Criteria for Research,diagnosed before 18 years of age during the study period. Results A total of 99 926 individuals (15.01%; 95% CI, 14.98%-15.17%), including 41 350 girls (14.63%; 95% CI, 14.48%-14.77%) and 58 576 boys (15.51%; 95% CI, 15.18%-15.84%), were diagnosed with a mental disorder before 18 years of age. Anxiety disorder was the most common diagnosis in girls (7.85%; 95% CI, 7.74%-7.97%); attention-deficit/hyperactivity disorder (ADHD) was the most common in boys (5.90%; 95% CI, 5.76%-6.03%). Girls had a higher risk than boys of schizophrenia (0.76% [95% CI, 0.72%-0.80%] vs 0.48% [95% CI, 0.39%-0.59%]), obsessive-compulsive disorder (0.96% [95% CI, 0.92%-1.00%] vs 0.63% [95% CI, 0.56%-0.72%]), and mood disorders (2.54% [95% CI, 2.47%-2.61%] vs 1.10% [95% CI, 0.84%-1.21%]). Incidence peaked earlier in boys than girls in ADHD (8 vs 17 years of age), intellectual disability (5 vs 14 years of age), and other developmental disorders (5 vs 16 years of age). The overall risk of being diagnosed with a mental disorder before 6 years of age was 2.13% (95% CI, 2.11%-2.16%) and was higher in boys (2.78% [95% CI, 2.44%-3.15%]) than in girls (1.45% [95% CI, 1.42%-1.49%]). Conclusions and Relevance This nationwide population-based cohort study provides a first comprehensive assessment of the incidence and risks of mental disorders in childhood and adolescence. By 18 years of age, 15.01% of children and adolescents in this study were diagnosed with a mental disorder. The incidence of several neurodevelopmental disorders peaked in late adolescence in girls, suggesting possible delayed detection. The distinct signatures of the different mental disorders with respect to sex and age may have important implications for service planning and etiological research.

Mental Health in the Coronavirus Disease 2019 Emergency-The Italian Response.

Abstract: Importance This article briefly reports the experience of mental health services and the lessons learned during the coronavirus disease 2019 (COVID-19) crisis. In particular, this report offers opportunities to build on experience gained in managing the COVID-19 emergency in the Departments of Mental Health and Addiction (DMHAs) in Lombardy, the wealthiest Italian region, which has approximately 10 million inhabitants. Observations Italy has a National Mental Health System divided into 134 DMHAs, 27 of which are in Lombardy. In the 4 weeks after the epidemic started, important changes occurred in the management of DMHAs in Lombardy. Many challenges have occurred in the management of health services. In many hospitals, entire wards, including some psychiatric wards, have been reorganized to admit patients with COVID-19, and many physicians and nurses have been diverted to wards managing patients with COVID-19. Most day facilities for patients with psychiatric needs have been temporarily closed, whereas in residential facilities, patients who usually are free to come and go during the day have had to be confined in the facilities with very limited or no leave. These changes have produced considerable stresses on people with severe mental disorders. Many outpatient clinics have limited appointments to those with the most urgent cases, and home visits, a common practice in most DMHAs, have been drastically reduced with potentially detrimental consequences for patients’ well-being. Another potential detrimental consequence of being forced to stay at home has been an increase in the hours spent face to face with families with high amounts of conflict. Conclusions and Relevance Departments of Mental Health need to be equipped with appropriate e-health technologies and procedures to cope with situations such as the COVID-19 pandemic. Additionally, interventions are needed to mitigate the potentially harmful consequences of quarantine. Departments of Mental Health should be able to assume a leadership position in the psychosocial management of disasterlike situations, and this requires the acquisition of new skills, notably how to correctly inform the population about risk, train and disseminate effective preventive and management procedures for disasters, support health personnel and rescuers, and support those experiencing bereavement.

Long-term Outcomes of Cognitive Behavioral Therapy for Anxiety-Related Disorders: A Systematic Review and Meta-analysis

Abstract: Importance Cognitive behavioral therapy is recommended for anxiety-related disorders, but evidence for its long-term outcome is limited. Objective This systematic review and meta-analysis aimed to assess the long-term outcomes after cognitive behavioral therapy (compared with care as usual, relaxation, psychoeducation, pill placebo, supportive therapy, or waiting list) for anxiety disorders, posttraumatic stress disorder (PTSD), and obsessive-compulsive disorder (OCD). Data Sources English-language publications were identified from PubMed, PsycINFO, Embase, Cochrane, OpenGrey (1980 to January 2019), and recent reviews. The search strategy included a combination of terms associated with anxiety disorders (eg,panicorphobi*) and study design (eg,clinical trialorrandomized controlled trial). Study Selection Randomized clinical trials on posttreatment and at least 1-month follow-up effects of cognitive behavioral therapy compared with control conditions among adults with generalized anxiety disorder, panic disorder with or without agoraphobia, social anxiety disorder, specific phobia, PTSD, or OCD. Data Extraction and Synthesis Researchers independently screened records, extracted statistics, and assessed study quality. Data were pooled using a random-effects model. Main Outcomes and Measures Hedgesgwas calculated for anxiety symptoms immediately after treatment and at 1 to 6 months, 6 to 12 months, and more than 12 months after treatment completion. Results Of 69 randomized clinical trials (4118 outpatients) that were mainly of low quality, cognitive behavioral therapy compared with control conditions was associated with improved outcomes after treatment completion and at 1 to 6 months and at 6 to 12 months of follow-up for a generalized anxiety disorder (Hedgesg, 0.07-0.40), panic disorder with or without agoraphobia (Hedgesg, 0.22-0.35), social anxiety disorder (Hedgesg, 0.34-0.60), specific phobia (Hedgesg, 0.49-0.72), PTSD (Hedgesg, 0.59-0.72), and OCD (Hedgesg, 0.70-0.85). After 12-month follow-up, these associations were still significant for generalized anxiety disorder (Hedgesg, 0.22; number of studies [k] = 10), social anxiety disorder (Hedgesg, 0.42;k = 3), and PTSD (Hedgesg, 0.84;k = 5), but not for panic disorder with or without agoraphobia (k = 5) and could not be calculated for specific phobia (k = 1) and OCD (k = 0). Relapse rates after 3 to 12 months were 0% to 14% but were reported in only 6 randomized clinical trials (predominantly for panic disorder with or without agoraphobia). Conclusions and Relevance The findings of this meta-analysis suggest that cognitive behavioral therapy for anxiety-related disorders is associated with improved outcomes compared with control conditions until 12 months after treatment completion. After 12 months, effects were small to medium for generalized anxiety disorder and social anxiety disorder, large for PTSD, and not significant or not available for other disorders. High-quality randomized clinical trials with more than 12 months of follow-up and reported relapse rates are needed.

