Defining the Genetic, Genomic, Cellular, and Diagnostic Architectures of Psychiatric Disorders.

Studies of the genetics of psychiatric disorders have become one of the most exciting and fast-moving areas in human genetics. A decade ago, there were few reproducible findings, and now there are hundreds. In this review, we focus on the findings that have illuminated the genetic architecture of psychiatric disorders and the challenges of using these findings to inform our understanding of pathophysiology. The evidence is now overwhelming that psychiatric disorders are "polygenic"-that many genetic loci contribute to risk. With the exception of a subset of those with ASD, few individuals with a psychiatric disorder have a single, deterministic genetic cause; rather, developing a psychiatric disorder is influenced by hundreds of different genetic variants, consistent with a polygenic model. As progressively larger studies have uncovered more about their genetic architecture, the need to elucidate additional architectures has become clear. Even if we were to have complete knowledge of the genetic architecture of a psychiatric disorder, full understanding requires deep knowledge of the functional genomic architecture-the implicated loci impact regulatory processes that influence gene expression and the functional coordination of genes that control biological processes. Following from this is cellular architecture: of all brain regions, cell types, and developmental stages, where and when are the functional architectures operative? Given that the genetic architectures of different psychiatric disorders often strongly overlap, we are challenged to re-evaluate and refine the diagnostic architectures of psychiatric disorders using fundamental genetic and neurobiological data.

The causal effect of mental health on labor market outcomes: The case of stress-related mental disorders following a human-made disaster.

As disasters increase due to climate change, population density, epidemics, and technology, information is needed about postdisaster consequences for people's mental health and how stress-related mental disorders affect multiple spheres of life, including labor-market attachment. We tested the causal hypothesis that individuals who developed stress-related mental disorders as a consequence of their disaster exposure experienced subsequent weak labor-market attachment and poor work-related outcomes. We leveraged a natural experiment in an instrumental variables model, studying a 2004 fireworks factory explosion disaster that precipitated the onset of stress-related disorders (posttraumatic stress disorder, anxiety, and depression) among individuals in the local community (N = 86,726). We measured labor-market outcomes using longitudinal population-level administrative data: sick leave, unemployment benefits, early retirement pension, and income from wages from 2007 to 2010. We found that individuals who developed a stress-related disorder after the disaster were likely to go on sickness benefit, both in the short- and long-term, were likely to use unemployment benefits and to lose wage income in the long term. Stress-related disorders did not increase the likelihood of early retirement. The natural experiment design minimized the possibility that omitted confounders biased these effects of mental health on work outcomes. Addressing the mental health and employment needs of survivors after a traumatic experience may improve their labor-market outcomes and their nations' economic outputs.

Prevalence of adolescent mental disorders in Kenya, Indonesia, and Viet Nam measured by the National Adolescent Mental Health Surveys (NAMHS): a multi-national cross-sectional study.

BACKGROUND: Mental disorders are the leading global cause of health burden among adolescents. However, prevalence data for mental disorders among adolescents in low-income and middle-income countries are scarce with often limited generalisability. This study aimed to generate nationally representative prevalence estimates for mental disorders in adolescents in Kenya, Indonesia, and Viet Nam. METHODS: As part of the National Adolescent Mental Health Surveys (NAMHS), a multinational cross-sectional study, nationally representative household surveys were conducted in Kenya, Indonesia, and Viet Nam between March and December, 2021. Adolescents aged 10-17 years and their primary caregiver were interviewed from households selected randomly according to sampling frames specifically designed to elicit nationally representative results. Six mental disorders (social phobia, generalised anxiety disorder, major depressive disorder, post-traumatic stress disorder, conduct disorder, and attention-deficit hyperactivity disorder) were assessed with the Diagnostic Interview Schedule for Children, Version 5. Suicidal behaviours and self-harm in the past 12 months were also assessed. Prevalence in the past 12 months and past 4 weeks was calculated for each mental disorder and collectively for any mental disorder (ie, of the six mental disorders assessed). Prevalence of suicidal behaviours (ie, ideation, planning, and attempt) and self-harm in the past 12 months was calculated, along with adjusted odds ratios (aORs) to show the association with prevalence of any mental disorder in the past 12 months. Inverse probability weighting was applied to generate national estimates with corresponding 95% CIs. FINDINGS: Final samples consisted of 5155 households (ie, adolescent and primary caregiver pairs) from Kenya, 5664 households from Indonesia, and 5996 households from Viet Nam. In Kenya, 2416 (46·9%) adolescents were male and 2739 (53·1%) were female; in Indonesia, 2803 (49·5%) adolescents were male and 2861 (50·5%) were female; and in Viet Nam, 3151 (52·5%) were male and 2845 (47·4%) were female. Prevalence of any mental disorder in the past 12 months was 12·1% (95% CI 10·9-13·5) in Kenya, 5·5% (4·3-6·9) in Indonesia, and 3·3% (2·7-4·1) in Viet Nam. Prevalence in the past 4 weeks was 9·4% (8·3-10·6) in Kenya, 4·4% (3·4-5·6) in Indonesia, and 2·7% (2·2-3·3) in Viet Nam. The prevalence of suicidal behaviours in the past 12 months was low in all three countries, with suicide ideation ranging from 1·4% in Indonesia (1·0-2·0) and Viet Nam (1·0-1·9) to 4·6% (3·9-5·3) in Kenya, suicide planning ranging from 0·4% in Indonesia (0·3-0·8) and Viet Nam (0·2-0·6) to 2·4% (1·9-2·9) in Kenya, and suicide attempts ranging from 0·2% in Indonesia (0·1-0·4) and Viet Nam (0·1-0·3) to 1·0% (0·7-1·4) in Kenya. The prevalence of self-harm in the past 12 months was also low in all three countries, ranging from 0·9% (0·6-1·3) in Indonesia to 1·2% (0·9-1·7) in Kenya. However, the prevalence of suicidal behaviours and self-harm in the past 12 months was significantly higher among those with any mental disorder in the past 12 months than those without (eg, aORs for suicidal ideation ranged from 7·1 [3·1-15·9] in Indonesia to 14·7 [7·5-28·6] in Viet Nam). INTERPRETATION: NAMHS provides the first national adolescent mental disorders prevalence estimates for Kenya, Indonesia, and Viet Nam. These data can inform mental health and broader health policies in low-income and middle-income countries. FUNDING: The University of Queensland in America (TUQIA) through support from Pivotal Ventures, a Melinda French Gates company.

