Project description:BackgroundA minority of persons who have traumatic experiences go on to develop post-traumatic stress disorder (PTSD), leading to interest in who is at risk for psychopathology after these experiences. Complicating this effort is the observation that post-traumatic psychopathology is heterogeneous. The goal of this nested case-control study was to identify pre-trauma predictors of severe post-traumatic psychiatric comorbidity, using data from Danish registries.MethodsThe source population for this study was the population of Denmark from 1994 through 2016. Cases had received three or more psychiatric diagnoses (across all ICD-10 categories) within 5 years of a traumatic experience (n = 20 361); controls were sampled from the parent cohort using risk-set sampling (n = 81 444). Analyses were repeated in samples stratified by pre-trauma psychiatric diagnoses. We used machine learning methods (classification and regression trees and random forest) to determine the important predictors of severe post-trauma psychiatric comorbidity from among hundreds of pre-trauma predictor variables spanning demographic and social variables, psychiatric and somatic diagnoses and filled medication prescriptions.ResultsIn the full sample, pre-trauma psychiatric diagnoses (e.g. stress disorders, alcohol-related disorders, personality disorders) were the most important predictors of severe post-trauma psychiatric comorbidity. Among persons with no pre-trauma psychiatric diagnoses, demographic and social variables (e.g. marital status), type of trauma, medications used primarily to treat psychiatric symptomatology, anti-inflammatory medications and gastrointestinal distress were important to prediction. Results among persons with pre-trauma psychiatric diagnoses were consistent with the overall sample.ConclusionsThis study builds on the understanding of pre-trauma factors that predict psychopathology following traumatic experiences, by examining a broad range of predictors of post-trauma psychopathology and comorbidity beyond PTSD.

Project description:Atmospheric particulate matter (PM) is a recognized risk factor for the global burden of disease in human populations. We are presenting here the application of toxicogenomics in the evaluation of the toxic effects of organic content of atmospheric particle matter (PM), from urban and rural environments (city of Barcelona and village of La Pobla, NE Spain), using the developing zebrafish embryo. The main goal is to identify the metabolic pathways involved in the adverse effects observed in zebrafish embryos exposed to PM organic content from urban and rural environments, also allowing the selection of genes of interest that are differentially expressed. The relevance of particle size to the PM toxicity is also addressed. Indeed, the zebrafish embryos were exposed to PM of aerodynamic diameter larger than 7.2 μm and smaller than 0.5 μm (PM10 and PM0.5, respectively). PM0.5 concentrated biological and toxic activities linked to organic substances. Transcriptomic analyses showed strong induction of the AhR signalling pathway (a.k.a. dioxin-like activity) for embryos exposed to both rural and urban extracts, correlating with the concentrations of PAHs. Urban extracts, with strong contribution of traffic emissions, specifically de-regulated oxidative stress-related genes, as well as pancreatic and eye-lens specific genes, two organs known to be affected by air pollution in humans. Exposure to rural extracts, with high contribution of wood burning emissions, affected genes implicated in basic cellular functions, in agreement with their strong embryotoxicity. Extracts from rural and urban samples elicited both common and specific transcriptome responses, suggesting different potentially adverse outcomes depending on PM source and composition. The authors thank the financial support of the Spanish Ministry (project TEA-PARTICLE, grant number CGL2011-29621) and the Portuguese Foundation for Science and Technology for the doctoral grant of Sofia R. Mesquita (SFRH/BD/80710/2011) funded by the Program POPH-QREN through the Portuguese Ministry of Education and Science and the European Social Fund, and support through project PEst-C/MAR/LA0015/2013.