Psychosocial interventions and immune system function: a systematic review and meta-analysis of randomized clinical trials

Abstract: Importance Recent estimates suggest that more than 50% of all deaths worldwide are currently attributable to inflammation-related diseases. Psychosocial interventions may represent a potentially useful strategy for addressing this global public health problem, but which types of interventions reliably improve immune system function, under what conditions, and for whom are unknown. Objective To address this issue, we conducted a systematic review and meta-analysis of randomized clinical trials (RCTs) in which we estimated associations between 8 different psychosocial interventions and 7 markers of immune system function, and examined 9 potential moderating factors. Data Sources PubMed, Scopus, PsycInfo, and ClinicalTrials.gov databases were systematically searched from February 1, 2017, to December 31, 2018, for all relevant RCTs published through December 31, 2018. Study Selection Eligible RCTs included a psychosocial intervention, immune outcome, and preintervention and postintervention immunologic assessments. Studies were independently examined by 2 investigators. Of 4621 studies identified, 62 were eligible and 56 included. Data Extraction and Synthesis Data were extracted and analyzed from January 1, 2019, to July 29, 2019. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline was followed. Data were extracted by 2 investigators who were blind to study hypotheses and analyses, and were then analyzed using robust variance estimation. Analysis included 8 psychosocial interventions (behavior therapy, cognitive therapy, cognitive behavior therapy [CBT], CBT plus additive treatment or mode of delivery that augmented the CBT, bereavement or supportive therapy, multiple or combined interventions, other psychotherapy, and psychoeducation), 7 immune outcomes (proinflammatory cytokine or marker levels, anti-inflammatory cytokine levels, antibody levels, immune cell counts, natural killer cell activity, viral load, and other immune outcomes), and 9 moderating factors (intervention type, intervention format, intervention length, immune marker type, basal vs stimulated markers, immune marker measurement timing, disease state or reason for treatment, age, and sex). Main Outcomes and Measures The primary a priori outcomes were pretest-posttest-control (ppc) group effect sizes (ppcg) for the 7 immunologic outcomes investigated. Results Across 56 RCTs and 4060 participants, psychosocial interventions were associated with enhanced immune system function (ppcg = 0.30, 95% CI, 0.21-0.40;t50.9 = 6.22;P Conclusions and Relevance These findings suggest that psychosocial interventions are reliably associated with enhanced immune system function and may therefore represent a viable strategy for improving immune-related health.

Psychotherapy for Depression Across Different Age Groups: A Systematic Review and Meta-analysis.

Abstract: Importance It is not clear whether psychotherapies for depression have comparable effects across the life span. Finding out is important from a clinical and scientific perspective. Objective To compare the effects of psychotherapies for depression between different age groups. Data Sources Four major bibliographic databases (PubMed, PsychINFO, Embase, and Cochrane) were searched for trials comparing psychotherapy with control conditions up to January 2019. Study Selection Randomized trials comparing psychotherapies for depression with control conditions in all age groups were included. Data Extraction and Synthesis Effect sizes (Hedgesg) were calculated for all comparisons and pooled with random-effects models. Differences in effects between age groups were examined with mixed-effects subgroup analyses and in meta-regression analyses. Main Outcomes and Measures Depressive symptoms were the primary outcome. Results After removing duplicates, 16 756 records were screened and 2608 full-text articles were screened. Of these, 366 trials (36 702 patients) with 453 comparisons between a therapy and a control condition were included in the qualitative analysis, including 13 (3.6%) in children (13 years and younger), 24 (6.6%) in adolescents (≥13 to 18 years), 19 (5.2%) in young adults (≥18 to 24 years), 242 (66.1%) in middle-aged adults (≥24 to 55 years), 58 (15.8%) in older adults (≥55 to 75 years), and 10 (2.7%) in older old adults (75 years and older). The overall effect size of all comparisons across all age groups wasg= 0.75 (95% CI, 0.67-0.82), with very high heterogeneity (I2= 80%; 95% CI: 78-82). Mean effect sizes for depressive symptoms in children (g = 0.35; 95% CI, 0.15-0.55) and adolescents (g = 0.55; 95% CI, 0.34-0.75) were significantly lower than those in middle-aged adults (g = 0.77; 95% CI, 0.67-0.87). The effect sizes in young adults (g = 0.98; 95% CI, 0.79-1.16) were significantly larger than those in middle-aged adults. No significant difference was found between older adults (g = 0.66; 95% CI, 0.51-0.82) and those in older old adults (g = 0.97; 95% CI, 0.42-1.52). The outcomes should be considered with caution because of the suboptimal quality of most of the studies and the high levels of heterogeneity. However, most primary findings proved robust across sensitivity analyses, addressing risk of bias, target populations included, type of therapy, diagnosis of mood disorder, and method of data analysis. Conclusions and Relevance Trials included in this meta-analysis reported effect sizes of psychotherapies that were smaller in children than in adults, probably also smaller in adolescents, that the effects may be somewhat larger in young adults, and without meaningful differences between middle-aged adults, older adults, and older old adults.

