scholarly journals Genomic Characterization of Posttraumatic Stress Disorder in a Large US Military Veteran Sample

2019 ◽  
Author(s):  
Murray B. Stein ◽  
Daniel F. Levey ◽  
Zhongshan Cheng ◽  
Frank R. Wendt ◽  
Kelly Harrington ◽  
...  
Keyword(s):  
Posttraumatic Stress Disorder ◽  
Posttraumatic Stress ◽  
Stress Disorder ◽  
Drug Repositioning ◽  
Genetic Correlations ◽  
Postmortem Brain ◽  
Association Analyses ◽  
Symptom Level ◽  
Life Threatening ◽  
New Treatments

ABSTRACTIndividuals vary in their liability to develop Posttraumatic Stress Disorder (PTSD), the symptoms of which are highly heterogeneous, following exposure to life-threatening trauma. Understanding genetic factors that contribute to the biology of PTSD is critical for refining diagnosis and developing new treatments. Using genetic data from more than 250,000 participants in the Million Veteran Program, genomewide association analyses were conducted using a validated electronic health record-based algorithmically-defined PTSD diagnosis phenotype (48,221 cases and 217,223 controls), and PTSD quantitative symptom phenotypes (212,007 individuals). We identified several genome-wide significant loci in the case-control analyses, and numerous such loci in the quantitative trait analyses, including some (e.g., MAD1L1; TCF4; CRHR1) that were associated with multiple symptom sub-domains and total symptom score, and others that were more specific to certain symptom sub-domains (e.g., CAMKV to re-experiencing; SOX6 to hyperarousal). Genetic correlations between all pairs of symptom sub-domains and their total were very high (rg 0.93 – 0.98) supporting validity of the PTSD diagnostic construct. We also demonstrate strong shared heritability with a range of traits, show that heritability persists when conditioned on other major psychiatric disorders, present independent replication results, provide support for one of the implicated genes in postmortem brain of individuals with PTSD, and use this information to identify potential drug repositioning candidates. These results point to the utility of genetics to inform and validate the biological coherence of the PTSD syndrome despite considerable heterogeneity at the symptom level, and to provide new directions for treatment development.

scholarly journals Biomarkers in Posttraumatic Stress Disorder: Overview and Implications for Future Research

2013 ◽  
Vol 35 ◽  
pp. 43-54 ◽  
Author(s):  
Ulrike Schmidt ◽  
Sebastian F. Kaltwasser ◽  
Carsten T. Wotjak
Keyword(s):  
Posttraumatic Stress Disorder ◽  
Sexual Abuse ◽  
Anxiety Disorder ◽  
Posttraumatic Stress ◽  
Stress Disorder ◽  
Future Research ◽  
Clinical Use ◽  
Current State ◽  
Life Threatening ◽  
State Of Research

PTSD can develop in the aftermath of traumatic incidents like combat, sexual abuse, or life threatening accidents. Unfortunately, there are still no biomarkers for this debilitating anxiety disorder in clinical use. Anyhow, there are numerous studies describing potential PTSD biomarkers, some of which might progress to the point of practical use in the future. Here, we outline and comment on some of the most prominent findings on potential imaging, psychological, endocrine, and molecular PTSD biomarkers and classify them into risk, disease, and therapy markers. Since for most of these potential PTSD markers a causal role in PTSD has been demonstrated or at least postulated, this review also gives an overview on the current state of research on PTSD pathobiology.

scholarly journals Cortical Transcriptomic Alterations in Association With Appetitive Neuropeptides and Body Mass Index in Posttraumatic Stress Disorder

2020 ◽  
Author(s):  
Lauren A Stone ◽  
Matthew J Girgenti ◽  
Jiawei Wang ◽  
Dingjue Ji ◽  
Hongyu Zhao ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Posttraumatic Stress Disorder ◽  
Posttraumatic Stress ◽  
Body Mass ◽  
Stress Disorder ◽  
Postmortem Brain ◽  
Pathway Annotation ◽  
Postmortem Brain Tissue ◽  
And Control ◽  
Upstream Regulators

Abstract Background The molecular pathology underlying posttraumatic stress disorder (PTSD) remains unclear mainly due to a lack of human PTSD postmortem brain tissue. The orexigenic neuropeptides ghrelin, neuropeptide Y, and hypocretin were recently implicated in modulating negative affect. Drawing from the largest functional genomics study of human PTSD postmortem tissue, we investigated whether there were molecular changes of these and other appetitive molecules. Further, we explored the interaction between PTSD and body mass index (BMI) on gene expression. Methods We analyzed previously reported transcriptomic data from 4 prefrontal cortex regions from 52 individuals with PTSD and 46 matched neurotypical controls. We employed gene co-expression network analysis across the transcriptomes of these regions to uncover PTSD-specific networks containing orexigenic genes. We utilized Ingenuity Pathway Analysis software for pathway annotation. We identified differentially expressed genes (DEGs) among individuals with and without PTSD, stratified by sex and BMI. Results Three PTSD-associated networks (P < .01) contained genes in signaling families of appetitive molecules: 2 in females and 1 in all subjects. We uncovered DEGs (P < .05) between PTSD and control subjects stratified by sex and BMI with especially robust changes in males with PTSD with elevated vs normal BMI. Further, we identified putative upstream regulators (P < .05) driving these changes, many of which were enriched for involvement in inflammation. Conclusions PTSD-associated cortical transcriptomic modules contain transcripts of appetitive genes, and BMI further interacts with PTSD to impact expression. DEGs and inferred upstream regulators of these modules could represent targets for future pharmacotherapies for obesity in PTSD.

