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1.
J Affect Disord ; 282: 894-905, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33601733

RESUMO

BACKGROUND: A range of factors have been identified that contribute to greater incidence, severity, and prolonged course of post-traumatic stress disorder (PTSD), including: comorbid and/or prior psychopathology; social adversity such as low socioeconomic position, perceived discrimination, and isolation; and biological factors such as genomic variation at glucocorticoid receptor regulatory network (GRRN) genes. This complex etiology and clinical course make identification of people at higher risk of PTSD challenging. Here we leverage machine learning (ML) approaches to identify a core set of factors that may together predispose persons to PTSD. METHODS: We used multiple ML approaches to assess the relationship among DNA methylation (DNAm) at GRRN genes, prior psychopathology, social adversity, and prospective risk for PTS severity (PTSS). RESULTS: ML models predicted prospective risk of PTSS with high accuracy. The Gradient Boost approach was the top-performing model with mean absolute error of 0.135, mean square error of 0.047, root mean square error of 0.217, and R2 of 95.29%. Prior PTSS ranked highest in predicting the prospective risk of PTSS, accounting for >88% of the prediction. The top ranked GRRN CpG site was cg05616442, in AKT1, and the top ranked social adversity feature was loneliness. CONCLUSION: Multiple factors including prior PTSS, social adversity, and DNAm play a role in predicting prospective risk of PTSS. ML models identified factors accounting for increased PTSS risk with high accuracy, which may help to target risk factors that reduce the likelihood or course of PTSD, potentially pointing to approaches that can lead to early intervention. LIMITATION: One of the limitations of this study is small sample size.

2.
Mol Psychiatry ; 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33483690

RESUMO

People who experience childhood abuse are at increased risk of mental illness. Twin studies suggest that inherited genetic risk for mental illness may account for some of these associations. Yet, the hypothesis that individuals who have experienced childhood abuse may carry genetic loading for mental illness has never been tested with genetic data. Using polygenic risk scores for six psychiatric disorders-attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BPD), major depressive disorder (MDD), neuroticism, and schizophrenia-we tested whether genetic risk for mental illness was associated with increased risk of experiencing three types of childhood abuse: physical/emotional abuse, physical assault, and sexual abuse, in a cohort of white non-Hispanic women (n = 11,315). ADHD and MDD genetic risk scores were associated with a higher risk of experiencing each type of childhood abuse, while neuroticism, schizophrenia, BPD, and ASD genetic scores were associated with a higher risk of experiencing physical/emotional abuse and physical assault, but not sexual abuse. Sensitivity analyses examining potential bias from the differential recall of childhood trauma, parental socioeconomic status, and population stratification were consistent with the main findings. A one-standard-deviation increase in genetic risk for mental illness was associated with a modestly elevated risk of experiencing childhood abuse (OR range: 1.05-1.19). Therefore, inherited genetic risk may partly account for the association of childhood abuse with mental illness. In addition, future treatments for mental illness will benefit from taking into consideration the co-occurrence of childhood trauma and genetic loading.

3.
Mol Psychiatry ; 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33414500

RESUMO

Maternal anxiety during pregnancy is associated with adverse foetal, neonatal, and child outcomes, but biological mechanisms remain unclear. Altered foetal DNA methylation (DNAm) has been proposed as a potential underlying mechanism. In the current study, we performed a meta-analysis to examine the associations between maternal anxiety, measured prospectively during pregnancy, and genome-wide DNAm from umbilical cord blood. Sixteen non-overlapping cohorts from 12 independent longitudinal studies of the Pregnancy And Childhood Epigenetics Consortium participated, resulting in a combined dataset of 7243 mother-child dyads. We examined prenatal anxiety in relation to genome-wide DNAm and differentially methylated regions. We observed no association between the general symptoms of anxiety during pregnancy or pregnancy-related anxiety, and DNAm at any of the CpG sites, after multiple-testing correction. Furthermore, we identify no differentially methylated regions associated with maternal anxiety. At the cohort-level, of the 21 associations observed in individual cohorts, none replicated consistently in the other cohorts. In conclusion, contrary to some previous studies proposing cord blood DNAm as a promising potential mechanism explaining the link between maternal anxiety during pregnancy and adverse outcomes in offspring, we found no consistent evidence for any robust associations between maternal anxiety and DNAm in cord blood. Larger studies and analysis of DNAm in other tissues may be needed to establish subtle or subgroup-specific associations between maternal anxiety and the foetal epigenome.

