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BackgroundTraumatic 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.MethodsData 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.ResultsThe 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.ConclusionsPTSD 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.

The 2013 US Veterans Administration/Department of Defense Clinical Practice Guidelines (VA/DoD CPG) require comprehensive suicide risk assessments for VA/DoD patients with mental disorders but provide minimal guidance on how to carry out these assessments. Given that clinician-based assessments are not known to be strong predictors of suicide, we investigated whether a precision medicine model using administrative data after outpatient mental health specialty visits could be developed to predict suicides among outpatients. We focused on male nondeployed Regular US Army soldiers because they account for the vast majority of such suicides. Four machine learning classifiers (naive Bayes, random forests, support vector regression and elastic net penalized regression) were explored. Of the Army suicides in 2004-2009, 41.5% occurred among 12.0% of soldiers seen as outpatient by mental health specialists, with risk especially high within 26 weeks of visits. An elastic net classifier with 10-14 predictors optimized sensitivity (45.6% of suicide deaths occurring after the 15% of visits with highest predicted risk). Good model stability was found for a model using 2004-2007 data to predict 2008-2009 suicides, although stability decreased in a model using 2008-2009 data to predict 2010-2012 suicides. The 5% of visits with highest risk included only 0.1% of soldiers (1047.1 suicides/100 000 person-years in the 5 weeks after the visit). This is a high enough concentration of risk to have implications for targeting preventive interventions. An even better model might be developed in the future by including the enriched information on clinician-evaluated suicide risk mandated by the VA/DoD CPG to be recorded.

We performed a genome-wide association study of 6447 bipolar disorder (BD) cases and 12 639 controls from the International Cohort Collection for Bipolar Disorder (ICCBD). Meta-analysis was performed with prior results from the Psychiatric Genomics Consortium Bipolar Disorder Working Group for a combined sample of 13 902 cases and 19 279 controls. We identified eight genome-wide significant, associated regions, including a novel associated region on chromosome 10 (rs10884920; P=3.28 × 10-8) that includes the brain-enriched cytoskeleton protein adducin 3 (ADD3), a non-coding RNA, and a neuropeptide-specific aminopeptidase P (XPNPEP1). Our large sample size allowed us to test the heritability and genetic correlation of BD subtypes and investigate their genetic overlap with schizophrenia and major depressive disorder. We found a significant difference in heritability of the two most common forms of BD (BD I SNP-h2=0.35; BD II SNP-h2=0.25; P=0.02). The genetic correlation between BD I and BD II was 0.78, whereas the genetic correlation was 0.97 when BD cohorts containing both types were compared. In addition, we demonstrated a significantly greater load of polygenic risk alleles for schizophrenia and BD in patients with BD I compared with patients with BD II, and a greater load of schizophrenia risk alleles in patients with the bipolar type of schizoaffective disorder compared with patients with either BD I or BD II. These results point to a partial difference in the genetic architecture of BD subtypes as currently defined.

BACKGROUND: Prior studies in the USA have reported higher rates of mental disorders among persons with arthritis but no cross-national studies have been conducted. In this study the prevalence of specific mental disorders among persons with arthritis was estimated and their association with arthritis across diverse countries assessed. METHOD: The study was a series of cross-sectional population sample surveys. Eighteen population surveys of household-residing adults were carried out in 17 countries in different regions of the world. Most were carried out between 2001 and 2002, but others were completed as late as 2007. Mental disorders were assessed with the World Health Organization (WHO) World Mental Health-Composite International Diagnostic Interview (WMH-CIDI). Arthritis was ascertained by self-report. The association of anxiety disorders, mood disorders and alcohol use disorders with arthritis was assessed, controlling for age and sex. Prevalence rates for specific mental disorders among persons with and without arthritis were calculated and odds ratios (ORs) with 95% confidence intervals were used to estimate the association. RESULTS: After adjusting for age and sex, specific mood and anxiety disorders occurred among persons with arthritis at higher rates than among persons without arthritis. Alcohol abuse/dependence showed a weaker and less consistent association with arthritis. The pooled estimates of the age- and sex-adjusted ORs were about 1.9 for mood disorders and for anxiety disorders and about 1.5 for alcohol abuse/dependence among persons with versus without arthritis. The pattern of association between specific mood and anxiety disorders and arthritis was similar across countries. CONCLUSIONS: Mood and anxiety disorders occur with greater frequency among persons with arthritis than those without arthritis across diverse countries. The strength of association of specific mood and anxiety disorders with arthritis was generally consistent across disorders and across countries. [ABSTRACT FROM AUTHOR]

BACKGROUND: Physical morbidity is a potent risk factor for depression onset and clearly increases with age, yet prior research has often found depressive disorders to decrease with age. This study tests the possibility that the relationship between age and mental disorders differs as a function of physical co-morbidity. METHOD: Eighteen general population surveys were carried out among household-residing adults as part of the World Mental Health (WMH) surveys initiative (n=42 697). DSM-IV disorders were assessed using face-to-face interviews with the Composite International Diagnostic Interview (CIDI 3.0). The effect of age was estimated for 12-month depressive and/or anxiety disorders with and without physical or pain co-morbidity, and for physical and/or pain conditions without mental co-morbidity. RESULTS: Depressive and anxiety disorders decreased with age, a result that cannot be explained by organic exclusion criteria. No significant difference was found in the relationship between mental disorders and age as a function of physical/pain co-morbidity. The majority of older persons have chronic physical or pain conditions without co-morbid mental disorders; by contrast, the majority of those with mental disorders have physical/pain co-morbidity, particularly among the older age groups. CONCLUSIONS: CIDI-diagnosed depressive and anxiety disorders in the general population decrease with age, despite greatly increasing physical morbidity with age. Physical morbidity among persons with mental disorder is the norm, particularly in older populations. Health professionals, including mental health professionals, need to address barriers to the management of physical co-morbidity among those with mental disorders. [ABSTRACT FROM AUTHOR]

