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

Understanding whether and how the schizophrenia polygenic risk score (SZ PRS) predicts course of illness could improve diagnosis and prognostication in psychotic disorders. We tested whether the SZ PRS predicts symptoms, cognition, illness severity, and diagnostic changes over the 20 years following first admission. The Suffolk County Mental Health Project is an inception cohort study of first-admission patients with psychosis. Patients were assessed six times over 20 years, and 249 provided DNA. Geographically- and demographically-matched never psychotic adults were recruited at year 20, and 205 provided DNA. Symptoms were rated using the Schedule for the Assessment of Positive Symptoms and Schedule for the Assessment of Negative Symptoms. Cognition was evaluated with a comprehensive neuropsychological battery. Illness severity and diagnosis were determined by consensus of study psychiatrists. SZ PRS was significantly higher in first-admission than never psychotic groups. Within the psychosis cohort, the SZ PRS predicted more severe negative symptoms (β = 0.21), greater illness severity (β = 0.28), and worse cognition (β = −0.35), across the follow-up. The SZ PRS was the strongest predictor of diagnostic shifts from affective to non-affective psychosis over the 20 years (AUC = 0.62). The SZ PRS predicts persistent differences in cognition and negative symptoms. The SZ PRS also predicts who among those who appear to have a mood disorder with psychosis at first admission will ultimately be diagnosed with a schizophrenia spectrum disorder. These findings show potential for the SZ PRS to become a tool for diagnosis and treatment planning.

Objective This study examined whether World Trade Center (WTC) exposures and chronic posttraumatic stress disorder (PTSD) were associated with incidence of mild cognitive impairment (MCI) in a longitudinal analysis of a prospective cohort study of WTC responders. Methods Incidence of MCI was assessed in a clinical sample of WTC responders (N = 1800) who were cognitively intact at baseline assessment. Crude incidence rates were calculated and compared to population estimates using standardized incidence ratios. Multivariable analyses used Cox proportional-hazards regression. Results Responders were 53.1 years old (SD = 7.9) at baseline. Among eligible cognitively intact responders, 255 (14.2%) developed MCI at follow-up. Incidence of MCI was higher than expected based on expectations from prior published research. Incidence was higher among those with increased PTSD symptom severity, and prolonged exposure was a risk factor in apolipoprotein-e4 carriers. Conclusions PTSD and prolonged WTC exposures were associated with increased incidence of MCI in WTC responders, results that may portend future high rates of dementia in WTC-exposed responders.

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

Background: Cross-national variance in smoking prevalence is relatively well documented. The aim of this study is to estimate levels of smoking persistence across 21 countries with a hypothesized inverse relationship between country income level and smoking persistence. Methods: Data from the World Health Organization World Mental Health Survey Initiative were used to estimate cross-national differences in smoking persistence—the proportion of adults who started to smoke and persisted in smoking by the date of the survey. Results: There is large variation in smoking persistence from 25% (Nigeria) to 85% (China), with a random-effects meta-analytic summary estimate of 55% with considerable cross-national variation. (Cochran’s heterogeneity Q statistic = 6845; p

Differences in susceptibility to posttraumatic stress disorder (PTSD) may be related to epigenetic differences between PTSD cases and trauma-exposed controls. Such epigenetic differences may provide insight into the biological processes underlying the disorder. Here we describe the results of the largest DNA methylation meta-analysis of PTSD to date with data from the Psychiatric Genomics Consortium (PGC) PTSD Epigenetics Workgroup. Ten cohorts, military and civilian, contributed blood-derived DNA methylation data (HumanMethylation450 BeadChip) from 1,896 PTSD cases (42%) and trauma-exposed controls (58%). Utilizing a common QC and analysis strategy, we identified ten CpG sites associated with PTSD (9.61E-07AHRR) locus and were associated with lower DNA methylation in PTSD cases relative to controls. Interestingly, this association appeared to uncorrelated with smoking status and was most pronounced in non-smokers with PTSD. Additional evaluation of metabolomics data supported our findings and revealed that AHRR methylation associated with kynurenine levels, which were lower among subjects with PTSD relative to controls. Overall, this study supports epigenetic differences in those with PTSD and suggests a role for decreased kynurenine as a contributor to immune dysregulation in PTSD.

Little is known about the effect of natural disasters on children's neural development. Additionally, despite evidence that stress and parenting may both influence the development of neural systems underlying reward and threat processing, few studies have brought together these areas of research. The current investigation examined the effect of parenting styles and hurricane-related stress on the development of neural reactivity to reward and threat in children. Approximately 8 months before and 9 months after Hurricane Sandy, 74 children experiencing high and low levels of hurricane-related stress completed tasks that elicited the reward positivity and error-related negativity, event-related potentials indexing sensitivity to reward and threat, respectively. At the post-Hurricane assessment, children completed a self-report questionnaire to measure promotion- and prevention-focused parenting styles. Among children exposed to high levels of hurricane-related stress, lower levels of promotion-focused, but not prevention-focused, parenting were associated with a reduced post-Sandy reward positivity. In addition, in children with high stress exposure, greater prevention-focused, but not promotion-focused, parenting was associated with a larger error-related negativity after Hurricane Sandy. These findings highlight the need to consider contextual variables such as parenting when examining how exposure to stress alters the development of neural reactivity to reward and threat in children.