4.
Cancer Epidemiol Biomarkers Prev ; 30(3): 492-498, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33355196

RESUMO

BACKGROUND: Posttraumatic stress disorder (PTSD) is associated with higher risk of certain chronic diseases, including ovarian cancer, but underlying mechanisms remain unclear. Although prior work has linked menopausal hormone therapy (MHT) use with elevated ovarian cancer risk, little research considers PTSD to likelihood of MHT use. We examined whether PTSD was prospectively associated with greater likelihood of initiating MHT use over 26 years. METHODS: Using data from the Nurses' Health Study II, with trauma and PTSD (symptoms and onset date) assessed by screener in 2008 and MHT assessed via biennial survey (from 1989), we performed Cox proportional regression models with women contributing person-years from age 36 years. Relevant covariates were assessed at biennial surveys. We considered potential effect modification by race/ethnicity, age at baseline, and period (1989-2002 vs. 2003-2015). RESULTS: Over follow-up, 22,352 of 43,025 women reported initiating MHT use. For example, compared with women with no trauma, the HR for initiating MHT was 1.18 for those with trauma/1-3 PTSD symptoms [95% confidence interval (CI), 1.13-1.22] and 1.31 for those with trauma/4-7 PTSD symptoms (95% CI, 1.25-1.36; P trend < 0.001), adjusting for sociodemographic factors. Associations were maintained when adjusting for reproductive factors and health conditions. We found evidence of effect modification by age at baseline. CONCLUSIONS: Trauma and number of PTSD symptoms were associated with greater likelihood of initiating MHT use in a dose-response manner. IMPACT: MHT may be a pathway linking PTSD to altered chronic disease risk. It is important to understand why women with PTSD initiate MHT use.

5.
Nat Commun ; 11(1): 5965, 2020 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-33235198

RESUMO

Epigenetic differences may help to distinguish between PTSD cases and trauma-exposed controls. Here, we describe the results of the largest DNA methylation meta-analysis of PTSD to date. Ten cohorts, military and civilian, contribute blood-derived DNA methylation data from 1,896 PTSD cases and trauma-exposed controls. Four CpG sites within the aryl-hydrocarbon receptor repressor (AHRR) associate with PTSD after adjustment for multiple comparisons, with lower DNA methylation in PTSD cases relative to controls. Although AHRR methylation is known to associate with smoking, the AHRR association with PTSD is most pronounced in non-smokers, suggesting the result was independent of smoking status. Evaluation of metabolomics data reveals that AHRR methylation associated with kynurenine levels, which are lower among subjects with PTSD. This study supports epigenetic differences in those with PTSD and suggests a role for decreased kynurenine as a contributor to immune dysregulation in PTSD.

6.
Am J Psychiatry ; 177(10): 944-954, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32791893

RESUMO

OBJECTIVE: Efforts to prevent depression, the leading cause of disability worldwide, have focused on a limited number of candidate factors. Using phenotypic and genomic data from over 100,000 UK Biobank participants, the authors sought to systematically screen and validate a wide range of potential modifiable factors for depression. METHODS: Baseline data were extracted for 106 modifiable factors, including lifestyle (e.g., exercise, sleep, media, diet), social (e.g., support, engagement), and environmental (e.g., green space, pollution) variables. Incident depression was defined as minimal depressive symptoms at baseline and clinically significant depression at follow-up. At-risk individuals for incident depression were identified by polygenic risk scores or by reported traumatic life events. An exposure-wide association scan was conducted to identify factors associated with incident depression in the full sample and among at-risk individuals. Two-sample Mendelian randomization was then used to validate potentially causal relationships between identified factors and depression. RESULTS: Numerous factors across social, sleep, media, dietary, and exercise-related domains were prospectively associated with depression, even among at-risk individuals. However, only a subset of factors was supported by Mendelian randomization evidence, including confiding in others (odds ratio=0.76, 95% CI=0.67, 0.86), television watching time (odds ratio=1.09, 95% CI=1.05, 1.13), and daytime napping (odds ratio=1.34, 95% CI=1.17, 1.53). CONCLUSIONS: Using a two-stage approach, this study validates several actionable targets for preventing depression. It also demonstrates that not all factors associated with depression in observational research may translate into robust targets for prevention. A large-scale exposure-wide approach combined with genetically informed methods for causal inference may help prioritize strategies for multimodal prevention in psychiatry.