Exploring the genetic etiology across the continuum of the general psychopathology factor: a Swedish population-based family and twin study.

Psychiatric comorbidity can be accounted for by a latent general psychopathology factor (p factor), which quantifies the variance that is shared to varying degrees by every dimension of psychopathology. It is unclear whether the entire continuum of the p factor shares the same genetic origin. We investigated whether mild, moderate, and extreme elevations on the p factor shared the same genetic etiology by, first, examining the linearity of the association between p factors across siblings (N = 580,891 pairs). Second, we estimated the group heritability in a twin sample (N = 17,170 pairs), which involves testing whether the same genetic variants influence both extreme and normal variations in the p factor. In both samples, the p factor was based on 10 register-based psychiatric diagnoses. Results showed that the association between siblings' p factors appeared linear, even into the extreme range. Likewise, the twin group heritabilities ranged from 0.42 to 0.45 (95% CI: 0.33-0.57) depending on the thresholds defining the probands (2-3.33 SD beyond the mean; >2 SD beyond the mean; >4.33 SD beyond the mean; and >5.33 SD beyond the mean), and these estimates were highly similar to the estimated individual differences heritability (0.41, 95% CI: 0.39-0.43), indicating that scores above and below these thresholds shared a common genetic origin. Together, these results suggest that the entire continuum of the p factor shares the same genetic origin, with common genetic variants likely playing an important role. This implies, first, genetic risk factors for the aspect that is shared between all forms of psychopathology (i.e., genetic risk factors for the p factor) might be generalizable between population-based cohorts with a higher prevalence of milder cases, and clinical samples with a preponderance of more severe cases. Second, prioritizing low-cost genome-wide association studies capable of identifying common genetic variants, rather than expensive whole genome sequencing that can identify rare variants, may increase the efficiency when studying the genetic architecture of the p factor.

Patterns of stressful life events and polygenic scores for five mental disorders and neuroticism among adults with depression.

The dominant ('general') version of the diathesis-stress theory of depression views stressors and genetic vulnerability as independent risks. In the Australian Genetics of Depression Study (N = 14,146; 75% female), we tested whether polygenic scores (PGS) for major depression, bipolar disorder, schizophrenia, anxiety, ADHD, and neuroticism were associated with reported exposure to 32 childhood, past-year, lifetime, and accumulated stressful life events (SLEs). In false discovery rate-corrected models, the clearest PGS-SLE relationships were for the ADHD- and depression-PGSs, and to a lesser extent, the anxiety- and schizophrenia-PGSs. We describe the associations for childhood and accumulated SLEs, and the 2-3 strongest past-year/lifetime SLE associations. Higher ADHD-PGS was associated with all childhood SLEs (emotional abuse, emotional neglect, physical neglect; ORs = 1.09-1.14; p's < 1.3 × 10-5), more accumulated SLEs, and reported exposure to sudden violent death (OR = 1.23; p = 3.6 × 10-5), legal troubles (OR = 1.15; p = 0.003), and sudden accidental death (OR = 1.14; p = 0.006). Higher depression-PGS was associated with all childhood SLEs (ORs = 1.07-1.12; p's < 0.013), more accumulated SLEs, and severe human suffering (OR = 1.17; p = 0.003), assault with a weapon (OR = 1.12; p = 0.003), and living in unpleasant surroundings (OR = 1.11; p = 0.001). Higher anxiety-PGS was associated with childhood emotional abuse (OR = 1.08; p = 1.6 × 10-4), more accumulated SLEs, and serious accident (OR = 1.23; p = 0.004), physical assault (OR = 1.08; p = 2.2 × 10-4), and transportation accident (OR = 1.07; p = 0.001). Higher schizophrenia-PGS was associated with all childhood SLEs (ORs = 1.12-1.19; p's < 9.3-8), more accumulated SLEs, and severe human suffering (OR = 1.16; p = 0.003). Higher neuroticism-PGS was associated with living in unpleasant surroundings (OR = 1.09; p = 0.007) and major financial troubles (OR = 1.06; p = 0.014). A reversed pattern was seen for the bipolar-PGS, with lower odds of reported physical assault (OR = 0.95; p = 0.014), major financial troubles (OR = 0.93; p = 0.004), and living in unpleasant surroundings (OR = 0.92; p = 0.007). Genetic risk for several mental disorders influences reported exposure to SLEs among adults with moderately severe, recurrent depression. Our findings emphasise that stressors and diatheses are inter-dependent and challenge diagnosis and subtyping (e.g., reactive/endogenous) based on life events.