Association between flashbacks and structural brain abnormalities in posttraumatic stress disorder

2011 ◽  
Vol 26 (8) ◽  
pp. 525-531 ◽  
Author(s):  
M.C.W. Kroes ◽  
M.G. Whalley ◽  
M.D. Rugg ◽  
C.R. Brewin
Keyword(s):  
Posttraumatic Stress Disorder ◽  
Posttraumatic Stress ◽  
Stress Disorder ◽  
Brain Volume ◽  
Structural Mri ◽  
Healthy Controls ◽  
Visual Stream ◽  
Brain Volumes ◽  
Symptom Level ◽  
Mri Scans

AbstractObjectivePosttraumatic stress disorder (PTSD) is reliably associated with reduced brain volume relative to healthy controls, in areas similar to those found in depression. We investigated whether in a PTSD sample brain volumes in these areas were related to reporting specific symptoms of PTSD or to overall symptom severity.MethodStructural MRI scans were obtained from 28 participants diagnosed with PTSD according to DSM-IV-TR. Participants reported the extent of individual PTSD symptoms using the Posttraumatic Diagnostic Scale. Voxel-based morphometry applying the Dartel algorithm implemented within SPM5 was used to identify volumetric changes, related to PTSD total, symptom cluster, and individual symptom scores.ResultsBrain volume was unrelated to overall PTSD severity, but greater reexperiencing scores predicted reduced volumes in the middle temporal and inferior occipital cortices. Increased reports of flashbacks predicted reduced volume in the insula/parietal operculum and in the inferior temporal gyrus.ConclusionThe data illustrate the value of analyses at the symptom level within a patient population to supplement group comparisons of patients and healthy controls. Areas identified were consistent with a neurobiological account of flashbacks implicating specific abnormalities in the ventral visual stream.

Posttraumatic Stress Symptoms in a Population of Rural Children in South Africa

1999 ◽  
Vol 85 (2) ◽  
pp. 646-650 ◽  
Author(s):  
Karl Peltzer
Keyword(s):  
Posttraumatic Stress Disorder ◽  
Posttraumatic Stress ◽  
Stress Disorder ◽  
Traumatic Event ◽  
Posttraumatic Stress Symptoms ◽  
Unexpected Death ◽  
Loved One ◽  
Stress Symptoms ◽  
Life Threatening ◽  
Age Range

The purpose of the study was to identify exposure to experiences such as violence and the consequences for health in children in a rural South African community. The stratified random sample included 148 children below 17 yr., which comprised 68 (46%) boys and 80 (54%) girls in the age range of 6 to 16 years ( M = 12.1 yr., SD = 3.1). Their ethnicity was Northern Sotho. The interviews included the Children's Posttraumatic Stress Disorder Inventory and the Reporting Questionnaire for Children. The experiences could be grouped into either traumatic or other events. 99 (67%) had directly or vicariously experienced a traumatic event which included witnessing someone killed or seriously injured, serious accident, violent or very unexpected death or suicide of loved one, sexual abuse or rape of relative or friend, violent crime, child abuse, and other life-threatening situations. Scores on the Children's Posttraumatic Stress Disorder Inventory of 17 (8.4%) fulfilled the criterion for posttraumatic stress disorder. 71% had more than one score and 53% had more than four scores on the Reporting Questionnaire for Children. Posttraumatic stress symptoms were significantly related to age and experiences such as those mentioned above.

Network approach to the symptom-level association between alcohol use disorder and posttraumatic stress disorder

2016 ◽  
Vol 52 (3) ◽  
pp. 329-339 ◽  
Author(s):  
Mohammad H. Afzali ◽  
Matthew Sunderland ◽  
Philip J. Batterham ◽  
Natacha Carragher ◽  
Alison Calear ◽  
...  
Keyword(s):  
Posttraumatic Stress Disorder ◽  
Alcohol Use ◽  
Posttraumatic Stress ◽  
Alcohol Use Disorder ◽  
Stress Disorder ◽  
Network Approach ◽  
Symptom Level

scholarly journals Posttraumatic stress disorder among women after the war in Sarajevo: a rationale for genetic study.