Assuntos
Depressão/prevenção & controle , Adulto , Bases de Dados como Assunto , Depressão/etiologia , Depressão/genética , Dieta , Exercício Físico/psicologia , Feminino , Humanos , Masculino , Análise da Randomização Mendeliana , Herança Multifatorial/genética , Fatores de Risco , Tempo de Tela , Higiene do Sono
8.
BMC Emerg Med ; 20(1): 16, 2020 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-32122334

RESUMO

BACKGROUND: Previous work has indicated that post-traumatic stress disorder (PTSD) symptoms, measured by the Clinician-Administered PTSD Scale (CAPS) within 60 days of trauma exposure, can reliably produce likelihood estimates of chronic PTSD among trauma survivors admitted to acute care centers. Administering the CAPS is burdensome, requires skilled professionals, and relies on symptoms that are not fully expressed upon acute care admission. Predicting chronic PTSD from peritraumatic responses, which are obtainable upon acute care admission, has yielded conflicting results, hence the rationale for a stepwise screening-and-prediction practice. This work explores the ability of peritraumatic responses to produce risk likelihood estimates of early CAPS-based PTSD symptoms indicative of chronic PTSD risk. It specifically evaluates the Peritraumatic Dissociative Experiences Questionnaire (PDEQ) as a risk-likelihood estimator. METHODS: We used individual participant data (IPD) from five acute care studies that used both the PDEQ and the CAPS (n = 647). Logistic regression calculated the probability of having CAPS scores ≥ 40 between 30 and 60 days after trauma exposure across the range of initial PDEQ scores, and evaluated the added contribution of age, sex, trauma type, and prior trauma exposure. Brier scores, area under the receiver-operating characteristic curve (AUC), and the mean slope of the calibration line evaluated the accuracy and precision of the predicted probabilities. RESULTS: Twenty percent of the sample had CAPS ≥ 40. PDEQ severity significantly predicted having CAPS ≥ 40 symptoms (p < 0.001). Incremental PDEQ scores produced a reliable estimator of CAPS ≥ 40 likelihood. An individual risk estimation tool incorporating PDEQ and other significant risk indicators is provided. CONCLUSION: Peritraumatic reactions, measured here by the PDEQ, can reliably quantify the likelihood of acute PTSD symptoms predictive of chronic PTSD and requiring clinical attention. Using them as a screener in a stepwise chronic PTSD prediction strategy may reduce the burden of later CAPS-based assessments. Other peritraumatic metrics may perform similarly and their use requires similar validation. TRIAL REGISTRATION: Jerusalem Trauma Outreach and Prevention Study (J-TOPS): NCT00146900.