Project description:Atmospheric particulate matter (PM) is a recognized risk factor for the global burden of disease in human populations. We are presenting here the application of toxicogenomics in the evaluation of the toxic effects of organic content of atmospheric particle matter (PM), from urban and rural environments (city of Barcelona and village of La Pobla, NE Spain), using the developing zebrafish embryo. The main goal is to identify the metabolic pathways involved in the adverse effects observed in zebrafish embryos exposed to PM organic content from urban and rural environments, also allowing the selection of genes of interest that are differentially expressed. The relevance of particle size to the PM toxicity is also addressed. Indeed, the zebrafish embryos were exposed to PM of aerodynamic diameter larger than 7.2 Î¼m and smaller than 0.5 Î¼m (PM10 and PM0.5, respectively). PM0.5 concentrated biological and toxic activities linked to organic substances. Transcriptomic analyses showed strong induction of the AhR signalling pathway (a.k.a. dioxin-like activity) for embryos exposed to both rural and urban extracts, correlating with the concentrations of PAHs. Urban extracts, with strong contribution of traffic emissions, specifically de-regulated oxidative stress-related genes, as well as pancreatic and eye-lens specific genes, two organs known to be affected by air pollution in humans. Exposure to rural extracts, with high contribution of wood burning emissions, affected genes implicated in basic cellular functions, in agreement with their strong embryotoxicity. Extracts from rural and urban samples elicited both common and specific transcriptome responses, suggesting different potentially adverse outcomes depending on PM source and composition. The authors thank the financial support of the Spanish Ministry (project TEA-PARTICLE, grant number CGL2011-29621) and the Portuguese Foundation for Science and Technology for the doctoral grant of Sofia R. Mesquita (SFRH/BD/80710/2011) funded by the Program POPH-QREN through the Portuguese Ministry of Education and Science and the European Social Fund, and support through project PEst-C/MAR/LA0015/2013. The PM filter samples used in the present study were PM10 and PM0.5 from the urban site - total of 4 samples from 2 sampling months; and PM0.5 from the rural site - total of 2 samples from 2 sampling months (PM10 samples from the rural site were not tested due to their very low concentration in organic compounds, and insignificant biological activity, previously measured). Sampling occurred during the cold periods of the year 2012/2013. The organic fraction of PM samples was extracted by sonication using a mixture of dichloromethane:methanol. Then, the extracts were filtered, evaporated and re-dissolved in Dimethyl sulfoxide (DMSO). Zebrafish fertilized eggs were exposed to PM organic extracts (0.2% DMSO) from the urban and rural sites from 24 to 120h post-fertilization. Total RNA was isolated from whole embryos (pools of 20 individuals), using Trizol reagent protocol (Invitrogen Life Technologies, Carlsberg, CA). The microarray study was performed using the Agilent Two-colour D. rerio Oligo Microarray v3 platform, following the Agilent Microarray â?? Based Gene Expression Analysis protocol. Three biological replicates were performed for each PM sample and controls. Biological replicates, a technical replicate and a self-to-self, were simultaneously amplified and labelled using Cyanine 3 (Cy3) and Cyanine 5 (Cy5) dye. After cRNA purification (RNeasy Kit, Quiagen GmbH, Hilden, Germany), the cRNA concentration and labelling were quantified in the NanoDrop spectrophotometer, obtaining incorporation rates in the range of 15-20pmol of cyanide dye/Âµl cRNA and yield values > 0.825ug, as recommended. cRNA was fragmented and hybridized in 4x44K arrays, for 17h at 65oC. After the hybridization the array slides were washed, and immediately scanned using Microarray Scanner Agilent G2505C system. Data was extracted using Agilent Feature Extraction Software v10.5.1.1, and the quality of microarray data was evaluated using the Quality Control report provided by Agilent Software. Based on the microarray data analysis, 22 primers were selected and designed using Primer Express 2.0 software (Applied Biosystems, Foster City, CA). Genes were quantified by real-time PCR to validate the microarray data, and a subset of 13 genes were further selected by their robust behaviour in the validation assays, allowing to differentiate the toxic potential of PM from urban and rural sources.

Project description:Integrating psychiatric services within substance abuse treatment settings is a promising service delivery model, but has not been evaluated using random assignment to psychiatric treatment setting and controlled delivery of psychiatric care. This study evaluates the efficacy of on-site and integrated psychiatric service delivery in an opioid-agonist treatment program on psychiatric and substance use outcomes.Participants at the Addiction Treatment Services (ATS) were assigned randomly to receive on-site and integrated substance abuse and psychiatric care (on-site: n?=?160) versus off-site and non-integrated substance abuse and psychiatric care (off-site: n?=?156), and observed for 1 year. On-site participants received all psychiatric care within the substance abuse program by the same group of treatment providers. The same type and schedule of psychiatric services were available to off-site participants at a community psychiatry program.All participants received routine methadone maintenance at the ATS program in Baltimore, Maryland, USA.Participants were opioid-dependent men and women with at least one comorbid psychiatric disorder, as assessed by the Structured Clinical Interview for DSM-IV and confirmed by expert clinical reappraisal.Outcomes included psychiatric service utilization and retention, Hopkins Symptom Checklist Global Severity Index (GSI) change scores and urinalysis test results.On-site participants were more likely to initiate psychiatric care 96.9 to 79.5%; P?<?0.001), remain in treatment longer (195.9 versus 101.9 days; P?<?0.001), attend more psychiatrist appointments (12.9 versus 2.7; P?<?0.001) and have greater reductions in GSI scores (4.2 versus 1.7; P?=?0.003) than off-site participants; no differences were observed for drug use.On-site and integrated psychiatric and substance misuse services in a methadone treatment setting might improve psychiatric outcomes compared with off-site and non-integrated substance misuse and psychiatric care. However, this might not translate into improved substance misuse outcomes.