BACKGROUND: The psychological aftermath of the Chernobyl accident is regarded as the largest public health problem unleashed by the accident to date. Yet the mental health of the clean-up workers, who faced the greatest radiation exposure and threat to life, has not been systematically evaluated. This study describes the long-term psychological effects of Chernobyl in a sample of clean-up workers in Ukraine.MethodThe cohorts were 295 male clean-up workers sent to Chernobyl between 1986 and 1990 interviewed 18 years after the accident (71% participation rate) and 397 geographically matched controls interviewed as part of the Ukraine World Mental Health (WMS) Survey 16 years after the accident. The World Health Organization (WHO) Composite International Diagnostic Interview (CIDI) was administered. We examined group differences in common psychiatric disorders, suicide ideation and severe headaches, differential effects of disorder on days lost from work, and in the clean-up workers, the relationship of exposure severity to disorder and current trauma and somatic symptoms. Analyses were adjusted for age in 1986 and mental health prior to the accident. RESULTS: Relatively more clean-up workers than controls experienced depression (18.0% v. 13.1%) and suicide ideation (9.2% v. 4.1%) after the accident. In the year preceding interview, the rates of depression (14.9% v. 7.1%), post-traumatic stress disorder (PTSD) (4.1% v. 1.0%) and headaches (69.2% v. 12.4%) were elevated. Affected workers lost more work days than affected controls. Exposure level was associated with current somatic and PTSD symptom severity. CONCLUSIONS: Long-term mental health consequences of Chernobyl were observed in clean-up workers. [ABSTRACT FROM AUTHOR]

BACKGROUND: The cognitive and academic outcomes of infants exposed to radiation after the meltdown at Chornobyl have been intensely debated. Western-based investigations indicate that no adverse effects occurred, but local studies reported increased cognitive impairments in exposed compared with non-exposed children. Our initial study found that at age 11 years, school grades and neuropsychological performance were similar in 300 children evacuated to Kiev as infants or in utero compared with 300 classmate controls, yet more evacuee mothers believed that their children had memory problems. This study re-examined the children's performance and academic achievement at age 19 years.MethodIn 2005-2006, we conducted an 8-year follow-up of the evacuees (n=265) and classmate controls (n=261) assessed in Kiev in 1997. Outcomes included university attendance, tests of intelligence, attention, and memory, and subjective appraisals of memory problems. Scores were standardized using a local population-based control group (n=327). Analyses were stratified by parental education. RESULTS: Evacuees and classmates performed similarly and in the normal range on all tests, and no differential temporal changes were found. The results were comparable for the in utero subsample. The rates of university attendance and self-reported memory problems were also similar. Nevertheless, the evacuee mothers were almost three times as likely to report that their children had memory problems compared with controls. CONCLUSIONS: Chornobyl did not influence the cognitive functioning of exposed infants although more evacuee mothers still believed that their offspring had memory problems. These lingering worries reflect a wider picture of persistent health concerns as a consequence of the accident. [ABSTRACT FROM AUTHOR]

ABSTRACT BACKGROUND: Few studies have examined the course of illness among severely depressed patients ascertained at first hospitalization. Using data from the Suffolk County Mental Health Project (SCMHP), we investigated the times to and predictors of the first full remission and the first relapse during a 4-year period in a first-admission cohort with major depressive disorder (MDD) with psychotic features.MethodThe cohort included 87 county-wide, first-admission patients with a longitudinal consensus diagnosis of MDD with psychotic features who were systematically followed over a 4-year period. We examined the associations of background, clinical and treatment factors, and time-varying indices of antidepressant (AD) and antipsychotic (AP) medication use to time to remission and relapse using Cox regression. RESULTS: By the 4-year follow-up, 60 respondents (69.0%) had achieved a period of full remission (median time of 22 weeks among remitters and 54 weeks in the full sample). In the multivariable analysis, longer time to remission was associated with longer latency between initial episode and hospitalization, lower pre-hospital Global Assessment of Functioning (GAF) score, and lack of insurance, but not use of medication. Twenty-six remitters (43.3%) relapsed (median time of 50 weeks among those who relapsed and 192 weeks among all remitters). None of the risk factors or time-varying medication variables was significantly associated with time to relapse.ConclusionOnly two-thirds of the sample had at least one full remission by 4 years, and almost half of them subsequently relapsed. Poorer pre-hospital resources predicted remission but not relapse. Medication use over the follow-up was not associated with remission or relapse. [ABSTRACT FROM AUTHOR]

BACKGROUND: It is now well documented that both black and white patients with severe mental illness are likely to use different types of treatment facilities, have different lengths of hospital stays, and receive different types and dosages of psychotropic medications. It is still uncertain, however, whether these differences exist at the early stages of treatment. METHOD: We examined treatment patterns for a countywide sample of patients with psychotic disorders recruited at their initial psychiatric hospitalization. Illness characteristics, prior treatment histories, admission conditions, and psychotropic medication use during this hospitalization were compared for both black and white patients. RESULTS: Black patients were less likely to have had out-patient treatment prior to their first hospitalization and were more likely to be hospitalized in public than in community psychiatric units than were white patients. Black patients were also more likely to be hospitalized primarily for a behavioral disturbance and escorted to the hospital by the emergency medical services or police, while white patients were more often hospitalized primarily for subjective suffering. These patterns were particularly significant for those with a non-schizophrenia diagnosis. However, there were few statistically significant differences between black and white patients on psychotropic medication use during the first hospitalization. CONCLUSIONS: Differences during the early stages of treatment between black and white patients with psychotic disorders appear to arise most prominently before, rather than during, their first hospitalization. [ABSTRACT FROM AUTHOR]

