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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.

Introduction Identifying predictors of mental health symptoms after the initial phase of the pandemic may inform the development of targeted interventions to reduce its negative long-term mental health consequences. In the current study, we aimed to simultaneously evaluate the prospective influence of life change stress, personal COVID-19 impact, prior mental health, worry about COVID-19, state-level indicators of pandemic threat, and socio-demographic factors on mood and anxiety symptoms in November 2020 among adults and children in the US and UK. Methods We used a longitudinal cohort study using the Coronavirus Health Impact Survey (CRISIS) collected at 3 time points: an initial assessment in April 2020 (“April”), a reassessment 3 weeks later (“May”), and a 7-month follow-up in November 2020 (“November”). Online surveys were collected in the United States and United Kingdom by Prolific Academic, a survey recruitment service, with a final sample of 859 Adults and 780 children (collected via parent report). We found subtypes of pandemic-related life change stress in social and economic domains derived through Louvain Community Detection. We assessed recalled mood and perceived mental health prior to the pandemic, worries about COVID-19, personal and family impacts of COVID-19, and socio-demographic characteristics. We used a conditional random forest approach to predict November mood states using these data from April and May and to rank the variable importance of each of the predictor items. Results Levels of mood symptoms in November 2020 measured with the circumplex model of affect. We found 3 life change stress subtypes among adults and children: Lower Social/Lower Economic (adults and children), Higher Social/Higher Economic (adults and children), Lower Social/Higher Economic (adults), and Intermediate Social/Lower Economic (children). Overall, mood symptoms decreased between April and November 2020, but shifting from lower to higher-stress subtypes between time points was associated with increasing symptoms. For both adults and children, the most informative predictors of mood symptoms in November identified by conditional random forest models were prior mood and perceived mental health, worries about COVID, and sources of life change. Discussion The relative importance of these predictors was the most prominent difference in findings between adults and children, with lifestyle changes stress regarding friendships being more predictive of mood outcomes than worries about COVID in children. In the US, objective state-level indicators of COVID-19 threat were less predictive of November mood than these other predictors. We found that in addition to the well-established influences of prior mood and worry, heterogeneous subtypes of pandemic-related stress were differentially associated with mood after the initial phase of the pandemic. Greater research on diverse patterns of pandemic experience may elucidate modifiable targets for treatment and prevention.

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 ObjectivesPosttraumatic 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.MethodsWe 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.ResultsWithin 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.DiscussionWTC 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.

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. Here, the authors summarize the evidence concerning the neurological health of individuals affected by the 11 September 2001 terrorist attacks and present the outcome of a meeting convened by the US National Institute for Occupational Safety and Health that aimed to generate recommendations for future research in this population.

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 [18F] florbetaben (FBB) to detect β-amyloidosis and six separate responders with MCI received [18F] 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.

Introduction World Trade Center (WTC) responders have a high risk of early-onset cognitive impairment (CI), but little is known about the etiology including the extent to which CI in WTC responders is accompanied by cortical atrophy as is common in progressive diseases causing age-related CI such as Alzheimer’s disease and related dementias. In the current study, we entrained an artificial neural network (ANN) to determine the accuracy of cortical thickness (CTX) on magnetic resonance imaging to identify World Trade Center responders at midlife (aged 44–65 years) with possible dementia. Methods A total of 119 WTC responders (57 with CI and 62 with intact cognition) underwent a structural MRI scanning protocol including T1-weighted MPRAGE as part of two imaging studies. The discovery study was divided into training and validation samples, while a second replication sample was used. An ANN was trained using regional CTX measured across 34 unilateral regions of interest (ROIs) using Freesurfer software and ‘Desikan-Killiany’ brain atlas. The discovery sample was used for model development, and the replication sample was used to evaluate predictive accuracy. Results In the WTC responder cohort, the ANN algorithm showed high discrimination performance for CI. The ANN model using regional CTX data from both hemispheres achieved an area under the receiver operating characteristic curve (AUC) of 0.96 95% C.I. ​= ​[0.91–1.00] (Accuracy ​= ​96.0%, Precision ​= ​97.8%, Recall ​= ​95.8%, Sensitivity ​= ​95.8%, Specificity ​= ​98.0%, F1 ​= ​96.8%) for the discovery sample and AUC ​= ​0.90 [0.70–1.00] (Accuracy ​= ​90.0%, Precision ​= ​90.0%, Sensitivity ​= ​90.0%, Specificity ​= ​90.0%, F1 ​= ​90.0%) in the replication sample. Conclusion Analysis of bilateral regional CTX data derived from T1-weighted MPRAGE images by ANN analysis demonstrated excellent accuracy in distinguishing WTC responders with early-onset CI.