Neurobiology, Clinical Presentation, and Treatment of Methamphetamine Use Disorder: A Review

Abstract: Importance The prevalence of and mortality associated with methamphetamine use has doubled during the past 10 years. There is evidence suggesting that methamphetamine use disorder could be the next substance use crisis in the United States and possibly worldwide. Observation The neurobiology of methamphetamine use disorder extends beyond the acute effect of the drug as a monoaminergic modulator and includes intracellular pathways focused on oxidative stress, neurotoxic and excitotoxic effects, and neuroinflammation. Similarly, the clinical picture extends beyond the acute psychostimulatory symptoms to include complex cardiovascular and cerebrovascular signs and symptoms that need to be identified by the clinician. Although there are no pharmacologic treatments for methamphetamine use disorder, cognitive behavioral therapy, behavioral activation, and contingency management show modest effectiveness. Conclusions and Relevance There is a need to better understand the complex neurobiology of methamphetamine use disorder and to develop interventions aimed at novel biological targets. Parsing the disorder into different processes (eg, craving or mood-associated alterations) and targeting the neural systems and biological pathways underlying these processes may lead to greater success in identifying disease-modifying interventions. Finally, mental health professionals need to be trained in recognizing early cardiovascular and cerebrovascular warning signs to mitigate the mortality associated with methamphetamine use disorder.

Association of OPRM1 Functional Coding Variant With Opioid Use Disorder: A Genome-Wide Association Study.

Abstract: Importance With the current opioid crisis, it is important to improve understanding of the biological mechanisms of opioid use disorder (OUD). Objectives To detect genetic risk variants for OUD and determine genetic correlations and causal association with OUD and other traits. Design, setting, and participants A genome-wide association study of electronic health record-defined OUD in the Million Veteran Program sample was conducted, comprising 8529 affected European American individuals and 71 200 opioid-exposed European American controls (defined by electronic health record trajectory analysis) and 4032 affected African American individuals and 26 029 opioid-exposed African American controls. Participants were enrolled from January 10, 2011, to May 21, 2018, with electronic health record data for OUD diagnosis from October 1, 1999, to February 7, 2018. Million Veteran Program results and additional OUD case-control genome-wide association study results from the Yale-Penn and Study of Addiction: Genetics and Environment samples were meta-analyzed (total numbers: European American individuals, 10 544 OUD cases and 72 163 opioid-exposed controls; African American individuals, 5212 cases and 26 876 controls). Data on Yale-Penn participants were collected from February 14, 1999, to April 1, 2017, and data on Study of Addiction: Genetics and Environment participants were collected from 1990 to 2007. The key result was replicated in 2 independent cohorts: proxy-phenotype buprenorphine treatment in the UK Biobank and newly genotyped Yale-Penn participants. Genetic correlations between OUD and other traits were tested, and mendelian randomization analysis was conducted to identify potential causal associations. Main outcomes and measures Main outcomes were International Classification of Diseases, Ninth Revision-diagnosed OUD or International Statistical Classification of Diseases and Related Health Problems, Tenth Revision-diagnosed OUD (Million Veteran Program), and DSM-IV-defined opioid dependence (Yale-Penn and Study of Addiction: Genetics and Environment). Results A total of 114 759 individuals (101 016 men [88%]; mean [SD] age, 60.1 [12.8] years) were included. In 82 707 European American individuals, a functional coding variant (rs1799971, encoding Asn40Asp) in OPRM1 (μ-opioid receptor gene, the main biological target for opioid drugs; OMIM 600018) reached genome-wide significance (G allele: mean [SE], β = -0.066 [0.012]; P = 1.51 × 10-8). The finding was replicated in 2 independent samples. Mean (SE) single-nucleotide polymorphism-based heritability of OUD was 11.3% (1.8%). Opioid use disorder was genetically correlated with 83 traits, including multiple substance use traits, psychiatric illnesses, cognitive performance, and others. Mendelian randomization analysis revealed the following associations with OUD: risk of tobacco smoking, depression, neuroticism, worry neuroticism subcluster, and cognitive performance. No genome-wide significant association was detected for African American individuals or in transpopulation meta-analysis. Conclusions and relevance This genome-wide meta-analysis identified a significant association of OUD with an OPRM1 variant, which was replicated in 2 independent samples. Post-genome-wide association study analysis revealed associated pleiotropic characteristics. Recruitment of additional individuals with OUD for future studies-especially those of non-European ancestry-is a crucial next step in identifying additional significant risk loci.

Dialectical Behavior Therapy for Posttraumatic Stress Disorder (DBT-PTSD) Compared With Cognitive Processing Therapy (CPT) in Complex Presentations of PTSD in Women Survivors of Childhood Abuse: A Randomized Clinical Trial.

