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Depression, telomeres and mitochondrial DNA: between- and within-person associations from a 10-year longitudinal study

Abstract

Alterations in cellular aging, indexed by leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNAcn), might partly account for the increased health risks in persons with depression. Although some studies indeed found cross-sectional associations of depression with LTL and mtDNAcn, the longitudinal associations remain unclear. This 10-year longitudinal study examined between- and within-person associations of depressive symptoms with LTL and mtDNAcn in a large community sample. Data are from years 15, 20 and 25 follow-up evaluations in 977 subjects from the Coronary Artery Risk Development in Young Adults study. