Internalizing disorders and leukocyte telomere erosion

A prospective study of depression, generalized anxiety disorder and post-Traumatic stress disorder

Idan 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

Research output: Contribution to journalArticle

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Abstract

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 languageEnglish (US)
Pages (from-to)1163-1170
Number of pages8
JournalMolecular Psychiatry
Volume19
Issue number11
DOIs
StatePublished - Nov 5 2014

Fingerprint

Leukocyte Disorders
Telomere
Post-Traumatic Stress Disorders
Anxiety Disorders
Prospective Studies
Psychiatry
Depression
Leukocytes
Half-Life
Confidence Intervals
Premature Mortality
Health
Social Class
Sex Characteristics
Substance-Related Disorders
Longitudinal Studies
Biomarkers
Smoking
DNA
Population

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Shalev, Idan ; 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. / Internalizing disorders and leukocyte telomere erosion : A prospective study of depression, generalized anxiety disorder and post-Traumatic stress disorder. In: Molecular Psychiatry. 2014 ; Vol. 19, No. 11. pp. 1163-1170.
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abstract = "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, I, Moffitt, TE, Braithwaite, AW, Danese, A, Fleming, NI, Goldman-Mellor, S, Harrington, HL, Houts, RM, Israel, S, Poulton, R, Robertson, SP, Sugden, K, Williams, B & Caspi, A 2014, 'Internalizing disorders and leukocyte telomere erosion: A prospective study of depression, generalized anxiety disorder and post-Traumatic stress disorder', Molecular Psychiatry, vol. 19, no. 11, pp. 1163-1170. https://doi.org/10.1038/mp.2013.183

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

In: Molecular Psychiatry, Vol. 19, No. 11, 05.11.2014, p. 1163-1170.

Research output: Contribution to journalArticle

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T2 - A prospective study of depression, generalized anxiety disorder and post-Traumatic stress disorder

AU - Shalev, Idan

AU - Moffitt, T. E.

AU - Braithwaite, A. W.

AU - Danese, A.

AU - Fleming, N. I.

AU - Goldman-Mellor, S.

AU - Harrington, H. L.

AU - Houts, R. M.

AU - Israel, S.

AU - Poulton, R.

AU - Robertson, S. P.

AU - Sugden, K.

AU - Williams, B.

AU - Caspi, A.

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