Suicide Attempts After a Diagnosis of Polycystic Ovary Syndrome : A Cohort Study.

BACKGROUND: Limited evidence exists about suicide risk in persons with polycystic ovary syndrome (PCOS). OBJECTIVE: To assess suicide risk in persons with PCOS, accounting for psychiatric comorbid conditions and age group. DESIGN: Cohort study. SETTING: Data from the Taiwanese nationwide database from 1997 to 2012. PATIENTS: A cohort of 18 960 patients diagnosed with PCOS, each matched with control participants in a 1:10 ratio on the basis of age, psychiatric comorbid conditions, urbanization level, and income. Suicide attempts were evaluated using Cox regression models. MEASUREMENTS: Suicide risk with hazard ratios (HRs). RESULTS: Participants with PCOS had a notable 8.47-fold increase in risk for suicide attempt compared with the control group (HR, 8.47 [95% CI, 7.54 to 9.51]), after adjustment for demographic characteristics, psychiatric comorbid conditions, Charlson Comorbidity Index scores, and frequency of all-cause clinical visits. The elevated risk was evident across the adolescent (HR, 5.38 [CI, 3.93 to 7.37]), young adult (<40 years; HR, 9.15 [CI, 8.03 to 10.42]), and older adult (HR, 3.75 [CI, 2.23 to 6.28]) groups. Sensitivity analyses involving the exclusion of data from the first year or the first 3 years of observation yielded consistent results. LIMITATION: Potential underestimation of PCOS and mental disorder prevalence due to use of administrative claims data; lack of clinical data, such as body mass index and depressive symptoms; and no assessment of a confounding effect of valproic acid exposure. CONCLUSION: This study underscores the heightened risk for suicide attempt that persons with PCOS face, even after adjustment for demographics, psychiatric comorbid conditions, physical conditions, and all-cause clinical visits. This suggests the importance of routine monitoring of mental health and suicide risk in persons diagnosed with PCOS. PRIMARY FUNDING SOURCE: Taipei Veterans General Hospital, Yen Tjing Ling Medical Foundation, and Ministry of Science and Technology of Taiwan.

Severe mental illness: cardiovascular risk assessment and management.

Patients with severe mental illness (SMI) including schizophrenia and bipolar disorder die on average 15-20 years earlier than the general population often due to sudden death that, in most cases, is caused by cardiovascular disease. This state-of-the-art review aims to address the complex association between SMI and cardiovascular risk, explore disparities in cardiovascular care pathways, describe how to adequately predict cardiovascular outcomes, and propose targeted interventions to improve cardiovascular health in patients with SMI. These patients have an adverse cardiovascular risk factor profile due to an interplay between biological factors such as chronic inflammation, patient factors such as excessive smoking, and healthcare system factors such as stigma and discrimination. Several disparities in cardiovascular care pathways have been demonstrated in patients with SMI, resulting in a 47% lower likelihood of undergoing invasive coronary procedures and substantially lower rates of prescribed standard secondary prevention medications compared with the general population. Although early cardiovascular risk prediction is important, conventional risk prediction models do not accurately predict long-term cardiovascular outcomes as cardiovascular disease and mortality are only partly driven by traditional risk factors in this patient group. As such, SMI-specific risk prediction models and clinical tools such as the electrocardiogram and echocardiogram are necessary when assessing and managing cardiovascular risk associated with SMI. In conclusion, there is a necessity for differentiated cardiovascular care in patients with SMI. By addressing factors involved in the excess cardiovascular risk, reconsidering risk stratification approaches, and implementing multidisciplinary care models, clinicians can take steps towards improving cardiovascular health and long-term outcomes in patients with SMI.

