title: Longitudinal changes of telomere length and epigenetic age related to traumatic stress and post-traumatic stress disorder.
abstract: Several studies have reported an association between traumatic stress and telomere length suggesting that traumatic stress has an impact on ageing at the cellular level. A newly derived tool provides an additional means to investigate cellular ageing by estimating epigenetic age based on DNA methylation profiles. We therefore hypothesise that in a longitudinal study of traumatic stress both indicators of cellular ageing will show increased ageing. We expect that particularly in individuals that developed symptoms of post-traumatic stress disorder (PTSD) increases in these ageing parameters would stand out. From an existing longitudinal cohort study, ninety-six male soldiers were selected based on trauma exposure and the presence of symptoms of PTSD. All military personnel were deployed in a combat zone in Afghanistan and assessed before and 6 months after deployment. The Self-Rating Inventory for PTSD was used to measure the presence of PTSD symptoms, while exposure to combat trauma during deployment was measured with a 19-item deployment experiences checklist. These groups did not differ for age, gender, alcohol consumption, cigarette smoking, military rank, length, weight, or medication use. In DNA from whole blood telomere length was measured and DNA methylation levels were assessed using the Illumina 450K DNA methylation arrays. Epigenetic ageing was estimated using the DNAm age estimator procedure. The association of trauma with telomere length was in the expected direction but not significant (B=-10.2, p=0.52). However, contrary to our expectations, development of PTSD symptoms was associated with the reverse process, telomere lengthening (B=1.91, p=0.018). In concordance, trauma significantly accelerated epigenetic ageing (B=1.97, p=0.032) and similar to the findings in telomeres, development of PTSD symptoms was inversely associated with epigenetic ageing (B=-0.10, p=0.044). Blood cell count, medication and premorbid early life trauma exposure did not confound the results. Overall, in this longitudinal study of military personnel deployed to Afghanistan we show an acceleration of ageing by trauma. However, development of PTSD symptoms was associated with telomere lengthening and reversed epigenetic ageing. These findings warrant further study of a perhaps dysfunctional compensatory cellular ageing reversal in PTSD.
authors.affiliation: Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, The Netherlands. Electronic address: mboks@umcutrecht.nl.
authors.forename: Marco P
authors.initials: MP
authors.lastname: Boks
authors.affiliation: Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, The Netherlands.
authors.forename: Hans C
authors.initials: HC
authors.lastname: van Mierlo
authors.affiliation: School for Mental Health and Neuroscience, Department of Psychiatry and Neuropsychology, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Bart P F
authors.initials: BP
authors.lastname: Rutten
authors.affiliation: Department of Rheumatology & Clinical Immunology, Laboratory of Translational Immunology, Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Timothy R D J
authors.initials: TR
authors.lastname: Radstake
authors.affiliation: Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, The Netherlands.
authors.forename: Lot
authors.initials: L
authors.lastname: De Witte
authors.affiliation: Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, The Netherlands; Research Centre Military Mental Healthcare, Ministry of Defence, Utrecht, The Netherlands.
authors.forename: Elbert
authors.initials: E
authors.lastname: Geuze
authors.affiliation: Department of Human Genetics, University of California, Los Angeles, CA, USA.
authors.forename: Steve
authors.initials: S
authors.lastname: Horvath
authors.affiliation: Social, Genetic and Developmental Psychiatry, Institute of Psychiatry, King's College London, SE5 8AF London, UK.
authors.forename: Leonard C
authors.initials: LC
authors.lastname: Schalkwyk
authors.affiliation: Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, The Netherlands.
authors.forename: Christiaan H
authors.initials: CH
authors.lastname: Vinkers
authors.affiliation: Department of Rheumatology & Clinical Immunology, Laboratory of Translational Immunology, Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Jasper C A
authors.initials: JC
authors.lastname: Broen
authors.affiliation: Research Centre Military Mental Healthcare, Ministry of Defence, Utrecht, The Netherlands; Department Psychiatry, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Eric
authors.initials: E
authors.lastname: Vermetten
mesh_terms: D000293:Adolescent; D000328:Adult; D055826:Afghan Campaign 2001-; D016922:Cellular Senescence / Q000235:genetics*; D003130:Combat Disorders / Q000235:genetics* / Q000523:psychology; D044127:Epigenesis, Genetic; D006801:Humans; D008297:Male; D008889:Military Personnel / Q000523:psychology*; D012307:Risk Factors; D013313:Stress Disorders, Post-Traumatic / Q000235:genetics* / Q000523:psychology; D016615:Telomere; D055815:Young Adult
keywords: Age; Combat trauma; DNA methylation; Epigenetics; PTSD; Post traumatic stress disorder; Telomeres; Traumatic stress