Abstract: Importance Childhood abuse significantly increases the risk of developing posttraumatic stress disorder (PTSD), often accompanied by symptoms of borderline personality disorder (BPD) and other co-occurring mental disorders. Despite the high prevalence, systematic evaluations of evidence-based treatments for PTSD after childhood abuse are sparse. Objective To compare the efficacy of dialectical behavior therapy for PTSD (DBT-PTSD), a new, specifically designed, phase-based treatment program, against that of cognitive processing therapy (CPT), one of the best empirically supported treatments for PTSD. Design, Setting, and Participants From January 2014 to October 2016, women who sought treatment were included in a multicenter randomized clinical trial with blinded outcome assessments at 3 German university outpatient clinics. The participants were prospectively observed for 15 months. Women with childhood abuse–associated PTSD who additionally met 3 or moreDSM-5criteria for BPD, including affective instability, were included. Data analysis took place from October 2018 to December 2019. Interventions Participants received equal dosages and frequencies of DBT-PTSD or CPT, up to 45 individual sessions within 1 year and 3 additional sessions during the following 3 months. Main Outcomes and Measures The predefined primary outcome was the course of the Clinician-Administered PTSD Scale forDSM-5(CAPS-5) score from randomization to month 15. Intent-to-treat analyses based on dimensional CAPS-5 scores were complemented by categorical outcome measures assessing symptomatic remission, reliable improvement, and reliable recovery. Results Of 955 consecutive individuals assessed for eligibility, 193 were randomized (DBT-PTSD, 98; CPT, 95; mean [SD] age, 36.3 [11.1] years) and included in the intent-to-treat analyses. Analysis revealed significantly improved CAPS-5 scores in both groups (effect sizes: DBT-PTSD:d, 1.35; CPT:d, 0.98) and a small but statistically significant superiority of DBT-PTSD (group difference: 4.82 [95% CI, 0.67-8.96];P = .02;d, 0.33). Compared with the CPT group, participants in the DBT-PTSD group were less likely to drop out early (37 [39.0%] vs 25 [25.5%];P = .046) and had higher rates of symptomatic remission (35 [40.7%] vs 52 [58.4%];P = .02), reliable improvement (53 [55.8%] vs 73 [74.5%];P = .006), and reliable recovery (34 [38.6%] vs 52 [57.1%];P = .01). Conclusions and Relevance These findings support the efficacy of DBT-PTSD and CPT in the treatment of women with childhood abuse–associated complex PTSD. Results pertaining to the primary outcomes favored DBT-PTSD. The study shows that even severe childhood abuse–associated PTSD with emotion dysregulation can be treated efficaciously. Trial Registration German Clinical Trials Register:DRKS00005578

Shared Neural Phenotypes for Mood and Anxiety Disorders: A Meta-analysis of 226 Task-Related Functional Imaging Studies.

Abstract: Importance Major depressive disorder, bipolar disorder, posttraumatic stress disorder, and anxiety disorders are highly comorbid and have shared clinical features. It is not yet known whether their clinical overlap is reflected at the neurobiological level. Objective To detect transdiagnostic convergence in abnormalities in task-related brain activation. Data Source Task-related functional magnetic resonance imaging articles published in PubMed, Web of Science, and Google Scholar during the last decade comparing control individuals with patients with mood, posttraumatic stress, and anxiety disorders were examined. Study Selection Following Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guidelines, articles were selected if they reported stereotactic coordinates of whole-brain–based activation differences between adult patients and control individuals. Data Extraction and Synthesis Coordinates of case-control differences coded by diagnosis and by cognitive domain based on the research domain criteria were analyzed using activation likelihood estimation. Main Outcomes and Measures Identification of transdiagnostic clusters of aberrant activation and quantification of the contribution of diagnosis and cognitive domain to each cluster. Results A total of 367 experiments (major depressive disorder, 149; bipolar disorder, 103; posttraumatic stress disorder, 55; and anxiety disorders, 60) were included comprising observations from 4507 patients and 4755 control individuals. Three right-sided clusters of hypoactivation were identified centered in the inferior prefrontal cortex/insula (volume, 2120 mm3), the inferior parietal lobule (volume, 1224 mm3), and the putamen (volume, 888 mm3); diagnostic differences were noted only in the putamen (χ23 = 8.66;P = .03), where hypoactivation was more likely in bipolar disorder (percentage contribution = 72.17%). Tasks associated with cognitive systems made the largest contribution to each cluster (percentage contributions >29%). Clusters of hyperactivation could only be detected using a less stringent threshold. These were centered in the perigenual/dorsal anterior cingulate cortex (volume, 2208 mm3), the left amygdala/parahippocampal gyrus (volume, 2008 mm3), and the left thalamus (volume, 1904 mm3). No diagnostic differences were observed (χ23 .38), while tasks associated with negative valence systems made the largest contribution to each cluster (percentage contributions >49%). All findings were robust to the moderator effects of age, sex, and magnetic field strength of the scanner and medication. Conclusions and Relevance In mood disorders, posttraumatic stress disorder, and anxiety disorders, the most consistent transdiagnostic abnormalities in task-related brain activity converge in regions that are primarily associated with inhibitory control and salience processing. Targeting these shared neural phenotypes could potentially mitigate the risk of affective morbidity in the general population and improve outcomes in clinical populations.

Association Between Recalled Exposure to Gender Identity Conversion Efforts and Psychological Distress and Suicide Attempts Among Transgender Adults

Abstract: Importance Gender identity conversion efforts (GICE) have been widely debated as potentially damaging treatment approaches for transgender persons. The association of GICE with mental health outcomes, however, remains largely unknown. Objective To evaluate associations between recalled exposure to GICE (by a secular or religious professional) and adult mental health outcomes. Design, Setting, and Participants In this cross-sectional study, a survey was distributed through community-based outreach to transgender adults residing in the United States, with representation from all 50 states, the District of Columbia, American Samoa, Guam, Puerto Rico, and US military bases overseas. Data collection occurred during 34 days between August 19 and September 21, 2015. Data analysis was performed from June 8, 2018, to January 2, 2019. Exposure Recalled exposure to GICE. Main Outcomes and Measures Severe psychological distress during the previous month, measured by the Kessler Psychological Distress Scale (defined as a score ≥13). Measures of suicidality during the previous year and lifetime, including ideation, attempts, and attempts requiring inpatient hospitalization. Results Of 27 715 transgender survey respondents (mean [SD] age, 31.2 [13.5] years), 11 857 (42.8%) were assigned male sex at birth. Among the 19 741 (71.3%) who had ever spoken to a professional about their gender identity, 3869 (19.6%; 95% CI, 18.7%-20.5%) reported exposure to GICE in their lifetime. Recalled lifetime exposure was associated with severe psychological distress during the previous month (adjusted odds ratio [aOR], 1.56; 95% CI, 1.09-2.24;P Conclusions and Relevance The findings suggest that lifetime and childhood exposure to GICE are associated with adverse mental health outcomes in adulthood. These results support policy statements from several professional organizations that have discouraged this practice.

