Rare coding variants in ten genes confer substantial risk for schizophrenia.

Rare coding variation has historically provided the most direct connections between gene function and disease pathogenesis. By meta-analysing the whole exomes of 24,248 schizophrenia cases and 97,322 controls, we implicate ultra-rare coding variants (URVs) in 10 genes as conferring substantial risk for schizophrenia (odds ratios of 3-50, P < 2.14 × 10-6) and 32 genes at a false discovery rate of <5%. These genes have the greatest expression in central nervous system neurons and have diverse molecular functions that include the formation, structure and function of the synapse. The associations of the NMDA (N-methyl-D-aspartate) receptor subunit GRIN2A and AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptor subunit GRIA3 provide support for dysfunction of the glutamatergic system as a mechanistic hypothesis in the pathogenesis of schizophrenia. We observe an overlap of rare variant risk among schizophrenia, autism spectrum disorders1, epilepsy and severe neurodevelopmental disorders2, although different mutation types are implicated in some shared genes. Most genes described here, however, are not implicated in neurodevelopment. We demonstrate that genes prioritized from common variant analyses of schizophrenia are enriched in rare variant risk3, suggesting that common and rare genetic risk factors converge at least partially on the same underlying pathogenic biological processes. Even after excluding significantly associated genes, schizophrenia cases still carry a substantial excess of URVs, which indicates that more risk genes await discovery using this approach.

The case for eliminating excessive worry as a requirement for generalized anxiety disorder: a cross-national investigation.

BACKGROUND: Around the world, people living in objectively difficult circumstances who experience symptoms of generalized anxiety disorder (GAD) do not qualify for a diagnosis because their worry is not 'excessive' relative to the context. We carried out the first large-scale, cross-national study to explore the implications of removing this excessiveness requirement. METHODS: Data come from the World Health Organization World Mental Health Survey Initiative. A total of 133 614 adults from 12 surveys in Low- or Middle-Income Countries (LMICs) and 16 surveys in High-Income Countries (HICs) were assessed with the Composite International Diagnostic Interview. Non-excessive worriers meeting all other DSM-5 criteria for GAD were compared to respondents meeting all criteria for GAD, and to respondents without GAD, on clinically-relevant correlates. RESULTS: Removing the excessiveness requirement increases the global lifetime prevalence of GAD from 2.6% to 4.0%, with larger increases in LMICs than HICs. Non-excessive and excessive GAD cases worry about many of the same things, although non-excessive cases worry more about health/welfare of loved ones, and less about personal or non-specific concerns, than excessive cases. Non-excessive cases closely resemble excessive cases in socio-demographic characteristics, family history of GAD, and risk of temporally secondary comorbidity and suicidality. Although non-excessive cases are less severe on average, they report impairment comparable to excessive cases and often seek treatment for GAD symptoms. CONCLUSIONS: Individuals with non-excessive worry who meet all other DSM-5 criteria for GAD are clinically significant cases. Eliminating the excessiveness requirement would lead to a more defensible GAD diagnosis.

Behavioral Impairments and Increased Risk of Cortical Atrophy Risk Scores Among World Trade Center Responders.

Objective: World Trade Center (WTC) responders are susceptible to both cognitive and neuropsychiatric impairments, particularly chronic posttraumatic stress disorder. The present study examined self-reported behavioral impairments in a sample of 732 WTC responders, 199 of whom were determined to have high risk of WTC-related cortical atrophy by an artificial neural network. Results: We found that responders at increased risk of cortical atrophy showed behavioral impairment across five domains: motivation, mood, disinhibition, empathy, and psychosis (14.6% vs 3.9% in the low-risk group; P = 3.90 × 10-7). Factor analysis models revealed that responders at high risk of cortical atrophy tended to have deficits generalized across all aspects of behavioral impairment with focal dysfunction in sensory psychosis. We additionally describe how relationships are modulated by exposure severity and pharmacological treatments. Discussion: Our findings suggest a potential link between sensory deficits and the development of cortical atrophy in WTC responders and may indicate symptoms consistent with a clinical portrait of parietal dominant Alzheimer's disease or a related dementia (ADRD). Results underscore the importance of investigating neuropsychiatric symptomatology in clinical evaluations of possible ADRD.