9.
Clin Epigenetics ; 12(1): 46, 2020 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-32171335

RESUMO

BACKGROUND: Previous studies using candidate gene and genome-wide approaches have identified epigenetic changes in DNA methylation (DNAm) associated with posttraumatic stress disorder (PTSD). METHODS: In this study, we performed an EWAS of PTSD in a cohort of Veterans (n = 378 lifetime PTSD cases and 135 controls) from the Translational Research Center for TBI and Stress Disorders (TRACTS) cohort assessed using the Illumina EPIC Methylation BeadChip which assesses DNAm at more than 850,000 sites throughout the genome. Our model included covariates for ancestry, cell heterogeneity, sex, age, and a smoking score based on DNAm at 39 smoking-associated CpGs. We also examined in EPIC-based DNAm data generated from pre-frontal cortex (PFC) tissue from the National PTSD Brain Bank (n = 72). RESULTS: The analysis of blood samples yielded one genome-wide significant association with PTSD at cg19534438 in the gene G0S2 (p = 1.19 × 10-7, padj = 0.048). This association was replicated in an independent PGC-PTSD-EWAS consortium meta-analysis of military cohorts (p = 0.0024). We also observed association with the smoking-related locus cg05575921 in AHRR despite inclusion of a methylation-based smoking score covariate (p = 9.16 × 10-6), which replicates a previously observed PGC-PTSD-EWAS association (Smith et al. 2019), and yields evidence consistent with a smoking-independent effect. The top 100 EWAS loci were then examined in the PFC data. One of the blood-based PTSD loci, cg04130728 in CHST11, which was in the top 10 loci in blood, but which was not genome-wide significant, was significantly associated with PTSD in brain tissue (in blood p = 1.19 × 10-5, padj = 0.60, in brain, p = 0.00032 with the same direction of effect). Gene set enrichment analysis of the top 500 EWAS loci yielded several significant overlapping GO terms involved in pathogen response, including "Response to lipopolysaccharide" (p = 6.97 × 10-6, padj = 0.042). CONCLUSIONS: The cross replication observed in independent cohorts is evidence that DNA methylation in peripheral tissue can yield consistent and replicable PTSD associations, and our results also suggest that that some PTSD associations observed in peripheral tissue may mirror associations in the brain.

10.
Psychol Med ; : 1-11, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32008580

RESUMO

BACKGROUND: Research exploring the longitudinal course of posttraumatic stress disorder (PTSD) symptoms has documented four modal trajectories (low, remitting, high, and delayed), with proportions varying across studies. Heterogeneity could be due to differences in trauma types and patient demographic characteristics. METHODS: This analysis pooled data from six longitudinal studies of adult survivors of civilian-related injuries admitted to general hospital emergency departments (EDs) in six countries (pooled N = 3083). Each study included at least three assessments of the clinician-administered PTSD scale in the first post-trauma year. Latent class growth analysis determined the proportion of participants exhibiting various PTSD symptom trajectories within and across the datasets. Multinomial logistic regression analyses examined demographic characteristics, type of event leading to the injury, and trauma history as predictors of trajectories differentiated by their initial severity and course. RESULTS: Five trajectories were found across the datasets: Low (64.5%), Remitting (16.9%), Moderate (6.7%), High (6.5%), and Delayed (5.5%). Female gender, non-white race, prior interpersonal trauma, and assaultive injuries were associated with increased risk for initial PTSD reactions. Female gender and assaultive injuries were associated with risk for membership in the Delayed (v. Low) trajectory, and lower education, prior interpersonal trauma, and assaultive injuries with risk for membership in the High (v. Remitting) trajectory. CONCLUSIONS: The results suggest that over 30% of civilian-related injury survivors admitted to EDs experience moderate-to-high levels of PTSD symptoms within the first post-trauma year, with those reporting assaultive violence at increased risk of both immediate and longer-term symptoms.

11.
Clin Epigenetics ; 12(1): 11, 2020 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-31931860

RESUMO

BACKGROUND: Epigenetic mechanisms have been suggested to play a role in the development of post-traumatic stress disorder (PTSD). Here, blood-derived DNA methylation data (HumanMethylation450 BeadChip) collected prior to and following combat exposure in three cohorts of male military members were analyzed to assess whether DNA methylation profiles are associated with the development of PTSD. A total of 123 PTSD cases and 143 trauma-exposed controls were included in the analyses. The Psychiatric Genomics Consortium (PGC) PTSD EWAS QC pipeline was used on all cohorts, and results were combined using a sample size weighted meta-analysis in a two-stage design. In stage one, we jointly analyzed data of two new cohorts (N = 126 and 78) for gene discovery, and sought to replicate significant findings in a third, previously published cohort (N = 62) to assess the robustness of our results. In stage 2, we aimed at maximizing power for gene discovery by combining all three cohorts in a meta-analysis. RESULTS: Stage 1 analyses identified four CpG sites in which, conditional on pre-deployment DNA methylation, post-deployment DNA methylation was significantly associated with PTSD status after epigenome-wide adjustment for multiple comparisons. The most significant (intergenic) CpG cg05656210 (p = 1.0 × 10-08) was located on 5q31 and significantly replicated in the third cohort. In addition, 19 differentially methylated regions (DMRs) were identified, but failed replication. Stage 2 analyses identified three epigenome-wide significant CpGs, the intergenic CpG cg05656210 and two additional CpGs located in MAD1L1 (cg12169700) and HEXDC (cg20756026). Interestingly, cg12169700 had an underlying single nucleotide polymorphism (SNP) which was located within the same LD block as a recently identified PTSD-associated SNP in MAD1L1. Stage 2 analyses further identified 12 significant differential methylated regions (DMRs), 1 of which was located in MAD1L1 and 4 were situated in the human leukocyte antigen (HLA) region. CONCLUSIONS: This study suggests that the development of combat-related PTSD is associated with distinct methylation patterns in several genomic positions and regions. Our most prominent findings suggest the involvement of the immune system through the HLA region and HEXDC, and MAD1L1 which was previously associated with PTSD.