2004 ◽  
Vol 4 (1) ◽  
pp. 50-52 ◽  
Author(s):  
Lilijana Oruč ◽  
Lejla Kapur ◽  
Naris Pojskić ◽  
Semra Čavaljuga ◽  
Slađana Ivezić ◽  
...  
Keyword(s):  
Posttraumatic Stress Disorder ◽  
Posttraumatic Stress ◽  
Life Events ◽  
Stress Disorder ◽  
Harvard Trauma Questionnaire ◽  
Significant Difference ◽  
Life Threatening ◽  
War Survivors ◽  
Gender Specific ◽  
Ptsd Prevalence

An exposure to extreme trauma events leads to posttraumatic stress disorder (PTSD) in up to 14-50% of war survivors. Recent findings suggest that genetic factors could play a certain role in PTSD development. In order to illustrate this possibility, we present results of a pilot study on gender specific sample of Sarajevo civilians immediately after the war cessation. During the period 1992-1995, Sarajevo civilians experienced continuous life threatening events with a great risk of developing PTSD in such conditions.Our study included 100 women adjusted to same socio-demographic characteristics. All women were interviewed using Harvard Trauma Questionnaire (HTQ) and divided into two groups (domestic and returnees) according to exposure length to extreme war life events of six or forty-three months. Above 50% of total analysed sample fulfilled criteria for PTSD. Regarding duration in trauma exposure no significant difference between these two groups were found. The only significant predictor found was physical abuse (p>0.01) that still cannot explain why some women develop PTSD while others not.Several years after the war, PTSD frequencies are decreased and disorder became chronic and more severe. However, the PTSD prevalence remains high when compared to general population rates. Therefore, Sarajevo population being exposed for almost four years to extreme war life events represents unique model for comparative research on PTSD etiology within the light of latest findings in molecular genetics of PTSD.

scholarly journals Constitutional thinness and anorexia nervosa differ on a genomic level

2021 ◽  
Author(s):  
Christopher Hübel ◽  
Mohamed Abdulkadir ◽  
Moritz Herle ◽  
Alish B. Palmos ◽  
Ruth J.F. Loos ◽  
...  
Keyword(s):  
Posttraumatic Stress Disorder ◽  
Anorexia Nervosa ◽  
Psychiatric Disorders ◽  
Genetic Correlation ◽  
Posttraumatic Stress ◽  
Stress Disorder ◽  
Genetic Correlations ◽  
Genomic Level ◽  
Increased Risk ◽  
Polygenic Scores

AbstractConstitutional thinness and anorexia nervosa are both characterised by persistent, extremely low weight with body mass indices (BMI) below 18.5 kg/m2. Individuals with anorexia nervosa concurrently show distorted perceptions of their own body and engage in weight-loss behaviours, whereas individuals with constitutional thinness typically wish to gain weight. Both are heritable, share genomics with BMI, but have not been shown to be genetically correlated with each other. We aim to differentiate between constitutional thinness and anorexia nervosa on a genomic level.First, we estimated genetic correlations between constitutional thinness and eleven psychiatric disorders and compared them with anorexia nervosa using publicly available data. Second, we identified individuals with constitutional thinness in the Avon Longitudinal Study of Parents and Children (ALSPAC) by latent class growth analysis of measured BMI from 10 to 24 years (n = 8,505) and assigned polygenic scores for eleven psychiatric disorders and a range of anthropometric traits to evaluate associations.In contrast to anorexia nervosa, attention deficit hyperactivity disorder (rgAN = 0.02 vs. rgCT = −0.24) and alcohol dependence (rgAN = 0.07 vs. rgCT = −0.44) showed a statistically significant negative genetic correlation with constitutional thinness. A higher polygenic score for posttraumatic stress disorder was associated with an increased risk of constitutional thinness in the ALSPAC cohort (OR = 1.27; Q = 0.03) whereas posttraumatic stress disorder shows no genetic correlation with anorexia nervosa (rg = −0.02). Overall, results suggest that constitutional thinness is different from anorexia nervosa on the genomic level.

A Sobering Look at Treatment Effectiveness of Military-Related Posttraumatic Stress Disorder

2021 ◽  
pp. 216770262110513
Author(s):  
Ofir Levi ◽  
Ariel Ben Yehuda ◽  
Daniel S. Pine ◽  
Yair Bar-Haim
Keyword(s):  
Posttraumatic Stress Disorder ◽  
Posttraumatic Stress ◽  
Diagnostic Criteria ◽  
Real World ◽  
Stress Disorder ◽  
Treatment Effectiveness ◽  
Clinical Effectiveness ◽  
Clinical Settings ◽  
New Treatments ◽  
Overall Effectiveness

Approximately two thirds of veterans with posttraumatic stress disorder (PTSD) remain with the disorder following treatment. Pinpointing the per-symptom effectiveness of treatments in real-world clinical settings can highlight relevant domains for treatment augmentation and development. Baseline and posttreatment assessments of PTSD and depression were performed in 709 veterans with PTSD. PTSD remission was 39.4%. Treatment was least effective for intrusion symptoms and had no effect on flashbacks or on poor recall of traumatic features. Of veterans who remitted, 72.8% still met diagnostic criteria for at least one cluster. Poor clinical effectiveness was noted for depression; only 4.1% of the patients remitted following treatment. Treatments for veterans with PTSD show limited overall effectiveness in real-world settings. Enhancing treatment response may require enhancing provider fidelity and patient compliance with extant treatments or the development of new treatments that specifically target the symptoms of PTSD that do not respond well to extant treatments.

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