Cardiovascular risk management among individuals with type 2 diabetes and severe mental illness: a cohort study.

AIMS/HYPOTHESIS: The aim of this study was to compare cardiovascular risk management among people with type 2 diabetes according to severe mental illness (SMI) status. METHODS: We used linked electronic data to perform a retrospective cohort study of adults diagnosed with type 2 diabetes in Scotland between 2004 and 2020, ascertaining their history of SMI from hospital admission records. We compared total cholesterol, systolic BP and HbA1c target level achievement 1 year after diabetes diagnosis, and receipt of a statin prescription at diagnosis and 1 year thereafter, by SMI status using logistic regression, adjusting for sociodemographic factors and clinical history. RESULTS: We included 291,644 individuals with type 2 diabetes, of whom 1.0% had schizophrenia, 0.5% had bipolar disorder and 3.3% had major depression. People with SMI were less likely to achieve cholesterol targets, although this difference did not reach statistical significance for all disorders. However, people with SMI were more likely to achieve systolic BP targets compared to those without SMI, with effect estimates being largest for schizophrenia (men: adjusted OR 1.72; 95% CI 1.49, 1.98; women: OR 1.64; 95% CI 1.38, 1.96). HbA1c target achievement differed by SMI disorder and sex. Among people without previous CVD, statin prescribing was similar or better in those with vs those without SMI at diabetes diagnosis and 1 year later. In people with prior CVD, SMI was associated with lower odds of statin prescribing at diabetes diagnosis (schizophrenia: OR 0.54; 95% CI 0.43, 0.68, bipolar disorder: OR 0.75; 95% CI 0.56, 1.01, major depression: OR 0.92; 95% CI 0.83, 1.01), with this difference generally persisting 1 year later. CONCLUSIONS/INTERPRETATION: We found disparities in cholesterol target achievement and statin prescribing by SMI status. This reinforces the importance of clinical review of statin prescribing for secondary prevention of CVD, particularly among people with SMI.

Higher Risk of Mental Illness in Patients With Diagnosed and Untreated Unruptured Intracranial Aneurysm: Findings From a Nationwide Cohort Study.

BACKGROUND: We aimed to investigate the association between a diagnosis of untreated unruptured intracranial aneurysms (UIAs) and the development of mental illness. METHODS: This retrospective, propensity-score-matched cohort study was based on the nationwide South Korean database. The UIA diagnosis group included participants newly diagnosed with UIA between 2011 and 2019. For a well-matched control group, patients diagnosed with an acute upper respiratory infection but without UIA during the same period were selected through 1:4 matching based on propensity scores, which were calculated using age, sex, economic status, and comorbidities. The study's outcome measure encompassed the incidence of mental illnesses over a 10-year period, using International Classification of Diseases-Tenth Revision codes for anxiety, stress, depressive, bipolar, and eating disorders, insomnia, and alcohol or drug misuse. RESULTS: After propensity score matching, 85 438 participants with untreated UIAs (50.75% male; average age, 56.41 [±13.82] years; follow-up, 4.21 [±2.56] years) and 331 123 controls (49.44% males; average age, 56.69 [±12.92] years; follow-up, 7.48 [±2.12] years) were compared. Incidence rate of mental illness was higher in the UIA group (113.07 versus 90.41 per 1000 person-years; hazard ratio, 1.104 [95% CI, 1.089-1.119]). The risk of mental illness varied slightly by sex (males: hazard ratio, 1.131 [95% CI, 1.108-1.155]; females: hazard ratio, 1.082 [95% CI, 1.063-1.103]). Hazard ratios showed a U-shaped relationship with age, peaking in younger age groups, decreasing in middle-aged groups, and slightly increasing in older age groups, especially in patients with severe mental illness receiving psychotherapy. CONCLUSIONS: Our findings indicate a higher risk of mental illness in patients with UIA diagnosis in specific demographic groups, suggesting a possible psychological burden associated with UIAs. Clinicians treating cerebral aneurysms should be aware that the psychological burden caused by the diagnosis of UIA itself could contribute to mental illness and strive to provide comprehensive care for these patients.

Incidence of oncogenic HPV infection in women with and without mental illness: A population-based cohort study in Sweden.