12.
Epidemiology ; 31(2): 301-309, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31596793

RESUMO

BACKGROUND: Assessing aspects of intersections that may affect the risk of pedestrian injury is critical to developing child pedestrian injury prevention strategies, but visiting intersections to inspect them is costly and time-consuming. Several research teams have validated the use of Google Street View to conduct virtual neighborhood audits that remove the need for field teams to conduct in-person audits. METHODS: We developed a 38-item virtual audit instrument to assess intersections for pedestrian injury risk and tested it on intersections within 700 m of 26 schools in New York City using the Computer-assisted Neighborhood Visual Assessment System (CANVAS) with Google Street View imagery. RESULTS: Six trained auditors tested this instrument for inter-rater reliability on 111 randomly selected intersections and for test-retest reliability on 264 other intersections. Inter-rater kappa scores ranged from -0.01 to 0.92, with nearly half falling above 0.41, the conventional threshold for moderate agreement. Test-retest kappa scores were slightly higher than but highly correlated with inter-rater scores (Spearman rho = 0.83). Items that were highly reliable included the presence of a pedestrian signal (K = 0.92), presence of an overhead structure such as an elevated train or a highway (K = 0.81), and intersection complexity (K = 0.76). CONCLUSIONS: Built environment features of intersections relevant to pedestrian safety can be reliably measured using a virtual audit protocol implemented via CANVAS and Google Street View.

13.
Nat Commun ; 10(1): 4558, 2019 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-31594949

RESUMO

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5-20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson's disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations.


Assuntos
Loci Gênicos , Predisposição Genética para Doença , Transtornos de Estresse Pós-Traumáticos/genética , Ubiquitina-Proteína Ligases/genética , Grupo com Ancestrais do Continente Africano/genética , Conjuntos de Dados como Assunto , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Fatores Sexuais , Veteranos/estatística & dados numéricos
14.
JAMA Netw Open ; 2(5): e193447, 2019 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-31050786

RESUMO

Importance: There is a well-established negative association of educational attainment (EA) and other traits related to cognitive ability with posttraumatic stress disorder (PTSD), but the underlying mechanisms are poorly understood. Objectives: To investigate the association of PTSD with traits related to EA. Design, Setting, and Participants: Genetic correlation, polygenic risk scoring, and mendelian randomization (MR) were conducted including 23 185 individuals with PTSD and 151 309 control participants from the Psychiatric Genomics Consortium for PTSD and up to 1 131 881 individuals assessed for EA and related traits from UK Biobank, 23andMe, and the Social Science Genetic Association Consortium. Data were analyzed from July 3 through November 19, 2018. Main Outcomes and Measures: Genetic correlation obtained from linkage disequilibrium score regression, phenotypic variance explained by polygenic risk scores, and association estimates from MR. Results: Summary association data from multiple genome-wide association studies were available for a total of 1 180 352 participants (634 391 [53.7%] women). Posttraumatic stress disorder showed negative genetic correlations with EA (rg = -0.26; SE = 0.05; P = 4.60 × 10-8). Mendelian randomization analysis, conducting considering a random-effects inverse-variance weighted method, indicated that EA has a negative association with PTSD (ß = -0.23; 95% CI, -0.07 to -0.39; P = .004). Investigating potential mediators of the EA-PTSD association, propensity for trauma exposure and risk-taking behaviors were observed as risk factors for PTSD independent of EA (trauma exposure: ß = 0.37; 95% CI, 0.19 to 0.52; P = 2.57 × 10-5; risk-taking: ß = 0.76; 95% CI, 0.38 to 1.13; P = 1.13 × 10-4), while income may mediate the association of EA with PSTD (MR income: ß = -0.18; 95% CI, -0.29 to -0.07; P = .001; MR EA: ß = -0.23; 95% CI, -0.39 to -0.07; P = .004; multivariable MR income: ß = -0.32; 95% CI, -0.57 to 0.07; P = .02; multivariable MR EA: ß = -0.04; 95% CI, -0.29 to 0.21; SE, 0.13; P = .79). Conclusions and Relevance: Large-scale genomic data sets add further evidence to the negative association of EA with PTSD, also supporting the role of economic status as a mediator in the association observed.