World Trade Center responders in their own words: predicting PTSD symptom trajectories with AI-based language analyses of interviews.

BACKGROUND: Oral histories from 9/11 responders to the World Trade Center (WTC) attacks provide rich narratives about distress and resilience. Artificial Intelligence (AI) models promise to detect psychopathology in natural language, but they have been evaluated primarily in non-clinical settings using social media. This study sought to test the ability of AI-based language assessments to predict PTSD symptom trajectories among responders. METHODS: Participants were 124 responders whose health was monitored at the Stony Brook WTC Health and Wellness Program who completed oral history interviews about their initial WTC experiences. PTSD symptom severity was measured longitudinally using the PTSD Checklist (PCL) for up to 7 years post-interview. AI-based indicators were computed for depression, anxiety, neuroticism, and extraversion along with dictionary-based measures of linguistic and interpersonal style. Linear regression and multilevel models estimated associations of AI indicators with concurrent and subsequent PTSD symptom severity (significance adjusted by false discovery rate). RESULTS: Cross-sectionally, greater depressive language (ß = 0.32; p = 0.049) and first-person singular usage (ß = 0.31; p = 0.049) were associated with increased symptom severity. Longitudinally, anxious language predicted future worsening in PCL scores (ß = 0.30; p = 0.049), whereas first-person plural usage (ß = -0.36; p = 0.014) and longer words usage (ß = -0.35; p = 0.014) predicted improvement. CONCLUSIONS: This is the first study to demonstrate the value of AI in understanding PTSD in a vulnerable population. Future studies should extend this application to other trauma exposures and to other demographic groups, especially under-represented minorities.

Dynamic interplay between life events and course of psychotic disorders: 10-year longitudinal study following first admission.

BACKGROUND: Life events (LEs) are a risk factor for first onset and relapse of psychotic disorders. However, the impact of LEs on specific symptoms - namely reality distortion, disorganization, negative symptoms, depression, and mania - remains unclear. Moreover, the differential effects of negative v. positive LEs are poorly understood. METHODS: The present study utilizes an epidemiologic cohort of patients (N = 428) ascertained at first-admission for psychosis and followed for a decade thereafter. Symptoms were assessed at 6-, 24-, 48-, and 120-month follow-ups. RESULTS: We examined symptom change within-person and found that negative events in the previous 6 months predicted an increase in reality distortion (ß = 0.07), disorganized (ß = 0.07), manic (ß = 0.08), and depressive symptoms (ß = 0.06), and a decrease in negative symptoms (ß = -0.08). Conversely, positive LEs predicted fewer reality distortion (ß = -0.04), disorganized (ß = -0.04), and negative (ß = -0.13) symptoms, and were unrelated to mood symptoms. A between-person approach to the same hypotheses confirmed that negative LEs predicted change in all symptoms, while positive LEs predicted change only in negative symptoms. In contrast, symptoms rarely predicted future LEs. CONCLUSIONS: These findings confirm that LEs have an effect on symptoms, and thus contribute to the burden of psychotic disorders. That LEs increase positive symptoms and decrease negative symptoms suggest at least two different mechanisms underlying the relationship between LEs and symptoms. Our findings underscore the need for increased symptom monitoring following negative LEs, as symptoms may worsen during that time.

Characterisation of age and polarity at onset in bipolar disorder.

BACKGROUND: Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools. AIMS: To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics. METHOD: Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts. RESULTS: Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (ß = -0.34 years, s.e. = 0.08), major depression (ß = -0.34 years, s.e. = 0.08), schizophrenia (ß = -0.39 years, s.e. = 0.08), and educational attainment (ß = -0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO. CONCLUSIONS: AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.

Pathways from performance monitoring to negative symptoms and functional outcomes in psychotic disorders.