Effect of Long-Acting Injectable Antipsychotics vs Usual Care on Time to First Hospitalization in Early-Phase Schizophrenia: A Randomized Clinical Trial.

Abstract: Importance Long-acting injectable antipsychotics (LAIs) can potentially reduce hospitalization risk by enhancing medication adherence but are rarely considered for early-phase schizophrenia treatment. Objective To determine whether encouraging use of a LAI compared with usual care delays the time to first hospitalization with patients with early-phase illness. Design, Setting, and Participants The Prevention of Relapse in Schizophrenia (PRELAPSE) trial was cluster randomized with a follow-up duration of 2 years. The study began in December 2014, was completed in March 2019, and was conducted in 39 mental health centers in 19 US states. Site randomization assigned 19 clinics to encourage treatment with long-acting aripiprazole monohydrate (aripiprazole once monthly [AOM] condition) and 20 to provide treatment as usual (clinician’s choice [CC] condition). Participant eligibility criteria included (1) schizophrenia diagnosis confirmed by a structured clinical interview, (2) fewer than 5 years of lifetime antipsychotic use, and (3) age 18 to 35 years. The AOM sites identified 576 potentially eligible participants, of whom 234 (40.6%) enrolled; CC sites identified 685 potentially eligible participants, of whom 255 (37.2%) enrolled. Interventions There were no restrictions on treatment at CC sites (including using LAIs) or at AOM sites with the exception that aripiprazole monohydrate had to be prescribed within US Food and Drug Administration–approved guidelines. Main Outcomes and Measures The primary outcome was time to first psychiatric hospitalization based on participant interviews every 2 months, the service use resource form administered every 4 months, and other sources (eg, health records) as available. Potential events were adjudicated by an independent committee masked to treatment assignment. Results The 489 participants (368 men [75.3%]) had a mean (SD) age of 25.2 (4.2) years and 225 (46.0%) had 1 year or less lifetime antipsychotic use. Fifty-two AOM (22%) and 91 CC participants (36%) had at least 1 hospitalization. The mean survival time until first hospitalization was 613.7 days (95% CI, 582.3-645.1 days) for AOM participants and 530.6 days (95% CI, 497.3-563.9 days) for CC participants. For time to first hospitalization, the hazard ratio was 0.56 (95% CI, 0.34- 0.92;P = .02), favoring AOM. Survival probabilities were 0.73 (95% CI, 0.65-0.83) for AOM participants and 0.58 (95% CI, 0.50-0.67) for CC participants. The number needed to treat to prevent 1 additional hospitalization was 7 participants treated with AOM compared with CC. Conclusions and Relevance Long-acting injectable antipsychotic use by patients with early-phase schizophrenia can significantly delay time to hospitalization, a personally and economically important outcome. Clinicians should more broadly consider LAI treatment for patients with early-phase illness. Trial Registration ClinicalTrials.gov Identifier:NCT02360319

Cognitive Behavioral Treatments for Anxiety in Children With Autism Spectrum Disorder: A Randomized Clinical Trial

Abstract: Importance Anxiety is common among youth with autism spectrum disorder (ASD), often interfering with adaptive functioning. Psychological therapies are commonly used to treat school-aged youth with ASD; their efficacy has not been established. Objective To compare the relative efficacy of 2 cognitive behavioral therapy (CBT) programs and treatment as usual (TAU) to assess treatment outcomes on maladaptive and interfering anxiety in children with ASD. The secondary objectives were to assess treatment outcomes on positive response, ASD symptom severity, and anxiety-associated adaptive functioning. Design, Setting, and Participants This randomized clinical trial began recruitment in April 2014 at 3 universities in US cities. A volunteer sample of children (7-13 years) with ASD and maladaptive and interfering anxiety was randomized to standard-of-practice CBT, CBT adapted for ASD, or TAU. Independent evaluators were blinded to groupings. Data were collected through January 2017 and analyzed from December 2018 to February 2019. Interventions The main features of standard-of-practice CBT were affect recognition, reappraisal, modeling/rehearsal, in vivo exposure tasks, and reinforcement. The CBT intervention adapted for ASD was similar but also addressed social communication and self-regulation challenges with perspective-taking training and behavior-analytic techniques. Main Outcomes and Measures The primary outcome measure per a priori hypotheses was the Pediatric Anxiety Rating Scale. Secondary outcomes included treatment response on the Clinical Global Impressions–Improvement scale and checklist measures. Results Of 214 children initially enrolled, 167 were randomized, 145 completed treatment, and 22 discontinued participation. Those who were not randomized failed to meet eligibility criteria (eg, confirmed ASD). There was no significant difference in discontinuation rates across conditions. Randomized children had a mean (SD) age of 9.9 (1.8) years; 34 were female (20.5%). The CBT program adapted for ASD outperformed standard-of-practice CBT (mean [SD] Pediatric Anxiety Rating Scale score, 2.13 [0.91] [95% CI, 1.91-2.36] vs 2.43 [0.70] [95% CI, 2.25-2.62];P = .04) and TAU (2.93 [0.59] [95% CI, 2.63-3.22];P Conclusions and Relevance In this study, CBT was efficacious for children with ASD and interfering anxiety, and an adapted CBT approach showed additional advantages. It is recommended that clinicians providing psychological treatments to school-aged children with ASD consider developing CBT expertise. Trial Registration ClinicalTrials.gov identifier:NCT02028247

Efficacy of Digital Cognitive Behavioral Therapy for the Treatment of Insomnia Symptoms Among Pregnant Women: A Randomized Clinical Trial.

