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Importance: Understanding the association of civil violence with mental disorders is important for developing effective postconflict recovery policies., Objective: To estimate the association between exposure to civil violence and the subsequent onset and persistence of common mental disorders (in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition [DSM-IV]) in representative surveys of civilians from countries that have experienced civil violence since World War II., Design, Setting, and Participants: This study used data from cross-sectional World Health Organization World Mental Health (WMH) surveys administered to households between February 5, 2001, and January 5, 2022, in 7 countries that experienced periods of civil violence after World War II (Argentina, Colombia, Lebanon, Nigeria, Northern Ireland, Peru, and South Africa). Data from respondents in other WMH surveys who immigrated from countries with civil violence in Africa and Latin America were also included. Representative samples comprised adults (aged ≥18 years) from eligible countries. Data analysis was performed from February 10 to 13, 2023., Exposures: Exposure was defined as a self-report of having been a civilian in a war zone or region of terror. Related stressors (being displaced, witnessing atrocities, or being a combatant) were also assessed. Exposures occurred a median of 21 (IQR, 12-30) years before the interview., Main Outcomes and Measures: The main outcome was the retrospectively reported lifetime prevalence and 12-month persistence (estimated by calculating 12-month prevalence among lifetime cases) of DSM-IV anxiety, mood, and externalizing (alcohol use, illicit drug use, or intermittent explosive) disorders., Results: This study included 18 212 respondents from 7 countries. Of these individuals, 2096 reported that they were exposed to civil violence (56.5% were men; median age, 40 [IQR, 30-52] years) and 16 116 were not exposed (45.2% were men; median age, 35 [IQR, 26-48] years). Respondents who reported being exposed to civil violence had a significantly elevated onset risk of anxiety (risk ratio [RR], 1.8 [95% CI, 1.5-2.1]), mood (RR, 1.5 [95% CI, 1.3-1.7]), and externalizing (RR, 1.6 [95% CI, 1.3-1.9]) disorders. Combatants additionally had a significantly elevated onset risk of anxiety disorders (RR, 2.0 [95% CI, 1.3-3.1]) and refugees had an increased onset risk of mood (RR, 1.5 [95% CI, 1.1-2.0]) and externalizing (RR, 1.6 [95% CI, 1.0-2.4]) disorders. Elevated disorder onset risks persisted for more than 2 decades if conflicts persisted but not after either termination of hostilities or emigration. Persistence (ie, 12-month prevalence among respondents with lifetime prevalence of the disorder), in comparison, was generally not associated with exposure., Conclusions: In this survey study of exposure to civil violence, exposure was associated with an elevated risk of mental disorders among civilians for many years after initial exposure. These findings suggest that policy makers should recognize these associations when projecting future mental disorder treatment needs in countries experiencing civil violence and among affected migrants.

Importance: Individuals with mental disorders often develop comorbidity over time. Past studies of comorbidity have often restricted analyses to a subset of disorders and few studies have provided absolute risks of later comorbidity., Objectives: To undertake a comprehensive study of comorbidity within mental disorders, by providing temporally ordered age- and sex-specific pairwise estimates between the major groups of mental disorders, and to develop an interactive website to visualize all results and guide future research and clinical practice., Design, Setting, and Participants: This population-based cohort study included all individuals born in Denmark between January 1, 1900, and December 31, 2015, and living in the country between January 1, 2000, and December 31, 2016. The analyses were conducted between June 2017 and May 2018., Main Outcomes and Measures: Danish health registers were used to identify mental disorders, which were examined within the broad 10-level International Statistical Classification of Diseases and Related Health Problems, 10th Revision, subchapter groups (eg, codes F00-F09 and F10-F19). For each temporally ordered pair of disorders, overall and lagged hazard ratios and 95% CIs were calculated using Cox proportional hazards regression models. Absolute risks were estimated using competing risks survival analyses. Estimates for each sex were generated., Results: A total of 5 940 778 persons were included in this study (2 958 293 men and 2 982 485 women; mean [SD] age at beginning of follow-up, 32.1 [25.4] years). They were followed up for 83.9 million person-years. All mental disorders were associated with an increased risk of all other mental disorders when adjusting for sex, age, and calendar time (hazard ratios ranging from 2.0 [95% CI, 1.7-2.4] for prior intellectual disabilities and later eating disorders to 48.6 [95% CI, 46.6-50.7] for prior developmental disorders and later intellectual disabilities). The hazard ratios were temporally patterned, with higher estimates during the first year after the onset of the first disorder, but with persistently elevated rates during the entire observation period. Some disorders were associated with substantial absolute risks of developing specific later disorders (eg, 30.6% [95% CI, 29.3%-32.0%] of men and 38.4% [95% CI, 37.5%-39.4%] of women with a diagnosis of mood disorders before age 20 years developed neurotic disorders within the following 5 years)., Conclusions and Relevance: Comorbidity within mental disorders is pervasive, and the risk persists over time. This study provides disorder-, sex-, and age-specific relative and absolute risks of the comorbidity of mental disorders. Web-based interactive data visualization tools are provided for clinical utility.