BACKGROUND: Performance monitoring entails rapid error detection to maintain task performance. Impaired performance monitoring is a candidate pathophysiological process in psychotic disorders, which may explain the broader deficit in executive function and its known associations with negative symptoms and poor functioning. The current study models cross-sectional pathways bridging neurophysiological measures of performance monitoring with executive function, symptoms, and functioning. METHODS: Data were from the 20-year assessment of the Suffolk County Mental Health Project. Individuals with psychotic disorders (N = 181) were originally recruited from inpatient psychiatric facilities. Data were also collected from a geographically and demographically matched group with no psychosis history (N = 242). Neural measures were the error-related negativity (ERN) and error positivity (Pe). Structural equation modeling tested mediation pathways. RESULTS: Blunted ERN and Pe in the clinical cohort related to impaired executive function (r = 0.26-0.35), negative symptom severity (r = 0.17-0.25), and poor real-world functioning (r = 0.17-0.19). Associations with executive function were consistent across groups. Multiple potential pathways were identified in the clinical cohort: reduced ERN to inexpressivity was mediated by executive function (ß = 0.10); reduced Pe to global functioning was mediated by executive function and avolition (ß = 0.10). CONCLUSIONS: This supports a transdiagnostic model of psychotic disorders by which poor performance monitoring contributes to impaired executive function, which contributes to negative symptoms and poor real-world functioning. If supported by future longitudinal research, these pathways could inform the development of targeted interventions to address cognitive and functional deficits that are central to psychotic disorders.

Patterns of care and dropout rates from outpatient mental healthcare in low-, middle- and high-income countries from the World Health Organization's World Mental Health Survey Initiative.

BACKGROUND: There is a substantial proportion of patients who drop out of treatment before they receive minimally adequate care. They tend to have worse health outcomes than those who complete treatment. Our main goal is to describe the frequency and determinants of dropout from treatment for mental disorders in low-, middle-, and high-income countries. METHODS: Respondents from 13 low- or middle-income countries (N = 60 224) and 15 in high-income countries (N = 77 303) were screened for mental and substance use disorders. Cross-tabulations were used to examine the distribution of treatment and dropout rates for those who screened positive. The timing of dropout was examined using Kaplan-Meier curves. Predictors of dropout were examined with survival analysis using a logistic link function. RESULTS: Dropout rates are high, both in high-income (30%) and low/middle-income (45%) countries. Dropout mostly occurs during the first two visits. It is higher in general medical rather than in specialist settings (nearly 60% v. 20% in lower income settings). It is also higher for mild and moderate than for severe presentations. The lack of financial protection for mental health services is associated with overall increased dropout from care. CONCLUSIONS: Extending financial protection and coverage for mental disorders may reduce dropout. Efficiency can be improved by managing the milder clinical presentations at the entry point to the mental health system, providing adequate training, support and specialist supervision for non-specialists, and streamlining referral to psychiatrists for more severe cases.

Contributions of common genetic variants to risk of schizophrenia among individuals of African and Latino ancestry.

Schizophrenia is a common, chronic and debilitating neuropsychiatric syndrome affecting tens of millions of individuals worldwide. While rare genetic variants play a role in the etiology of schizophrenia, most of the currently explained liability is within common variation, suggesting that variation predating the human diaspora out of Africa harbors a large fraction of the common variant attributable heritability. However, common variant association studies in schizophrenia have concentrated mainly on cohorts of European descent. We describe genome-wide association studies of 6152 cases and 3918 controls of admixed African ancestry, and of 1234 cases and 3090 controls of Latino ancestry, representing the largest such study in these populations to date. Combining results from the samples with African ancestry with summary statistics from the Psychiatric Genomics Consortium (PGC) study of schizophrenia yielded seven newly genome-wide significant loci, and we identified an additional eight loci by incorporating the results from samples with Latino ancestry. Leveraging population differences in patterns of linkage disequilibrium, we achieve improved fine-mapping resolution at 22 previously reported and 4 newly significant loci. Polygenic risk score profiling revealed improved prediction based on trans-ancestry meta-analysis results for admixed African (Nagelkerke's R2 = 0.032; liability R2 = 0.017; P < 10-52), Latino (Nagelkerke's R2 = 0.089; liability R2 = 0.021; P < 10-58), and European individuals (Nagelkerke's R2 = 0.089; liability R2 = 0.037; P < 10-113), further highlighting the advantages of incorporating data from diverse human populations.