Abstract: Importance Despite the prevalence and adverse consequences of prenatal insomnia, a paucity of research is available regarding interventions to improve insomnia symptoms during pregnancy. Objective To test the efficacy of digital cognitive behavioral therapy for insomnia (CBT-I) compared with standard treatment among pregnant women with insomnia symptoms. Design, Setting, and Participants This randomized clinical trial enrolled pregnant women from November 23, 2016, to May 22, 2018. Of the 2258 women assessed for eligibility using an online self-report questionnaire, 208 were randomized to receive digital CBT-I (n = 105) or standard treatment (n = 103) for insomnia. Participants were pregnant up to 28 weeks’ gestation, and they either had elevated insomnia symptom severity or met the criteria for insomnia caseness as determined by self-report questionnaires. Participants completed outcome measures at 10 weeks (postintervention) and 18 weeks (follow-up) after randomization. All study visits were completed remotely, and the intervention was delivered digitally. Data were analyzed between December 12, 2018, and July 2, 2019. Interventions Digital CBT-I consisted of 6 weekly sessions of approximately 20 minutes each. Standard treatment reflected standard care. Women receiving standard treatment had no limits placed on the receipt of nonstudy treatments, including medication and psychotherapy. Main Outcomes and Measures All outcomes were assessed remotely using self-report questionnaires administered via online survey. The primary outcome was the change in insomnia symptom severity (measured by the Insomnia Severity Index) from baseline to postintervention. Secondary outcomes were sleep efficiency and nightly sleep duration (defined by sleep diary), global sleep quality (measured by the Pittsburgh Sleep Quality Index), depressive symptom severity (measured by the Edinburgh Postnatal Depression Scale), and anxiety symptom severity (measured by the Generalized Anxiety Disorder Scale-7). For each outcome, we also examined the change from baseline to follow-up. Results The 208 participants had a mean (SD) age of 33.6 (3.7) years and a mean (SD) gestational age of 17.6 (6.3) weeks at baseline. Most of the participants were white (138 [66.3%]), married or cohabiting (196 [94.2%]), had a college degree (180 [86.5%]), and earned $100 000 or more per year (141 [67.8%]). Women randomized to receive digital CBT-I experienced statistically significantly greater improvements in insomnia symptom severity from baseline to postintervention compared with women randomized to receive standard treatment (time-by-group interaction, difference = −0.36; 95% CI, −0.48 to −0.23; χ2 = 29.8;P Conclusions and Relevance In this trial, digital CBT was an effective, scalable, safe, and acceptable intervention for improving insomnia symptoms during pregnancy. Trial Registration ClinicalTrials.gov identifier:NCT02805998

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

Abstract: 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;Pfor trend 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.

Association of Suicide Prevention Interventions With Subsequent Suicide Attempts, Linkage to Follow-up Care, and Depression Symptoms for Acute Care Settings: A Systematic Review and Meta-analysis.

Abstract: Importance To prevent suicide deaths, acute care settings need tools to ensure individuals at risk of suicide access mental health care and remain safe until they do so Objective To examine the association of brief acute care suicide prevention interventions with patients’ subsequent suicide attempts, linkage to follow-up care, and depression symptoms at follow-up Data Sources Ovid MEDLINE, Scopus, CINAHL, PsychINFO, Embase, and references of included studies using concepts of suicide, prevention, and clinical trial to identify relevant articles published January 2000 to May 2019 Study Selection Studies describing clinical trials of single-encounter suicide prevention interventions were included Two reviewers independently reviewed all articles to determine eligibility for study inclusion Data Extraction and Synthesis Two reviewers independently abstracted data according to PRISMA guidelines and assessed studies’ risk of bias using the Cochrane Risk of Bias tool Data were pooled for each outcome using random-effects models Small study effects including publication bias were assessed using Peter and Egger regression tests Main Outcomes and Measures Three primary outcomes were examined: subsequent suicide attempts, linkage to follow-up care, and depression symptoms at follow-up Suicide attempts and linkage to follow-up care were measured using validated patient self-report measures and medical record review; odds ratios and Hedgesgstandardized mean differences were pooled to estimate effect sizes Depression symptoms were measured 2 to 3 months after the encounter using validated self-report measures, and pooled Hedgesgstandardized mean differences were used to estimate effect sizes Results A total of 14 studies, representing outcomes for 4270 patients, were included Pooled-effect estimates showed that brief suicide prevention interventions were associated with reduced subsequent suicide attempts (pooled odds ratio, 069; 95% CI, 053-089), increased linkage to follow-up (pooled odds ratio, 304; 95% CI, 179-517) but were not associated with reduced depression symptoms (Hedgesg = 028 [95% CI, −002 to 059) Conclusions and Relevance In this meta-analysis, breif suicide prevention interventions were associated with reduced subsequent suicide attempts Suicide prevention interventions delivered in a single in-person encounter may be effective at reducing subsequent suicide attempts and ensuring that patients engage in follow-up mental health care

Association of High-Potency Cannabis Use With Mental Health and Substance Use in Adolescence.