BACKGROUND: Women with mental illness experience an increased risk of cervical cancer. The excess risk is partly due to low participation in cervical screening; however, it remains unknown whether it is also attributable to an increased risk of infection with human papillomavirus (HPV). We aimed to examine whether women with mental illness had an increased infection rate of HPV compared to women without mental illness. METHODS AND FINDINGS: Using a cohort design, we analyzed all 337,116 women aged 30 to 64 and living in Stockholm, who had a negative test result of 14 high-risk HPV subtypes in HPV-based screening, during August 2014 to December 2019. We defined women as exposed to mental illness if they had a specialist diagnosis of mental disorder or had a filled prescription of psychotropic medication. We identified incident infection of any high-risk HPV during follow-up and fitted multivariable Cox models to estimate hazard ratios (HR) with 95% confidence intervals (CI) for HPV infection. A total of 3,263 women were tested positive for high-risk HPV during follow-up (median: 2.21 years; range: 0 to 5.42 years). The absolute infection rate of HPV was higher among women with a specialist diagnosis of mental disorder (HR = 1.45; 95% CI [1.34, 1.57]; p < 0.001) or a filled prescription of psychotropic medication (HR = 1.67; 95% CI [1.55, 1.79]; p < 0.001), compared to women without such. The increment in absolute infection rate was noted for depression, anxiety, stress-related disorder, substance-related disorder, and ADHD, and for use of antidepressants, anxiolytics, sedatives, and hypnotics, and was consistent across age groups. The main limitations included selection of the female population in Stockholm as they must have at least 1 negative test result of HPV, and relatively short follow-up as HPV-based screening was only introduced in 2014 in Stockholm. CONCLUSIONS: Mental illness is associated with an increased infection rate of high-risk HPV in women. Our findings motivate refined approaches to facilitate the WHO elimination agenda of cervical cancer among these marginalized women worldwide.

Risk of common psychiatric disorders, suicidal behaviours, and premature mortality following violent victimisation: A matched cohort and sibling-comparison study of 127,628 people who experienced violence in Finland and Sweden.

BACKGROUND: Associations between violent victimisation and psychiatric disorders are hypothesised to be bidirectional, but the role of violent victimisation in the aetiologies of psychiatric disorders and other adverse outcomes remains unclear. We aimed to estimate associations between violent victimisation and subsequent common psychiatric disorders, suicidal behaviours, and premature mortality while accounting for unmeasured familial confounders. METHODS AND FINDINGS: Using nationwide registers, we identified a total of 127,628 individuals born in Finland (1987 to 2004) and Sweden (1973 to 2004) who had experienced violent victimisation, defined as either hospital admissions or secondary care outpatient visits for assault-related injuries. These were age- and sex-matched with up to 10 individuals in the general population (n = 1,276,215). Additionally, we matched those who had experienced violent victimisation with their unaffected siblings (n = 132,408). Outcomes included depression, anxiety, personality disorders, alcohol use disorders, drug use disorders, suicidal behaviours, and premature mortality. Participants were followed from the victimisation date until the date of the outcome, emigration, death, or December 31, 2020, whichever occurred first. Country-specific associations were estimated using stratified Cox regression models, which also accounted for unmeasured familial confounders via sibling comparisons. The country-specific associations were then pooled using meta-analytic models. Among 127,628 patients (69.0% male) who had experienced violent victimisation, the median age at first violent victimisation was 21 (interquartile range: 18 to 26) years. Incidence of all outcomes was larger in those who were exposed to violent victimisation compared to population controls, ranging from 2.3 (95% confidence interval (CI) [2.2; 2.4]) per 1,000 person-years for premature mortality (compared with 0.6, 95% CI [0.6; 0.6], in controls) to 22.5 (95% CI [22.3; 22.8]) per 1,000 person-years for anxiety (compared with 7.3, 95% CI [7.3; 7.4], in controls). In adjusted models, people who had experienced violent victimisation were between 2 to 3 times as likely as their siblings to develop any of the outcomes, ranging from adjusted hazard ratio [aHR] 1.7 (95% CI [1.7; 1.8]) for depression to 3.0 (95% CI [2.9; 3.1]) for drug use disorders. Risks remained elevated 2 years post-victimisation, ranging from aHR 1.4 (95% CI [1.3; 1.5]) for depression to 2.3 (95% CI [2.2; 2.4]) for drug use disorders. Our reliance on secondary care data likely excluded individuals with milder assault-related injuries and less severe psychiatric symptoms, thus suggesting that our estimates may be conservative. Another limitation is the possibility of residual genetic confounding, as full siblings share on average about half of their co-segregating genes. However, the associations remained robust even after adjusting for both measured and unmeasured familial confounders. CONCLUSIONS: In this longitudinal cross-national cohort study, we observed that those who had experienced violent victimisation were at least twice as likely as their unaffected siblings to develop common psychiatric disorders (i.e., depression, anxiety, personality disorder, and alcohol and drug use disorders), engage in suicidal behaviours, and to die prematurely. Importantly, these risk elevations remained 2 years after the first victimisation event. Improving clinical assessment, management, and aftercare psychosocial support could therefore potentially reduce rates of common psychiatric disorders, suicidality, and premature mortality in individuals experiencing violent victimisation.

Deaths with COVID-19 and from all-causes following first-ever SARS-CoV-2 infection in individuals with preexisting mental disorders: A national cohort study from Czechia.

