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Evaluating the Impact of Trauma and PTSD on Epigenetic Prediction of Lifespan and Neural Integrity

Citation

Katrinli, Seyma; Stevens, Jennifer; Wani, Agaz H.; Lori, Adriana; Kilaru, Varun; van Rooij, Sanne J. H.; Hinrichs, Rebecca; Powers, Abigail; Gillespie, Charles F.; & Michopoulos, Vasiliki, et al. (Online ahead of print). Evaluating the Impact of Trauma and PTSD on Epigenetic Prediction of Lifespan and Neural Integrity. Neuropsychopharmacology. PMCID: PMC Journal - In Process

Abstract

Post-traumatic stress disorder (PTSD) is a debilitating disorder that develops in some people following trauma exposure. Trauma and PTSD have been associated with accelerated cellular aging. This study evaluated the effect of trauma and PTSD on accelerated GrimAge, an epigenetic predictor of lifespan, in traumatized civilians. This study included 218 individuals with current PTSD, 427 trauma-exposed controls without any history of PTSD and 209 subjects with lifetime PTSD history who are not categorized as current PTSD cases. The Traumatic Events Inventory (TEI) and Clinician-Administered PTSD Scale (CAPS) were used to measure lifetime trauma burden and PTSD, respectively. DNA from whole blood was interrogated using the MethylationEPIC or HumanMethylation450 BeadChips. GrimAge estimates were calculated using the methylation age calculator. Cortical thickness of 69 female subjects was assessed by using T1-weighted structural MRI images. Associations between trauma exposure, PTSD, cortical thickness, and GrimAge acceleration were tested with multiple regression models. Lifetime trauma burden (p = 0.03), current PTSD (p = 0.02) and lifetime PTSD (p = 0.005) were associated with GrimAge acceleration, indicative of a shorter predicted lifespan. The association with lifetime PTSD was replicated in an independent cohort (p = 0.04). In the MRI sub sample, GrimAge acceleration also associated with cortical atrophy in the right lateral orbitofrontal cortex (p(adj) = 0.03) and right posterior cingulate (p(adj) = 0.04), brain areas associated with emotion-regulation and threat-regulation. Our findings suggest that lifetime trauma and PTSD may contribute to a higher epigenetic-based mortality risk. We also demonstrate a relationship between cortical atrophy in PTSD-relevant brain regions and shorter predicted lifespan.

URL

http://dx.doi.org/10.1038/s41386-020-0700-5

Reference Type

Journal Article

Journal Title

Neuropsychopharmacology

Author(s)

Katrinli, Seyma
Stevens, Jennifer
Wani, Agaz H.
Lori, Adriana
Kilaru, Varun
van Rooij, Sanne J. H.
Hinrichs, Rebecca
Powers, Abigail
Gillespie, Charles F.
Michopoulos, Vasiliki
Gautam, Aarti
Jett, Marti
Hammamieh, Rasha
Yang, Ruoting
Wildman, Derek
Qu, Annie
Koenen, Karestan C.
Aiello, Allison E.
Jovanovic, Tanja
Uddin, Monica
Ressler, Kerry J.
Smith, Alicia K.

Year Published

Online ahead of print

PMCID

PMC Journal - In Process

Reference ID

12722