Posttraumatic stress disorder (PTSD), a chronic disorder resulting from severe trauma, has been linked to immunologic dysregulation. Gene expression profiling has emerged as a promising tool for understanding the pathophysiology of PTSD. However, to date, all but one gene expression study was based on whole blood or unsorted peripheral blood mononuclear cell (PBMC), a complex tissue consisting of several populations of cells. The objective of this study was to utilize RNA sequencing to simultaneously profile the gene expression of four immune cell subpopulations (CD4T, CD8T, B cells, and monocytes) in 39 World Trade Center responders (20 with and 19 without PTSD) to determine which immune subsets play a role in the transcriptomic changes found in whole blood. Transcriptome-wide analyses identified cell-specific and shared differentially expressed genes across the four cell types. FKBP5 and PI4KAP1 genes were consistently upregulated across all cell types. Notably, REST and SEPT4, genes linked to neurodegeneration, were among the top differentially expressed genes in monocytes. Pathway analyses identified differentially expressed gene sets involved in mast cell activation and regulation in CD4T, interferon-beta production in CD8T, and neutrophil-related gene sets in monocytes. These findings suggest that gene expression indicative of immune dysregulation is common across several immune cell populations in PTSD. Furthermore, given notable differences between cell subpopulations in gene expression associated with PTSD, the results also indicate that it may be valuable to analyze different cell populations separately. Monocytes may constitute a key cell type to target in research on gene expression profile of PTSD.

Sequencing-based studies have identified novel risk genes for rare, severe epilepsies and revealed a role of rare deleterious variation in common epilepsies. To identify the shared and distinct ultra-rare genetic risk factors for rare and common epilepsies, we performed a whole-exome sequencing (WES) analysis of 9,170 epilepsy-affected individuals and 8,364 controls of European ancestry. We focused on three phenotypic groups; the rare but severe developmental and epileptic encephalopathies (DEE), and the commoner phenotypes of genetic generalized epilepsy (GGE) and non-acquired focal epilepsy (NAFE). We observed that compared to controls, individuals with any type of epilepsy carried an excess of ultra-rare, deleterious variants in constrained genes and in genes previously associated with epilepsy, with the strongest enrichment seen in DEE and the least in NAFE. Moreover, we found that inhibitory GABAA receptor genes were enriched for missense variants across all three classes of epilepsy, while no enrichment was seen in excitatory receptor genes. The larger gene groups for the GABAergic pathway or cation channels also showed a significant mutational burden in DEE and GGE. Although no single gene surpassed exome-wide significance among individuals with GGE or NAFE, highly constrained genes and genes encoding ion channels were among the top associations, including CACNA1G, EEF1A2, and GABRG2 for GGE and LGI1, TRIM3, and GABRG2 for NAFE. Our study confirms a convergence in the genetics of common and rare epilepsies associated with ultra-rare coding variation and highlights a ubiquitous role for GABAergic inhibition in epilepsy etiology in the largest epilepsy WES study to date.

Heterogeneity of psychosis presents significant challenges for classification. Between 2 and 12 symptom dimensions have been proposed, and consensus is lacking. The present study sought to identify uniquely informative models by comparing the validity of these alternatives. An epidemiologic cohort of 628 first-admission inpatients with psychosis was interviewed 6 times over 2 decades and completed an electrophysiological assessment of error processing at year 20. We first analyzed a comprehensive set of 49 symptoms rated by interviewers at baseline, progressively extracting from 1 to 12 factors. Next, we compared the ability of resulting factor solutions to (a) account for concurrent neural dysfunction and (b) predict 20-year role, social, residential, and global functioning, and life satisfaction. A four-factor model showed incremental validity with all outcomes, and more complex models did not improve explanatory power. The 4 dimensions-reality distortion, disorganization, inexpressivity, and apathy/asociality-were replicable in 5 follow-ups, internally consistent, stable across assessments, and showed strong discriminant validity. These results reaffirm the value of separating disorganization and reality distortion, are consistent with recent findings distinguishing inexpressivity and apathy/asociality, and suggest that these 4 dimensions are fundamental to understanding neural abnormalities and long-term outcomes in psychosis. (PsycINFO Database Record

Context The scarcity of cross-national reports and the changes in Diagnostic and Statistical Manual version 5 (DSM-5) regarding panic disorder (PD) and panic attacks (PAs) call for new epidemiological data on PD and PAs and its subtypes in the general population. Objective To present representative data about the cross-national epidemiology of PD and PAs in accordance with DSM-5 definitions. Design and setting Nationally representative cross-sectional surveys using the World Health Organization Composite International Diagnostic Interview version 3.0. Participants Respondents (n = 142,949) from 25 high, middle, and lower-middle income countries across the world aged 18 years or older. Main outcome measures PD and presence of single and recurrent PAs. Results Lifetime prevalence of PAs was 13.2% (SE 0.1%). Among persons that ever had a PA, the majority had recurrent PAs (66.5%; SE 0.5%), while only 12.8% fulfilled DSM-5 criteria for PD. Recurrent PAs were associated with a subsequent onset of a variety of mental disorders (OR 2.0; 95% CI 1.8–2.2) and their course (OR 1.3; 95% CI 1.2–2.4) whereas single PAs were not (OR 1.1; 95% CI 0.9–1.3 and OR 0.7; 95% CI 0.6–0.8). Cross-national lifetime prevalence estimates were 1.7% (SE 0.0%) for PD with a median age of onset of 32 (IQR 20–47). Some 80.4% of persons with lifetime PD had a lifetime comorbid mental disorder. Conclusions We extended previous epidemiological data to a cross-national context. The presence of recurrent PAs in particular is associated with subsequent onset and course of mental disorders beyond agoraphobia and PD, and might serve as a generic risk marker for psychopathology.

