Posttraumatic Stress Disorder, Accelerated Biological Aging, and Veteran Health

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Posttraumatic stress disorder (PTSD) is a prevalent and costly mental health disorder associated with poorer health and higher healthcare utilization. These outcomes are a particular concern among Veterans, who have higher rates of PTSD compared to civilian populations. Veterans with PTSD, for example, are twice as likely to experience premature death compared to Veterans without PTSD. How might PTSD affect health? Recent studies have shown that PTSD can accelerate biological aging—i.e., the rate at which people evidence gradual physiological decline consistent with chronological aging. Accelerated aging is theorized to result in more disability, disease, and premature death and could explain why Veterans with PTSD are at greater risk of poor health. There is great promise in slowing aging to prevent ill health, but methods of assessing biological aging have been constrained by long and costly data collection, limiting effective application to clinical settings. Recent methods have shown the potential to use markers of DNA methylation to calculate the speed at which people are aging using biomarkers collected at a single point in time. This novel methodology could provide the opportunity to identify and treat Veterans who are at risk of rapid aging—such as those with PTSD—years before poor health develops. These findings could help promote the importance and uptake of PTSD treatment among both Veterans and healthcare providers, reducing healthcare costs and human suffering. Doing so, however, would require applying these methods in Veteran samples and empirically validating this approach. This Research Plan proposes to examine the links between PTSD, accelerated aging, and later health. The main hypotheses guiding this work are that Veterans with PTSD will evidence accelerated aging, and this accelerated aging will be associated with poorer health 5 years later. A further goal will be to test whether candidate psychosocial characteristics— higher social support, fewer comorbid mental health disorders, positive health behaviors, and treatment for PTSD—might protect against accelerated aging for Veterans with PTSD. Specific Aims—Aim 1: Examine whether Veterans with PTSD have accelerated biological aging. Aim 2: Test whether accelerated biological aging predicts Veterans’ midlife health over the subsequent 5 years. Aim 3: Determine whether candidate psychosocial characteristics are associated with slower aging and better midlife health for Veterans with PTSD. These aims will be achieved using existing data from the Post-Deployment Mental Health (PDMH) study, a multi-site cohort of Afghanistan and Iraq era Veterans. PDMH data, including methylation data used to derived biological aging scores, will be linked to health outcomes in the VA electronic health record (EHR). This study will help determine whether Veterans with PTSD have accelerated biological aging compared to Veterans without PTSD, as well as if accelerated aging predicts poorer Veteran health. This study will provide the first evidence that biological aging explains how PTSD results in poor Veteran health, as well as what psychosocial characteristics could be targeted by intervention to slow aging. The results of these aims will be used to support a Merit Review award submission proposing to examine change in biological aging following behavioral intervention for Veterans with PTSD. The Training and Mentoring plans outline the professional development, training, and mentorship activities that will support the applicant’s development as an early-career investigator in the VA. Specifically, the Training and Mentoring plans will extend the applicant’s methodological expertise to include DNA methylation measures of biological aging in Veteran populations with PTSD, expanding the applicant’s expertise in using VA EHR health data, and support the applicant’s long-term career goal of using interventions to improve the health of Veterans with PTSD. The ongoing mentorship and support the applicant will receive during the CDA-2 award period and beyond will help his development as a Research Health Scientist at the Durham VAMC.