Elsevier

Journal of Affective Disorders

Volume 169, 1 December 2014, Pages 86-90
Journal of Affective Disorders

Preliminary communication
Adverse childhood experiences and leukocyte telomere maintenance in depressed and healthy adults

https://doi.org/10.1016/j.jad.2014.07.035Get rights and content

Abstract

Background

Adverse childhood experiences (ACEs) are associated with poor physical and mental health outcomes in adulthood. Adverse childhood experiences are also associated with shortened leukocyte telomere length (LTL) in adults, suggesting accelerated cell aging. No studies have yet assessed the relationship of ACEs to LTL in individuals with major depressive disorder (MDD), despite the high incidence of antecedent ACEs in individuals with MDD. Further, no studies in any population have assessed the relationship of ACEs to the activity of telomerase, the major enzyme responsible for maintaining LTL, or the relationship between telomerase and LTL in individuals with ACEs.

Methods

Twenty healthy, unmedicated adults with MDD and 20 healthy age-, sex- and ethnicity-matched controls had ACEs assessed and had blood drawn for LTL and peripheral blood mononuclear cell (PBMC) resting telomerase activity.

Results

In healthy controls, greater ACE exposure was associated with shorter LTL (p<.05) but was unassociated with telomerase activity. In MDD, however, the opposite pattern was seen: greater ACE exposure was unrelated to LTL but was associated with increased telomerase activity (p<.05) and with a higher telomerase:LTL ratio (p=.022).

Limitations

Study limitations include the small sample size, a single timepoint assessment of telomerase activity, and the use of retrospective self-report to assess ACEs.

Conclusions

These results replicate prior findings of shortened LTL in healthy adults with histories of multiple ACEs. However, in MDD, this relationship was substantially altered, raising the possibility that activation of telomerase in ACE-exposed individuals with MDD could represent a compensatory response to endangered telomeres.

Introduction

Serious adverse childhood experiences (ACEs) are remarkably prevalent, with between 52% and 64% of individuals in the United States experiencing at least one serious ACE before the age of 18 and between 6.2% and 12.5% of individuals experiencing four or more serious ACEs before that age (Anda et al., 2006, Felitti et al., 1998). ACEs are associated with increased risk of adult physical and mental disease and with shortened life expectancy (Anda et al., 2010, Brown et al., 2009, Chapman et al., 2004). The mechanisms underlying this increased risk are unknown, but one possibility is that ACEs are associated with premature biological aging. An emerging measure of biological age at the cellular level is the length of telomeres in circulating leukocytes. Shorter leukocyte telomere length (LTL) is associated with earlier onset or elevated risk of several common diseases of aging (Andrews et al., 2009, Epel et al., 2006).

Telomeres are deoxyribonucleic acid (DNA)–protein complexes found at the ends of linear chromosomes that cap and protect the genome from damage. Telomere shortening can occur with repeated cell division as well as with chronic exposure to cytotoxic stressors such as oxidative stress and inflammation (O’Donovan et al., 2011b, Von Zglinicki, 2002), and telomere length may provide a biomarker for assessing an individual׳s cumulative exposure to, or ability to cope with, stressful conditions (EPEL et al., 2004; Kotrschal et al., 2007). Telomere shortening can be counteracted or reversed by telomerase, an enzyme that elongates telomeres (Blackburn and Collins, 2011). However, the amount of telomerase in most somatic cells is insufficient to maintain telomere length indefinitely (Beyne-Rauzy et al., 2005, Kotrschal et al., 2007), and when telomeres reach a critically short length, cells become susceptible to senescence and apoptosis (Price et al., 2013, Epel et al., 2006).

Shortened LTL has been associated with psychiatric illness, such as anxiety and depressive disorders (Hartmann et al., 2010, O’Donovan et al., 2011a, Simon et al., 2006), and accelerated LTL shortening has been demonstrated in adults with ACEs (Kiecolt-Glaser et al., 2011, Tyrka et al., 2010, Price et al., 2013). Despite the high prevalence of both ACEs and poor health outcomes in MDD, no studies have assessed the relationship of ACEs to LTL in individuals with major depressive disorder (MDD). Further, the role of peripheral blood mononuclear cell (PBMC) telomerase activity (TA) has not been well characterized in stressed and psychiatrically ill individuals, nor in individuals with histories of ACEs.

This study examined LTL and TA in healthy unmedicated adults with MDD and in well-matched healthy controls. We hypothesized that graded exposure to ACEs would be associated with diminished LTL in both groups. We did not hypothesize specific TA changes or telomerase:LTL ratios that would be associated with graded exposure to ACEs due to the lack of prior data.

Section snippets

Participants

This study was approved by the University of California San Francisco Committee on Human Research. Participants gave informed consent to participate and were reimbursed for their participation.

Twenty subjects with MDD and 20 healthy controls (individually matched on age ±3 years, gender and ethnicity) participated and completed all procedures. The individuals with MDD and 18 of the controls have been described in other publications using different measures and testing different hypotheses (

Results

MDD and control groups did not significantly differ in age, sex, ethnicity, educational level, socioeconomic status, or alcohol or tobacco use. Individuals with MDD reported more difficulties with insomnia (t(22.8)=−4.89, p=.000), compared to healthy controls, but sleep was not associated with LTL or TA, in either group.

As expected, individuals with MDD reported a higher severity of depressive symptoms on the QIDS than healthy controls (t(17.5)=−11.64, p=.000) as well as a greater number of

Discussion

We replicated previous findings of shortened LTL in healthy non-depressed individuals with extensive ACEs (Kiecolt-Glaser et al., 2011, Tyrka et al., 2010, Price et al., 2013), but found a distinctly different pattern in healthy unmedicated individuals with MDD. Specifically, greater exposure to ACEs was correlated with significantly shorter LTL among the healthy controls but not among the MDDs. By contrast, greater exposure to ACEs was significantly correlated with increased TA in the

Conclusions

The present data are the first to relate ACEs to TA in any population and the first to relate ACEs to LTL in individuals with MDD. These data highlight biological sequellae of early life psychological and physical trauma and suggest that these sequellae may differ in depressed vs. non-depressed individuals. ACE-related alterations in cell aging in certain populations might also contribute to, and help explain, the excess medical morbidity and early mortality seen in adults with histories of

Role of funding source

This work was supported by the following grants: NIMH 1 R01 MH083784 (Co-PIs: OMW, ESE, SHM) and a grant from the Barbro and Barney Fund to EHB. This work was also supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through UCSF-CTSI Grant number UL1 RR024131. This publication׳s contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. The

Conflict of interest

EHB, JL and ESE were co-founders of a company providing telomere length measures.

Acknowledgments

This work was supported by the following Grants: NIMH 1 R01 MH083784 (Co-PIs: OMW, ESE, SHM) and a grant from the Barbro and Barney Fund to EHB. This work was also supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through UCSF-CTSI Grant number UL1 RR024131. This publication׳s contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. The

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