BACKGROUND: Evidence suggests reduced survival rates following Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in people with preexisting mental disorders, especially psychotic disorders, before the broad introduction of vaccines. It remains unknown whether this elevated mortality risk persisted at later phases of the pandemic and when accounting for the confounding effect of vaccination uptake and clinically recorded physical comorbidities. METHODS AND FINDINGS: We used data from Czech national health registers to identify first-ever serologically confirmed SARS-CoV-2 infections in 5 epochs related to different phases of the pandemic: 1st March 2020 to 30th September 2020, 1st October 2020 to 26th December 2020, 27th December 2020 to 31st March 2021, 1st April 2021 to 31st October 2021, and 1st November 2021 to 29th February 2022. In these people, we ascertained cases of mental disorders using 2 approaches: (1) per the International Classification of Diseases 10th Revision (ICD-10) diagnostic codes for substance use, psychotic, affective, and anxiety disorders; and (2) per ICD-10 diagnostic codes for the above mental disorders coupled with a prescription for anxiolytics/hypnotics/sedatives, antidepressants, antipsychotics, or stimulants per the Anatomical Therapeutic Chemical (ATC) classification codes. We matched individuals with preexisting mental disorders with counterparts who had no recorded mental disorders on age, sex, month and year of infection, vaccination status, and the Charlson Comorbidity Index (CCI). We assessed deaths with Coronavirus Disease 2019 (COVID-19) and from all-causes in the time period of 28 and 60 days following the infection using stratified Cox proportional hazards models, adjusting for matching variables and additional confounders. The number of individuals in matched-cohorts ranged from 1,328 in epoch 1 to 854,079 in epoch 5. The proportion of females ranged from 34.98% in people diagnosed with substance use disorders in epoch 3 to 71.16% in individuals diagnosed and treated with anxiety disorders in epoch 5. The mean age ranged from 40.97 years (standard deviation [SD] = 15.69 years) in individuals diagnosed with substance use disorders in epoch 5 to 56.04 years (SD = 18.37 years) in people diagnosed with psychotic disorders in epoch 2. People diagnosed with or diagnosed and treated for psychotic disorders had a consistently elevated risk of dying with COVID-19 in epochs 2, 3, 4, and 5, with adjusted hazard ratios (aHRs) ranging from 1.46 [95% confidence intervals (CIs), 1.18, 1.79] to 1.93 [95% CIs, 1.12, 3.32]. This patient group demonstrated also a consistently elevated risk of all-cause mortality in epochs 2, 3, 4, and 5 (aHR from 1.43 [95% CIs, 1.23, 1.66] to 1.99 [95% CIs, 1.25, 3.16]). The models could not be reliably fit for psychotic disorders in epoch 1. People diagnosed with substance use disorders had an increased risk of all-cause mortality 28 days postinfection in epoch 3, 4, and 5 (aHR from 1.30 [95% CIs, 1.14, 1.47] to 1.59 [95% CIs, 1.19, 2.12]) and 60 days postinfection in epoch 2, 3, 4, and 5 (aHR from 1.22 [95% CIs, 1.08, 1.38] to 1.52 [95% CIs, 1.16, 1.98]). Cases ascertained based on diagnosis of substance use disorders and treatment had increased risk of all-cause mortality in epoch 2, 3, 4, and 5 (aHR from 1.22 [95% CIs, 1.03, 1.43] to 1.91 [95% CIs, 1.25, 2.91]). The models could not be reliably fit for substance use disorders in epoch 1. In contrast to these, people diagnosed with anxiety disorders had a decreased risk of death with COVID-19 in epoch 2, 3, and 5 (aHR from 0.78 [95% CIs, 0.69, 0.88] to 0.89 [95% CIs, 0.81, 0.98]) and all-cause mortality in epoch 2, 3, 4, and 5 (aHR from 0.83 [95% CIs, 0.77, 0.90] to 0.88 [95% CIs, 0.83, 0.93]). People diagnosed and treated for affective disorders had a decreased risk of both death with COVID-19 and from all-causes in epoch 3 (aHR from 0.87 [95% CIs, 0.79, 0.96] to 0.90 [95% CIs, 0.83, 0.99]), but demonstrated broadly null effects in other epochs. Given the unavailability of data on a number of potentially influential confounders, particularly body mass index, tobacco smoking status, and socioeconomic status, part of the detected associations might be due to residual confounding. CONCLUSIONS: People with preexisting psychotic, and, less robustly, substance use disorders demonstrated a persistently elevated risk of death following SARS-CoV-2 infection throughout the pandemic. While it cannot be ruled out that part of the detected associations is due to residual confounding, this excess mortality cannot be fully explained by lower vaccination uptake and more clinically recorded physical comorbidities in these patient groups.

Key considerations for the future of mental health epidemiology.