Chronic Posttraumatic Stress Disorder and Comorbid Cognitive and Physical Impairments in World Trade Center Responders.

Posttraumatic stress disorder (PTSD) has been linked to increased prevalence and incidence of cognitive and physical impairment. When comorbid, these conditions may be associated with poor long-term outcomes. We examined associations between chronic PTSD and symptom domains with cognitive and physical functioning in World Trade Center (WTC) responders nearly 20 years after the September 11, 2001, terrorist attacks. Participants included a cross-sectional sample of 4,815 responders who attended a monitoring program in 2015-2018. Montreal Cognitive Assessment scores less than 23 indicated cognitive impairment (CogI); Short Physical Performance Battery scores 9 or lower on a hand-grip test indicated physical impairment (PhysI). Comorbid cognitive/physical impairment (Cog/PhysI) was defined as having cognitive impairment with at least one objective PhysI indicator. Clinical chart review provided PTSD diagnoses; symptom domains were assessed using the PTSD Checklist. Participants were on average 53.05 years (SD = 8.01); 13.44% had PTSD, 7.8% had CogI, 24.8% had PhysI, and 5.92% had comorbid Cog/PhysI. Multivariable-adjusted multinomial logistic regression demonstrated that Responders with PTSD have more than three times the risk of Cog/PhysI (adjusted RR = 3.29, 95% CI 2.44- 4.44). Domain-specific analyses revealed that emotional numbing symptoms predicted an increased risk of PhysI (adjusted RR = 1.57, 95% CI 1.08-2.28), whereas reexperiencing symptoms were associated with comorbid Cog/PhysI (adjusted RR = 3.96, 95% CI, 2.33-6.74). These results suggest that responders with chronic PTSD may have increased risk of deficits beyond age-expected impairment characterized by the emergence of comorbid Cog/PhysI at midlife.

Onset and remission of common mental disorders among adults living in temporary housing for three years after the triple disaster in Northeast Japan: comparisons with the general population.

BACKGROUND: People living in temporary housing for long periods after a disaster are at risk of poor mental health. This study investigated the post-disaster incidence and remission of common mental disorders among adults living in temporary housing for the 3 years following the 2011 Great East Japan Earthquake. METHODS: Three years after the disaster, face-to-face interviews were conducted with 1089 adult residents living in temporary housing in the disaster area, i.e., the shelter group, and a random sample of 852 community residents from non-disaster areas of East Japan. The World Health Organization Composite International Diagnostic Interview was used to diagnose DSM-IV mood, anxiety, and alcohol use disorders. Information on demographic variables and disaster experiences was also collected. RESULTS: Response rates were 49 and 46% for the shelter group and the community residents, respectively. The incidence of mood/anxiety disorder in the shelter group was elevated only in the first year post-disaster compared to that of the general population. The rate of remission for mood and anxiety disorders was significantly lower in the shelter group than in the community residents. The proportion seeking medical treatment was higher in the shelter group. CONCLUSIONS: The onset of common mental disorders increased in the first year, but then levelled off in the following years among residents in temporary housing after the disaster. Remission from incident post-disaster mental disorders was slower in the shelter group than in the general population. Post-disaster mental health service could consider the greater incidence in the first year and prolonged remission of mental disorders among survivors with a long-term stay in temporary housing after a disaster.

A comparison of DSM-5 and DSM-IV agoraphobia in the World Mental Health Surveys.