Importance: Community-based studies have linked psychotic experiences (PEs) with increased risks of suicidal thoughts and behaviors (STBs). However, it is not known if these associations vary across the life course or if mental disorders contribute to these associations., Objective: To examine the temporal association between PEs and subsequent STBs across the life span as well as the influence of mental disorders (antecedent to the STBs) on these associations., Design, Setting, and Participants: A total of 33 370 adult respondents across 19 countries from the World Health Organization World Mental Health Surveys were assessed for PEs, STBs (ie, ideation, plans, and attempts), and 21 DSM-IV mental disorders. Discrete-time survival analysis was used to investigate the associations of PEs with subsequent onset of STBs., Main Outcomes and Measures: Prevalence and frequency of STBs with PEs, and odds ratios and 95% CIs., Results: Of 33 370 included participants, among those with PEs (n = 2488), the lifetime prevalence (SE) of suicidal ideation, plans, and attempts was 28.5% (1.3), 10.8% (0.7), and 10.2% (0.7), respectively. Respondents with 1 or more PEs had 2-fold increased odds of subsequent STBs after adjusting for antecedent or intervening mental disorders (suicidal ideation: odds ratio, 2.2; 95% CI, 1.8-2.6; suicide plans: odds ratio, 2.1; 95% CI, 1.7-2.6; and suicide attempts: odds ratio, 1.9; 95% CI, 1.5-2.5). There were significant dose-response relationships of number of PE types with subsequent STBs that persisted after adjustment for mental disorders. Although PEs were significant predictors of subsequent STB onset across all life stages, associations were strongest in individuals 12 years and younger. After adjustment for antecedent mental disorders, the overall population attributable risk proportions for lifetime suicidal ideation, plans, and attempts associated with temporally prior PEs were 5.3%, 5.7%, and 4.8%, respectively., Conclusions and Relevance: Psychotic experiences are associated with elevated odds of subsequent STBs across the life course that cannot be explained by antecedent mental disorders. These results highlight the importance of including information about PEs in screening instruments designed to predict STBs.

Importance: Generalized anxiety disorder (GAD) is poorly understood compared with other anxiety disorders, and debates persist about the seriousness of this disorder. Few data exist on GAD outside a small number of affluent, industrialized nations. No population-based data exist on GAD as it is currently defined in DSM-5., Objective: To provide the first epidemiologic data on DSM-5 GAD and explore cross-national differences in its prevalence, course, correlates, and impact., Design, Setting, and Participants: Data come from the World Health Organization World Mental Health Survey Initiative. Cross-sectional general population surveys were carried out in 26 countries using a consistent research protocol and assessment instrument. A total of 147 261 adults from representative household samples were interviewed face-to-face in the community. The surveys were conducted between 2001 and 2012. Data analysis was performed from July 22, 2015, to December 12, 2016., Main Outcomes and Measures: The Composite International Diagnostic Interview was used to assess GAD along with comorbid disorders, role impairment, and help seeking., Results: Respondents were 147 261 adults aged 18 to 99 years. The surveys had a weighted mean response rate of 69.5%. Across surveys, DSM-5 GAD had a combined lifetime prevalence (SE) of 3.7% (0.1%), 12-month prevalence of 1.8% (0.1%), and 30-day prevalence of 0.8% (0). Prevalence estimates varied widely across countries, with lifetime prevalence highest in high-income countries (5.0% [0.1%]), lower in middle-income countries (2.8% [0.1%]), and lowest in low-income countries (1.6% [0.1%]). Generalized anxiety disorder typically begins in adulthood and persists over time, although onset is later and clinical course is more persistent in lower-income countries. Lifetime comorbidity is high (81.9% [0.7%]), particularly with mood (63.0% [0.9%]) and other anxiety (51.7% [0.9%]) disorders. Severe role impairment is common across life domains (50.6% [1.2%]), particularly in high-income countries. Treatment is sought by approximately half of affected individuals (49.2% [1.2%]), especially those with severe role impairment (59.4% [1.8%]) or comorbid disorders (55.8% [1.4%]) and those living in high-income countries (59.0% [1.3%])., Conclusions and Relevance: The findings of this study show that DSM-5 GAD is more prevalent than DSM-IV GAD and is associated with substantial role impairment. The disorder is especially common and impairing in high-income countries despite a negative association between GAD and socioeconomic status within countries. These results underscore the public health significance of GAD across the globe while uncovering cross-national differences in prevalence, course, and impairment that require further investigation.