BackgroundThis is the first cross-national study of intermittent explosive disorder (IED).MethodA total of 17 face-to-face cross-sectional household surveys of adults were conducted in 16 countries (n = 88 063) as part of the World Mental Health Surveys initiative. The World Health Organization Composite International Diagnostic Interview (CIDI 3.0) assessed DSM-IV IED, using a conservative definition.ResultsLifetime prevalence of IED ranged across countries from 0.1 to 2.7% with a weighted average of 0.8%; 0.4 and 0.3% met criteria for 12-month and 30-day prevalence, respectively. Sociodemographic correlates of lifetime risk of IED were being male, young, unemployed, divorced or separated, and having less education. The median age of onset of IED was 17 years with an interquartile range across countries of 13–23 years. The vast majority (81.7%) of those with lifetime IED met criteria for at least one other lifetime disorder; co-morbidity was highest with alcohol abuse and depression. Of those with 12-month IED, 39% reported severe impairment in at least one domain, most commonly social or relationship functioning. Prior traumatic experiences involving physical (non-combat) or sexual violence were associated with increased risk of IED onset.ConclusionsConservatively defined, IED is a low prevalence disorder but this belies the true societal costs of IED in terms of the effects of explosive anger attacks on families and relationships. IED is more common among males, the young, the socially disadvantaged and among those with prior exposure to violence, especially in childhood.

BackgroundThe Fukushima Daiichi and Daini Nuclear Power Plant workers experienced multiple stressors as both victims and onsite workers after the 2011 Great East Japan Earthquake and subsequent nuclear accidents. Previous studies found that disaster-related exposures, including discrimination/slurs, were associated with their mental health. Their long-term impact has yet to be investigated.MethodA total of 968 plant workers (Daiichi, n = 571; Daini, n = 397) completed self-written questionnaires 2–3 months (time 1) and 14–15 months (time 2) after the disaster (response rate 55.0%). Sociodemographics, disaster-related experiences, and peritraumatic distress were assessed at time 1. At time 1 and time 2, general psychological distress (GPD) and post-traumatic stress response (PTSR) were measured, respectively, using the K6 scale and Impact of Event Scale Revised. We examined multivariate covariates of time 2 GPD and PTSR, adjusting for autocorrelations in the hierarchical multiple regression analyses.ResultsHigher GPD at time 2 was predicted by higher GPD at time 1 (β = 0.491, p < 0.001) and discrimination/slurs experiences at time 1 (β = 0.065, p = 0.025, adjusted R2 = 0.24). Higher PTSR at time 2 was predicted with higher PTSR at time 1 (β = 0.548, p < 0.001), higher age (β = 0.085, p = 0.005), and discrimination/slurs experiences at time 1 (β = 0.079, p = 0.003, adjusted R2 = 0.36).ConclusionsHigher GPD at time 2 was predicted by higher GPD and discrimination/slurs experience at time 1. Higher PTSR at time 2 was predicted by higher PTSR, higher age, and discrimination/slurs experience at time 1.

The 2013 U.S. 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 known not 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 non-deployed Regular U.S. Army soldiers because they account for the vast majority of such suicides. Four machine learning classifiers (naïve Bayes, random forests, support vector regression, elastic net penalized regression) were explored. 41.5% of Army suicides in 2004-2009 occurred among the 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.

Purpose: To assess fatigue severity in World Trade Center (9/11) responders 13 years later. Methods: The participant pool consisted of male 9/11 responders enrolled in the Stony Brook World Trade Center Health Program (WTC-HP), one of five centers of excellence established by the Centers for Disease Control and Prevention. Fatigue severity was assessed with the Fatigue Severity Scale. WTC-related medical conditions were certified by a physician and diagnoses of 9/11-related post-traumatic stress disorder (PTSD) and major depressive disorder (MDD) were determined with the Structured Clinical Interview for DSM-IV (SCID). Results: High fatigue severity was reported by 20.8% of the sample (N = 1079) and was significantly associated with PTSD, major depressive disorder, sleep apnea, gastro-esophageal reflux disease, upper respiratory disease, and lower respiratory disease. These associations remained significant for PTSD, major depressive disorder and lower respiratory disease when adjusted for medicati...

Importance: It remains uncertain whether people with psychotic disorders experience progressive cognitive decline or normal cognitive aging after first hospitalization. This information is essential for prognostication in clinical settings, deployment of cognitive remediation, and public health policy. Objective: To examine long-term cognitive changes in individuals with psychotic disorders and to compare age-related differences in cognitive performance between people with psychotic disorders and matched control individuals (ie, individuals who had never had psychotic disorders). Design, Setting, and Participants: The Suffolk County Mental Health Project is an inception cohort study of first-admission patients with psychosis. Cognitive functioning was assessed 2 and 20 years later. Patients were recruited from the 12 inpatient facilities of Suffolk County, New York. At year 20, the control group was recruited by random digit dialing and matched to the clinical cohort on zip code and demographics. Data were collected between September 1991 and July 2015. Analysis began January 2016. Main Outcomes and Measures: Change in cognitive functioning in 6 domains: verbal knowledge (Wechsler Adult Intelligence Scale-Revised vocabulary test), verbal declarative memory (Verbal Paired Associates test I and II), visual declarative memory (Visual Reproduction test I and II), attention and processing speed (Symbol Digit Modalities Test-written and oral; Trail Making Test [TMT]-A), abstraction-executive function (Trenerry Stroop Color Word Test; TMT-B), and verbal fluency (Controlled Oral Word Association Test). Results: A total of 705 participants were included in the analyses (mean [SD] age at year 20, 49.4 [10.1] years): 445 individuals (63.1%) had psychotic disorders (211 with schizophrenia spectrum [138 (65%) male]; 164 with affective psychoses [76 (46%) male]; 70 with other psychoses [43 (61%) male]); and 260 individuals (36.9%) in the control group (50.5 [9.0] years; 134 [51.5%] male). Cognition in individuals with a psychotic disorder declined on all but 2 tests (average decline: d = 0.31; range, 0.17-0.54; all P