Assuntos
Cognição/fisiologia , Status Econômico , Escolaridade , Análise da Randomização Mendeliana/métodos , Transtornos de Estresse Pós-Traumáticos/psicologia , Estudos Transversais , Humanos , Polimorfismo de Nucleotídeo Único , Assunção de Riscos , Transtornos de Estresse Pós-Traumáticos/genética
15.
World Psychiatry ; 18(1): 77-87, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30600620

RESUMO

A timely determination of the risk of post-traumatic stress disorder (PTSD) is a prerequisite for efficient service delivery and prevention. We provide a risk estimate tool allowing a calculation of individuals' PTSD likelihood from early predictors. Members of the International Consortium to Predict PTSD (ICPP) shared individual participants' item-level data from ten longitudinal studies of civilian trauma survivors admitted to acute care centers in six countries. Eligible participants (N=2,473) completed an initial clinical assessment within 60 days of trauma exposure, and at least one follow-up assessment 4-15 months later. The Clinician-Administered PTSD Scale for DSM-IV (CAPS) evaluated PTSD symptom severity and diagnostic status at each assessment. Participants' education, prior lifetime trauma exposure, marital status and socio-economic status were assessed and harmonized across studies. The study's main outcome was the likelihood of a follow-up PTSD given early predictors. The prevalence of follow-up PTSD was 11.8% (9.2% for male participants and 16.4% for females). A logistic model using early PTSD symptom severity (initial CAPS total score) as a predictor produced remarkably accurate estimates of follow-up PTSD (predicted vs. raw probabilities: r=0.976). Adding respondents' female gender, lower education, and exposure to prior interpersonal trauma to the model yielded higher PTSD likelihood estimates, with similar model accuracy (predicted vs. raw probabilities: r=0.941). The current model could be adjusted for other traumatic circumstances and accommodate risk factors not captured by the ICPP (e.g., biological, social). In line with their use in general medicine, risk estimate models can inform clinical choices in psychiatry. It is hoped that quantifying individuals' PTSD risk will be a first step towards systematic prevention of the disorder.

16.
Depress Anxiety ; 36(6): 490-498, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30681235

RESUMO

OBJECTIVE: Posttraumatic stress disorder (PTSD) is frequently associated with depression and anxiety, but the nature of the relationship is unclear. By removing mood and anxiety diagnostic criteria, the 11th edition of the International Classification of Diseases (ICD-11) aims to delineate a distinct PTSD phenotype. We examined the effect of implementing ICD-11 criteria on rates of codiagnosed depression and anxiety in survivors with recent PTSD. METHOD: Participants were 1,061 survivors of traumatic injury admitted to acute care centers in Israel. ICD-10 and ICD-11 diagnostic rules were applied to the Clinician-Administered PTSD Scale for DSM-IV. Co-occurring disorders were identified using the Structured Clinical Interview for DSM-IV (SCID). Depression severity was measured by the Beck Depression Inventory-II (BDI-II). Assessments were performed 0-60 ("wave 1") and 90-240 ("wave 2") days after trauma exposure. RESULTS: Participants identified by ICD-11 PTSD criteria were equally or more likely than those identified by the ICD-10 alone to meet depression or anxiety disorder diagnostic criteria (for wave 1: depressive disorders, OR [odds ratio] = 1.98, 95% CI [confidence interval] = [1.36, 2.87]; anxiety disorders, OR = 1.04, 95% CI = [0.67, 1.64]; for wave 2: depressive disorders, OR = 1.70, 95% CI = [1.00, 2.91]; anxiety disorders, OR = 1.04, 95% CI = [0.54, 2.01]). ICD-11 PTSD was associated with higher BDI scores (M = 23.15 vs. 17.93, P < 0.001 for wave 1; M = 23.93 vs. 17.94, P < 0.001 for wave 2). PTSD symptom severity accounted for the higher levels of depression in ICD-11 PTSD. CONCLUSIONS: Despite excluding depression and anxiety symptom criteria, the ICD-11 identified equal or higher proportion of depression and anxiety disorders, suggesting that those are inherently associated with PTSD.


