title: Accelerated DNA methylation age: Associations with PTSD and neural integrity.
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.
authors.affiliation: 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.
authors.forename: Erika J
authors.initials: EJ
authors.lastname: Wolf
authors.affiliation: 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.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Logue
authors.affiliation: 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.
authors.forename: Jasmeet P
authors.initials: JP
authors.lastname: Hayes
authors.affiliation: 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.
authors.forename: Naomi
authors.initials: N
authors.lastname: Sadeh
authors.affiliation: Pharmacogenomics Analysis Laboratory, Research Service, Central Arkansas Veterans Healthcare System, Little Rock, AR, USA.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Schichman
authors.affiliation: Pharmacogenomics Analysis Laboratory, Research Service, Central Arkansas Veterans Healthcare System, Little Rock, AR, USA.
authors.forename: Annjanette
authors.initials: A
authors.lastname: Stone
authors.affiliation: Neuroimaging Research for Veterans Center, VA Boston Healthcare System, Boston, MA, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Salat
authors.affiliation: 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.
authors.forename: William
authors.initials: W
authors.lastname: Milberg
authors.affiliation: 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.
authors.forename: Regina
authors.initials: R
authors.lastname: McGlinchey
authors.affiliation: 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.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Miller
mesh_terms: D000328:Adult; D000375:Aging / Q000235:genetics* / Q000523:psychology; D016022:Case-Control Studies; D016922:Cellular Senescence / Q000235:genetics*; D003337:Corpus Callosum / Q000473:pathology*; D019175:DNA Methylation; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D008297:Male; D008570:Memory, Short-Term; D008875:Middle Aged; D012720:Severity of Illness Index; D013313:Stress Disorders, Post-Traumatic / Q000235:genetics* / Q000473:pathology / Q000523:psychology; D014728:Veterans / Q000523:psychology*; D055815:Young Adult
keywords: Accelerated aging; DNA methylation; Diffusion tensor imaging; Genu; PTSD; Working memory