We aimed to explore the effects of prolonged radiation risk perceptions on mental health after the Fukushima nuclear power plant accident occurred in 2011. We investigated the longitudinal associations of radiation risk perceptions five years after the accident with psychological distress and posttraumatic stress symptoms two years later among non-evacuee community residents of Fukushima prefecture. A two-wave questionnaire survey was administered for 4,900 randomly sampled residents in 49 municipalities of Fukushima prefecture excluding the evacuation area designated by the Japanese government. Radiation risk perceptions were assessed with a seven-item scale. Psychological distress and posttraumatic stress symptoms were measured by the K6 and the six-item abbreviated version of the Posttraumatic Stress Disorder Checklist-Specific version, respectively. We investigated the associations of radiation risk perceptions in the first survey conducted in 2016 with psychological distress and posttraumatic stress symptoms in the follow-up survey conducted in 2017–18, controlling for the baseline level of distress or symptoms using multivariate logistic regression analyses. Valid responses were obtained from 1,148 residents (23.4%). Higher risk perceptions of radiation exposure in the first survey predicted later posttraumatic stress symptoms but not psychological distress after controlling for baseline symptoms or distress. High risk perceptions of radiation exposure after nuclear power plant accidents can lead to posttraumatic stress symptoms., Highlights • Radiation anxiety predicted later posttraumatic stress symptoms. • Radiation anxiety did not predict later psychological distress. • Radiation anxiety affected later mental health status among non-evacuee residents.

BackgroundGenetic risk for bipolar disorder (BD) is conferred through many common alleles, while a role for rare copy number variants (CNVs) is less clear. BD subtypes schizoaffective disorder bipolar type (SAB), bipolar I disorder (BD I) and bipolar II disorder (BD II) differ according to the prominence and timing of psychosis, mania and depression. The factors contributing to the combination of symptoms within a given patient are poorly understood.MethodsRare, large CNVs were analyzed in 6353 BD cases (3833 BD I [2676 with psychosis, 850 without psychosis], 1436 BD II, 579 SAB) and 8656 controls. Measures of CNV burden were integrated with polygenic risk scores (PRS) for schizophrenia (SCZ) to evaluate the relative contributions of rare and common variants to psychosis risk.ResultsCNV burden did not differ in BD relative to controls when treated as a single diagnostic entity. Burden in SAB was increased compared to controls (p-value = 0.001), BD I (p-value = 0.0003) and BD II (p-value = 0.0007). Burden and SCZ PRS were higher in SAB compared to BD I with psychosis (CNV p-value = 0.0007, PRS p-value = 0.004) and BD I without psychosis (CNV p-value = 0.0004, PRS p-value = 3.9 × 10−5). Within BD I, psychosis was associated with higher SCZ PRS (p-value = 0.005) but not with CNV burden.ConclusionsCNV burden in BD is limited to SAB. Rare and common genetic variants may contribute differently to risk for psychosis and perhaps other classes of psychiatric symptoms.

Background Since the Iowa 500 study, residential and occupational status have been frequently used as indicators of everyday achievements in research on schizophrenia and bipolar disorder. The relationships of residential and occupational status with impairment in multiple domains including physical health indicators across these two diagnoses, however, have rarely been studied. We examined these relationships at the 20-year follow-up assessment of a first-admission sample. Methods We included 146 participants with schizophrenia and 87 with bipolar disorder with psychosis who participated in the 20-year follow-up of the Suffolk County Mental Health Project. In addition to interviewer-based ratings of employment and residential independence, we examined self-reported impairment derived from the WHODAS, standard measures of current psychopathology, indicators of obesity, as well as performance-based measures of physical and cognitive functioning. Results Participants with bipolar disorder were more likely to live independently and be gainfully employed; they also performed significantly better on each indicator of impairment apart from balance ability. In both groups, unemployment, but not residential independence, was associated with greater self-reported disability on the WHODAS. Residential independence, gainful employment, and subjective disability were also associated with better physical functioning. Across the two groups, psychiatric symptoms and physical functioning were the major determinants of subjective disability. Discussion People with psychotic bipolar disorder were more likely to be gainfully employed and living independently than participants with schizophrenia but as a group, much less frequently than population standards. Interventions aimed at physical fitness may have the potential to improve both objective functioning and perceived disability.

BackgroundResearch on post-traumatic stress disorder (PTSD) course finds a substantial proportion of cases remit within 6 months, a majority within 2 years, and a substantial minority persists for many years. Results are inconsistent about pre-trauma predictors.MethodsThe WHO World Mental Health surveys assessed lifetime DSM-IV PTSD presence-course after one randomly-selected trauma, allowing retrospective estimates of PTSD duration. Prior traumas, childhood adversities (CAs), and other lifetime DSM-IV mental disorders were examined as predictors using discrete-time person-month survival analysis among the 1575 respondents with lifetime PTSD.Results20%, 27%, and 50% of cases recovered within 3, 6, and 24 months and 77% within 10 years (the longest duration allowing stable estimates). Time-related recall bias was found largely for recoveries after 24 months. Recovery was weakly related to most trauma types other than very low [odds-ratio (OR) 0.2–0.3] early-recovery (within 24 months) associated with purposefully injuring/torturing/killing and witnessing atrocities and very low later-recovery (25+ months) associated with being kidnapped. The significant ORs for prior traumas, CAs, and mental disorders were generally inconsistent between early- and later-recovery models. Cross-validated versions of final models nonetheless discriminated significantly between the 50% of respondents with highest and lowest predicted probabilities of both early-recovery (66–55% v. 43%) and later-recovery (75–68% v. 39%).ConclusionsWe found PTSD recovery trajectories similar to those in previous studies. The weak associations of pre-trauma factors with recovery, also consistent with previous studies, presumably are due to stronger influences of post-trauma factors.

