A High Risk Twin Study of Combat-Related PTSD Comorbidity

Koenen, Karestan C.; Lyons, Michael J.; Goldberg, Jack; Simpson, John C.; Williams, Wesley M.; Toomey, Rosemary; Eisen, Seth A.; True, William R.; Cloitre, Marylène; Wolfe, Jessica; Tsuang, Ming T.

doi:10.1375/136905203765693870

Cited by 72 publications

(21 citation statements)

References 35 publications

(14 reference statements)

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“…Some of the other factors conferring risk to PTSD include heritability [9–12], family instability [13], biological factors [14], endocrine factors [15], neurochemical factors [16, 17], neurocircuitry factors [18, 19], genetic factors [20–23], gender differences [24], early developmental factors [25] and physical trauma [26]. Among these, genetic factors are known to confer 30% of the variance in PTSD [27].…”

Section: Introductionmentioning

confidence: 99%

Prediction of Possible Biomarkers and Novel Pathways Conferring Risk to Post-Traumatic Stress Disorder

Chitrala

Nagarkatti

2016

PLoS ONE

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Post-traumatic stress disorder is one of the common mental ailments that is triggered by exposure to traumatic events. Till date, the molecular factors conferring risk to the development of PTSD is not well understood. In this study, we have conducted a meta-analysis followed by hierarchical clustering and functional enrichment, to uncover the potential molecular networks and critical genes which play an important role in PTSD. Two datasets of expression profiles from Peripheral Blood Mononuclear Cells from 62 control samples and 63 PTSD samples were included in our study. In PTSD samples of GSE860 dataset, we identified 26 genes informative when compared with Post-deploy PTSD condition and 58 genes informative when compared with Pre-deploy and Post-deploy PTSD of GSE63878 dataset. We conducted the meta-analysis using Fisher, roP, Stouffer, AW, SR, PR and RP methods in MetaDE package. Results from the rOP method of MetaDE package showed that among these genes, the following showed significant changes including, OR2B6, SOX21, MOBP, IL15, PTPRK, PPBPP2 and SEC14L5. Gene ontology analysis revealed enrichment of these significant PTSD-related genes for cell proliferation, DNA damage and repair (p-value ≤ 0.05). Furthermore, interaction network analysis was performed on these 7 significant genes. This analysis revealed highly connected functional interaction networks with two candidate genes, IL15 and SEC14L5 highly enriched in networks. Overall, from these results, we concluded that these genes can be recommended as some of the potential targets for PTSD.

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Section: Introductionmentioning

confidence: 99%

Prediction of Possible Biomarkers and Novel Pathways Conferring Risk to Post-Traumatic Stress Disorder

Chitrala

Nagarkatti

2016

PLoS ONE

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“…If these profiles of mRNA-expression differences in PTSD cases can be further refined and replicated, and if SVM-based models are found to perform reliably in larger or more diverse populations, then this study proposes an avenue for early diagnosis among trauma-exposed individuals, potentially fostering earlier intervention. However, it is likely that a more accurate classification model can be constructed in the future by taking into account additional known risk factors for PTSD, such as family history, personality traits, pre-existing mental disorders (Koenen et al ., 2003a; Koenen et al ., 2003b), peri-traumatic dissociation and post-trauma social support (Brewin et al ., 2000; Ozer et al ., 2003), non-genomic biological markers available in the MRS dataset (Baker et al ., 2012b; Eraly et al ., 2014), and other factors not necessarily related to gene expression.…”

Section: Discussionmentioning

confidence: 99%

Blood-based gene-expression biomarkers of post-traumatic stress disorder among deployed marines: A pilot study

Tylee

Chandler²,

Nievergelt

et al. 2015

Psychoneuroendocrinology

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The etiology of post-traumatic stress disorder (PTSD) likely involves the interaction of numerous genes and environmental factors. Similarly, gene-expression levels in peripheral blood are influenced by both genes and environment, and expression levels of many genes show good correspondence between peripheral blood and brain tissues. In that context, this pilot study sought to test the following hypotheses: 1) post-trauma expression levels of a gene subset in peripheral blood would differ between Marines with and without PTSD; 2) a diagnostic biomarker panel of PTSD among high-risk individuals could be developed based on gene expression in readily assessable peripheral blood cells; and 3) a diagnostic panel based on expression of individual exons would surpass the accuracy of a model based on expression of full-length gene transcripts. Gene-expression levels in peripheral blood samples from 50 U.S. Marines (25 PTSD cases and 25 non-PTSD comparison subjects) were determined by microarray following their return from deployment to war-zones in Iraq or Afghanistan. The original sample was carved into training and test subsets for construction of support vector machine classifiers. The panel of peripheral blood biomarkers achieved 80% prediction accuracy in the test subset based on the expression of just two full-length transcripts (GSTM1 and GSTM2). A biomarker panel based on 20 exons attained an improved 90% accuracy in the test subset. Though further refinement and replication of these biomarker profiles are required, these preliminary results provide proof-of-principle for the diagnostic utility of blood-based mRNA-expression in PTSD among trauma-exposed individuals.

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“…Twin studies of PTSD demonstrate that heritability accounts for approximately 30% of the variance in risk for PTSD, and that genetic factors influence the risk of exposure to traumatic events (True et al, 1993; Xian et al, 2000; Stein et al, 2014; Koenen et al, 2003; Koenen et al, 2005). Both candidate gene and hypothesis-neutral genome-wide association studies (GWAS) have identified several genes that contribute to PTSD risk and symptomatology.…”

Section: Classic Findings In the Neurobiology Of Ptsdmentioning

confidence: 99%

Neuroimaging genetic approaches to Posttraumatic Stress Disorder

Lebois

Wolff

Ressler

2016

Experimental Neurology

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Neuroimaging genetic studies that associate genetic and epigenetic variation with neural activity or structure provide an opportunity to link genes to psychiatric disorders, often before psychopathology is discernable in behavior. Here we review neuroimaging genetics studies with participants who have Posttraumatic Stress Disorder (PTSD). Results show that genes related to the physiological stress response (e.g., glucocorticoid receptor and activity, neuroendocrine release), learning and memory (e.g., plasticity), mood, and pain perception are tied to neural intermediate phenotypes associated with PTSD. These genes are associated with and sometimes predict neural structure and function in areas involved in attention, executive function, memory, decision-making, emotion regulation, salience of potential threats, and pain perception. Evidence suggests these risk polymorphisms and neural intermediate phenotypes are vulnerabilities toward developing PTSD in the aftermath of trauma, or vulnerabilities toward particular symptoms once PTSD has developed. Work distinguishing between the re-experiencing and dissociative subtypes of PTSD, and examining other PTSD symptom clusters in addition to the re-experiencing and hyperarousal symptoms, will further clarify neurobiological mechanisms and inconsistent findings. Furthermore, an exciting possibility is that genetic associations with PTSD may eventually be understood through differential intermediate phenotypes of neural circuit structure and function, possibly underlying the different symptom clusters seen within PTSD.

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A High Risk Twin Study of Combat-Related PTSD Comorbidity

Cited by 72 publications

References 35 publications

Prediction of Possible Biomarkers and Novel Pathways Conferring Risk to Post-Traumatic Stress Disorder

Prediction of Possible Biomarkers and Novel Pathways Conferring Risk to Post-Traumatic Stress Disorder

Blood-based gene-expression biomarkers of post-traumatic stress disorder among deployed marines: A pilot study

Neuroimaging genetic approaches to Posttraumatic Stress Disorder

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