Abstract: Importance: Cannabis use is consistently linked to poorer mental health outcomes, and there is evidence that use of higher-potency cannabis increases these risks. To date, no studies have described the association between cannabis potency and concurrent mental health in a general population sample or addressed confounding using longitudinal data. Objective: To explore the association between cannabis potency and substance use and mental health outcomes, accounting for preceding mental health and frequency of cannabis use. Design, setting, and participants: This cohort study used data from the Avon Longitudinal Study of Parents and Children, a UK birth cohort of participants born between April 1, 1991, and December 31, 1992. Present data on outcomes and exposures were collected between June 2015 and October 2017 from 1087 participants at 24 years of age who reported recent cannabis use. Exposures: Self-reported type of cannabis most commonly used in the past year, coded to a binary exposure of use of high-potency cannabis or lower-potency cannabis. Main outcomes and measures: Outcomes were reported frequency of cannabis use, reported cannabis use problems, recent use of other illicit drugs, tobacco dependence, alcohol use disorder, depression, generalized anxiety disorder, and psychotic-like experiences. The study used secondary data; consequently, the hypotheses were formulated after data collection. Results: Past-year cannabis use was reported by 1087 participants (580 women; mean [SD] age at onset of cannabis use, 16.7 [3.0] years). Of these, 141 participants (13.0%) reported the use of high-potency cannabis. Use of high-potency cannabis was associated with increased frequency of cannabis use (adjusted odds ratio [AOR], 4.38; 95% CI, 2.89-6.63), cannabis problems (AOR, 4.08; 95% CI, 1.41-11.81), and increased likelihood of anxiety disorder (AOR, 1.92; 95% CI, 1.11-3.32). Adjustment for frequency of cannabis use attenuated the association with psychotic experiences (AOR 1.29; 95% CI, 0.67-2.50), tobacco dependence (AOR, 1.42; 95% CI, 0.89-2.27), and other illicit drug use (AOR, 1.29; 95% CI, 0.77-2.17). There was no evidence of association between the use of high-potency cannabis and alcohol use disorder or depression.

Male and Female Physician Suicidality: A Systematic Review and Meta-analysis.

Abstract: Importance Population-based findings on physician suicide are of great relevance because this is an important and understudied topic. Objective To evaluate male and female physician suicide risks compared with the general population from 1980 to date and test whether there is a reduction of SMR in cohorts after 1980 compared with before 1980 via a meta-analysis, modeling studies, and a systematic review emphasizing physician suicide risk factors. Data Sources This study uses studies retrieved from PubMed, Scielo, PsycINFO, and Lilacs for human studies published by October 3, 2019, using the search term “(((suicide) OR (self-harm) OR (suicidality)) AND ((physicians) OR (doctors))).” Databases were also searched from countries listed in articles selected for review. Data were also extracted from an existing article by other authors to facilitate comparisons of the pre-1980 suicide rate with the post-1980 changes. Study Selection Original articles assessing male and/or female physician suicide were included; for the meta-analysis, only cohorts from 1980 to the present were included. Data Extraction and Synthesis The preregistered systematic review and meta-analysis followed Cochrane, PRISMA, and MOOSE guidelines. Data were extracted into standardized tables per a prespecified structured checklist, and quality scores were added. Heterogeneity was tested viaQtest,I2, andτ2. For pooled effect estimates, we used random-effects models. The Begg and Egger tests, sensitivity analyses, and meta-regression were performed. Proportional mortality ratios were presented when SMR data could not be extracted. Main Outcomes and Measures Suicide SMRs for male and female physicians from 1980 to the present and changes over time (before and after 1980). Results Of 7877 search results, 32 articles were included in the systematic review and 9 articles and data sets in the meta-analysis. Meta-analysis showed a significantly higher suicide SMR in female physicians compared with women in general (1.46 [95% CI, 1.02-1.91]) and a significantly lower suicide SMR in male physicians compared with men in general (0.67 [95% CI, 0.55-0.79]). Male and female physician SMRs significantly decreased after 1980 vs before 1980 (male physicians: SMR, −0.84 [95% CI, −1.26 to −0.42];P Conclusions and Relevance In this study, suicide SMR was found to be high in female physicians and low in male physicians since 1980 but also to have decreased over time in both groups. Physician suicides are multifactorial, and further research into these factors is critical.

Prediction of Sex-Specific Suicide Risk Using Machine Learning and Single-Payer Health Care Registry Data From Denmark.

Abstract: Importance Suicide is a public health problem, with multiple causes that are poorly understood. The increased focus on combining health care data with machine-learning approaches in psychiatry may help advance the understanding of suicide risk. Objective To examine sex-specific risk profiles for death from suicide using machine-learning methods and data from the population of Denmark. Design, Setting, and Participants A case-cohort study nested within 8 national Danish health and social registries was conducted from January 1, 1995, through December 31, 2015. The source population was all persons born or residing in Denmark as of January 1, 1995. Data were analyzed from November 5, 2018, through May 13, 2019. Exposures Exposures included 1339 variables spanning domains of suicide risk factors. Main Outcomes and Measures Death from suicide from the Danish cause of death registry. Results A total of 14 103 individuals died by suicide between 1995 and 2015 (10 152 men [72.0%]; mean [SD] age, 43.5 [18.8] years and 3951 women [28.0%]; age, 47.6 [18.8] years). The comparison subcohort was a 5% random sample (n = 265 183) of living individuals in Denmark on January 1, 1995 (130 591 men [49.2%]; age, 37.4 [21.8] years and 134 592 women [50.8%]; age, 39.9 [23.4] years). With use of classification trees and random forests, sex-specific differences were noted in risk for suicide, with physical health more important to men’s suicide risk than women’s suicide risk. Psychiatric disorders and possibly associated medications were important to suicide risk, with specific results that may increase clarity in the literature. Generally, diagnoses and medications measured 48 months before suicide were more important indicators of suicide risk than when measured 6 months earlier. Individuals in the top 5% of predicted suicide risk appeared to account for 32.0% of all suicide cases in men and 53.4% of all cases in women. Conclusions and Relevance Despite decades of research on suicide risk factors, understanding of suicide remains poor. In this study, the first to date to develop risk profiles for suicide based on data from a full population, apparent consistency with what is known about suicide risk was noted, as well as potentially important, understudied risk factors with evidence of unique suicide risk profiles among specific subpopulations.