Background: Mental disorders are major causes of disability worldwide, including in the low-income and middle-income countries least able to bear such burdens. We describe mental health care in 17 countries participating in the WHO world mental health (WMH) survey initiative and examine unmet needs for treatment.Methods: Face-to-face household surveys were undertaken with 84,850 community adult respondents in low-income or middle-income (Colombia, Lebanon, Mexico, Nigeria, China, South Africa, Ukraine) and high-income countries (Belgium, France, Germany, Israel, Italy, Japan, Netherlands, New Zealand, Spain, USA). Prevalence and severity of mental disorders over 12 months, and mental health service use, were assessed with the WMH composite international diagnostic interview. Logistic regression analysis was used to study sociodemographic predictors of receiving any 12-month services.Findings: The number of respondents using any 12-month mental health services (57 [2%; Nigeria] to 1477 [18%; USA]) was generally lower in developing than in developed countries, and the proportion receiving services tended to correspond to countries' percentages of gross domestic product spent on health care. Although seriousness of disorder was related to service use, only five (11%; China) to 46 (61%; Belgium) of patients with severe disorders received any care in the previous year. General medical sectors were the largest sources of mental health services. For respondents initiating treatments, 152 (70%; Germany) to 129 (95%; Italy) received any follow-up care, and one (10%; Nigeria) to 113 (42%; France) received treatments meeting minimum standards for adequacy. Patients who were male, married, less-educated, and at the extremes of age or income were treated less.Interpretation: Unmet needs for mental health treatment are pervasive and especially concerning in less-developed countries. Alleviation of these unmet needs will require expansion and optimum allocation of treatment resources. [ABSTRACT FROM AUTHOR]

Since the 2011 Fukushima nuclear power plant accident, multiple social network disruptions have been reported among the community in Fukushima, while posttraumatic stress symptoms among the residents have persisted. In this study, we aimed to explore the influence of time and social networks on the recovery of posttraumatic stress symptoms based on longitudinal data from community residents in Fukushima, following up five to ten years after the nuclear power plant accident. We conducted five questionnaire surveys quasi-annually, the targets of which were randomly sampled 4900 non-evacuee community residents. In this study, the data of 1809 respondents who participated in at least one survey were used (36.9% of the initial target). Setting posttraumatic stress symptoms as the outcome, we examined the interaction between time and social network size using a mixed model, adjusting for sociodemographic characteristics and disaster-related events. Their interaction was statistically significant, and the posttraumatic stress symptoms of those with small social networks persisted, while those with larger social networks recovered. Maintaining and promoting social networks may contribute to mental health recovery after a nuclear disaster., Competing Interests: Declaration of competing interest The Department of Digital Mental Health where N.K. is employed at is an endowment department supported with an unrestricted grant from 15 enterprises (https://dmh.m.u-tokyo.ac.jp/c, accessed on November 7, 2022), outside the submitted work; N.K. also reports personal fees from the Occupational Health Foundation, SB AtWork Corp., RIKEN, Japan Aerospace Exploration Agency (JAXA), Sekisui Chemicals, Junpukai Health Care Center, and the Osaka Chamber of Commerce and Industry, all outside the submitted work. All other authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: Responders of the World Trade Center (WTC) disaster suffer from co-morbidities. A Mediterranean Diet (MedDiet) nutrition intervention with physical activity was implemented among WTC responders with overweight/obesity and post-traumatic stress disorder (PTSD)., Methods: WTC Health Program members ( N  = 62), 45-65 years, males 87%, body mass index (BMI) 27-45 kg/m 2 randomized to MedDiet ( n  = 31) or usual nutrition counseling ( n  = 31). The 10-week intervention included online nutrition education, text messages, and group experiential cooking; both groups had three in-person individual nutrition counseling. Anthropometrics, serum biomarkers, psychosocial factors, MedDiet score, and PTSD symptoms were assessed at baseline, post-intervention, and 3-months (follow-up). The primary outcome was intervention feasibility and secondary outcomes were within- and between-group changes of all measures at post-intervention and follow-up. Nonparametric Wilcoxon rank sum tests for between-group comparisons and Wilcoxon signed rank tests for pre-post within-group comparisons., Results: A total of 58(94%) and 46(74%) participants completed the post-intervention and follow-up measurements, respectively. Both groups experienced significant improvements in anthropometrics, MedDiet score, oxidized low-density lipoprotein, and PTSD symptoms. Baseline median (range) were weight 100.42 (73.66-135.17) kg, BMI 33.20 (27.50-41.75) kg/m 2 , and Waist circumference (WC) 109.22 (90.17-150.62) cm. Median % weight loss at post-intervention was MedDiet: -3% (-11%-7%), p  = 0.0002; Control: -1% (-13%-4%), p  = 0.008 and at follow-up MedDiet: -2% (-14%-12%), p  = 0.07; Control: -2% (-20%-3%), p  = 0.006. The overall BMI was reduced by -0.68 kg/m 2 (-4.61-2.09) kg/m 2 p  < 0.0001 at post-intervention and by -0.60 kg/m 2 (-6.91-3.39) kg/m 2 , p  < 0.0009 at follow-up. Overall, median WC was reduced ( p  < 0.0001); post-intervention -3.81 cm (-33.00-3.30)cm and follow-up -4.45(-38.10-4.57)cm. There were group differences in HbA1c ( p  = 0.019) and serum ω6/ω3 ( p  = 0.029) at post-intervention., Conclusion: Online intervention with personal counseling was feasible in this population. Improvements in anthropometrics, MedDiet score, selected serum biomarkers and PTSD symptoms were found in both groups; group differences in HbA1c and serum ω6/ω3. A larger study with a delayed control is needed to better assess intervention effects., Competing Interests: The authors declare no conflicts of interest., (© 2023 The Authors. Obesity Science & Practice published by World Obesity and The Obesity Society and John Wiley & Sons Ltd.)