Psychiatric epidemiology has led to substantial progress in our understanding of the causes of mental health disorders. The increasing sophistication of etiologic psychiatric research has been accompanied by a greater focus on the biological and genetic causes of psychiatric disorders, to some extent diverging from field's early focus on the burden of poor mental health due to a breadth of social and economic conditions. We argue that the moment is ripe for advancing a mental health epidemiology that can reconnect the field to these earlier-and still central-concerns while retaining the strengths of psychiatric epidemiology. Embracing 5 considerations can help advance the evolving field of mental health epidemiology. First, conceptually, an ambitious vision for the future of the field necessitates investment in refining our definitions and methodologies. Second, there is a need for a renewed focus on the macrosocial determinants of mental health. Third, a deeper engagement with mental health inequities should be central to our scholarship. Fourth, the field would benefit from a more deliberate assessment of the mechanisms leading to adverse mental health outcomes, which can then be used to inform novel interventions. Finally, realizing this future is contingent upon a wholesale commitment to studying population mental health globally. This article is part of a Special Collection on Mental Health.

Using unsupervised clustering approaches to identify common mental health profiles and associated mental health-care service-use patterns in Ontario, Canada.

Mental health is a complex, multidimensional concept that goes beyond clinical diagnoses, including psychological distress, life stress, and well-being. In this study, we aimed to use unsupervised clustering approaches to identify multidimensional mental health profiles that exist in the population, and their associated service-use patterns. The data source was the 2012 Canadian Community Health Survey-Mental Health, linked to administrative health-care data; all Ontario, Canada, adult respondents were included. We used a partitioning around medoids clustering algorithm with Gower's proximity to identify groups with distinct combinations of mental health indicators and described them according to their sociodemographic and service-use characteristics. We identified 4 groups with distinct mental health profiles, including 1 group that met the clinical threshold for a depressive diagnosis, with the remaining 3 groups expressing differences in positive mental health, life stress, and self-rated mental health. The 4 groups had different age, employment, and income profiles and exhibited differential access to mental health-care services. This study represents the first step in identifying complex profiles of mental health at the population level in Ontario. Further research is required to better understand the potential causes and consequences of belonging to each of the mental health profiles identified. This article is part of a Special Collection on Mental Health.

Assessing mental health treatment receipt among Asian adults with limited English proficiency using an intersectional approach.

US Asian adults and people with limited English proficiency (LEP) confront mental health treatment receipt disparities. At the intersection of racial and language injustice, Asian adults with LEP may face even greater disparity, but studies have not assessed this through explicitly intersectional approaches. Using 2019 and 2020 National Survey of Drug Use and Health data, we computed disparities in mental health treatment among those with mental illness comparing: non-Hispanic (NH) Asian adults with LEP to NH White adults without LEP (joint disparity), NH Asian adults without LEP to NH White adults without LEP (referent race disparity), NH Asian adults with LEP to those without LEP (referent LEP disparity), and the joint disparity versus the sum of referent disparities (excess intersectional disparity). In age- and gender-adjusted analyses, excess intersectional disparity was 26.8% (95% CI, -29.8 to 83.4) of the joint disparity in 2019 and 63.0% (95% CI, 29.1-96.8) in 2020. The 2019 joint disparity was 1.37 (95% CI, 0.31-2.42) times that if the race-related disparity did not vary by LEP, and if LEP-related disparity did not vary by race; this figure was 2.70 (95% CI, 0.23-5.17) in 2020. These findings highlight the necessity of considering the intersection of race and LEP in addressing mental health treatment disparities. This article is part of a Special Collection on Mental Health.

Three things we learned along the way: lessons for training in psychiatric epidemiology.

The coronavirus disease 2019 (COVID-19) pandemic, and its associated mortality, morbidity, and deep social and economic impacts, was a global traumatic stressor that challenged population mental health and our de facto mental health care system in unprecedented ways. Yet, in many respects, this crisis is not new. Psychiatric epidemiologists have recognized for decades the need and unmet need of people in distress and the limits of the public mental health services in the United States. We argue that psychiatric epidemiologists have a critical role to play as we endeavor to address population mental health and draw attention to 3 areas of consideration: elevating population-based solutions; engaging equitably with lived experience; and interrogating recovery. Psychiatric epidemiology has a long history of both responding to and shaping our understanding of the relationships among psychiatric disorders and society through evolving methods and training, and the current sociohistorical moment again suggests that shifts in our practice can strengthen our field and its impact. This article is part of a Special Collection on Mental Health.

Work-related causes of mental health conditions and interventions for their improvement in workplaces.

