Trauma exposure is high in HIV-infected individuals both prior and subsequent to infection. The incidence of post-traumatic stress disorder (PTSD) has been reported to be between approximately 5% - 15% among the 30 million people living with HIV (PLWH). PTSD is a severely debilitating, stress-related psychiatric illness associated with intrusive and fearful memories as well as flashbacks, and nightmares of the traumatic event(s) for much of the victims' lives, and significant impairment in routine daily activities. Th challenges presented by PTSD are magnified in PLWH because PTSD leads to poor adherence to antiretroviral (ART) medications, increasing the odds of virologic failure. PTSD also increases sexual risk behaviors, increasing the risk of transmission. The neurobiology of PTSD has been a topic of intense study over the past two decades; however, there is minimal understanding of the neurobiology of PTSD within the context of HIV. Two systems that have been repeatedly documented to drive PTSD symptoms are the neural circuitry that underlies the startle response and the endocrine axis that controls the body's response to stress. Therefore, the current application will test the central hypothesis that HIV exacerbates PTSD symptoms and augments underlying neurobiological correlates of PTSD in women. One limitation to studying the interaction of trauma and PTSD with HIV is the high likelihood of trauma exposure within PLWH, making it difficult to identify a control group for rigorous experimental analysis. In order to address this previous limitation, the current work will compare the impact of similar levels of trauma exposure between PLWH and individuals at high risk for HIV. The population selected for this study will be recruited from the Atlanta site of the NIH-funded Women's Interagency HIV Study (WIHS) which recruits from a population with overlapping recruitment for the NIH-funded Grady Trauma Project (GTP). The GTP has studied the impact of trauma exposure in a predominantly African American population for nearly 10 years focusing the proposed work on one of the most at-risk populations of PLWH, southern African-American women. The current project leverages the expertise in these two established studies and synergistically combines their individual areas of expertise positioning the generated body of work for maximum impact in the shortest amount of time possible. In the proposed project, we will examine the clinical, physiological, and neuroendocrine correlates of fear extinction as an intermediate phenotype of trauma-related symptoms. We will use dimensional approaches to symptom analyses (Aim 1), innovative biobehavioral assessments (Aim 2), and cutting-edge biomolecular techniques (Aim 3) in order to better understand the pathophysiology of PTSD co-morbid with HIV. The identification of the biological correlates of interactions among trauma processes and HIV infection has the potential to lead to better treatment approaches in terms of both pharmacological and behavioral interventions ultimately leading to improved ART adherence, reduced risk behaviors, and an enriched quality of life.
Post-traumatic stress disorder is a debilitating psychiatric condition that can manifest following trauma exposure and incidence is disproportionately high in women living with HIV. PTSD co-morbid with HIV reduces antiretroviral adherence, daily life function, and manifestation of physiological co-morbidities with HIV. The current proposal is designed to identify the combined effects of HIV and PTSD on symptom, neurophysiological, and neuroendocrine manifestations with the goal of establishing a framework for more effective interventions to ultimately improve quality of life while reducing HIV-associated economic burden.
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| Bekhbat, Mandakh; Neigh, Gretchen N (2018) Sex differences in the neuro-immune consequences of stress: Focus on depression and anxiety. Brain Behav Immun 67:1-12 |
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| Bekhbat, Mandakh; Rowson, Sydney A; Neigh, Gretchen N (2017) Checks and balances: The glucocorticoid receptor and NF?B in good times and bad. Front Neuroendocrinol 46:15-31 |
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| Neigh, Gretchen N; Ali, Fariya F (2016) Co-morbidity of PTSD and immune system dysfunction: opportunities for treatment. Curr Opin Pharmacol 29:104-10 |
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