Erika J Wolf1, Mark W Logue2, Jasmeet P Hayes3, Naomi Sadeh4, Steven A Schichman5, Annjanette Stone5, David H Salat6, William Milberg7, Regina McGlinchey7, Mark W Miller4. 1. National Center for PTSD, Behavioral Science Division, VA Boston Healthcare System, Boston, MA, USA; Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA. Electronic address: erika.wolf@va.gov. 2. Research Service, VA Boston Healthcare System, Boston, MA, USA; Biomedical Genetics, Boston University School of Medicine, Boston, MA, USA; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA. 3. National Center for PTSD, Behavioral Science Division, VA Boston Healthcare System, Boston, MA, USA; Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA; Neuroimaging Research for Veterans Center, VA Boston Healthcare System, Boston, MA, USA. 4. National Center for PTSD, Behavioral Science Division, VA Boston Healthcare System, Boston, MA, USA; Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA. 5. Pharmacogenomics Analysis Laboratory, Research Service, Central Arkansas Veterans Healthcare System, Little Rock, AR, USA. 6. Neuroimaging Research for Veterans Center, VA Boston Healthcare System, Boston, MA, USA. 7. Geriatric Research Educational and Clinical Center and Translational Research, Center for TBI and Stress Disorders, VA Boston Healthcare System, Boston, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
Abstract
BACKGROUND: Accumulating evidence suggests that posttraumatic stress disorder (PTSD) may accelerate cellular aging and lead to premature morbidity and neurocognitive decline. METHODS: This study evaluated associations between PTSD and DNA methylation (DNAm) age using recently developed algorithms of cellular age by Horvath (2013) and Hannum et al. (2013). These estimates reflect accelerated aging when they exceed chronological age. We also examined if accelerated cellular age manifested in degraded neural integrity, indexed via diffusion tensor imaging. RESULTS: Among 281 male and female veterans of the conflicts in Iraq and Afghanistan, DNAm age was strongly related to chronological age (rs ∼.88). Lifetime PTSD severity was associated with Hannum DNAm age estimates residualized for chronological age (β=.13, p=.032). Advanced DNAm age was associated with reduced integrity in the genu of the corpus callosum (β=-.17, p=.009) and indirectly linked to poorer working memory performance via this region (indirect β=-.05, p=.029). Horvath DNAm age estimates were not associated with PTSD or neural integrity. CONCLUSIONS: Results provide novel support for PTSD-related accelerated aging in DNAm and extend the evidence base of known DNAm age correlates to the domains of neural integrity and cognition. Published by Elsevier Ltd.
BACKGROUND: Accumulating evidence suggests that posttraumatic stress disorder (PTSD) may accelerate cellular aging and lead to premature morbidity and neurocognitive decline. METHODS: This study evaluated associations between PTSD and DNA methylation (DNAm) age using recently developed algorithms of cellular age by Horvath (2013) and Hannum et al. (2013). These estimates reflect accelerated aging when they exceed chronological age. We also examined if accelerated cellular age manifested in degraded neural integrity, indexed via diffusion tensor imaging. RESULTS: Among 281 male and female veterans of the conflicts in Iraq and Afghanistan, DNAm age was strongly related to chronological age (rs ∼.88). Lifetime PTSD severity was associated with Hannum DNAm age estimates residualized for chronological age (β=.13, p=.032). Advanced DNAm age was associated with reduced integrity in the genu of the corpus callosum (β=-.17, p=.009) and indirectly linked to poorer working memory performance via this region (indirect β=-.05, p=.029). Horvath DNAm age estimates were not associated with PTSD or neural integrity. CONCLUSIONS: Results provide novel support for PTSD-related accelerated aging in DNAm and extend the evidence base of known DNAm age correlates to the domains of neural integrity and cognition. Published by Elsevier Ltd.
Entities:
Keywords:
Accelerated aging; DNA methylation; Diffusion tensor imaging; Genu; PTSD; Working memory
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