Internalizing disorders and leukocyte telomere erosion: a prospective study of depression, generalized anxiety disorder and post-traumatic stress disorder
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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.
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Shalev et al. (2014) found, in men, that duration of internalizing disorders (including MDD) between ages 11-38 predicted LTL at age 38 in a dose-response manner.
“The “dose-response” hypothesis is supported by the longitudinal study of Shalev et al. (2014), which found, in men, that duration of “internalizing disorders” (including MDD) between the ages of 11– 38 years old predicted LTL at age 38 years, in a dose-response manner.”
From Psychiatric disorders and leukocyte telomere length: Underlying mechanisms linking mental illness with cellular aging (2015) · cites this paper as Shalev et al. (2014)
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- Authors
- Shalev, I., Moffitt, T. E., Braithwaite, A. W., Danese, A., Fleming, N. I., Goldman-Mellor, S., Harrington, H. L., Houts, R. M., Israel, S., Poulton, R., Robertson, S. P., Sugden, K., Williams, B., & Caspi, A.
- Affiliations
- Duke University (US)
- The University of Sydney (AU)
- King's College London (GB)
- University of Otago (NZ)
- Corresponding author
- Moffitt, T E
- ORCID
- Venue
- Molecular Psychiatry
- Published
- 2014-01-14
- Volume
- 19
- Issue
- 11
- Pages
- 1163-1170
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC4098012
- OpenAlex
- W2062172666
- Cited by
- 155
- References
- 87
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 6 · 2023: 6 · 2022: 5 · 2021: 16 · 2020: 6 · 2019: 19 · 2018: 17 · 2017: 18 · 2016: 21 · 2015: 21 · 2014: 13
- FWCI
- 16.18
- Type
- journal article
- Language
- en
- Open access
- green
- kclpure.kcl.ac.uk
- Licence
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (publishedVersion, other-oa)
- PubMed Central (acceptedVersion)
- Funders
- Jacobs Foundation
- Medical Research Council (MR/K00381X/1)
- National Institute on Aging (R01AG048895, AG-032282, R01AG032282)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P2CHD065563, R24HD065563)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Social Sciences › Health › Health disparities and outcomes
- Keywords
- internalizing disorders, leukocyte telomere length, telomere shortening, depression, generalized anxiety disorder, post-traumatic stress disorder, biological aging, sex differences, child abuse, premature mortality, age-related diseases, Dunedin Study
- MeSH terms
- Adolescent, Adult, Aging, Anxiety Disorders, Child, Depressive Disorder, Female, Humans, Leukocytes, Longitudinal Studies, Male, Prospective Studies, Sex Characteristics, Stress Disorders, Post-Traumatic, Telomere, Young Adult
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