Assuntos
Transtornos de Ansiedade/diagnóstico , Transtorno Depressivo/diagnóstico , Manual Diagnóstico e Estatístico de Transtornos Mentais , Classificação Internacional de Doenças , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Adulto , Idoso , Ansiedade/complicações , Ansiedade/diagnóstico , Transtornos de Ansiedade/complicações , Depressão/complicações , Depressão/diagnóstico , Transtorno Depressivo/complicações , Diagnóstico Diferencial , Feminino , Humanos , Israel , Masculino , Pessoa de Meia-Idade , Transtornos de Estresse Pós-Traumáticos/complicações , Sobreviventes/psicologia
17.
Psychol Med ; 49(3): 483-490, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29754591

RESUMO

BACKGROUND: Projected changes to post-traumatic stress disorder (PTSD) diagnostic criteria in the upcoming International Classification of Diseases (ICD)-11 may affect the prevalence and severity of identified cases. This study examined differences in rates, severity, and overlap of diagnoses using ICD-10 and ICD-11 PTSD diagnostic criteria during consecutive assessments of recent survivors of traumatic events. METHODS: The study sample comprised 3863 survivors of traumatic events, evaluated in 11 longitudinal studies of PTSD. ICD-10 and ICD-11 diagnostic rules were applied to the Clinician-Administered PTSD Scale (CAPS) to derive ICD-10 and ICD-11 diagnoses at different time intervals between trauma occurrence and 15 months. RESULTS: The ICD-11 criteria identified fewer cases than the ICD-10 across assessment intervals (range -47.09% to -57.14%). Over 97% of ICD-11 PTSD cases met concurrent ICD-10 PTSD criteria. PTSD symptom severity of individuals identified by the ICD-11 criteria (CAPS total scores) was 31.38-36.49% higher than those identified by ICD-10 criteria alone. The latter, however, had CAPS scores indicative of moderate PTSD. ICD-11 was associated with similar or higher rates of comorbid mood and anxiety disorders. Individuals identified by either ICD-10 or ICD-11 shortly after traumatic events had similar longitudinal course. CONCLUSIONS: This study indicates that significantly fewer individuals would be diagnosed with PTSD using the proposed ICD-11 criteria. Though ICD-11 criteria identify more severe cases, those meeting ICD-10 but not ICD-11 criteria remain in the moderate range of PTSD symptoms. Use of ICD-11 criteria will have critical implications for case identification in clinical practice, national reporting, and research.


Assuntos
Classificação Internacional de Doenças , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Comorbidade , Bases de Dados Factuais , Humanos , Entrevista Psicológica , Prevalência , Índice de Gravidade de Doença , Transtornos de Estresse Pós-Traumáticos/classificação
18.
Front Aging Neurosci ; 10: 311, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30405391