Background: Information on the frequency and timing of mental disorder onsets across the lifespan is of fundamental importance for public health planning. Broad, cross-national estimates of this information from coordinated general population surveys were last updated in 2007. We aimed to provide updated and improved estimates of age-of-onset distributions, lifetime prevalence, and morbid risk., Methods: In this cross-national analysis, we analysed data from respondents aged 18 years or older to the World Mental Health surveys, a coordinated series of cross-sectional, face-to-face community epidemiological surveys administered between 2001 and 2022. In the surveys, the WHO Composite International Diagnostic Interview, a fully structured psychiatric diagnostic interview, was used to assess age of onset, lifetime prevalence, and morbid risk of 13 DSM-IV mental disorders until age 75 years across surveys by sex. We did not assess ethnicity. The surveys were geographically clustered and weighted to adjust for selection probability, and standard errors of incidence rates and cumulative incidence curves were calculated using the jackknife repeated replications simulation method, taking weighting and geographical clustering of data into account., Findings: We included 156 331 respondents from 32 surveys in 29 countries, including 12 low-income and middle-income countries and 17 high-income countries, and including 85 308 (54·5%) female respondents and 71 023 (45·4%) male respondents. The lifetime prevalence of any mental disorder was 28·6% (95% CI 27·9-29·2) for male respondents and 29·8% (29·2-30·3) for female respondents. Morbid risk of any mental disorder by age 75 years was 46·4% (44·9-47·8) for male respondents and 53·1% (51·9-54·3) for female respondents. Conditional probabilities of first onset peaked at approximately age 15 years, with a median age of onset of 19 years (IQR 14-32) for male respondents and 20 years (12-36) for female respondents. The two most prevalent disorders were alcohol use disorder and major depressive disorder for male respondents and major depressive disorder and specific phobia for female respondents., Interpretation: By age 75 years, approximately half the population can expect to develop one or more of the 13 mental disorders considered in this Article. These disorders typically first emerge in childhood, adolescence, or young adulthood. Services should have the capacity to detect and treat common mental disorders promptly and to optimise care that suits people at these crucial parts of the life course., Funding: None., Competing Interests: Declaration of interests LD receives educational grants from Indivior and Seqirus. OVD receives funding from Kowa Research Institute and has been an advisor in the PROMINENT trial. SMK and PWW receive grant funding from Hamad Medical Corporation through the Cambridgeshire and Peterborough National Health Service Foundation trust and from Qatar University. PWW has received financial support from the Qatar National Research Fund and an honorarium from Gresham College. RCK has been a consultant for Cambridge Health Alliance, Canandaigua Veterans Affairs Medical Center, Holmusk, Partners Healthcare, RallyPoint Networks, and Sage Therapeutics. He holds stock options in Cerebral, Mirah, Prepare Your Mind, Roga Sciences, and Verisense Health. DN receives honoraria from AIG General Insurance and Takeda Pharmaceutical and financial support from Startia, En-power, and MD.net. DJS receives royalties from American Psychiatric Press, Cambridge University Press, and Elsevier–Academic Press. He has received honoraria from Discovery Vitality, Johnson & Johnson, Kanna, L'Oreal, Lundbeck, Orion, Sanofi, Servier, Takeda, and Vistagen. He was the president of the African College of Neuropsychopharmacology and is financially supported by the Medical Research Council of South Africa. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

World Trade Center (WTC) responders exposed to traumatic and environmental stressors during rescue and recovery efforts have a high prevalence of chronic WTC-related post-traumatic stress disorder (WTC-PTSD). We investigated neural mechanisms underlying WTC-PTSD by applying eigenvector centrality (EC) metrics and data-driven methods on resting state functional magnetic resonance (fMRI). We identified how EC differences relate to WTC-exposure and behavioral symptoms. We found that connectivity differentiated significantly between WTC-PTSD and non-PTSD responders in nine brain regions, as these differences allowed an effective discrimination of PTSD and non-PTSD responders based solely on analysis of resting state data. Further, we found that WTC exposure duration (months on site) moderates the association between PTSD and EC values in two of the nine brain regions; the right anterior parahippocampal gyrus and the left amygdala (p = 0.010; p = 0.005, respectively, adjusted for multiple comparisons). Within WTC-PTSD, a dimensional measure of symptom severity was positively associated with EC values in the right anterior parahippocampal gyrus and brainstem. Functional neuroimaging can provide effective tools to identify neural correlates of diagnostic and dimensional indicators of PTSD., (© 2023. The Author(s).)

Community residents exposed to nuclear power plant (NPP) accidents have long-term worry about the effects of radiation. After the 2011 Fukushima NPP accident, those who experienced traumatic events during the Great East Japan Earthquake (GEJE) tended to have greater worry about radiation. Along with the prolonged worry about radiation, there may also be cognitive changes caused by the traumatic events. We hypothesized that if there were cognitive changes underlying the prolonged worry about radiation, those who experienced the traumatic events would tend to have greater worry about other issues unrelated to radiation. We examined the effects of the traumatic events during the GEJE on community residents' worry about radiation and COVID-19 a decade after the Fukushima NPP accident. Using the data of a longitudinal questionnaire survey following a random sample of 4900 community residents outside the evacuation zone in Fukushima, this study analyzed 774 responses (15.8%). The traumatic events consisted of (1) injury, (2) injury or death of a family member, and (3) the loss of a house or other property. We developed a mediation model drawing paths from the traumatic events to worry about radiation and COVID-19, including posttraumatic stress symptoms (PTSS) as a mediator, using structural equation modeling. The traumatic events directly affected worry about radiation. Although it did not directly affect worry about COVID-19, it did so indirectly through worry about radiation and PTSS. Traumatic events can increase trauma-related worry independently of PTSS and increase trauma-unrelated worry indirectly through trauma-related worry and PTSS., Competing Interests: Declaration of competing interest The Department of Digital Mental Health where N.K. is employed at is an endowment department supported with an unrestricted grant from 15 enterprises (https://dmh.m.u-tokyo.ac.jp/c, accessed on November 7, 2022), outside the submitted work; N.K. also reports personal fees from the Occupational Health Foundation, SB AtWork Corp., RIKEN, Japan Aerospace Exploration Agency (JAXA), Sekisui Chemicals, Junpukai Health Care Center, and the Osaka Chamber of Commerce and Industry, all outside the submitted work. All other authors declare no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Chronically re-experiencing the memory of a traumatic event might cause a glial response. This study examined whether glial activation would be associated with PTSD in a study of responders present after the 9/11 World Trade Center attacks without comorbid cerebrovascular disease., Methods: Plasma was retrieved from 1,520 WTC responders and stored for a cross-sectional sample of responders of varying levels of exposure and PTSD. Plasma levels (pg/ml) of glial fibrillary acidic protein (GFAP) were assayed. Because stroke and other cerebrovascular diseases cause distributional shifts in GFAP levels, multivariable-adjusted finite mixture models analyzed GFAP distributions in responders with and without possible cerebrovascular disease., Results: Responders were aged 56.3 years and primarily male; 11.07% (n = 154) had chronic PTSD. Older age was associated with increased GFAP, whereas higher body mass was associated with decreased GFAP. Multivariable-adjusted finite mixture models revealed that severe re-experiencing trauma from 9/11 was associated with lower GFAP (B = -0.558, p = 0.003)., Conclusion: This study presents evidence of reduced plasma GFAP levels among WTC responders with PTSD. Results suggest re-experiencing traumatic events might cause glial suppression., Competing Interests: This is an epidemiological study examining biomarkers associated with posttraumatic stress disorder. The authors have no conflicts of interest to disclose., (© 2023 The Authors.)