BACKGROUND: The Diagnostic and Statistical Manual of Mental Disorders, version 5 (DSM-5) definition of agoraphobia (AG) as an independent diagnostic entity makes it timely to re-examine the epidemiology of AG. Study objective was to present representative data on the characteristics of individuals who meet DSM-IV criteria for AG (AG without a history of panic disorder [PD] and PD with AG) but not DSM-5 criteria, DSM-5 but not DSM-IV criteria, or both sets of criteria. METHODS: Population-based surveys from the World Mental Health Survey Initiative including adult respondents (n = 136,357) from 27 countries across the world. The Composite International Diagnostic Interview was used to assess AG and other disorders. RESULTS: Lifetime and 12-month prevalence estimates of DSM-5 AG (1.5% and 1.0%) were comparable to DSM-IV (1.4% and 0.9%). Of respondents meeting criteria in either system, 57.1% met criteria in both, while 24.2% met criteria for DSM-5 only and 18.8% for DSM-IV only. Severe role impairment due to AG was reported by a lower proportion of respondents who met criteria only for DSM-IV AG (30.4%) than those with both DSM-5 and DSM-IV AG (44.0%; χ 21 = 4.7; P = 0.031). The proportion of cases with any comorbidity was lower among respondents who met criteria only for DSM-IV AG (78.7%) than those who met both sets (92.9%; χ 21 = 14.5; P < 0.001). CONCLUSIONS: This first large survey shows that, compared to the DSM-IV, the DSM-5 identifies a substantial group of new cases with AG, while the prevalence rate remains stable at 1.5%. Severity and comorbidity are higher in individuals meeting DSM-5 AG criteria compared with individuals meeting DSM-IV AG criteria only.

Differential effect of Hurricane Sandy exposure on PTSD symptom severity: comparison of community members and responders.

OBJECTIVES: To evaluate whether the association between Hurricane Sandy exposures and post-traumatic stress disorder (PTSD) symptom severity was greater for exposed community members compared with responders. METHODS: Data were analysed from three existing studies with similar methodologies (N=1648): two community studies, Leaders in Gathering Hope Together (n=531) and Project Restoration (n=763); and the Sandy/World Trade Center Responders Study (n=354). Sandy-related PTSD symptoms were measured using the PTSD checklist-specific traumatic event and dichotomised as elevated (>30) versus low/no (<30) PTSD symptoms. Sandy exposures were measured with a summed checklist. Multivariable logistic regression was performed to evaluate the differential effect of exposures on PTSD by responder status, adjusting for demographics and time elapsed since Sandy. RESULTS: Responders were somewhat older (50.5 years (SD=8.3) vs 45.8 years (SD=20.0)), more likely to identify as white (92.4% vs 48.1%) and were male (90.7% vs 38.4%). Responders were less likely to have elevated PTSD symptoms than community members (8.6% vs 31.1%; adjusted OR=0.28, 95% CI 0.17 to 0.46). While exposure was significantly related to elevated PTSD status, the effects were similar for responders and community members. CONCLUSIONS: Responders appear to be more resilient to PTSD symptoms post-Sandy than community members. Understanding the mechanisms that foster such resilience can inform interventions aimed at populations that are more vulnerable to experiencing PTSD after natural disasters.

Risk factors for incident prostate cancer in a cohort of world trade center responders.

BACKGROUND: Despite a relatively young average age and no routine screening, prostate cancer is one of the most common cancers in men who worked at the World Trade Center (WTC) following the 9/11/2001 disaster. This study evaluated whether re-experiencing stressful memories of a traumatic event was associated with prostate cancer incidence. METHODS: Participants were males from one clinical center that monitors the health of first-responders (N = 6857). Monitoring began in July 2002 and occurs annually but does not include prostate cancer screening. Severity of physical exposures and of re-experiencing memories and stress responses were measured at study enrollment using standardized and validated methods in all participants. The outcome was incidence of diagnosed prostate cancer after enrollment (n = 68). Bivariate analyses provided age-adjusted incidence rates (aIR). Cox proportional hazards modeling was used to calculate incidence; hazards ratios (HR) were reported. RESULTS: The mean age of responders on 9/11/2001 was 37.9 years. Prostate cancer incidence was lowest in responders with no re-experiencing stress (aIR = 250.83/100,000 person-years, [233.41-268.25]) and highest in responders with severe re-experiencing stress (aIR = 818.49/100,000 person-years, [801.07-835.91]). Cox proportional hazards regression revealed that re-experiencing the stressful events of 9/11/2001 was associated with increased prostate cancer incidence (HR = 1.96 [1.26-3.05], P = 0.003), even upon adjusting for confounders. CONCLUSIONS: This is the first study to identify a positive association between re-experiencing a traumatic event and prostate cancer incidence. Our results are consistent with recent rodent model evidence demonstrating a direct biological link between stress pathways and prostate tumorigenesis and offer new hypotheses in the causality of prostate cancer.