RESUMO

Background: Delirium in elderly patients is common and dangerous. Major risk factors include aging and exogenous insults, such as infection or surgery. In animal models, aging enhances pro-inflammatory cytokine release from microglia in response to exogenous insults. The epigenetic mechanism DNA methylation (DNAm) regulates gene expression and changes with age. Older individuals may have methylation changes that influence the increased cytokine upon insult, but the degree to which aging affects DNAm of cytokine genes is not fully understood. Methods: The relationship between DNAm and aging of pro-inflammatory cytokine genes (TNF-alpha, IL1-beta, IL-6) was investigated using methylation array data in two cohorts. Brain and blood samples were collected from a neurosurgery cohort (NSG) of 21 subjects who underwent brain resection. A second cohort, the Grady Trauma Project (GTP), included blood samples from 265 subjects. Results: In the NSG cohort, a significant negative correlation between age and DNAm in brain was found at a CpG in IL-6. With the GTP dataset, significant negative correlations between age and DNAm were seen at most of the CpGs in TNF-alpha. Also, TNF-Alpha expression increases with age. These GTP DNAm correlations were also nominally significant in NSG blood samples. In neuronal negative NSG brain tissue, a similar negative trend was observed. Conclusions: With aging, a decrease in DNAm of cytokines gene CpGs in glia and blood was seen. As this can affect their expression, additional research is needed to fully elucidate the role of DNAm in aging and how it may influence the pathogenesis of delirium.

19.
Epigenomics ; 10(12): 1585-1601, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30456986

RESUMO

AIM: Trauma exposure is a necessary, but not deterministic, contributor to post-traumatic stress disorder (PTSD). Epigenetic factors may distinguish between trauma-exposed individuals with versus without PTSD. MATERIALS & METHODS: We conducted a meta-analysis of PTSD epigenome-wide association studies in trauma-exposed cohorts drawn from civilian contexts. Whole blood-derived DNA methylation levels were analyzed in 545 study participants, drawn from the three civilian cohorts participating in the PTSD working group of the Psychiatric Genomics Consortium. RESULTS: Two CpG sites significantly associated with current PTSD in NRG1 (cg23637605) and in HGS (cg19577098). CONCLUSION: PTSD is associated with differential methylation, measured in blood, within HGS and NRG1 across three civilian cohorts.


Assuntos
Metilação de DNA , Complexos Endossomais de Distribuição Requeridos para Transporte/genética , Epigenômica , Neuregulina-1/genética , Fosfoproteínas/genética , Transtornos de Estresse Pós-Traumáticos/genética , Adulto , Idoso , Biomarcadores/análise , Estudos de Coortes , Demografia , Feminino , Genômica , Humanos , Masculino , Pessoa de Meia-Idade
20.
Eur J Psychotraumatol ; 9(1): 1476442, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29938009

RESUMO

Background: Understanding the development of post-traumatic stress disorder (PTSD) is a precondition for efficient risk assessment and prevention planning. Studies to date have been site and sample specific. Towards developing generalizable models of PTSD development and prediction, the International Consortium to Predict PTSD (ICPP) compiled data from 13 longitudinal, acute-care based PTSD studies performed in six different countries. Objective: The objectives of this study were to describe the ICPP's approach to data pooling and harmonization, and present cross-study descriptive results informing the longitudinal course of PTSD after acute trauma. Methods: Item-level data from 13 longitudinal studies of adult civilian trauma survivors were collected. Constructs (e.g. PTSD, depression), measures (questions or scales), and time variables (days from trauma) were identified and harmonized, and those with inconsistent coding (e.g. education, lifetime trauma exposure) were recoded. Administered in 11 studies, the Clinician Administered PTSD Scale (CAPS) emerged as the main measure of PTSD diagnosis and severity. Results: The pooled data set included 6254 subjects (39.9% female). Studies' average retention rate was 87.0% (range 49.1-93.5%). Participants' baseline assessments took place within 2 months of trauma exposure. Follow-up durations ranged from 188 to 1110 days. Reflecting studies' inclusion criteria, the prevalence of baseline PTSD differed significantly between studies (range 3.1-61.6%), and similar differences were observed in subsequent assessments (4.3-38.2% and 3.8-27.0% for second and third assessments, respectively). Conclusion: Pooling data from independently collected studies requires careful curation of individual data sets for extracting and optimizing informative commonalities. However, it is an important step towards developing robust and generalizable prediction models for PTSD and can exceed findings of single studies. The large differences in prevalence of PTSD longitudinally cautions against using any individual study to infer trauma outcome. The multiplicity of instruments used in individual studies emphasizes the need for common data elements in future studies.

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