Regular Research Article
Is Post-Traumatic Stress Disorder Associated with Premature Senescence? A Review of the Literature

https://doi.org/10.1016/j.jagp.2015.04.001Get rights and content

Objective

Post-traumatic stress disorder (PTSD) has major public health significance. Evidence that PTSD may be associated with premature senescence (early or accelerated aging) would have major implications for quality of life and healthcare policy. We conducted a comprehensive review of published empirical studies relevant to early aging in PTSD.

Method

Our search included the PubMed, PsycINFO, and PILOTS databases for empirical reports published since the year 2000 relevant to early senescence and PTSD, including: 1) biomarkers of senescence (leukocyte telomere length [LTL] and pro-inflammatory markers), 2) prevalence of senescence-associated medical conditions, and 3) mortality rates.

Results

All six studies examining LTL indicated reduced LTL in PTSD (pooled Cohen's d = 0.76). We also found consistent evidence of increased pro-inflammatory markers in PTSD (mean Cohen's ds), including C-reactive protein = 0.18, Interleukin-1 beta = 0.44, Interleukin-6 = 0.78, and tumor necrosis factor alpha = 0.81. The majority of reviewed studies also indicated increased medical comorbidity among several targeted conditions known to be associated with normal aging, including cardiovascular disease, type 2 diabetes mellitus, gastrointestinal ulcer disease, and dementia. We also found seven of 10 studies indicated PTSD to be associated with earlier mortality (average hazard ratio: 1.29).

Conclusion

In short, evidence from multiple lines of investigation suggests that PTSD may be associated with a phenotype of accelerated senescence. Further research is critical to understand the nature of this association. There may be a need to re-conceptualize PTSD beyond the boundaries of mental illness, and instead as a full systemic disorder.

Section snippets

Methods

We searched PubMed, PsycINFO, and PILOTS databases for papers published between January 1, 2000, and November 30, 2014. The year 2000 was chosen because it included studies published after 9/11/2001 and the wars in Iraq and Afghanistan, which represented the beginning of a period of intensified public and scientific interest in PTSD.

Targeted outcomes for the present review included: biomarkers of senescence (leukocyte telomere length [LTL], blood pro-inflammatory indices, and oxidative stress),

Results

Our search yielded 64 studies that met inclusion and exclusion criteria for review (Fig. 1). Of these, 22 were suitable for calculating overall effect sizes (Cohen's d) for biomarkers and 10 for mortality (hazard ratio). Interestingly, only two articles that met our inclusion and exclusion criteria were published between 2000 and 2003,17, 18 supporting our choice of the year 2000 as a cutpoint for review. Except where otherwise indicated, our review focused on results comparing people with PTSD

Discussion

We reviewed 64 studies representing three different categories of evidence linking PTSD with accelerated aging (biomarkers of senescence, senescence-associated medical comorbidities, and mortality rates). We found at least partial evidence of an association in each category, discussed in detail in the following.

References (101)

  • J. Baumert et al.

    No evidence for an association of posttraumatic stress disorder with circulating levels of CRP and IL-18 in a population-based study

    Cytokine

    (2013)
  • J.M. Gill et al.

    Women in recovery from PTSD have similar inflammation and quality of life as non-traumatized controls

    J Psychosom Res

    (2013)
  • L. Plantinga et al.

    Association between posttraumatic stress disorder and inflammation: a twin study

    Brain Behav Immun

    (2013)
  • D. Lindqvist et al.

    Proinflammatory milieu in combat-related PTSD is independent of depression and early life stress

    Brain Behav Immun

    (2014)
  • L. Michels et al.

    Prefrontal GABA and glutathione imbalance in posttraumatic stress disorder: preliminary findings

    Psychiatry Res

    (2014)
  • H.K. Kang et al.

    Risk of selected cardiovascular diseases and posttraumatic stress disorder among former World War II prisoners of war

    Ann Epidemiol

    (2006)
  • T.E. Seeman et al.

    Cumulative biological risk and socio-economic differences in mortality: MacArthur Studies of Successful Aging

    Soc Sci Med

    (2004)
  • V. Vaccarino et al.

    Post-traumatic stress disorder and incidence of coronary heart disease: a twin study

    J Am Coll Cardiol

    (2013)
  • J.H. Turner et al.

    Objective evidence of myocardial ischemia in patients with posttraumatic stress disorder

    Biol Psychiatry

    (2013)
  • K.M. Scott et al.

    Associations between DSM-IV mental disorders and onset of self-reported peptic ulcer in the World Mental Health Surveys

    J Psychosom Res

    (2013)
  • D.G. Baker et al.

    Biomarkers of PTSD: neuropeptides and immune signaling

    Neuropharmacology

    (2012)
  • D. Edmondson et al.