Introduction: World Trade Center (WTC) responders are experiencing a high risk of mild cognitive impairment (MCI) and dementia, though the etiology remains inadequately characterized. This study investigated whether WTC exposures and chronic post-traumatic stress disorder (PTSD) were correlated with plasma biomarkers characteristic of Alzheimer's disease (AD) neuropathology., Methods: Eligible participants included WTC-exposed individuals with a baseline cognitive assessment and available plasma sample. We examined levels of the amyloid beta (Aβ)40/42 ratio, phosphorylated tau 181 (p-tau181), and neurofilament light chain (NfL) and associations with a WTC exposures (duration on site ≥15 weeks, dust cloud), the PTSD Symptom Checklist for Diagnostic and Statistical Manual of Mental Disorders, 4th edition PTSD, and classification of amyloid/tau/neurodegeneration (AT[N]) profiles. Multinomial logistic regressions assessed whether biomarkers predicted increased risk of MCI or dementia., Results: Of 1179 eligible responders, 93.0% were male, mean (standard deviation) age 56.6 years (7.8). Aβ40/42, p-tau181, and NfL intercorrelated and increased with age. In subgroup analyses of responders with available neuroimaging data ( n = 75), Aβ40/42 and p-tau181 were further associated with decreased hippocampal volume (Spearman's  ρ = -0.3). Overall, 58.08% of responders with dementia had ≥1 elevated biomarker, and 3.45% had elevations across all biomarkers. In total, 248 (21.05%) had MCI and 70 (5.94%) had dementia. Increased risk of dementia was associated with plasma AT(N) profile T+ or A+N+. Exposure on site ≥15 weeks was independently associated with T+ (adjusted risk ratio [aRR] = 1.03 [1.01-1.05], P = 0.009), and T+N+ profile (aRR = 2.34 [1.12-4.87]). The presence of PTSD was independently associated with risk of A+ (aRR = 1.77 [1.11-2.82])., Discussion: WTC exposures and chronic PTSD are associated with plasma biomarkers consistent with neurodegenerative disease., Competing Interests: The authors declare no conflicts of interest. Author disclosures are available in the supporting information., (© 2023 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.)

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 ( β = 0.32; p = 0.049) and first-person singular usage ( β = 0.31; p = 0.049) were associated with increased symptom severity. Longitudinally, anxious language predicted future worsening in PCL scores ( β = 0.30; p = 0.049), whereas first-person plural usage ( β = -0.36; p = 0.014) and longer words usage ( β = -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.

Responders to the World Trade Center (WTC) attacks on 9/11/2001 inhaled toxic dust and experienced severe trauma for a prolonged period. Studies report that WTC site exposure duration is associated with peripheral inflammation and risk for developing early-onset dementia (EOD). Free Water Fraction (FWF) can serve as a biomarker for neuroinflammation by measuring in vivo movement of free water across neurons. The present case-controlled study aimed to examine associations between WTC site exposure duration as well as EOD status with increased hippocampal and cerebral neuroinflammation. Ninety-nine WTC responders (mean age of 56) were recruited between 2017 and 2019 (N = 48 with EOD and 51 cognitively unimpaired). Participants were matched on age, sex, occupation, race, education, and post-traumatic stress disorder (PTSD) status. Participants underwent neuroimaging using diffusion tensor imaging protocols for FWF extraction. Region of interest (ROI) analysis and correlational tractography explored topographical distributions of FWF associations. Apolipoprotein-e4 allele (APOEε4) status was available for most responders (N = 91). Hippocampal FWF was significantly associated with WTC site exposure duration (r = 0.30, p = 0.003), as was cerebral white matter FWF (r = 0.20, p = 0.044). ROI analysis and correlational tractography identified regions within the limbic, frontal, and temporal lobes. Hippocampal FWF and its association with WTC exposure duration were highest when the APOEε4 allele was present (r = 0.48, p = 0.039). Our findings demonstrate that prolonged WTC site exposure is associated with increased hippocampal and cerebral white matter neuroinflammation in WTC responders, possibly exacerbated by possession of the APOEε4 allele., (© 2022. The Author(s).)

Worry about radiation persists long after nuclear power plant accidents. Young age, low socioeconomic status, being married, and disaster-related experiences are known to be associated with greater worry about radiation. This study explored the duration of the effects of these risk factors on worry about radiation after the 2011 Fukushima nuclear power plant accident, using the longitudinal data of randomly sampled non-evacuee community residents who were followed five to ten years after the accident. Questionnaire surveys were conducted five times with 1825 respondents (37.2% of the 4900 initial targets). We examined the interaction of time and risk factors of worry about radiation using a mixed model. Fear or anxiety immediately after the accident had effects on worry about radiation that continued even after 10 years, though it slightly attenuated with time. Family problems stemming from the disaster retained their effects. While direct damage and evacuation experience were significantly associated with worry about radiation in the early phase, their effects diminished and became non-significant during the study period. Being under the age of 65, having low educational attainment, and being married were significantly associated with worry about radiation, although the association with age weakened over time. Individuals who experience intense fear or anxiety post-nuclear power plant accidents or disaster-related family problems may need continuous monitoring for their worry about radiation even 10 years after such accidents.

