Evelyn J. Bromet

Schizophrenia has a heritability of 60–80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies. A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

Background: Although post-traumatic stress disorder (PTSD) onset-persistence is thought to vary significantly by trauma type, most epidemiological surveys are incapable of assessing this because they evaluate lifetime PTSD only for traumas nominated by respondents as their ‘worst.’Objective: To review research on associations of trauma type with PTSD in the WHO World Mental Health (WMH) surveys, a series of epidemiological surveys that obtained representative data on trauma-specific PTSD.Method: WMH Surveys in 24 countries (n = 68,894) assessed 29 lifetime traumas and evaluated PTSD twice for each respondent: once for the ‘worst’ lifetime trauma and separately for a randomly-selected trauma with weighting to adjust for individual differences in trauma exposures. PTSD onset-persistence was evaluated with the WHO Composite International Diagnostic Interview.Results: In total, 70.4% of respondents experienced lifetime traumas, with exposure averaging 3.2 traumas per capita. Substantial between-trauma differences were found in PTSD onset but less in persistence. Traumas involving interpersonal violence had highest risk. Burden of PTSD, determined by multiplying trauma prevalence by trauma-specific PTSD risk and persistence, was 77.7 person-years/100 respondents. The trauma types with highest proportions of this burden were rape (13.1%), other sexual assault (15.1%), being stalked (9.8%), and unexpected death of a loved one (11.6%). The first three of these four represent relatively uncommon traumas with high PTSD risk and the last a very common trauma with low PTSD risk. The broad category of intimate partner sexual violence accounted for nearly 42.7% of all person-years with PTSD. Prior trauma history predicted both future trauma exposure and future PTSD risk.Conclusions: Trauma exposure is common throughout the world, unequally distributed, and differential across trauma types with respect to PTSD risk. Although a substantial minority of PTSD cases remits within months after onset, mean symptom duration is considerably longer than previously recognized.

BACKGROUND: Traumatic events are common globally; however, comprehensive population-based cross-national data on the epidemiology of posttraumatic stress disorder (PTSD), the paradigmatic trauma-related mental disorder, are lacking. METHODS: Data were analyzed from 26 population surveys in the World Health Organization World Mental Health Surveys. A total of 71 083 respondents ages 18+ participated. The Composite International Diagnostic Interview assessed exposure to traumatic events as well as 30-day, 12-month, and lifetime PTSD. Respondents were also assessed for treatment in the 12 months preceding the survey. Age of onset distributions were examined by country income level. Associations of PTSD were examined with country income, world region, and respondent demographics. RESULTS: The cross-national lifetime prevalence of PTSD was 3.9% in the total sample and 5.6% among the trauma exposed. Half of respondents with PTSD reported persistent symptoms. Treatment seeking in high-income countries (53.5%) was roughly double that in low-lower middle income (22.8%) and upper-middle income (28.7%) countries. Social disadvantage, including younger age, female sex, being unmarried, being less educated, having lower household income, and being unemployed, was associated with increased risk of lifetime PTSD among the trauma exposed. CONCLUSIONS: PTSD is prevalent cross-nationally, with half of all global cases being persistent. Only half of those with severe PTSD report receiving any treatment and only a minority receive specialty mental health care. Striking disparities in PTSD treatment exist by country income level. Increasing access to effective treatment, especially in low- and middle-income countries, remains critical for reducing the population burden of PTSD.

BACKGROUND: Considerable research has documented that exposure to traumatic events has negative effects on physical and mental health. Much less research has examined the predictors of traumatic event exposure. Increased understanding of risk factors for exposure to traumatic events could be of considerable value in targeting preventive interventions and anticipating service needs. METHOD: General population surveys in 24 countries with a combined sample of 68 894 adult respondents across six continents assessed exposure to 29 traumatic event types. Differences in prevalence were examined with cross-tabulations. Exploratory factor analysis was conducted to determine whether traumatic event types clustered into interpretable factors. Survival analysis was carried out to examine associations of sociodemographic characteristics and prior traumatic events with subsequent exposure. RESULTS: Over 70% of respondents reported a traumatic event; 30.5% were exposed to four or more. Five types - witnessing death or serious injury, the unexpected death of a loved one, being mugged, being in a life-threatening automobile accident, and experiencing a life-threatening illness or injury - accounted for over half of all exposures. Exposure varied by country, sociodemographics and history of prior traumatic events. Being married was the most consistent protective factor. Exposure to interpersonal violence had the strongest associations with subsequent traumatic events. CONCLUSIONS: Given the near ubiquity of exposure, limited resources may best be dedicated to those that are more likely to be further exposed such as victims of interpersonal violence. Identifying mechanisms that account for the associations of prior interpersonal violence with subsequent trauma is critical to develop interventions to prevent revictimization.