Clinical Validity of DSM-5 Attenuated Psychosis Syndrome: Advances in Diagnosis, Prognosis, and Treatment.

Abstract: Importance Since the release of theDSM-5diagnosis of attenuated psychosis syndrome (DSM-5–APS) in 2013, several research studies have investigated its clinical validity. Although critical and narrative reviews have reviewed these progresses, no systematic review has comprehensively summarized the available evidence regarding the clinical validity ofDSM-5–APS. Objective To provide current evidence on the clinical validity ofDSM-5–APS, focusing on recent advances in diagnosis, prognosis, and treatment. Evidence Review A multistep literature search using the Web of Science database, Cochrane Central Register of Reviews, Ovid/PsychINFO, conference proceedings, and trial registries from database inception to June 16, 2019, was conducted following PRISMA and MOOSE guidelines and PROSPERO protocol. Studies with original data investigating individuals diagnosed usingDSM-5–APS or meeting comparable criteria were included. The results of the systematic review were summarized in tables and narratively synthesized against established evidence-based antecedent, concurrent, and prognostic validators. A quantitative meta-analysis was conducted to explore the cumulative risk of psychosis onset at 6, 12, 24, and 36 months in individuals diagnosed usingDSM-5–APS criteria. Findings The systematic review included 56 articles, which reported on 124 validators, including 15 antecedent, 55 concurrent, and 54 prognostic validators. The epidemiological prevalence of the general non–help-seeking young population meetingDSM-5–APS criteria was 0.3%; the prevalence of individuals meetingDSM-5–APS criteria was variable in clinical samples. The interrater reliability forDSM-5–APS criteria was comparable with that of otherDSM-5mental disorders and can be optimized by the use of specific psychometric instruments.DSM-5–APS criteria were associated with frequent depressive comorbid disorders, distress, suicidality, and functional impairment. The meta-analysis included 23 prospective cohort studies, including 2376 individuals. The meta-analytical risk of psychosis onset was 11% at 6 months, 15% at 12 months, 20% at 24 months, and 23% at 36 months. Research into predisposing and precipitating epidemiological factors, neurobiological correlates, and effective treatments forDSM-5–APS criteria has been limited. Conclusions and Relevance Over recent years,DSM-5–APS criteria have received substantial concurrent and prognostic validation, mostly driven by research into the clinical high-risk state for psychosis. Precipitating and predisposing factors, neurobiological correlates, and effective treatments are undetermined to date.

Association of Outdoor Artificial Light at Night With Mental Disorders and Sleep Patterns Among US Adolescents

Abstract: Importance Indoor nighttime light exposure influences sleep and circadian rhythms and is known to affect mood-associated brain circuits in animals. However, little is known about the association between levels of nighttime outdoor light and sleep and mental health in the population, especially among adolescents. Objective To estimate associations of outdoor artificial light at night (ALAN) with sleep patterns and past-year mental disorder among US adolescents. Design, Setting, and Participants This population-based, cross-sectional study of US adolescents used the National Comorbidity Survey–Adolescent Supplement, a nationally representative cross-sectional survey conducted from February 2001 through January 2004. A probability sample of adolescents aged 13 to 18 years was included. Analyses were conducted between February 2019 and April 2020. Exposures Levels of outdoor ALAN, measured by satellite, with means calculated within census block groups. ALAN values were transformed into units of radiance (nW/cm2/sr). Main Outcomes and Measures Self-reported habitual sleep patterns (weeknight bedtime, weeknight sleep duration, weekend bedtime delay, and weekend oversleep) and past-year mood, anxiety, behavior, and substance use disorders, measured via an in-person structured diagnostic interview. Parent-reported information was included in behavior disorder diagnoses. Results Among 10 123 adolescents (4953 boys [51.3%]; mean [SE] age, 15.2 [0.06] years [weighted]; 6483 for behavior disorder outcomes), ALAN was positively associated with indicators of social disadvantage, such as racial/ethnic minority status (median [IQR] ALAN: white adolescents, 12.96 [30.51] nW/cm2/sr; Hispanic adolescents: 38.54 [47.84] nW/cm2/sr; non-Hispanic black adolescents: 37.39 [51.88] nW/cm2/sr; adolescents of other races/ethnicities: 30.94 [49.93] nW/cm2/sr;P 6: 21.46 [34.38] nW/cm2/sr;P = .005). After adjustment for several sociodemographic characteristics, as well as area-level population density and socioeconomic status, this study found that higher ALAN levels were associated with later weeknight bedtime, and those in the lowest quartile of ALAN reported the longest weeknight sleep duration. Those in the highest quartile of ALAN went to bed 29 (95% CI, 15-43) minutes later and reported 11 (95% CI, 19-2) fewer minutes of sleep than those in the lowest quartile. ALAN was also positively associated with prevalence of past-year mood and anxiety disorder: each median absolute deviation increase in ALAN was associated with 1.07 (95% CI, 1.00-1.14) times the odds of mood disorder and 1.10 (95% CI, 1.05-1.16) times the odds of anxiety disorder. Further analyses revealed associations with bipolar disorder (odds ratio [OR], 1.19 [95% CI, 1.05-1.35]), specific phobias (OR, 1.18 [95% CI, 1.11-1.26]), and major depressive disorder or dysthymia (OR, 1.07 [95% CI, 1.00-1.15]). Among adolescent girls, differences in weeknight bedtime by ALAN (third and fourth quartiles vs first quartile) were greater with increasing years since menarche (F3, 8.15;P Conclusions and Relevance In this study, area-level outdoor ALAN was associated with less favorable sleep patterns and mood and anxiety disorder in adolescents. Future studies should elucidate whether interventions to reduce exposure to ALAN may positively affect mental and sleep health.