Internalizing disorders and leukocyte telomere erosion: A prospective study of depression, generalized anxiety disorder and post-Traumatic stress disorder

I. Shalev, T. E. Moffitt*, A. W. Braithwaite, A. Danese, N. I. Fleming, S. Goldman-Mellor, H. L. Harrington, R. M. Houts, S. Israel, R. Poulton, S. P. Robertson, K. Sugden, B. Williams, A. Caspi

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

131 Scopus citations


There is evidence that persistent psychiatric disorders lead to age-related disease and premature mortality. Telomere length has emerged as a promising biomarker in studies that test the hypothesis that internalizing psychiatric disorders are associated with accumulating cellular damage. We tested the association between the persistence of internalizing disorders (depression, generalized anxiety disorder and post-Traumatic stress disorder) and leukocyte telomere length (LTL) in the prospective longitudinal Dunedin Study (n=1037). Analyses showed that the persistence of internalizing disorders across repeated assessments from ages 11 to 38 years predicted shorter LTL at age 38 years in a dose-response manner, specifically in men (β=-0.137, 95% confidence interval (CI): -0.232, -0.042, P=0.005). This association was not accounted for by alternative explanatory factors, including childhood maltreatment, tobacco smoking, substance dependence, psychiatric medication use, poor physical health or low socioeconomic status. Additional analyses using DNA from blood collected at two time points (ages 26 and 38 years) showed that LTL erosion was accelerated among men who were diagnosed with internalizing disorder in the interim (β=-0.111, 95% CI: -0.184, -0.037, P=0.003). No significant associations were found among women in any analysis, highlighting potential sex differences in internalizing-related telomere biology. These findings point to a potential mechanism linking internalizing disorders to accelerated biological aging in the first half of the life course, particularly in men. Because internalizing disorders are treatable, the findings suggest the hypothesis that treating psychiatric disorders in the first half of the life course may reduce the population burden of age-related disease and extend health expectancy.

Original languageAmerican English
Pages (from-to)1163-1170
Number of pages8
JournalMolecular Psychiatry
Issue number11
StatePublished - 5 Nov 2014
Externally publishedYes

Bibliographical note

Funding Information:
We thank the Dunedin Study members, Unit research staff, Bob Hancox, Murray Thomson and Study founder Phil Silva. This research received support from the US National Institute on Aging (AG032282) and the UK Medical Research Council (MR/K00381X). The Dunedin Multidisciplinary Health and Development Research Unit is supported by the New Zealand Health Research Council. Additional support was provided by the Klaus-Grawe Foundation and the Jacobs Foundation. The study protocol was approved by the institutional ethical review boards of the participating universities. Study members gave informed consent before participating.

Publisher Copyright:
© 2014 Macmillan Publishers Limited All rights reserved.


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