Importance: Previous research has documented significant variation in the prevalence of posttraumatic stress disorder (PTSD) depending on the type of traumatic experience (TE) and history of TE exposure, but the relatively small sample sizes in these studies resulted in a number of unresolved basic questions., Objective: To examine disaggregated associations of type of TE history with PTSD in a large cross-national community epidemiologic data set., Design, Setting, and Participants: The World Health Organization World Mental Health surveys assessed 29 TE types (lifetime exposure, age at first exposure) with DSM-IV PTSD that was associated with 1 randomly selected TE exposure (the random TE) for each respondent. Surveys were administered in 20 countries (n = 34 676 respondents) from 2001 to 2012. Data were analyzed from October 1, 2015, to September 1, 2016., Main Outcomes and Measures: Prevalence of PTSD assessed with the Composite International Diagnostic Interview., Results: Among the 34 676 respondents (55.4% [SE, 0.6%] men and 44.6% [SE, 0.6%] women; mean [SE] age, 43.7 [0.2] years), lifetime TE exposure was reported by a weighted 70.3% of respondents (mean [SE] number of exposures, 4.5 [0.04] among respondents with any TE). Weighted (by TE frequency) prevalence of PTSD associated with random TEs was 4.0%. Odds ratios (ORs) of PTSD were elevated for TEs involving sexual violence (2.7; 95% CI, 2.0-3.8) and witnessing atrocities (4.2; 95% CI, 1.0-17.8). Prior exposure to some, but not all, same-type TEs was associated with increased vulnerability (eg, physical assault; OR, 3.2; 95% CI, 1.3-7.9) or resilience (eg, participation in sectarian violence; OR, 0.3; 95% CI, 0.1-0.9) to PTSD after the random TE. The finding of earlier studies that more general history of TE exposure was associated with increased vulnerability to PTSD across the full range of random TE types was replicated, but this generalized vulnerability was limited to prior TEs involving violence, including participation in organized violence (OR, 1.3; 95% CI, 1.0-1.6), experience of physical violence (OR, 1.4; 95% CI, 1.2-1.7), rape (OR, 2.5; 95% CI, 1.7-3.8), and other sexual assault (OR, 1.6; 95% CI, 1.1-2.3)., Conclusion and Relevance: The World Mental Health survey findings advance understanding of the extent to which PTSD risk varies with the type of TE and history of TE exposure. Previous findings about the elevated PTSD risk associated with TEs involving assaultive violence was refined by showing agreement only for repeated occurrences. Some types of prior TE exposures are associated with increased resilience rather than increased vulnerability, connecting the literature on TE history with the literature on resilience after adversity. These results are valuable in providing an empirical rationale for more focused investigations of these specifications in future studies.

Importance: It is clear that mental disorders in treatment settings are associated with a higher incidence of chronic physical conditions, but whether this is true of mental disorders in the community, and how generalized (across a range of physical health outcomes) these associations are, is less clear. This information has important implications for mental health care and the primary prevention of chronic physical disease., Objective: To investigate associations of 16 temporally prior DSM-IV mental disorders with the subsequent onset or diagnosis of 10 chronic physical conditions., Design, Setting, and Participants: Eighteen face-to-face, cross-sectional household surveys of community-dwelling adults were conducted in 17 countries (47,609 individuals; 2,032,942 person-years) from January 1, 2001, to December 31, 2011. The Composite International Diagnostic Interview was used to retrospectively assess the lifetime prevalence and age at onset of DSM-IV-identified mental disorders. Data analysis was performed from January 3, 2012, to September 30, 2015., Main Outcomes and Measures: Lifetime history of physical conditions was ascertained via self-report of physician's diagnosis and year of onset or diagnosis. Survival analyses estimated the associations of temporally prior first onset of mental disorders with subsequent onset or diagnosis of physical conditions., Results: Most associations between 16 mental disorders and subsequent onset or diagnosis of 10 physical conditions were statistically significant, with odds ratios (ORs) (95% CIs) ranging from 1.2 (1.0-1.5) to 3.6 (2.0-6.6). The associations were attenuated after adjustment for mental disorder comorbidity, but mood, anxiety, substance use, and impulse control disorders remained significantly associated with onset of between 7 and all 10 of the physical conditions (ORs [95% CIs] from 1.2 [1.1-1.3] to 2.0 [1.4-2.8]). An increasing number of mental disorders experienced over the life course was significantly associated with increasing odds of onset or diagnosis of all 10 types of physical conditions, with ORs (95% CIs) for 1 mental disorder ranging from 1.3 (1.1-1.6) to 1.8 (1.4-2.2) and ORs (95% CIs) for 5 or more mental disorders ranging from 1.9 (1.4-2.7) to 4.0 (2.5-6.5). In population-attributable risk estimates, specific mental disorders were associated with 1.5% to 13.3% of physical condition onsets., Conclusions and Relevance: These findings suggest that mental disorders of all kinds are associated with an increased risk of onset of a wide range of chronic physical conditions. Current efforts to improve the physical health of individuals with mental disorders may be too narrowly focused on the small group with the most severe mental disorders. Interventions aimed at the primary prevention of chronic physical diseases should optimally be integrated into treatment of all mental disorders in primary and secondary care from early in the disorder course.