Background: Previous work has identified associations between psychotic experiences (PEs) and general medical conditions (GMCs), but their temporal direction remains unclear as does the extent to which they are independent of comorbid mental disorders. Methods: In total, 28 002 adults in 16 countries from the WHO World Mental Health (WMH) Surveys were assessed for PEs, GMCs and 21 Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) mental disorders. Discrete-time survival analyses were used to estimate the associations between PEs and GMCs with various adjustments. Results: After adjustment for comorbid mental disorders, temporally prior PEs were significantly associated with subsequent onset of 8/12 GMCs (arthritis, back or neck pain, frequent or severe headache, other chronic pain, heart disease, high blood pressure, diabetes and peptic ulcer) with odds ratios (ORs) ranging from 1.3 [95% confidence interval (CI) 1.1–1.5] to 1.9 (95% CI 1.4–2.4). In contrast, only three GMCs (frequent or severe headache, other chronic pain and asthma) were significantly associated with subsequent onset of PEs after adjustment for comorbid GMCs and mental disorders, with ORs ranging from 1.5 (95% CI 1.2–1.9) to 1.7 (95% CI 1.2–2.4). Conclusions: PEs were associated with the subsequent onset of a wide range of GMCs, independent of comorbid mental disorders. There were also associations between some medical conditions (particularly those involving chronic pain) and subsequent PEs. Although these findings will need to be confirmed in prospective studies, clinicians should be aware that psychotic symptoms may be risk markers for a wide range of adverse health outcomes. Whether PEs are causal risk factors will require further research. The ESEMeD surveys were funded by the European Commission (Contracts QLG5‐1999‐01042; SANCO 2004123, and EAHC 20081308), the Piedmont Region (Italy)), Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Spain (FIS 00/0028), Ministerio de Ciencia y Tecnología, Spain (SAF 2000‐158‐CE), Departament de Salut, Generalitat de Catalunya, Spain, Instituto de Salud Carlos III (CIBER CB06/02/0046, RETICS RD06/0011 REM‐TAP), and other local agencies and by an unrestricted educational grant from GlaxoSmithKline.

Post-traumatic Stress Disorder (PTSD) is a stress related syndrome. Chronic PTSD has increasingly been associated with poor health outcomes, neurodegeneration and risk for cognitive impairment (CI). However, the biological mechanisms underlying the development and maintenance of symptoms and potential associations in accelerating aging are not well understood. The aim of this study was to evaluate whether specific biomarkers influence functional limitations and cognitive impairment in rescue and recovery workers (i.e. responders) from the attacks on the World Trade Center (WTC) in New York. Plasma biomarkers were collected during annual health and wellness visits at the WTC responder clinic between 2012 and 2014. Short Physical Performance Battery (SPPB) and clinical data were examined with prospective PTSD symptom scores collected during participant’s initial enrollment into the parent study as early as 2002. We examined the relationship between cardiovascular (Diastolic Blood Pressure, Systolic Blood Pressure, pulse rate), metabolic (Total Cholesterol, HDL cholesterol, Triglycerides, Glucose, Body Mass Index) and inflammation markers (Albumin, White Blood Count) with Post-traumatic Stress Disorder (PTSD), cognitive functioning (Montreal Cognitive Assessment) and frailty (Short Physical Performance Battery) in responders from the World Trade Center (WTC). We first examined correlations between biomarkers, PTSD symptom severity, PTSD dimensions, cognitive functioning and frailty. We then conducted multivariate regression analyses. In models adjusted for potential confounders, among N=1,045 responders, elevated PTSD was strongly associated with increased frailty, cardiovascular dysregulation and mild cognitive impairment. Current work is ongoing to identify trajectories of change in cognition with frailty and biological factors.

Several studies have reported differences between African Americans and Caucasians in relative proportion of psychotic symptoms and disorders, but whether this reflects racial bias in the assessment of psychosis is unclear. The purpose of this study was to examine the distribution of psychotic symptoms and potential bias in symptoms assessed via semi-structured interview using a cohort of 3,389 African American and 5,692 Caucasian participants who were diagnosed with schizophrenia, schizoaffective disorder, or bipolar disorder. In this cohort, the diagnosis of schizophrenia was relatively more common, and the diagnosis of bipolar disorder and schizoaffective disorder-bipolar type was less relatively common, among African Americans than Caucasians. With regard to symptoms, relatively more African Americans than Caucasians endorsed hallucinations and delusions symptoms, and this pattern was striking among cases diagnosed with bipolar disorder and schizoaffective-bipolar disorder. In contrast, the relative endorsement of psychotic symptoms was more similar among cases diagnosed with schizophrenia and schizoaffective disorder-depressed type. Differential item function analysis revealed that African Americans with mild psychosis over-endorsed "hallucinations in any modality" and under-endorsed "widespread delusions" relative to Caucasians. Other symptoms did not show evidence of racial bias. Thus, racial bias in assessment of psychotic symptoms does not appear to explain differences in the proportion of symptoms between Caucasians and African Americans. Rather, this may reflect ascertainment bias, perhaps indicative of a disparity in access to services, or differential exposure to risk factors for psychosis by race. © 2015 Wiley Periodicals, Inc.

BackgroundPost-traumatic symptomatology is one of the signature effects of the pernicious exposures endured by responders to the World Trade Center (WTC) disaster of 11 September 2001 (9/11), but the long-term extent of diagnosed Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) post-traumatic stress disorder (PTSD) and its impact on quality of life are unknown. This study examines the extent of DSM-IV PTSD 11–13 years after the disaster in WTC responders, its symptom profiles and trajectories, and associations of active, remitted and partial PTSD with exposures, physical health and psychosocial well-being.MethodMaster's-level psychologists administered sections of the Structured Clinical Interview for DSM-IV and the Range of Impaired Functioning Tool to 3231 responders monitored at the Stony Brook University World Trade Center Health Program. The PTSD Checklist (PCL) and current medical symptoms were obtained at each visit.ResultsIn all, 9.7% had current, 7.9% remitted, and 5.9% partial WTC-PTSD. Among those with active PTSD, avoidance and hyperarousal symptoms were most commonly, and flashbacks least commonly, reported. Trajectories of symptom severity across monitoring visits showed a modestly increasing slope for active and decelerating slope for remitted PTSD. WTC exposures, especially death and human remains, were strongly associated with PTSD. After adjusting for exposure and critical risk factors, including hazardous drinking and co-morbid depression, PTSD was strongly associated with health and well-being, especially dissatisfaction with life.ConclusionsThis is the first study to demonstrate the extent and correlates of long-term DSM-IV PTSD among responders. Although most proved resilient, there remains a sizable subgroup in need of continued treatment in the second decade after 9/11.