Psychotic experiences and general medical conditions: a cross-national analysis based on 28 002 respondents from 16 countries in the WHO World Mental Health Surveys.

BACKGROUND: Previous work has identified associations between psychotic experiences (PEs) and general medical conditions (GMCs), but their temporal direction remains unclear as does the extent to which they are independent of comorbid mental disorders. METHODS: In total, 28 002 adults in 16 countries from the WHO World Mental Health (WMH) Surveys were assessed for PEs, GMCs and 21 Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) mental disorders. Discrete-time survival analyses were used to estimate the associations between PEs and GMCs with various adjustments. RESULTS: After adjustment for comorbid mental disorders, temporally prior PEs were significantly associated with subsequent onset of 8/12 GMCs (arthritis, back or neck pain, frequent or severe headache, other chronic pain, heart disease, high blood pressure, diabetes and peptic ulcer) with odds ratios (ORs) ranging from 1.3 [95% confidence interval (CI) 1.1-1.5] to 1.9 (95% CI 1.4-2.4). In contrast, only three GMCs (frequent or severe headache, other chronic pain and asthma) were significantly associated with subsequent onset of PEs after adjustment for comorbid GMCs and mental disorders, with ORs ranging from 1.5 (95% CI 1.2-1.9) to 1.7 (95% CI 1.2-2.4). CONCLUSIONS: PEs were associated with the subsequent onset of a wide range of GMCs, independent of comorbid mental disorders. There were also associations between some medical conditions (particularly those involving chronic pain) and subsequent PEs. Although these findings will need to be confirmed in prospective studies, clinicians should be aware that psychotic symptoms may be risk markers for a wide range of adverse health outcomes. Whether PEs are causal risk factors will require further research.

Hurricane Sandy Exposure Alters the Development of Neural Reactivity to Negative Stimuli in Children.

This study examined whether exposure to Hurricane Sandy-related stressors altered children's brain response to emotional information. An average of 8 months (Mage  = 9.19) before and 9 months after (Mage  = 10.95) Hurricane Sandy, 77 children experiencing high (n = 37) and low (n = 40) levels of hurricane-related stress exposure completed a task in which the late positive potential, a neural index of emotional reactivity, was measured in response to pleasant and unpleasant, compared to neutral, images. From pre- to post-Hurricane Sandy, children with high stress exposure failed to show the same decrease in emotional reactivity to unpleasant versus neutral stimuli as those with low stress exposure. Results provide compelling evidence that exposure to natural disaster-related stressors alters neural emotional reactivity to negatively valenced information.

Civilians in World War II and DSM-IV mental disorders: results from the World Mental Health Survey Initiative.

PURPOSE: Understanding the effects of war on mental disorders is important for developing effective post-conflict recovery policies and programs. The current study uses cross-sectional, retrospectively reported data collected as part of the World Mental Health (WMH) Survey Initiative to examine the associations of being a civilian in a war zone/region of terror in World War II with a range of DSM-IV mental disorders. METHODS: Adults (n = 3370) who lived in countries directly involved in World War II in Europe and Japan were administered structured diagnostic interviews of lifetime DSM-IV mental disorders. The associations of war-related traumas with subsequent disorder onset-persistence were assessed with discrete-time survival analysis (lifetime prevalence) and conditional logistic regression (12-month prevalence). RESULTS: Respondents who were civilians in a war zone/region of terror had higher lifetime risks than other respondents of major depressive disorder (MDD; OR 1.5, 95% CI 1.1, 1.9) and anxiety disorder (OR 1.5, 95% CI 1.1, 2.0). The association of war exposure with MDD was strongest in the early years after the war, whereas the association with anxiety disorders increased over time. Among lifetime cases, war exposure was associated with lower past year risk of anxiety disorders (OR 0.4, 95% CI 0.2, 0.7). CONCLUSIONS: Exposure to war in World War II was associated with higher lifetime risk of some mental disorders. Whether comparable patterns will be found among civilians living through more recent wars remains to be seen, but should be recognized as a possibility by those projecting future needs for treatment of mental disorders.