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.

Gene expression has provided promising insights into the pathophysiology of post-traumatic stress disorder (PTSD); however, specific regulatory transcriptomic mechanisms remain unknown. The present study addressed this limitation by performing transcriptome-wide RNA-Seq of whole-blood samples from 226 World Trade Center responders. The investigation focused on differential expression (DE) at the gene, isoform, and for the first time, alternative splicing (AS) levels associated with the symptoms of PTSD: total burden, re-experiencing, avoidance, numbing, and hyperarousal subdimensions. These symptoms were associated with 76, 1, 48, 15, and 49 DE genes, respectively (FDR

The COVID-19 pandemic and its social and economic consequences have had adverse impacts on physical and mental health worldwide and exposed all segments of the population to protracted uncertainty and daily disruptions. The CoRonavIruS health and Impact Survey (CRISIS) was developed for use as an easy to implement and robust questionnaire covering key domains relevant to mental distress and resilience during the pandemic. Ongoing studies using CRISIS include international studies of COVID-related ill health conducted during different phases of the pandemic and follow-up studies of cohorts characterized before the COVID pandemic. In the current work, we demonstrate the feasibility, psychometric structure, and construct validity of this survey. We then show that pre-existing mood states, perceived COVID risk, and lifestyle changes are strongly associated with negative mood states during the pandemic in population samples of adults and in parents reporting on their children in the US and UK. These findings are highly reproducible and we find a high degree of consistency in the power of these factors to predict mental health during the pandemic.

Background: Individuals who participated in response efforts at the World Trade Center (WTC) following 9/11/2001 are experiencing elevated incidence of mild cognitive impairment (MCI) at midlife. Objective: We hypothesized that white matter connectivity measured using diffusion spectrum imaging (DSI) would be restructured in WTC responders with MCI versus cognitively unimpaired responders. Methods: Twenty responders (mean age 56; 10 MCI/10 unimpaired) recruited from an epidemiological study were characterized using NIA-AA criteria alongside controls matched on demographics (age/sex/occupation/race/education). Axial DSI was acquired on a 3T Siemen’s Biograph mMR scanner (12-channel head coil) using a multi-band diffusion sequence. Connectometry examined whole-brain tract-level differences in white matter integrity. Fractional anisotropy (FA), mean diffusivity (MD), and quantified anisotropy were extracted for region of interest (ROI) analyses using the Desikan-Killiany atlas. Results: Connectometry identified both increased and decreased connectivity within regions of the brains of responders with MCI identified in the corticothalamic pathway and cortico-striatal pathway that survived adjustment for multiple comparisons. MCI was also associated with higher FA values in five ROIs including in the rostral anterior cingulate; lower MD values in four ROIs including the left rostral anterior cingulate; and higher MD values in the right inferior circular insula. Analyses by cognitive domain revealed nominal associations in domains of response speed, verbal learning, verbal retention, and visuospatial learning. Conclusions: WTC responders with MCI at midlife showed early signs of neurodegeneration characterized by both increased and decreased white matter diffusivity in regions commonly affected by early-onset Alzheimer’s disease.

Background The prevalence of burnout and depressive symptoms is high among physician trainees. Research Question What is the burden of burnout and depressive symptoms among fellows training in pulmonary and critical care medicine (PCCM) and what are associated individual fellow, program, and institutional characteristics? Study Design and Methods We conducted a cross-sectional electronic survey of fellows enrolled in pulmonary, PCCM, and critical care medicine training programs in the United States to assess burnout and depressive symptoms. Burnout symptoms were measured using the Maslach Burnout Index two-item measure. The two-item Primary Care Evaluation of Mental Disorders Procedure was used to screen for depressive symptoms. For each of the two outcomes (burnout and depressive symptoms), we constructed three multivariate logistic regression models to assess individual fellow characteristics, program structure, and institutional polices associated with either burnout or depressive symptoms. Results Five hundred two of the 976 fellows who received the survey completed it—including both outcome measures—giving a response rate of 51%. Fifty percent of fellows showed positive results for either burnout or depressive symptoms, with 41% showing positive results for depressive symptoms, 32% showing positive results for burnout, and 23% showing positive results for both. Reporting a coverage system in the case of personal illness or emergency (adjusted OR [aOR], 0.44; 95% CI, 0.26-0.73) and access to mental health services (aOR, 0.14; 95% CI, 0.04-0.47) were associated with lower odds of burnout. Financial concern was associated with higher odds of depressive symptoms (aOR, 1.13; 95% CI, 1.05-1.22). Working more than 70 hours in an average clinical week and the burdens of electronic health record (EHR) documentation were associated with a higher odds of both burnout and depressive symptoms. Interpretation Given the high prevalence of burnout and depressive symptoms among fellows training in PCCM, an urgent need exists to identify solutions that address this public health crisis. Strategies such as providing an easily accessible coverage system, access to mental health resources, reducing EHR burden, addressing work hours, and addressing financial concerns among trainees may help to reduce burnout or depressive symptoms and should be studied further by the graduate medical education community.