Purpose The current longitudinal study examined posttraumatic stress disorder (PTSD) symptom severity in relation to smoking abstinence and reduction over time among responders to the World Trade Center (WTC) disaster. Method Participants were 763 police and 1881 non-traditional (e.g., construction workers) WTC responders who reported being smokers at an initial examination obtained between July 2002 and July 2011 at the WTC Health Program (WTC-HP). WTC responders were reassessed, on average, 2.5 years later. Results For police WTC responders, higher levels of WTC-related PTSD symptoms at the initial visit were associated with a decreased likelihood of smoking abstinence (OR = 0.98, p = .002) and with decreased smoking reduction ( β = −.06, p = .012) at the follow-up visit. WTC-related PTSD symptom severity was not related to likelihood of smoking abstinence or change in number of cigarettes smoked among non-traditional responders. Post hoc analyses suggested that for police, hyperarousal PTSD symptoms were predictive of decreased abstinence likelihood at the follow-up visit (OR = 0.56, p = .006). Discussion The present findings suggest that PTSD symptoms may be differentially related to smoking behavior among police and non-traditional WTC responders in a naturalistic, longitudinal investigation. Future work may benefit from exploring further which aspects of PTSD (as compared to each other and to common variance) explain smoking maintenance.

Introduction Posttraumatic stress disorder (PTSD) is associated with various aspects of cigarette smoking, including higher levels of nicotine dependence and cessation difficulties. Affect-regulatory smoking motives are thought to, in part, underlie the association between emotional disorders such as PTSD and smoking maintenance, although few studies have empirically tested this possibility. Methods Data were analyzed from 135 treatment-seeking smokers who were directly exposed to the World Trade Center disaster on September 11, 2001. We modeled the direct effect of 9/11 PTSD symptom severity on nicotine dependence, perceived barriers to smoking cessation, and severity of problematic symptoms experienced during prior cessation attempts. We also examined the indirect effect of PTSD on these outcomes via negative affect reduction smoking motives. Parallel models were constructed for additional emotional disorder symptoms, including panic and depressive symptoms. Results PTSD symptom severity was associated with nicotine dependence and perceived barriers to cessation, but not problems during prior quit attempts indirectly via negative affect reduction smoking motives. Panic and depressive symptoms both had significant indirect effects, via negative affect reduction smoking motives, on all three criterion variables. Conclusions Affect-regulatory smoking motives appear to underlie associations between the symptoms of emotional disorders such as PTSD, panic, and depression in terms of smoking dependence and certain cessation-related criterion variables. Implications Overall, this investigation suggests negative affect reduction smoking motives help to explain the relationship of PTSD, depression, and panic symptoms to nicotine dependence, severity of problems experienced during prior quit attempts and perceived barriers to cessation. These results highlight the importance of assessing motivations for smoking in the context of cessation treatment, especially among those with emotional disorder symptoms. Future interventions might seek to utilize motivational interviewing and cognitive restructuring techniques to address coping-oriented motives for smoking, in addition to skills for managing negative affect, as a means of improving quit outcomes.

BackgroundCivilian suicide rates vary by occupation in ways related to occupational stress exposure. Comparable military research finds suicide rates elevated in combat arms occupations. However, no research has evaluated variation in this pattern by deployment history, the indicator of occupation stress widely considered responsible for the recent rise in the military suicide rate.MethodThe joint associations of Army occupation and deployment history in predicting suicides were analysed in an administrative dataset for the 729 337 male enlisted Regular Army soldiers in the US Army between 2004 and 2009.ResultsThere were 496 suicides over the study period (22.4/100 000 person-years). Only two occupational categories, both in combat arms, had significantly elevated suicide rates: infantrymen (37.2/100 000 person-years) and combat engineers (38.2/100 000 person-years). However, the suicide rates in these two categories were significantly lower when currently deployed (30.6/100 000 person-years) than never deployed or previously deployed (41.2–39.1/100 000 person-years), whereas the suicide rate of other soldiers was significantly higher when currently deployed and previously deployed (20.2–22.4/100 000 person-years) than never deployed (14.5/100 000 person-years), resulting in the adjusted suicide rate of infantrymen and combat engineers being most elevated when never deployed [odds ratio (OR) 2.9, 95% confidence interval (CI) 2.1–4.1], less so when previously deployed (OR 1.6, 95% CI 1.1–2.1), and not at all when currently deployed (OR 1.2, 95% CI 0.8–1.8). Adjustment for a differential ‘healthy warrior effect’ cannot explain this variation in the relative suicide rates of never-deployed infantrymen and combat engineers by deployment status.ConclusionsEfforts are needed to elucidate the causal mechanisms underlying this interaction to guide preventive interventions for soldiers at high suicide risk.