Importance: The inverse social gradient in mental disorders is a well-established research finding with important implications for causal models and policy. This research has used traditional objective social status (OSS) measures, such as educational level, income, and occupation. Recently, subjective social status (SSS) measurement has been advocated to capture the perception of relative social status, but to our knowledge, there have been no studies of associations between SSS and mental disorders., Objectives: To estimate associations of SSS with DSM-IV mental disorders in multiple countries and to investigate whether the associations persist after comprehensive adjustment of OSS., Design, Setting, and Participants: Face-to-face cross-sectional household surveys of community-dwelling adults in 18 countries in Asia, South Pacific, the Americas, Europe, and the Middle East (N=56,085). Subjective social status was assessed with a self-anchoring scale reflecting respondent evaluations of their place in the social hierarchies of their countries in terms of income, educational level, and occupation. Scores on the 1 to 10 SSS scale were categorized into 4 categories: low (scores 1-3), low-mid (scores 4-5), high-mid (scores 6-7), and high (scores 8-10). Objective social status was assessed with a wide range of fine-grained objective indicators of income, educational level, and occupation., Main Outcomes and Measures: The Composite International Diagnostic Interview assessed the 12-month prevalence of 16 DSM-IV mood, anxiety, and impulse control disorders., Results: The weighted mean survey response rate was 75.2% (range, 55.1%-97.2%). Graded inverse associations were found between SSS and all 16 mental disorders. Gross odds ratios (lowest vs highest SSS categories) in the range of 1.8 to 9.0 were attenuated but remained significant for all 16 disorders (odds ratio, 1.4-4.9) after adjusting for OSS indicators. This pattern of inverse association between SSS and mental disorders was significant in 14 of 18 individual countries, and in low-, middle-, and high-income country groups but was significantly stronger in high- vs lower-income countries., Conclusions and Relevance: Significant inverse associations between SSS and numerous DSM-IV mental disorders exist across a wide range of countries even after comprehensive adjustment for OSS. Although it is unclear whether these associations are the result of social selection, social causation, or both, these results document clearly that research relying exclusively on standard OSS measures underestimates the steepness of the social gradient in mental disorders.

Objectives: To develop and apply a model for prioritization of candidate glaucoma genes., Methods: This Affymetrix GeneChip (Affymetrix, Santa Clara, Calif) study of gene expression in primary culture human trabecular meshwork cells uses a positional differential expression profile model for prioritization of candidate genes within the GLC1C genetic inclusion interval., Results: Sixteen genes were expressed under all conditions within the GLC1C interval. TMEM22 was the only gene within the interval with differential expression in the same direction under both conditions tested. Two genes, ATP1B3 and COPB2, are of interest in the context of a protein-misfolding model for candidate selection. SLC25A36, PCCB, and FNDC6 are of lesser interest because of moderate expression and changes in expression. Transcription factor ZBTB38 emerges as an interesting candidate gene because of the overall expression level, differential expression, and function., Conclusions: Only 1 gene in the GLC1C interval fits our model for differential expression under multiple glaucoma risk conditions. The use of multiple prioritization models resulted in filtering 7 candidate genes of higher interest out of the 41 known genes in the region., Clinical Relevance: This study identified a small subset of genes that are most likely to harbor mutations that cause glaucoma linked to GLC1C.