Background and Objectives: Posttraumatic stress disorder (PTSD) has been linked to increased risk of cognitive dysfunction and physical functional impairment (PFI). The objective of this prospective cohort study was to examine whether PFI was associated with increased risk of incident mild cognitive impairment (MCI) among World Trade Center (WTC) responders with PTSD. We hypothesized that responders with PTSD would have an elevated risk of incident MCI and that PFI would mediate this increase., Methods: We examined responder participants in the WTC Aging Study whose baseline physical assessments were completed by May 2016-April 2017 and were followed up at least once before December 2019. Those without complete demographic, medical, or behavioral data were excluded. PFI was assessed using measures of upper body strength (maximal handgrip strength [HGS]) and lower extremity physical functioning (Short Physical Performance Battery). PTSD was rated using a diagnostic interview and symptom checklist; MCI and dementia were assessed using the Montreal Cognitive Assessment and diagnosed using the National Institute on Aging-Alzheimer's Association criteria. Group differences and longitudinal comparisons were examined. Cox proportional hazards models were evaluated from time to incident MCI and conversion to dementia. A mediation analysis examined whether PFI mediated associations between PTSD and MCI., Results: Within the sample of 2,687 WTC responders, 324 (12.06%, 95% CI = [10.83-13.29]) had lower extremity PFI. Responders with lower extremity PFI were older, had lower education and higher body mass, and were at a higher risk of pulmonary embolisms and PTSD. Responders with lower extremity PFI demonstrated lower baseline cognition and had increased hazards of MCI (multivariable-adjusted hazards ratio [aHR] = 1.55 [95% CI 1.21-1.98]); those with MCI converted to dementia more rapidly than those without PFI (2.73 [1.38-5.39] p = 0.004). In addition, each standard deviation decrease in HGS was associated with increased hazards of developing MCI (aHR = 1.35 [95% CI 1.10-1.66]). A mediation model suggested PFI played an intermediary role in the relationship between PTSD and MCI., Discussion: WTC responders with PFI demonstrated worse cognitive and behavioral outcomes, and PFI played an intermediary role in the relationship between PTSD and incident MCI, suggesting that PFI may be an early indicator of MCI in responders with PTSD. Regular monitoring of PFI should be considered among PTSD populations., (© 2022 American Academy of Neurology.)

Aim: Exposure to traumatic events (TEs) is associated with substance use disorders (SUDs). However, most studies focus on a single TE, and are limited to single countries, rather than across countries with variation in economic, social and cultural characteristics. We used cross-national data to examine associations of diverse TEs with SUD onset, and variation in associations over time., Methods: Data come from World Mental Health surveys across 22 countries. Adults (n = 65,165) retrospectively reported exposure to 29 TEs in six categories: "exposure to organised violence"; "participation in organised violence"; "interpersonal violence"; "sexual-relationship violence"; "other life-threatening events"; and those involving loved ones ("network traumas"). Discrete-time survival analyses were used to examine associations with subsequent first SUD onset., Results: Most (71.0%) reported experiencing at least one TE, with network traumas (38.8%) most common and exposure to organised violence (9.5%) least. One in five (20.3%) had been exposed to sexual-relationship violence and 26.6% to interpersonal violence. Among the TE exposed, lifetime SUD prevalence was 14.5% compared to 5.1% with no trauma exposure. Most TE categories (except organised violence) were associated with increased odds of SUD. Increased odds of SUD were also found following interpersonal violence exposure across all age ranges (ORs from 1.56 to 1.78), and sexual-relationship violence exposure during adulthood (ORs from 1.33 to 1.44), with associations persisting even after >11 years., Conclusion: Sexual and interpersonal violence have the most consistent associations with progression to SUD; increased risk remains for many years post-exposure. These need to be considered when working with people exposed to such traumas., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Negative symptoms are among the greatest sources of functional impairment for individuals with schizophrenia, yet their mechanisms remain poorly understood. Olfactory impairment is associated with negative symptoms. The processing of pleasant olfactory stimuli is subserved by reward-related neural circuitry while unpleasant olfactory processing is subserved by emotion-related neural circuitry, suggesting that these two odor dimensions may offer a window into differential mechanisms of negative symptoms. We examined whether pleasant and unpleasant odor identification bears differential relationships with avolition and inexpressivity dimensions of negative symptoms, whether these relationships are transdiagnostic, and whether pleasant and unpleasant odor processing also relate differently to other domains of functioning in a sample of individuals diagnosed with schizophrenia (N = 54), other psychotic disorders (N = 65), and never-psychotic adults (N = 160). Hierarchical regressions showed that pleasant odor identification was uniquely associated with avolition, while unpleasant odor identification was uniquely associated with inexpressivity. These relationships were largely transdiagnostic across groups. Additionally, pleasant and unpleasant odor identification displayed signs of specificity with other functional and cognitive measures. These results align with past work suggesting dissociable pathomechanisms of negative symptoms and provide a potential avenue for future work using valence-specific olfactory dysfunction as a semi-objective and low-cost marker for understanding and predicting the severity of specific negative symptom profiles., Competing Interests: Declaration of competing interest All authors declare no conflicts of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose  Incidence of early onset neurocognitive dysfunction has been reported in World Trade Center (WTC) responders. Ongoing studies are investigating the underlying etiology, as we are concerned that an underlying risk of neurodegenerative dementia may be occurring because of their stressful and neurotoxic exposures to particulate matter when they responded to the search and rescue efforts on September 11, 2001. The purpose of this study is to report preliminary results from two ongoing positron emission tomography (PET)/magnetic resonance imaging (MRI) imaging studies investigating the presence of Alzheimer's disease (AD) biomarkers, such as β-amyloid, tau, and neurodegeneration, and compare our findings to published norms. Methods  We present findings on 12 WTC responders diagnosed with either cognitive impairment (CI) or mild cognitive impairment (MCI), now at midlife, who underwent PET/MRI brain imaging as part of ongoing studies. Six responders with CI received [ 18 F] florbetaben (FBB) to detect β-amyloidosis and six separate responders with MCI received [ 18 F] flortaucipir (FTP) to detect tauopathy. All 12 responders underwent concomitant MRI scans for gray matter volume analysis of neurodegeneration. Results  PET analysis revealed 50% FBB and 50% of FTP scans were clinically read as positive and that 50% of FTP scans identified as consistent with Braak's stage I or II. Furthermore, one responder identified as centiloid positive for AD. Gray matter volumes from MRI analyses were compared with age/sex-matched norms (Neuroquant), identifying abnormally low cortical volumes in the occipital and temporal lobes, as well as the inferior temporal gyri and the entorhinal cortex. Conclusion  These preliminary results suggest that WTC responders with neurocognitive dysfunction may be at increased risk for a neurodegenerative dementia process as a result of their exposures at September 11, 2001., Competing Interests: Conflict of Interest The authors have no disclosures to report., (World Association of Radiopharmaceutical and Molecular Therapy (WARMTH). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