PURPOSE: The current study examined the role of World Trade Center (WTC) disaster exposure (hours spent working on the site, dust cloud exposure, and losing friend/loved one) in exacerbating the effects of post-disaster life stress on posttraumatic stress disorder (PTSD) symptoms and overall functioning among WTC responders. METHOD: Participants were 18,896 responders (8,466 police officers and 10,430 non-traditional responders) participating in the WTC Health Program who completed an initial examination between July, 2002 and April, 2010 and were reassessed an average of two years later. RESULTS: Among police responders, there was a significant interaction, such that the effect of post-disaster life stress on later PTSD symptoms and overall functioning was stronger among police responders who had greater WTC disaster exposure (β's =.029 and.054, respectively, for PTSD symptoms and overall functioning). This moderating effect was absent in non-traditional responders. Across both groups, post-disaster life stress also consistently was related to the dependent variables in a more robust manner than WTC exposure. DISCUSSION: The present findings suggest that WTC exposure may compound post-disaster life stress, thereby resulting in a more chronic course of PTSD symptoms and reduced functioning among police responders. Language: en

Posttraumatic stress disorder (PTSD) is associated with high medical morbidity, but the nature of this association remains unclear. Among responders to the World Trade Center (WTC) disaster, PTSD is highly comorbid with lower respiratory symptoms (LRS), which cannot be explained by exposure alone. We sought to examine this association longitudinally to establish the direction of the effects and evaluate potential pathways to comorbidity.18,896 responders (8466 police and 10,430 nontraditional responders) participating in the WTC-Health Program were first evaluated between 2002 and 2010 and assessed again 2.5 years later. LRS were ascertained by medical staff, abnormal pulmonary function by spirometry, and probable WTC-related PTSD with a symptom inventory.In both groups of responders, initial PTSD (standardized regression coefficient: β = 0.20 and 0.23) and abnormal pulmonary function (β = 0.12 and 0.12) predicted LRS 2.5 years later after controlling for initial LRS and covariates. At follow-up, LRS onset was 2.0 times more likely and remission 1.8 times less likely in responders with initial PTSD than in responders without. Moreover, PTSD mediated, in part, the association between WTC exposures and development of LRS (p.0001). Initial LRS and abnormal pulmonary function did not consistently predict PTSD onset.These analyses provide further evidence that PTSD is a risk factor for respiratory symptoms and are consistent with evidence implicating physiological dysregulation associated with PTSD in the development of medical conditions. If these effects are verified experimentally, treatment of PTSD may prove helpful in managing physical and mental health of disaster responders.

Aims.A substantial proportion of persons with mental disorders seek treatment from complementary and alternative medicine (CAM) professionals. However, data on how CAM contacts vary across countries, mental disorders and their severity, and health care settings is largely lacking. The aim was therefore to investigate the prevalence of contacts with CAM providers in a large cross-national sample of persons with 12-month mental disorders.Methods.In the World Mental Health Surveys, the Composite International Diagnostic Interview was administered to determine the presence of past 12 month mental disorders in 138 801 participants aged 18–100 derived from representative general population samples. Participants were recruited between 2001 and 2012. Rates of self-reported CAM contacts for each of the 28 surveys across 25 countries and 12 mental disorder groups were calculated for all persons with past 12-month mental disorders. Mental disorders were grouped into mood disorders, anxiety disorders or behavioural disorders, and further divided by severity levels. Satisfaction with conventional care was also compared with CAM contact satisfaction.Results.An estimated 3.6% (standard error 0.2%) of persons with a past 12-month mental disorder reported a CAM contact, which was two times higher in high-income countries (4.6%; standard error 0.3%) than in low- and middle-income countries (2.3%; standard error 0.2%). CAM contacts were largely comparable for different disorder types, but particularly high in persons receiving conventional care (8.6–17.8%). CAM contacts increased with increasing mental disorder severity. Among persons receiving specialist mental health care, CAM contacts were reported by 14.0% for severe mood disorders, 16.2% for severe anxiety disorders and 22.5% for severe behavioural disorders. Satisfaction with care was comparable with respect to CAM contacts (78.3%) and conventional care (75.6%) in persons that received both.Conclusions.CAM contacts are common in persons with severe mental disorders, in high-income countries, and in persons receiving conventional care. Our findings support the notion of CAM as largely complementary but are in contrast to suggestions that this concerns person with only mild, transient complaints. There was no indication that persons were less satisfied by CAM visits than by receiving conventional care. We encourage health care professionals in conventional settings to openly discuss the care patients are receiving, whether conventional or not, and their reasons for doing so.

The gene expression approach has provided promising insights into the pathophysiology of posttraumatic stress disorder (PTSD). However, few studies used hypothesis-free transcriptome-wide approach to comprehensively understand gene expression underpinning PTSD. A transcriptome-wide expression study using RNA sequencing of whole blood was conducted in 324 World Trade Center responders (201 with never, 81 current, 42 past PTSD). Samples from current and never PTSD reponders were randomly split to form discovery (N = 195) and replication (N = 87) cohorts. Differentially expressed genes were used in pathway analysis and to create a polygenic expression score. There were 448 differentially expressed genes in the discovery cohort, of which 99 remained significant in the replication cohort, including FKBP5, which was found to be up-regulated in current PTSD regardless of the genotypes. Several enriched biological pathways were found, including glucocorticoid receptor signaling and immunity-related pathways, but these pathways did not survive FDR correction. The polygenic expression score computed by aggregating 30 differentially expressed genes using the elastic net algorithm achieved sensitivity/specificity of 0.917/0.508, respectively for identifying current PTSD in the replication cohort. Polygenic scores were similar in current and past PTSD, with both groups scoring higher than trauma-exposed controls without any history of PTSD. Together with the pathway analysis results, these findings point to HPA-axis and immune dysregulation as key biological processes underpinning PTSD. A novel polygenic expression aggregate that differentiates PTSD patients from trauma-exposed controls might be a useful screening tool for research and clinical practice, if replicated in other populations.

