Post-traumatic Stress Disorder (PTSD) is one of the most highly prevalent psychiatric disorders and its prevalence is likely increasing in the United States and worldwide due to the rising numbers of natural disasters (earthquakes, hurricanes, tsunamis), man-made disasters (oil spills), terrorism and wars, as well as violent crime and automobile accidents. Although the majority of trauma victims experience the cardinal symptoms of re-experiencing, avoidance and hyperarousal, for the large majority of such individuals, these symptoms do not become chronic nor do they develop syndromal PTSD. It is important to identify the large minority of trauma victims with a high likelihood of developing PTSD because of the very significant medical and psychiatric morbidity and mortality associated with this disorder. There is already considerable evidence that the likelihood of developing PTSD after trauma exposure is due to a combination of genetic and environmental factors. This two-site, linked R-01 application seeks to utilize state-of-the art advances in genomics, transcriptomics and epigenetics, coupled with comprehensive clinical and psychological measures, to address this seminal unanswered question in PTSD clinical service and research. To achieve this goal, 500 trauma-exposed subjects will be recruited at the University of Miami Ryder Trauma Center and the Emory University affiliated Grady Memorial Hospital and followed at regular intervals for one year. This focused, hypothesis-driven study will scrutinize previously identified psychological and biological risk factors. Genetic risk factors include polymorphisms of the ADCYAP1R1, FKBP5, DAT, BDNF, COMT, CRFR1, 5HTTLPR, RGS2, GABA2 and 5HT3R genes, novel genetic and epigenetic risk factors and most importantly, the primary downstream effects of these genomic and epigenetic findings by the use of conventional and newer statistical modeling methods. These findings should provide the means to identify trauma survivors who will likely develop PTSD and can therefore be referred for appropriate psychotherapeutic and/or psychopharmacologic treatment. Such a strategy has the potential to help redefine psychobiological subtypes of PTSD as well as to reduce the burden of chronic PTSD on our healthcare system.
Exposure to severe trauma is, unfortunately, extraordinarily common in the United States and worldwide, and consequently the prevalence rate of posttraumatic stress disorder (PTSD) is among the most common of the severe major psychiatric disorders. The fundamental unanswered question in the field is how to identify markers in trauma victims that predict who will later develop PTSD. The ability to identify those individuals with a high likelihood of developing PTSD will permit the development of a preventative intervention strategy that can be implemented appropriately and efficiently.
|Stevens, Jennifer S; Kim, Ye Ji; Galatzer-Levy, Isaac R et al. (2017) Amygdala Reactivity and Anterior Cingulate Habituation Predict Posttraumatic Stress Disorder Symptom Maintenance After Acute Civilian Trauma. Biol Psychiatry 81:1023-1029|
|Syed, Shariful A; Nemeroff, Charles B (2017) Early Life Stress, Mood, and Anxiety Disorders. Chronic Stress (Thousand Oaks) 1:|
|Nemeroff, Charles B (2016) Paradise Lost: The Neurobiological and Clinical Consequences of Child Abuse and Neglect. Neuron 89:892-909|
|Beurel, Eléonore; Nemeroff, Charles B (2014) Interaction of stress, corticotropin-releasing factor, arginine vasopressin and behaviour. Curr Top Behav Neurosci 18:67-80|
|Sussman, Daniel A; Santaolalla, Rebeca; Bejarano, Pablo A et al. (2014) In silico and Ex vivo approaches identify a role for toll-like receptor 4 in colorectal cancer. J Exp Clin Cancer Res 33:45|
|Myers, Amanda J; Williams, Leanne; Gatt, Justine M et al. (2014) Variation in the oxytocin receptor gene is associated with increased risk for anxiety, stress and depression in individuals with a history of exposure to early life stress. J Psychiatr Res 59:93-100|
|Ozomaro, Uzoezi; Wahlestedt, Claes; Nemeroff, Charles B (2013) Personalized medicine in psychiatry: problems and promises. BMC Med 11:132|
|Jope, Richard S; Nemeroff, Charles B (2013) The ups and downs of bipolar disorder research. Biol Psychiatry 73:597-9|
|Nemeroff, Charles B (2013) Psychoneuroimmunoendocrinology: the biological basis of mind-body physiology and pathophysiology. Depress Anxiety 30:285-7|
|Nemeroff, Charles B; Goldschmidt-Clermont, Pascal J (2012) Heartache and heartbreak--the link between depression and cardiovascular disease. Nat Rev Cardiol 9:526-39|