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 ( β = 0.07), disorganized ( β = 0.07), manic ( β = 0.08), and depressive symptoms ( β = 0.06), and a decrease in negative symptoms ( β = -0.08). Conversely, positive LEs predicted fewer reality distortion ( β = -0.04), disorganized ( β = -0.04), and negative ( β = -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.

Importance: Schizophrenia is associated with major cognitive deficits and has been conceptualized as both a neurodevelopmental and a neurodegenerative disorder. However, when deficits develop and how they change over the course of illness is uncertain., Objective: To trace cognition from elementary school to old age to test neurodevelopmental and neurodegenerative theories of psychotic disorders., Design, Setting, and Participants: Data were taken from the Suffolk County Mental Health Project, a first-admission longitudinal cohort study of individuals with psychotic disorders. Participants were recruited from all 12 inpatient psychiatric facilities in Suffolk County, New York. This analysis concerns the 428 participants with at least 2 estimates of general cognitive ability. Data were collected between September 1989 and October 2019, and data were analyzed from January 2020 to October 2021., Exposures: Psychiatric hospitalization for psychosis., Main Outcomes and Measures: Preadmission cognitive scores were extracted from school and medical records. Postonset cognitive scores were based on neuropsychological testing at 6-month, 24-month, 20-year, and 25-year follow-ups., Results: Of the 428 included individuals (212 with schizophrenia and 216 with other psychotic disorders), 254 (59.6%) were male, and the mean (SD) age at psychosis onset was 27 (9) years. Three phases of cognitive change were observed: normative, declining, and deteriorating. In the first phase, cognition was stable. Fourteen years before psychosis onset, those with schizophrenia began to experience cognitive decline at a rate of 0.35 intelligence quotient (IQ) points per year (95% CI, 0.29-0.42; P < .001), a significantly faster decline than those with other psychotic disorders (0.15 IQ points per year; 95% CI, 0.08-0.22, P < .001). At 22 years after onset, both groups declined at a rate of 0.59 IQ points per year (95% CI, 0.25-0.94; P < .001)., Conclusions and Relevance: In this cohort study, cognitive trajectories in schizophrenia were consistent with both a neurodevelopmental and neurodegenerative pattern, resulting in a loss of 16 IQ points over the period of observation. Cognitive decline began long prior to psychosis onset, suggesting the window for primary prevention is earlier than previously thought. A window for secondary prevention emerges in the third decade of illness, when cognitive declines accelerate in individuals with schizophrenia and other psychotic disorders.

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., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

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 disorders 1 , epilepsy and severe neurodevelopmental disorders 2 , 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 risk 3 , 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., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Prior research has demonstrated high levels of cognitive and physical functional impairments in World Trade Center (WTC) responders. A follow-up neuroimaging study identified changes to white matter connectivity within the cerebellum in responders with cognitive impairment (CI). In the first study to examine cerebellar cortical thickness in WTC responders with CI, we fielded a structural magnetic resonance imaging protocol. WTC responders (N = 99) participated in a structural magnetic resonance imaging (MRI) study, of whom 48 had CI. Participants with CI did not differ demographically or by intracranial volume when compared to cognitively unimpaired participants. MRIs were processed using the CERES imaging pipeline; bilateral cortical thickness in 12 cerebellar lobules was reported. Analyses were completed comparing mean cerebellar cortical thickness across groups. Lobules were examined to determine the location and functional correlates of reduced cerebellar cortical thickness. Multivariable-adjusted analyses accounted for the false discovery rate. Mean cerebellar cortical thickness was reduced by 0.17 mm in responders with CI. Decrements in cerebellar cortical thickness were symmetric and located in the Cerebellar Crus (I and II), and in Lobules IV, VI, VIIb, VIIIa, VIIIb, and IX. Cerebellar cortical thickness was associated with episodic memory, response speed, and tandem balance. WTC responders with CI had evidence of reduced cerebellar cortical thickness that was present across lobules in a pattern unique to this cohort., (© 2022. The Author(s).)

On 11 September 2001 the World Trade Center (WTC) in New York was attacked by terrorists, causing the collapse of multiple buildings including the iconic 110-story 'Twin Towers'. Thousands of people died that day from the collapse of the buildings, fires, falling from the buildings, falling debris, or other related accidents. Survivors of the attacks, those who worked in search and rescue during and after the buildings collapsed, and those working in recovery and clean-up operations were exposed to severe psychological stressors. Concurrently, these 'WTC-affected' individuals breathed and ingested a mixture of organic and particulate neurotoxins and pro-inflammogens generated as a result of the attack and building collapse. Twenty years later, researchers have documented neurocognitive and motor dysfunctions that resemble the typical features of neurodegenerative disease in some WTC responders at midlife. Cortical atrophy, which usually manifests later in life, has also been observed in this population. Evidence indicates that neurocognitive symptoms and corresponding brain atrophy are associated with both physical exposures at the WTC and chronic post-traumatic stress disorder, including regularly re-experiencing traumatic memories of the events while awake or during sleep. Despite these findings, little is understood about the long-term effects of these physical and mental exposures on the brain health of WTC-affected individuals, and the potential for neurocognitive disorders. Here, we review the existing evidence concerning neurological outcomes in WTC-affected individuals, with the aim of contextualizing this research for policymakers, researchers and clinicians and educating WTC-affected individuals and their friends and families. We conclude by providing a rationale and recommendations for monitoring the neurological health of WTC-affected individuals., (© 2021. Springer Nature Limited.)