Mental health problems and disorders are common among working people and are costly for the affected individuals, employers, and whole of society. This discussion paper provides an overview of the current state of knowledge on the relationship between work and mental health to inform research, policy, and practice. We synthesise available evidence, examining both the role of working conditions in the development of mental disorders, and what can be done to protect and promote mental health in the workplace. We show that exposure to some working conditions is associated with an increased risk of the onset of depressive disorders, the most studied mental disorders. The causality of the association, however, is still debated. Causal inference should be supported by more research with stronger linkage to theory, better exposure assessment, better understanding of biopsychosocial mechanisms, use of innovative analytical methods, a life-course perspective, and better understanding of the role of context, including the role of societal structures in the development of mental disorders. There is growing evidence for the effectiveness of interventions to protect and promote mental health and wellbeing in the workplace; however, there is a disproportionate focus on interventions directed towards individual workers and illnesses, compared with interventions for improving working conditions and enhancing mental health. Moreover, research on work and mental health is mainly done in high-income countries, and often does not address workers in lower socioeconomic positions. Flexible and innovative approaches tailored to local conditions are needed in implementation research on workplace mental health to complement experimental studies. Improvements in translating workplace mental health research to policy and practice, such as through workplace-oriented concrete guidance for interventions, and by national policies and programmes focusing on the people most in need, could capitalise on the growing interest in workplace mental health, possibly yielding important mental health gains in working populations.

Use of co-production to explore food insecurity in adults with severe mental illness living in Northern England: a mixed-methods study.

BACKGROUND: People living with severe mental illness experience premature mortality from diet-related preventable illnesses. Yet, little research focuses on food insecurity with adults with severe mental illness. This coproduced study aimed to understand the experiences of adults with severe mental illness and food insecurity and strategies to help. METHODS: Following a pragmatism philosophical foundation, we undertook a mixed-methods study involving a survey (online and paper versions) and one-to-one semi-structured interviews (online and telephone) during March 7 to Dec 16, 2022. We recruited participants via existing severe mental illness service user groups and social media in Northern England. Eligible participants were adults (≥18 years) self-reporting a diagnosis of severe mental illness. Ethics approval was obtained from Teesside University and the Health Research Authority (Reference: 22/NR/0010; IRAS ID: 306281), with informed consent given. The target sample size, accounting for a typical survey response rate for people with severe mental illness of 10-20%, was 135. A target sample of 20 interviews was agreed to capture a range of views. Food insecurity was defined as the lack of financial resources needed to ensure someone has reliable access to enough food to meet their dietary, nutritional, and social needs. It is sometimes called food poverty. Quantitative data were analysed using descriptive statistics and binary logistic regression and qualitative data using thematic analysis. FINDINGS: 135 participants completed the survey (mean age 44·67 years [SD 14·1]). Participants were predominantly male (53%, n=72), white (87%, n=117), and from the Yorkshire region (50%, n=68). Overall, prevalence of food insecurity was 50·4% (n=68). Discussion across 13 interviews found food insecurity being a long-rooted experience, including familial and intergenerational experiences of food insecurity: "I grew up… with this insecurity around food" (P002). Recommendations for tackling food insecurity centred on food banks, increasing accessibility, and reducing stigma: "I would like to get more information on where the centres are..." (P006) and "I was referred to, erm, a foodbank … but it's still the stigma that's attached to it." (P002). INTERPRETATION: We found a higher prevalence of food insecurity in this study than in the general population (being 15%), yet limited research with adults with severe mental illness perpetuates food insecurity intergenerational injustices. Food insecurity should be eliminated. However, in the meanwhile, there should be widespread easy access to food banks offering nutritional foods. Limitations of this research include not reaching target sample size and a lack of ethnic diversity. FUNDING: National Institute of Health and Care Research (NIHR) Research for Patient Benefit.

The associations of chronic pain and 24-h movement behaviors with incident mental disorders: evidence from a large-scale cohort study.

BACKGROUND: Chronic pain was associated with a higher risk of mental disorders (e.g., depression and anxiety). However, the role of 24-h movement behaviors in the association remains unclear. METHODS: A total of 72,800 participants with accelerometer data and free of mental disorders from the UK Biobank were analyzed. The compositional mediation model and isotemporal substitution model were used to explore the associations between chronic pain, 24-h movement behaviors, and the incidence of overall mental disorders, depression, and anxiety. RESULTS: With a median follow-up of 13.36 years, participants with chronic pain had a higher rate of incident overall mental disorders (hazard ratio (HR): 1.281, 95% confidence interval (CI): 1.219 to 1.344), anxiety (HR: 1.391, 95% CI: 1.280 to 1.536), and depression (HR: 1.703, 95% CI: 1.551 to 1.871). Increased sedentary behavior (SB) and reduced moderate-to-vigorous physical activity (MVPA) caused by chronic pain both increased the risk of mental disorders. Twenty-four-hour movement behaviors explained the relationship between chronic pain and overall mental disorders, depression, and anxiety by 10.77%, 5.70%, and 6.86%, respectively. Interaction effects were found between MVPA and chronic pain when predicting the incidence of depression and between MVPA, sleep (SLP), and chronic pain when predicting the incidence of mental disorders. People with chronic pain would recommend at least 0.5 h per day of MVPA and 7 h per day of SLP and restricting SB below 11.5 h per day. CONCLUSIONS: Twenty-four-hour movement behaviors played a significant mediating role in the association between chronic pain and mental disorders. Individuals with chronic pain should engage in more MVPA, less sedentary behavior, and have 7-h sleep per day.