Why do some individuals exposed to traumatic events develop Post-traumatic Stress Disorder (PTSD), while others do not? Risk and resilience are two concepts that are important in understanding the etiology of PTSD. Past research on PTSD has identified different factors that may put individuals at greater risk of developing PTSD, such as family history, childhood experiences, personality variables, and preexisting mental disorders. The concept of resilience, often considered to represent resistance to the negative effects of a traumatic event, is also very important in any consideration of PTSD. Resilience can be defined as """"""""the ability to successfully adapt to stressors, maintaining psychological well-being in the face of adversity."""""""" Equally as important, however, is the concept of resilience as the ability to improve after the development of PTSD. The biological factors associated with the risk of developing PTSD, as well as both aspects of resilience are poorly understood. This project will investigate biological risk and resilience factors associated with the development of PTSD among a sample of Marines before and after they are exposed to combat stress utilizing genomic methodologies and a battery of behavioral and biological assessments. Specifically, we propose to investigate gene- expression based biomarkers of PTSD risk and resilience. The development of PTSD following initial traumatic exposure is quite variable, with some individuals never exhibiting signs of PTSD, while others are plagued with incapacitating symptoms despite years of combinations of therapy. At present, the basic characteristics underlying resilience are unknown, and it is not currently possible to predict the development of the disorder, much less any eventual outcome in any given individual. If biomarkers related to risk can be discovered, they may help to identify which individuals are at risk, and lead to more effective primary prevention protocols. Although environmental factors are clearly essential for the development of PTSD, the disorder also has a demonstrable genetic component. We plan in this study to identify gene-based biomarkers of PTSD in an effort to better understand the biological factors related to both the risk of developing PTSD;and to resilience as represented by resistance to development of PTSD. To accomplish these objectives, we have proposed two specific aims as follows:
Specific Aim 1 : Identify gene-expression-based biomarker profiles of PTSD risk and resilience in peripheral blood mononuclear cells and Specific Aim 2: Identify changes in gene-expression-based biomarker profiles of risk and resilience in peripheral blood mononuclear cells.

Public Health Relevance

The development of Post Traumatic Stress Disorder (PTSD) following initial traumatic exposure is extremely variable. While some individuals never exhibit signs of PTSD, others are plagued with incapacitating symptoms despite years of combinations of therapy. Understanding the gene expression patterns of combat-exposed individuals who go one to experience PTSD, as compared to the gene expression patterns of combat-exposed individuals who did not go on to experience PTSD, will shed light on the biological mechanisms involved in PTSD and provide a basis for more effective prevention and treatment of this devastating disorder.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21MH085240-02
Application #
7891279
Study Section
Behavioral Genetics and Epidemiology Study Section (BGES)
Program Officer
Tuma, Farris K
Project Start
2009-07-10
Project End
2012-06-30
Budget Start
2010-07-01
Budget End
2012-06-30
Support Year
2
Fiscal Year
2010
Total Cost
$199,923
Indirect Cost
Name
University of California San Diego
Department
Psychiatry
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
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Tylee, Daniel S; Chandler, Sharon D; Nievergelt, Caroline M et al. (2015) Blood-based gene-expression biomarkers of post-traumatic stress disorder among deployed marines: A pilot study. Psychoneuroendocrinology 51:472-94
McLoughlin, GrĂ¡inne; Makeig, Scott; Tsuang, Ming T (2014) In search of biomarkers in psychiatry: EEG-based measures of brain function. Am J Med Genet B Neuropsychiatr Genet 165B:111-21
Glatt, Stephen J; Tylee, Daniel S; Chandler, Sharon D et al. (2013) Blood-based gene-expression predictors of PTSD risk and resilience among deployed marines: a pilot study. Am J Med Genet B Neuropsychiatr Genet 162B:313-26
Woelk, Christopher H; Singhania, Akul; Perez-Santiago, Josue et al. (2011) The utility of gene expression in blood cells for diagnosing neuropsychiatric disorders. Int Rev Neurobiol 101:41-63