The cross-national epidemiology of social anxiety disorder: Data from the World Mental Health Survey Initiative.

BACKGROUND: There is evidence that social anxiety disorder (SAD) is a prevalent and disabling disorder. However, most of the available data on the epidemiology of this condition originate from high income countries in the West. The World Mental Health (WMH) Survey Initiative provides an opportunity to investigate the prevalence, course, impairment, socio-demographic correlates, comorbidity, and treatment of this condition across a range of high, middle, and low income countries in different geographic regions of the world, and to address the question of whether differences in SAD merely reflect differences in threshold for diagnosis. METHODS: Data from 28 community surveys in the WMH Survey Initiative, with 142,405 respondents, were analyzed. We assessed the 30-day, 12-month, and lifetime prevalence of SAD, age of onset, and severity of role impairment associated with SAD, across countries. In addition, we investigated socio-demographic correlates of SAD, comorbidity of SAD with other mental disorders, and treatment of SAD in the combined sample. Cross-tabulations were used to calculate prevalence, impairment, comorbidity, and treatment. Survival analysis was used to estimate age of onset, and logistic regression and survival analyses were used to examine socio-demographic correlates. RESULTS: SAD 30-day, 12-month, and lifetime prevalence estimates are 1.3, 2.4, and 4.0% across all countries. SAD prevalence rates are lowest in low/lower-middle income countries and in the African and Eastern Mediterranean regions, and highest in high income countries and in the Americas and the Western Pacific regions. Age of onset is early across the globe, and persistence is highest in upper-middle income countries, Africa, and the Eastern Mediterranean. There are some differences in domains of severe role impairment by country income level and geographic region, but there are no significant differences across different income level and geographic region in the proportion of respondents with any severe role impairment. Also, across countries SAD is associated with specific socio-demographic features (younger age, female gender, unmarried status, lower education, and lower income) and with similar patterns of comorbidity. Treatment rates for those with any impairment are lowest in low/lower-middle income countries and highest in high income countries. CONCLUSIONS: While differences in SAD prevalence across countries are apparent, we found a number of consistent patterns across the globe, including early age of onset, persistence, impairment in multiple domains, as well as characteristic socio-demographic correlates and associated psychiatric comorbidities. In addition, while there are some differences in the patterns of impairment associated with SAD across the globe, key similarities suggest that the threshold for diagnosis is similar regardless of country income levels or geographic location. Taken together, these cross-national data emphasize the international clinical and public health significance of SAD.

Childhood adversities and post-traumatic stress disorder: evidence for stress sensitisation in the World Mental Health Surveys.

BackgroundAlthough childhood adversities are known to predict increased risk of post-traumatic stress disorder (PTSD) after traumatic experiences, it is unclear whether this association varies by childhood adversity or traumatic experience types or by age.AimsTo examine variation in associations of childhood adversities with PTSD according to childhood adversity types, traumatic experience types and life-course stage.MethodEpidemiological data were analysed from the World Mental Health Surveys (n = 27 017).ResultsFour childhood adversities (physical and sexual abuse, neglect, parent psychopathology) were associated with similarly increased odds of PTSD following traumatic experiences (odds ratio (OR) = 1.8), whereas the other eight childhood adversities assessed did not predict PTSD. Childhood adversity-PTSD associations did not vary across traumatic experience types, but were stronger in childhood-adolescence and early-middle adulthood than later adulthood.ConclusionsChildhood adversities are differentially associated with PTSD, with the strongest associations in childhood-adolescence and early-middle adulthood. Consistency of associations across traumatic experience types suggests that childhood adversities are associated with generalised vulnerability to PTSD following traumatic experiences.