Depression and telomere length: A meta-analysis

Highlights

• This is a meta-analysis of 38 studies (N=34,347).

• Depression and telomere length are significantly associated (Cohen's d of −0.205).

• Depression severity is associated with telomere length.

• Depression and telomere measurement techniques affect this relationship.

• Source tissue and medical conditions affect this relationship.

Abstract

Background

Several recent studies have investigated the relationship between telomere length and depression with inconsistent results. This meta-analysis examined whether telomere length and depression are associated and explored factors that might affect this association.

Methods

Studies measuring telomere length in subjects with clinically significant unipolar depression were included. A comprehensive search strategy identified studies in PubMed, MEDLINE, PsycINFO, Global Health, The Cochrane Library, and Web of Science. A structured data abstraction form was used and studies were appraised for inclusion or exclusion using a priori conditions. Analyses were conducted using standardized mean differences in a continuous random effects model.

Results

Thirty-eight studies (N=34,347) met the inclusion criteria. The association between depression and telomere length was significant, with a Cohen's d effect size of −0.205 (p<0.0001, I²=42%). Depression severity significantly associated with telomere length (p=0.03). Trim and fill analysis indicated the presence of publication bias (p=0.003), but that the association remained highly significant after accounting for the bias. Subgroup analysis revealed depression assessment tools, telomere measurement techniques, source tissue and comorbid medical conditions significantly affected the relationship.

Limitations

Other potentially important sub-groups, including antidepressant use, have not been investigated in sufficient detail or number yet and thus were not addressed in this meta-analysis.

Conclusions

There is a negative association between depression and telomere length. Further studies are needed to clarify potential causality underlying this association and to elucidate the biology linking depression and this cellular marker of stress exposure and aging.

Introduction

Individuals with major depressive disorder (MDD) have excess morbidity (Young et al., 2014) and mortality (Lou et al., 2014, Young et al., 2014, Zivin et al., 2012) as compared to the general population (Lou et al., 2014). One hypothesis regarding the cause of this excess morbidity and mortality that has gained much attention involves telomere biology. Telomeres are nucleotide sequences consisting of tandem TTAGGG repeats ranging from a few to 15 kilobases in length that provide genomic stability and shorten with each cellular division (Blackburn, 2005). Telomere shortening is strongly associated with age in most somatic tissues (Aubert and Lansdorp, 2008) and is influenced by genetic and epigenetic regulation, as well as by cellular stress and inflammation (Ridout et al., 2015). Conceptualizing chronic disease as a prolonged stress exposure, several studies have reported an association between telomere length and various somatic diseases, such as heart disease (Haycock et al., 2014, Hoen et al., 2011) and diabetes (Zhao et al., 2013). It has been proposed that telomere shortening resulting from chronic stress exposure may be a mechanism of excess morbidity or mortality (Deelen et al., 2014) or a useful indicator of progression of a process of senescence that raises mortality rates by other mechanisms (Ridout et al., 2015).

Simon et al. (2006) examined the relationship between mood disorders and telomere length and found that telomeres were significantly shorter in patients with mood disorders overall (n=44) and also in the group of subjects with MDD (n=15). Since this initial study, there have been numerous efforts to replicate these findings, which have variously reported that depression has no effect or is associated with a reduction in telomere length (see Supplementary Table 1 for references). Several factors might influence these divergent findings, including differences in telomere measurement technique, depression assessment method, population of interest, co-existing somatic illness, gender, and age. Additionally, a majority of these studies have had small sample sizes, limiting the power to draw definitive conclusions. One meta-analysis has pointed to an association between depression and telomere length (Schutte and Malouff, 2015). However, on review of the literature 39% more subjects could be included in the present meta-analysis. Additionally, that meta-analysis did not examine how depression severity, duration, tissue source, smoking, or comorbid chronic medical conditions may moderate the association between depression and telomere length. In the present study, we aimed to expand the subjects included by doubling the databases searched and expanding the search terms to capture all relevant articles. Furthermore, we included studies examining telomere length from all tissue sources, including leukocytes, brain tissue, and saliva, and studies of subjects with comorbid medical factors. The objective of this meta-analysis was to clarify the relationship between depression and telomere length by means of a systematic examination of the literature, comparing subjects with MDD to those without, and to identify moderators of this association.