Personality is linked to important health outcomes, but most prior studies have relied on self-reports, making it possible that shared-method variance explains the associations. The present study examined self- versus informant-reports of personality and multi-method outcomes. World Trade Center (WTC) responders and informants, 283 pairs, completed five-factor model personality measures and multi-method assessments of stressful events, functioning, mental disorders, 9/11-related treatment costs, BMI, and daily activity across three years. Self-reports were uniquely related to stressful events and functioning. Both self-reports and informant-reports showed incremental validity over one another for mental disorder diagnoses and treatment costs. For objective outcomes daily activity and BMI, informant-reports showed incremental validity over self-reports, accounting for all self-report variance and more. The findings suggest that informant-reports of personality provide better validity for objective health outcomes, which has implications for understanding personality and its role in mental and physical health.

Background: More than 8% of responders who participated in the search and rescue efforts at the World Trade Center (WTC) following 9/11 developed early-onset cognitive impairment (CI). Approximately 23% were also diagnosed with chronic post-traumatic stress disorder (PTSD)., Objective: To shed light on the pathophysiology of these WTC-related conditions, we examined diffusion connectometry to identify altered white matter tracts in WTC responders with CI and/or PTSD compared to unaffected responders., Methods: 99 WTC responders (mean age 56 years) consisting of CI-/PTSD- (n = 27), CI+/PTSD- (n = 25), CI-/PTSD+ (n = 24), and CI+/PTSD+ (n = 23) were matched on age, sex, occupation, race, and education. Cognitive status was determined using the Montreal Cognitive Assessment and PTSD status was determined using the DSM-IV SCID. Diffusion tensor imaging was acquired on a 3T Siemens Biograph mMR scanner. Connectometry analysis was used to examine whole-brain tract-level differences in white matter integrity as reflected by fractional anisotropy (FA) values after adjusting for confounders., Results: Analyses identified that FA was negatively correlated with CI and PTSD status in the fornix, cingulum, forceps minor of the corpus callosum and the right uncinate fasciculus. Furthermore, FA was negatively correlated with PTSD status, regardless of CI status in the superior thalamic radiation and the cerebellum., Conclusion: This is the first connectometry study to examine altered white matter tracts in a sample of WTC responders with CI and/or PTSD. Results from this study suggest that WTC responders with early-onset CI may be experiencing an early neurodegenerative process characterized by decreased FA in white matter tracts.

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 (β = -0.34 years, s.e. = 0.08), major depression (β = -0.34 years, s.e. = 0.08), schizophrenia (β = -0.39 years, s.e. = 0.08), and educational attainment (β = -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.

Approximately 23% of World Trade Center (WTC) responders are experiencing chronic posttraumatic stress disorder (PTSD) associated with their exposures at the WTC following the terrorist attacks of 9/11/2001, which has been demonstrated to be a risk factor for cognitive impairment raising concerns regarding their brain health. Cortical complexity, as measured by analyzing Fractal Dimension (FD) from T 1 MRI brain images, has been reported to be reduced in a variety of psychiatric and neurological conditions. In this report, we hypothesized that FD would be also reduced in a case-control sample of 99 WTC responders as a result of WTC-related PTSD. The results of our surface-based morphometry cluster analysis found alterations in vertex clusters of complexity in WTC responders with PTSD, with marked reductions in regions within the frontal, parietal, and temporal cortices, in addition to whole-brain absolute bilateral and unilateral complexity. Furthermore, region of interest analysis identified that the magnitude of changes in regional FD severity was associated with increased PTSD symptoms (reexperiencing, avoidance, hyperarousal, negative affect) severity. This study confirms prior findings on FD and psychiatric disorders and extends our understanding of FD associations with posttraumatic symptom severity. The complex and traumatic experiences that led to WTC-related PTSD were associated with reductions in cortical complexity. Future work is needed to determine whether reduced cortical complexity arose prior to, or concurrently with, onset of PTSD., (© 2021. The Author(s).)

Background: Recent research on artificial intelligence has demonstrated that natural language can be used to provide valid indicators of psychopathology. The present study examined artificial intelligence-based language predictors (ALPs) of seven trauma-related mental and physical health outcomes in responders to the World Trade Center disaster., Methods: The responders (N = 174, M age  = 55.4 years) provided daily voicemail updates over 14 days. Algorithms developed using machine learning in large social media discovery samples were applied to the voicemail transcriptions to derive ALP scores for several risk factors (depressivity, anxiousness, anger proneness, stress, and personality). Responders also completed self-report assessments of these risk factors at baseline and trauma-related mental and physical health outcomes at two-year follow-up (including symptoms of depression, posttraumatic stress disorder, sleep disturbance, respiratory problems, and GERD)., Results: Voicemail ALPs were significantly associated with a majority of the trauma-related outcomes at two-year follow-up, over and above corresponding baseline self-reports. ALPs showed significant convergence with corresponding self-report scales, but also considerable uniqueness from each other and from self-report scales., Limitations: The study has a relatively short follow-up period relative to trauma occurrence and a limited sample size., Conclusions: This study shows evidence that ALPs may provide a novel, objective, and clinically useful approach to forecasting, and may in the future help to identify individuals at risk for negative health outcomes., (Copyright © 2021 Elsevier Ltd. All rights reserved.)