World Trade Center (WTC) responders exposed to traumatic and environmental stressors during rescue and recovery efforts have higher prevalence (23%) of persistent, clinically significant WTC-related post-traumatic stress disorder (WTC-PTSD). Here, we applied eigenvector centrality (EC) metrics and data driven methods on resting state functional magnetic resonance (fMRI) outcomes to investigate neural mechanisms underlying WTC-PTSD and to identify how EC shifts in brain areas relate to WTC-exposure and behavioral symptoms. Nine brain areas differed significantly and contributed the most to differentiate functional neuro-profiles between WTC-PTSD and non-PTSD responders. The association between WTC-exposure and EC values differed significantly between WTC-PTSD and non-PTSD in the right anterior parahippocampal gyrus and left amygdala (p= 0.010; p= 0.005, respectively, adjusted for multiple comparisons). Within WTC-PTSD, the index of PTSD symptoms was positively associated with EC values in the right anterior parahippocampal gyrus and brainstem. Our understanding of functional changes in neural mechanisms underlying WTC-related PTSD is key to advance intervention and treatment.

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 1, 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.

Background: Distrust in authorities has negative effects on mental health. Aims: In this study, we aimed to explore whether the impact of distrust in government on mental health became stronger in the area heavily affected by the 2011 Fukushima nuclear power plant accident. Methods: We examined the effects of distrust in the national government on depressive symptoms three years after the accident among community residents in Fukushima prefecture using those in the Kanto area (the area surrounding Tokyo) as a control. A questionnaire survey was administered to a random sample of 1000 residents in Fukushima prefecture and 1650 residents in the Kanto area. Distrust in the national government was assessed using a four-point single-item scale. Depressive symptoms were measured using the Patient Health Questionnaire-9. The associations of residential area (i.e. living in Fukushima prefecture or in the Kanto area) and distrust in the national government with depressive symptoms were examined, controlling for socio-demographic characteristics and disaster-related experiences using multivariate linear regression analyses. We used the interaction term of residential area and distrust in the government to explore the difference in the association between the respondents in Fukushima prefecture and those in the Kanto area. Results: Valid responses were obtained from 976 (36.8%) residents. Distrust in the government was associated with depressive symptoms and the association was stronger in Fukushima prefecture than in the Kanto area. Conclusion: The deleterious effects of distrust in the government on mental health may become more serious after a nuclear power plant accident and require careful attention during support activities in an affected area.

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.

BackgroundGenetics hold promise of predicting long-term post-traumatic stress disorder (PTSD) outcomes following trauma. The aim of the current study was to test whether six hypothesized polygenic risk scores (PRSs) developed to capture genetic vulnerability to psychiatric conditions prospectively predict PTSD onset, severity, and 18-year course after trauma exposure.MethodsParticipants were 1490 responders to the World Trade Center (WTC) disaster (mean age at 9/11 = 38.81 years, s.d. = 8.20; 93.5% male; 23.8% lifetime WTC-related PTSD diagnosis). Prospective longitudinal data on WTC-related PTSD symptoms were obtained from electronic medical records and modelled as PTSD trajectories using growth mixture model analysis. Independent regression models tested whether six hypothesized psychiatric PRSs (PTSD-PRS, Re-experiencing-PRS, Generalized Anxiety-PRS, Schizophrenia-PRS, Depression-PRS, and Neuroticism-PRS) are predictive of WTC-PTSD outcomes: lifetime diagnoses, average symptom severity, and 18-year symptom trajectory. All analyses were adjusted for population stratification, 9/11 exposure severity, and multiple testing.ResultsDepression-PRS predicted PTSD diagnostic status (OR 1.37, CI 1.17–1.61, adjusted p = 0.001). All PRSs, except PTSD-PRS, significantly predicted average PTSD symptoms (β = 0.06–0.10, adjusted p < 0.05). Re-experiencing-PRS, Generalized Anxiety-PRS and Schizophrenia-PRS predicted the high severity PTSD trajectory class (ORs 1.21–1.28, adjusted p < 0.05). Finally, PRSs prediction was independent of 9/11 exposure severity and jointly accounted for 3.7 times more variance in PTSD symptoms than the exposure severity.ConclusionsPsychiatric PRSs prospectively predicted WTC-related PTSD lifetime diagnosis, average symptom severity, and 18-year trajectory in responders to 9/11 disaster. Jointly, PRSs were more predictive of subsequent PTSD than the exposure severity. In the future, PRSs may help identify at-risk responders who might benefit from targeted prevention approaches.

