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Depressive and anxiety disorders and short leukocyte telomere length: mediating effects of metabolic stress and lifestyle factors

Published online by Cambridge University Press:  07 June 2016

D. Révész*
Department of Psychiatry and EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands
J. E. Verhoeven*
Department of Psychiatry and EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands
Y. Milaneschi
Department of Psychiatry and EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands
B. W. J. H. Penninx
Department of Psychiatry and EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands
*Address for correspondence: J. E. Verhoeven, Department of Psychiatry, VU University Medical Center, A.J. Ernststraat 1187, 1081 HL Amsterdam, The Netherlands. (Email: [D.R.] (Email: [J.E.V.]
*Address for correspondence: J. E. Verhoeven, Department of Psychiatry, VU University Medical Center, A.J. Ernststraat 1187, 1081 HL Amsterdam, The Netherlands. (Email: [D.R.] (Email: [J.E.V.]



Depressive and anxiety disorders are associated with shorter leukocyte telomere length (LTL), an indicator of cellular aging. It is, however, unknown which pathways underlie this association. This study examined the extent to which lifestyle factors and physiological changes such as inflammatory or metabolic alterations mediate the relationship.


We applied mediation analysis techniques to data from 2750 participants of the Netherlands Study of Depression and Anxiety. LTL was assessed using quantitative polymerase chain reaction. Independent variables were current depressive (30-item Inventory of Depressive Symptoms – Self Report) and anxiety (21-item Beck's Anxiety Inventory) symptoms and presence of a depressive or anxiety disorder diagnosis based on DSM-IV; mediator variables included physiological stress systems, metabolic syndrome components and lifestyle factors.


Short LTL was associated with higher symptom severity (B = −2.4, p = 0.002) and current psychiatric diagnosis (B = −63.3, p = 0.024). C-reactive protein, interleukin-6, waist circumference, triglycerides, high-density lipoprotein cholesterol and cigarette smoking were significant mediators in the relationship between psychopathology and LTL. When all significant mediators were included in one model, the effect sizes of the relationships between LTL and symptom severity and current diagnosis were reduced by 36.7 and 32.7%, respectively, and the remaining direct effects were no longer significant.


Pro-inflammatory cytokines, metabolic alterations and cigarette smoking are important mediators of the association between depressive and anxiety disorders and LTL. This calls for future research on intervention programs that take into account lifestyle changes in mental health care settings.

Original Articles
Copyright © Cambridge University Press 2016 

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