    Posttraumatic stress disorder and risk for coronary heart disease: a meta-analytic review

    Am Heart J

    (2013)
  • S. Schuitevoerder et al.

    A meta-analysis of cognitive functioning in older adults with PTSD

    J. Anxiety Disord

    (2013)
  • J.A. Boscarino

    Posttraumatic stress disorder and mortality among U.S. Army veterans 30 years after military service

    Ann Epidemiol

    (2006)
  • A.M. Flood et al.

    Prospective study of externalizing and internalizing subtypes of posttraumatic stress disorder and their relationship to mortality among Vietnam veterans

    Compr Psychiatry

    (2010)
  • N. Ahmadi et al.

    Post-traumatic stress disorder, coronary atherosclerosis, and mortality

    Am J Cardiol

    (2011)
  • Y. Xue et al.

    Cardiac biomarkers, mortality, and post-traumatic stress disorder in military veterans

    Am J Cardiol

    (2012)
  • J. Zohar et al.

    Mortality rates between treated post-traumatic stress disorder Israeli male veterans compared to non-diagnosed veterans

    Eur Neuropsychopharmacol

    (2014)
  • I. Bramsen et al.

    Wartime stressors and mental health symptoms as predictors of late-life mortality in World War II survivors

    J Affect Disord

    (2007)
  • M.D. Flather et al.

    Strengths and limitations of meta-analysis: Larger studies may be more reliable

    Control Clin Trials

    (1997)
  • H. Boxenbaum

    Gompertz mortality analysis: aging, longevity hormesis and toxicity

    Arch Gerontol Geriatr

    (1991)
  • D.V. Jeste et al.

    Divergent trajectories of physical, cognitive, and psychosocial aging in schizophrenia

    Schizophr Bull

    (2011)
  • O.M. Wolkowitz et al.

    Of sound mind and body: depression, disease, and accelerated aging

    Dialogues Clin Neurosci

    (2011)
  • B. Kirkpatrick et al.

    Is schizophrenia a syndrome of accelerated aging?

    Schizophr Bull

    (2008)
  • E.S. Epel

    Psychological and metabolic stress: a recipe for accelerated cellular aging?

    Hormones

    (2009)
  • N. Ishikawa et al.

    Accelerated in vivo epidermal telomere loss in Werner syndrome

    Aging (Albany NY)

    (2011)
  • W.B. Zigman

    Atypical aging in down syndrome

    Dev Disab Res Rev

    (2013)
  • R.L. Pollex et al.

    Hutchinson-Gilford progeria syndrome

    Clin Genet

    (2004)
  • S. Pathai et al.

    Is HIV a model of accelerated or accentuated aging?

    J Gerontol A Biol Sci Med Sci

    (2013)
  • M. Gerhard-Herman et al.

    Mechanisms of premature vascular aging in children with Hutchinson-Gilford progeria syndrome

    Hypertension

    (2012)
  • Farriols Danés C

    Specific aspects of ageing in Down's syndrome

    Int Med Rev Down Syndr

    (2012)
  • I. Akushevich et al.

    Age patterns of incidence of geriatric disease in the U.S. elderly population: Medicare-based analysis

    J Am Geriatr Soc

    (2012)
  • D.R. Johnson et al.

    Long-term course of treatment-seeking Vietnam veterans with posttraumatic stress disorder: mortality, clinical condition, and life satisfaction

    J Nerv Ment Dis

    (2004)
  • E.F. Crawford et al.

    Predicting mortality in veterans with posttraumatic stress disorder thirty years after Vietnam

    J Nerv Ment Dis

    (2009)
  • B.I. O'Toole et al.

    Factors associated with civilian mortality in Australian Vietnam veterans three decades after the war

    Mil Med

    (2010)
  • D.G. Baker et al.

    Plasma and cerebrospinal fluid interleukin-6 concentrations in posttraumatic stress disorder

    Neuroimmunomodulation

    (2001)
  • E. Tezcan et al.

    Free radicals in patients with post-traumatic stress disorder

    Eur Arch Psychiatry Clin Neurosci

    (2003)
  • S. Linnville et al.

    Posttraumatic stress disorder and metabolic syndrome: retrospective study of repatriated prisoners of war

    Mil Med

    (2011)
  • R.H. Pietrzak et al.

    Physical health conditions associated with posttraumatic stress disorder in U.S. older adults: results from wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions

    J Am Geriatr Soc

    (2012)
  • P.S. Heppner et al.

    The association of posttraumatic stress disorder and metabolic syndrome: a study of increased health risk in veterans

    BMC Med

    (2009)
  • Cited by (180)

    View all citing articles on Scopus

    Supplemental digital content is available for this article in the HTML and PDF versions of this article on the journal's Web site (www.ajgponline.org).

    James B. Lohr and Barton W. Palmer contributed equally to the paper.

    View full text