After natural disasters, mothers and children are vulnerable to internalizing symptoms, such as depression and anxiety, and levels of mothers' and children's symptoms are significantly associated. However, the disaster literature has rarely examined reciprocal effects within families. The present study capitalizes on the occurrence of Hurricane Sandy during the course of an ongoing longitudinal study to address this gap. Three-hundred and 47 children (54.2% male, 84.7% Caucasian) and their mothers completed measures of internalizing symptoms when the children were 9-years-old. Hurricane Sandy occurred an average of 1 year later. Eight weeks after the hurricane, mothers and children completed the same measures again. Mothers also reported on their family's stress exposure from Hurricane Sandy. After controlling for predisaster symptoms, longitudinal actor-partner interdependence models indicated that mother's and children's internalizing symptoms were linked. Mothers' prehurricane depression symptoms also predicted increases in children's depression symptoms over time independent of hurricane-related stress. Children's prehurricane anxiety symptoms predicted increases in mothers' depression symptoms only at low levels of hurricane-related stress. Rather than the emergence of reciprocal effects, mother's depression symptoms and children's internalizing symptoms changed in tandem after Hurricane Sandy. High levels of Hurricane Sandy stress did not produce symptom spillover effects, but rather may have interrupted the unfolding of normative developmental parent-child reciprocal symptom processes. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Introduction World Trade Center (WTC) responders who aided in the search and rescue efforts are now at midlife, and evidence has demonstrated that many are experiencing early-onset cognitive impairment and are at risk of developing dementia, such as Alzheimer’s disease (AD). According to the recent NIA-AA framework, AD is characterized by a neuropathological cascade commencing with β-amyloid deposition (A), followed by tauopathy (T) and neurodegeneration (N). However, the ATN model has not been replicated utilizing recently validated plasma-based biomarkers, and the role of the Aβ40 subtype in A is not well understood. This study examined plasma-based neuropathological markers of Aβ42 and Aβ40 for A, total tau for T, and NfL for N in a cohort of World Trade Center responders at midlife in order to determine the role for the two β-amyloid subtypes in the ATN model. Methods Ultrasensitive Simoa technology was utilized to measure neuropathology in plasma collected from a consecutive clinical sample (n =398). Generalized structural equation modeling was utilized for modeling linkages between pathological markers. Model fit was utilized to determine proposed directions of association. Results Our findings support the ATN neuropathological cascade model of AD and further identify an associative role for Aβ40 in A as playing a central role linking T to N. A strong correlation was found between CI and age, and it was found that women may be at increased risk of elevated T levels, with plasma NfL levels higher in responders with CI. Notably, our model reported associations between: Aβ42, CI and N; Aβ40, T and N; T and CI; Aβ42 and Aβ40. Conclusions The current ATN model of AD does not specify the subtype of β-amyloid to be considered, which may be overlooking the differential roles that these two subtypes serve in the pathogenesis of AD.

BackgroundThere 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.MethodsRespondents 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.ResultsDropout 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.ConclusionsExtending 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.

Objective:At first hospitalization, a long duration of untreated psychosis (DUP) predicts illness severity and worse treatment outcomes. The mechanism of this association, however, remains unclear....

Objective The ability to experience positive affect (PA) has clinical and quality of life implications, particularly in vulnerable populations such as trauma-exposed disaster responders. Low PA is included in the diagnostic criteria for posttraumatic stress disorder (PTSD), however evidence for PA reduction in PTSD has been mixed. In contrast, negative affect (NA) has consistently been found to be elevated among individuals with PTSD. Multiday, ecological momentary assessment (EMA) can provide more ecologically valid evidence about experiences of affect; however, no such studies have been conducted in traumatized individuals with PTSD to date. Method World Trade Center (WTC) responders (N = 202) oversampled for the presence of PTSD were recruited from the WTC Health Program. Participants were administrated the Structured Clinical Interview for DSM-IV and the PTSD Checklist for DSM-5 at baseline, then completed EMA surveys of affect four times a day over seven consecutive days. Results Participants with current PTSD (19.3% of the sample) showed significantly higher levels of daily NA compared with those without PTSD. However, there was no group difference in daily PA, nor was PA associated with a dimensional measure of PTSD. Conclusion Results suggest that for chronic PTSD among disaster responders, positive emotions are not inhibited across daily living. Such findings add to evidence suggesting that PA reduction may not be diagnostically relevant to PTSD, whereas NA remains an important target for therapeutic interventions. Moreover, results show that WTC responders can experience and benefit from positive emotion, even if they continue to have PTSD symptoms. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