BACKGROUND: To examine barriers to initiation and continuation of mental health treatment among individuals with common mental disorders. METHOD: Data were from the World Health Organization (WHO) World Mental Health (WMH) surveys. Representative household samples were interviewed face to face in 24 countries. Reasons to initiate and continue treatment were examined in a subsample (n = 63,678) and analyzed at different levels of clinical severity. RESULTS: Among those with a DSM-IV disorder in the past 12 months, low perceived need was the most common reason for not initiating treatment and more common among moderate and mild than severe cases. Women and younger people with disorders were more likely to recognize a need for treatment. A desire to handle the problem on one's own was the most common barrier among respondents with a disorder who perceived a need for treatment (63.8%). Attitudinal barriers were much more important than structural barriers to both initiating and continuing treatment. However, attitudinal barriers dominated for mild-moderate cases and structural barriers for severe cases. Perceived ineffectiveness of treatment was the most commonly reported reason for treatment drop-out (39.3%), followed by negative experiences with treatment providers (26.9% of respondents with severe disorders). CONCLUSIONS: Low perceived need and attitudinal barriers are the major barriers to seeking and staying in treatment among individuals with common mental disorders worldwide. Apart from targeting structural barriers, mainly in countries with poor resources, increasing population mental health literacy is an important endeavor worldwide.

BACKGROUND: Although significant associations of childhood adversities with adult mental disorders are widely documented, most studies focus on single childhood adversities predicting single disorders. AIMS: To examine joint associations of 12 childhood adversities with first onset of 20 DSM-IV disorders in World Mental Health (WMH) Surveys in 21 countries. METHOD: Nationally or regionally representative surveys of 51 945 adults assessed childhood adversities and lifetime DSM-IV disorders with the WHO Composite International Diagnostic Interview (CIDI). RESULTS: Childhood adversities were highly prevalent and interrelated. Childhood adversities associated with maladaptive family functioning (e.g. parental mental illness, child abuse, neglect) were the strongest predictors of disorders. Co-occurring childhood adversities associated with maladaptive family functioning had significant subadditive predictive associations and little specificity across disorders. Childhood adversities account for 29.8% of all disorders across countries. CONCLUSIONS: Childhood adversities have strong associations with all classes of disorders at all life-course stages in all groups of WMH countries. Long-term associations imply the existence of as-yet undetermined mediators.

Data are reported on the background and performance of the K6 screening scale for serious mental illness (SMI) in the World Health Organization (WHO) World Mental Health (WMH) surveys. The K6 is a six-item scale developed to provide a brief valid screen for Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV) SMI based on the criteria in the US ADAMHA Reorganization Act. Although methodological studies have documented good K6 validity in a number of countries, optimal scoring rules have never been proposed. Such rules are presented here based on analysis of K6 data in nationally or regionally representative WMH surveys in 14 countries (combined N = 41,770 respondents). Twelve-month prevalence of DSM-IV SMI was assessed with the fully-structured WHO Composite International Diagnostic Interview. Nested logistic regression analysis was used to generate estimates of the predicted probability of SMI for each respondent from K6 scores, taking into consideration the possibility of variable concordance as a function of respondent age, gender, education, and country. Concordance, assessed by calculating the area under the receiver operating characteristic curve, was generally substantial (median 0.83; range 0.76-0.89; inter-quartile range 0.81-0.85). Based on this result, optimal scaling rules are presented for use by investigators working with the K6 scale in the countries studied.

BACKGROUND: Suicide is a leading cause of death worldwide; however, the prevalence and risk factors for the immediate precursors to suicide - suicidal ideation, plans and attempts - are not wellknown, especially in low- and middle-income countries. AIMS: To report on the prevalence and risk factors for suicidal behaviours across 17 countries. METHOD: A total of 84 850 adults were interviewed regarding suicidal behaviours and socio-demographic and psychiatric risk factors. RESULTS: The cross-national lifetime prevalence of suicidal ideation, plans, and attempts is 9.2% (s.e.=0.1), 3.1% (s.e.=0.1), and 2.7% (s.e.=0.1). Across all countries, 60% of transitions from ideation to plan and attempt occur within the first year after ideation onset. Consistent cross-national risk factors included being female, younger, less educated, unmarried and having a mental disorder. Interestingly, the strongest diagnostic risk factors were mood disorders in high-income countries but impulse control disorders in low- and middle-income countries. CONCLUSION: There is cross-national variability in the prevalence of suicidal behaviours, but strong consistency in the characteristics and risk factors for these behaviours. These findings have significant implications for the prediction and prevention of suicidal behaviours.