The interaction between stressful life events and leukocyte telomere length is associated with PTSD

Zhang, L; Xz, Hu; Dm, Benedek; Cs, Fullerton; Rd, Forsten; Naifeh, James A.; X, Li; H, Li; Kn, Benevides; Smerin, Stanley E.; Le, Tao; Choi, Kwang Ho; Ursano, Robert J.

doi:10.1038/mp.2013.141

Cited by 57 publications

(53 citation statements)

References 10 publications

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“…Previous cross sectional studies in PTSD have suggested an association with decreased telomere length (Ladwig et al 2013;Malan et al 2011;O'Donovan et al 2011) although sometimes only in interaction with pre--existent youth trauma (Zhang et al 2013). Although the relationship of the two aging parameters with PTSD is in the opposite direction as previously reported, these findings are not without precedent.…”

Section: Discussioncontrasting

confidence: 52%

Longitudinal changes of telomere length and epigenetic age related to traumatic stress and post-traumatic stress disorder

Boks

Mierlo

Rutten

et al. 2015

Psychoneuroendocrinology

195

182

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Several studies have reported an association between traumatic stress and telomere length suggesting that traumatic stress has an impact on aging at the cellular level. A newly derived tool provides an additional means to investigate cellular aging by estimating epigenetic age based on DNA methylation profiles. We therefore hypothesise that in a longitudinal study of traumatic stress both indicators of cellular aging will show increased aging. We expect that particularly in individuals that developed symptoms of post--traumatic stress disorder (PTSD) increases in these aging 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 aging 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 aging (B=1.97, p=0.032) and similar to the findings in telomeres, development of PTSD symptoms was inversely associated with epigenetic aging (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 aging. These findings warrant further study of a perhaps dysfunctional compensatory cellular aging reversal in PTSD.3

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Section: Discussioncontrasting

confidence: 52%

Longitudinal changes of telomere length and epigenetic age related to traumatic stress and post-traumatic stress disorder

Boks

Mierlo

Rutten

et al. 2015

Psychoneuroendocrinology

195

182

View full text Add to dashboard Cite

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“…One study found significantly shorter LTL in PTSD, but found that this effect was largely explained by early life stress, which is a risk factor for developing PTSD (O'Donovan et al, 2011a). In another study, involving combat deployed soldiers, individuals with PTSD had significantly shorter LTL compared to combat-deployed soldiers without PTSD (Zhang et al, 2014). That study did not detect a relationship between early life trauma and LTL, although the childhood trauma measure used was brief and non-validated.…”

Section: Telomere Length In Psychiatric Illnessesmentioning

confidence: 99%

Psychiatric disorders and leukocyte telomere length: Underlying mechanisms linking mental illness with cellular aging

Lindqvist

Epel

Mellon³

et al. 2015

Neuroscience & Biobehavioral Reviews

269

231

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Many psychiatric illnesses are associated with early mortality and with an increased risk of developing physical diseases that are more typically seen in the elderly. Moreover, certain psychiatric illnesses may be associated with accelerated cellular aging, evidenced by shortened leukocyte telomere length (LTL), which could underlie this association. Shortened LTL reflects a cell's mitotic history and cumulative exposure to inflammation and oxidation as well as the availability of telomerase, a telomere-lengthening enzyme. Critically short telomeres can cause cells to undergo senescence, apoptosis or genomic instability, and shorter LTL correlates with poorer health and predicts mortality. Emerging data suggest that LTL may be reduced in certain psychiatric illnesses, perhaps in proportion to exposure to the psychiatric illnesses, although conflicting data exist. Telomerase has been less well characterized in psychiatric illnesses, but a role in depression and in antidepressant and neurotrophic effects has been suggested by preclinical and clinical studies. In this article, studies on LTL and telomerase activity in psychiatric illnesses are critically reviewed, potential mediators are discussed, and future directions are suggested. A deeper understanding of cellular aging in psychiatric illnesses could lead to re-conceptualizing Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. DISCLOSURESJL is a consultant to Telomere Diagnostics Inc., formerly Telome Health, and owns stock in the company. The company had no role in this research or in writing this review. The remaining authors report no current disclosures or conflicts of interest. HHS Public Access

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“…Reduced telomere length has also been documented in MDD (10, 40–44), although some studies have been negative (45, 46). A few investigations also found reduced leukocyte telomere length in anxiety disorders (45, 47), post-traumatic stress disorder (PTSD) (48–51), bipolar II disorder (52), schizophrenia (53), and substance use disorders (54, 55). Chronicity of MDD is linked to leukocyte telomere shortening (43, 47, 56), suggesting that loss of telomere length may be a consequence of other aspects of the disease process.…”

Section: Introductionmentioning

confidence: 99%

Alterations of Mitochondrial DNA Copy Number and Telomere Length With Early Adversity and Psychopathology

Tyrka

Parade

Price

et al. 2016

Biological Psychiatry

228

177

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Background Telomere shortening and alterations of mitochondrial biogenesis are involved in cellular aging. Childhood adversity is associated with telomere shortening, and several investigations have shown short telomeres in psychiatric disorders. Recent studies have examined whether mitochondria might be involved in neuropsychiatric conditions; findings are limited and no prior work has examined this in relation to stress exposure. Methods Two-hundred and ninety healthy adults provided information on childhood parental loss and maltreatment and completed diagnostic interviews. Participants were categorized into four groups based upon the presence or absence of childhood adversity and the presence or absence of lifetime psychopathology (depressive, anxiety, and substance use disorders). Telomere length and mtDNA copy number were measured from leukocyte DNA by qPCR. Results Childhood adversity and lifetime psychopathology were each associated with shorter telomeres (p < .01) and higher mtDNA copy numbers (p < .001). Significantly higher mtDNA copy numbers and shorter telomeres were seen in individuals with major depression, depressive disorders, and anxiety disorders, as well as those with parental loss and childhood maltreatment. A history of substance disorders was also associated with significantly higher mtDNA copy numbers. Conclusion This study provides the first evidence of an alteration of mitochondrial biogenesis with early life stress and with anxiety and substance use disorders. We replicate prior work on telomere length and psychopathology, and show that this effect is not secondary to medication use or comorbid medical illness. Finally, we show that early life stress and psychopathology are each associated with these markers of cellular aging.

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The interaction between stressful life events and leukocyte telomere length is associated with PTSD

Cited by 57 publications

References 10 publications

Longitudinal changes of telomere length and epigenetic age related to traumatic stress and post-traumatic stress disorder

Longitudinal changes of telomere length and epigenetic age related to traumatic stress and post-traumatic stress disorder

Psychiatric disorders and leukocyte telomere length: Underlying mechanisms linking mental illness with cellular aging

Alterations of Mitochondrial DNA Copy Number and Telomere Length With Early Adversity and Psychopathology

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