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. In the present study, we examined self-reports versus informant-reports of personality and multimethod outcomes. World Trade Center (WTC) responders and informants, 283 pairs, completed five-factor model personality measures and multimethod assessments of stressful events, functioning, mental disorders, 9/11-related treatment costs, body mass index (BMI), and daily activity across 3 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.

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 T1 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.

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.

Little is known about the characteristics and causes of early-onset cognitive impairment. Responders to the 2001 New York World Trade Center disaster represent an ageing population that was recently shown to have an excess prevalence of cognitive impairment. Neuroimaging and molecular data demonstrate that a subgroup of affected responders may have a unique form of parietal-dominant Alzheimer’s Disease. Recent neuropsychological testing and artificial intelligence approaches have emerged as methods that can be used to identify and monitor subtypes of cognitive impairment. We utilized data from World Trade Center responders participating in a health monitoring program and applied a deep learning approach to evaluate neuropsychological and neuroimaging data to generate a cortical atrophy risk score. We examined risk factors associated with the prevalence and incidence of high risk for brain atrophy in responders who are now at midlife. Training was conducted in a randomly selected two-thirds sample (N = 99) enrolled using of the results of a structural neuroimaging study. Testing accuracy was estimated for each training cycle in the remaining third subsample. After training was completed, the scoring methodology that was generated was applied to longitudinal data from 1441 World Trade Center responders. The artificial neural network provided accurate classifications of these responders in both the testing (Area Under the Receiver Operating Curve, 0.91) and validation samples (Area Under the Receiver Operating Curve, 0.87). At baseline and follow-up, responders identified as having a high risk of atrophy (n = 378) showed poorer cognitive functioning, most notably in domains that included memory, throughput, and variability as compared to their counterparts at low risk for atrophy (n = 1063). Factors associated with atrophy risk included older age [adjusted hazard ratio, 1.045 (95% confidence interval = 1.027–1.065)], increased duration of exposure at the WTC site [adjusted hazard ratio, 2.815 (1.781–4.449)], and a higher prevalence of post-traumatic stress disorder [aHR, 2.072 (1.408–3.050)]. High atrophy risk was associated with an increased risk of all-cause mortality [adjusted risk ratio, 3.19 (1.13–9.00)]. In sum, the high atrophy risk group displayed higher levels of previously identified risk factors and characteristics of cognitive impairment, including advanced age, symptoms of post-traumatic stress disorder, and prolonged duration of exposure to particulate matter. Thus, this study suggests that a high risk of brain atrophy may be accurately monitored using cognitive data., Dementia has a rising major impact on the health of ageing populations. World Trade Center responders are at increased risk for dementia, as characterized particularly by parietal-dominant cortical atrophy on neuroimaging. Clouston et al. used deep learning to predict the risk of developing cortical atrophy based on neuropsychological test results., Graphical abstract Graphical Abstract

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.

AIM: We examined prevalence and factors associated with receiving perceived helpful alcohol use disorder (AUD) treatment, and persistence in help-seeking after earlier unhelpful treatment.METHODS: Data came from 27 community epidemiologic surveys of adults in 24 countries using the World Health Organization World Mental Health surveys (n = 93,843). Participants with a lifetime history of treated AUD were asked if they ever received helpful AUD treatment, and how many professionals they had talked to up to and including the first time they received helpful treatment (or how many ever, if they had not received helpful treatment).RESULTS: 11.8% of respondents with lifetime AUD reported ever obtaining treatment (n = 9378); of these, 44% reported that treatment was helpful. The probability of obtaining helpful treatment from the first professional seen was 21.8%; the conditional probability of subsequent professionals being helpful after earlier unhelpful treatment tended to decrease as more professionals were seen. The cumulative probability of receiving helpful treatment at least once increased from 21.8% after the first professional to 79.7% after the seventh professional seen, following earlier unhelpful treatment. However, the cumulative probability of persisting with up to seven professionals in the face of prior treatments being unhelpful was only 13.2%.CONCLUSION: Fewer than half of people with AUDs who sought treatment found treatment helpful; the most important factor was persistence in seeking further treatment if a previous professional had not helped. Future research should examine how to increase the likelihood that AUD treatment is found to be helpful on any given contact.