This is a renewal application for R01MH101269, ?Assessing causality: Is PTSD Cardiotoxic? and builds on our work in R21MH102570, ?PTSD and Cognitive Decline in Women.? Results provide compelling evidence that posttraumatic stress disorder (PTSD) increases risk of many physical health problems. Our data further suggest that PTSD is associated with subtle cognitive deficits that may be early indicators of dementia and developing Alzheimer's disease. Together, our findings suggest adverse systemic effects of PTSD, predisposing women with PTSD to greater susceptibility to multiple diseases of aging. By leveraging and enhancing data with an existing cohort, we aim to address a critical research question: Does PTSD accelerate aging in women? We propose 3 strategies to address this question, and will draw on data from the Nurses' Health Study II (NHSII), with a sub-cohort of 54,282 women followed since 1989 who have data on PTSD and will be 52-69 years at the start of this renewal. First, we will evaluate if PTSD is prospectively associated with patterns of cognitive decline linked to dementia and Alzheimer's disease. Second, we will examine the relation of PTSD with two genomic indicators of accelerated biological aging: DNA methylation (DNAm) or the `epigenetic clock' and shortened leukocyte telomere length (TL) each of which has been linked to age-related health outcomes. Third, we will examine how PTSD influences accelerated aging by examining symptom clusters as well as mediators and modifiers. We will address the following Specific Aims: 1) To evaluate prospectively if trauma exposure and/or PTSD severity are associated with cognitive decline; 2) To evaluate longitudinally if trauma exposure and chronic PTSD are associated with 2 well- established genomic markers of aging: DNAm (epigenetic clock) and TL shortening; and 3) To gain greater insight into how PTSD affects cognitive decline and genomic markers of accelerated aging in order to identify targets for interventions. Evidence that PTSD causes accelerated aging would suggest: (1) effective PTSD treatment may reduce risk of cognitive decline, subsequent dementia, and accelerated aging more broadly; (2) persons with PTSD may benefit from greater surveillance of health risk factors and early interventions to reduce acceleration of the aging process. Learning which cognitive domains and/or genomic biomarkers PTSD alters will provide new opportunities understanding the pathophysiology of the disorder and inform early identification and prevention of accelerated aging in women with PTSD. Taken together, the proposed research advances our understanding of a possible relationship between PTSD and accelerated aging and with risk of cognitive decline and impairment as well as with the pathophysiology of PTSD more broadly.

Public Health Relevance

This purpose of this research is to better understand whether posttraumatic stress disorder (PTSD) causes accelerated aging in women and to identify underlying disease mechanisms. If PTSD truly contributes to accelerated aging, then new avenues for ameliorating the adverse effects of PTSD must be considered and the effectiveness of various prevention or intervention strategies compared. For example, effective treatment of PTSD may reduce risk of adverse effects across multiple health domains. Even if PTSD is resistant to treatment, persons with PTSD may yet benefit from greater surveillance and efforts to improve long-term health.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
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Behavioral Genetics and Epidemiology Study Section (BGES)
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Evans, Jovier D
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Harvard University
Public Health & Prev Medicine
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United States
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