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

Compelling evidence suggests that epigenetic mechanisms such as DNA methylation play a role in stress regulation and in the etiologic basis of stress related disorders such as Post traumatic Stress Disorder (PTSD). Here we describe the purpose and methods of an international consortium that was developed to study the role of epigenetics in PTSD. Inspired by the approach used in the Psychiatric Genomics Consortium, we brought together investigators representing seven cohorts with a collective sample size of N=1147 that included detailed information on trauma exposure, PTSD symptoms, and genome-wide DNA methylation data. The objective of this consortium is to increase the analytical sample size by pooling data and combining expertise so that DNA methylation patterns associated with PTSD can be identified. Several quality control and analytical pipelines were evaluated for their control of genomic inflation and technical artifacts with a joint analysis procedure established to derive comparable data over the cohorts for meta-analysis. We propose methods to deal with ancestry population stratification and type I error inflation and discuss the advantages and disadvantages of applying robust error estimates. To evaluate our pipeline, we report results from an epigenome-wide association study (EWAS) of age, which is a well-characterized phenotype with known epigenetic associations. Overall, while EWAS are highly complex and subject to similar challenges as genome-wide association studies (GWAS), we demonstrate that an epigenetic meta-analysis with a relatively modest sample size can be well-powered to identify epigenetic associations. Our pipeline can be used as a framework for consortium efforts for EWAS.

OBJECTIVE: Kraepelin considered declining course a hallmark of schizophrenia, but others have suggested that outcomes usually stabilize or improve after treatment initiation. The authors investigated this question in an epidemiologically defined cohort with psychotic disorders followed for 20 years after first hospitalization. METHOD: The Suffolk County Mental Health Project recruited first-admission patients with psychosis from all inpatient units of Suffolk County, New York (response rate, 72%). Participants were assessed in person six times over two decades; 373 completed the 20-year follow-up (68% of survivors); 175 had schizophrenia/schizoaffective disorder. Global Assessment of Functioning (GAF), psychotic symptoms, and mood symptoms were rated at each assessment. Month 6, when nearly all participants were discharged from the index hospitalization, was used as a reference. RESULTS: In the schizophrenia group, mean GAF scores declined from 49 at month 6 to 36 at year 20. Negative and positive symptoms also worsened (Cohen's d values, 0.45-0.73). Among participants without schizophrenia, GAF scores were higher initially (a mean of approximately 64) but declined by 9 points over the follow-up period. Worsening began between years 5 and 8. Neither aging nor changes in antipsychotic treatment accounted for the declines. In all disorders, depression improved and manic symptoms remained low across the 20 years. CONCLUSIONS: The authors found substantial symptom burden across disorders that increased with time and ultimately may undo initial treatment gains. Previous studies have suggested that better health care delivery models may preempt this decline. In the United States, these care needs are often not met, and addressing them is an urgent priority.

During the World Trade Center (WTC) attacks, responders who helped in search, rescue, and recovery endured multiple traumatic and toxic exposures. One-fifth subsequently developed posttraumatic stress disorder (PTSD), a chronic stress disorder that has been shown to be associated with risk of dementia in Veterans. To date only a few small studies have examined associations between intrusive stress and cognitive functioning. We fielded an objective neuropsychological battery to a sequential cohort of World Trade Center (WTC) responders (N=654) without any history of WTC-related head injury or any previous strokes who attended monitoring visits at the WTC health program on Long Island, NY. Data were linked with diagnoses of WTC-related PTSD, WTC-exposures, and other WTC-related conditions. WTC exposure was associated with poorer cognitive function, but this association was attenuated upon adjustment for PTSD. Analyses revealed that having current PTSD was associated with slower reaction time and processing speed as well as poorer working memory and cognitive throughput. In subdomain analyses, associations were concentrated amongst those who reported re-experiencing symptoms in the years immediately following the WTC disaster (in all cases, standardized effect sizes ranged from 0.85–1.20 SDs and p

This chapter explores the prevalence, correlates, and consequences of posttraumatic stress disorder (PTSD) in World Trade Center (WTC) responders. Rates of WTC-related PTSD varied depending on when and how the assessments were conducted. In the Stony Brook cohort, 17% developed PTSD during the first 13 years after the accident; half had active illness 11–13 years later. Consistent with clinical and epidemiologic research, several studies found that PTSD was associated with medical conditions and impaired functioning. PTSD was also highly comorbid with depression, and comorbidity was associated with very poor outcomes. In the Stony Brook cohort, the majority of responders with comorbid PTSD and depression were out of the workforce (65.2%), diagnosed with a WTC medical condition (81.9%), and had impairments in life satisfaction (83.2%), relationships with friend (52.4%), and social support (63.1%). The data support the need for continued monitoring and treatment of both conditions.

Objective Respiratory illness and posttraumatic stress disorder (PTSD) are common debilitating conditions that frequently co-occur. Observational studies indicate that PTSD, independently of smoking, is a major risk and maintenance factor for lower respiratory symptoms (LRS). The current study experimentally tested this etiologic pathway by investigating whether LRS can be reduced by treating PTSD symptoms. Method Ninety daily smokers exposed to the World Trade Center (WTC) disaster (mean age 50 years, 28% female; 68% White) completed 8-session group-based weekly comprehensive trauma management and smoking cessation treatment that focused on skills to alleviate PTSD symptoms. LRS, PTSD symptoms, and smoking were assessed weekly. Data was analyzed using multilevel models of within-person associations between LRS, PTSD symptoms, smoking, and treatment dose across 8 weekly sessions with concurrent and lagged outcomes. Results LRS improved significantly with treatment (reduction of .50 standard deviations). Reduction in PTSD symptoms uniquely predicted improvement in LRS at consecutive sessions 1 week apart and fully accounted for the treatment effect on LRS. The effect of PTSD symptoms was stronger than that of smoking, and the only effect to remain significant when both entered the model. Notably, reduction in LRS did not predict future improvement in PTSD symptoms. Conclusions The results are in line with the etiologic pathway suggesting that PTSD symptoms are a risk and maintenance factor for chronic LRS and that treatment of PTSD can help to alleviate LRS in trauma-exposed populations. PTSD is emerging as a novel and important treatment target for chronic respiratory problems. (PsycINFO Database Record

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.