Project description:BackgroundNepal, like many other low-income countries, has a great burden of mental health issues but few resources to meet them. In addition, Nepal has endured several traumatic events in recent decades but the impact on mental health has not been studied in clinical settings. This study explores trauma-related psychiatric disorders and their correlates.Methods100 patients with a history of trauma who visited the outpatient psychiatry clinic at a University hospital in Kathmandu were assessed. The Composite International Diagnostic Interview 2.1 (CIDI) was used to evaluate lifetime and current depressive disorder, generalized anxiety disorder (GAD) and lifetime post-traumatic stress disorder (PTSD). Current PTSD was evaluated using PSTD Checklist-Civilian Version (PCL-C).ResultsThe median number of lifetime traumatic events was two. Natural disaster was the most common trauma type (84%) compared to other types of trauma. Rape was reported as the most traumatizing. Current PTSD was found in 15%, depression in 33% and GAD in 38% of the patients. The lifetime rates were PTSD 83%, depression 45% and GAD 40%. There was high comorbidity between the disorders. The 31 to 45 years age group, above high school education level and trauma types other than earthquake were independently associated with current PTSD. Marital status and upper socioeconomic status (SES) compared to upper-middle SES were independently associated with lifetime PTSD. Both lifetime and current depression rates were independently associated with the upper SES compared to upper-middle SES. Place of living, education above high school and lower-middle SES were significantly associated with lifetime and current GAD.ConclusionPTSD, depression and GAD were prevalent in a trauma exposed patient population visiting a psychiatric clinic in Nepal. High rates of comorbidities and several risk factors were identified. Our findings highlight the need for addressing trauma related disorders in clinical settings in developing countries.

Project description:ImportanceAll of Us is a landmark initiative for population-scale research into a variety of health conditions, including psychiatric disorders.ObjectiveTo analyze the prevalence, comorbidity, and sociodemographic covariates of psychiatric disorders in the All of Us biobank.Design, setting, and participantsWe estimated prevalence, overlap, and sociodemographic correlates for psychiatric disorders as reported in electronic health records for All of Us release 5 (N = 331 380).ExposuresSocial and demographic covariates.Main outcomes and measuresPsychiatric disorders derived from International Statistical Classification of Diseases, Tenth Revision, Clinical Modification, codes across 6 broad domains: mood disorders, anxiety disorders, substance use disorders, stress-related disorders, schizophrenia, and personality disorders.ResultsThe analytic sample (N = 329 038) was 60.7% female (mean [SD] age, 50.9 [16.8] years). The prevalence of disorders ranged from 11.00% (95% CI, 10.68% to 11.32%) for any mood disorder to less than 1% (eg, obsessive-compulsive disorder, 0.18%; 95% CI, -0.16% to 0.52%), with mood disorders being the most common and personality disorders being the least. There was substantial overlap among disorders, with the majority of participants with a disorder (30 113/58 806, approximately 51%) having 2 or more registered diagnoses and tetrachoric correlations ranging from 0.43 to 0.74. Comparisons of prevalence across demographic categories revealed that non-Hispanic White people, individuals with low socioeconomic status, women and individuals assigned female at birth, and sexual minority individuals are at greatest risk for most disorders.Conclusions and relevanceAlthough rates of disorders among the All of Us cohort are lower than in the general population, considerable variation, comorbidity, and disparities exist across social groups. To improve the practice of equitable precision medicine, researchers can use comprehensive health data from large-scale resources such as All of Us.

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The prevalence and correlates of lifetime psychiatric disorders and trauma exposures in urban and rural settings: results from the national comorbidity survey replication (NCS-R).

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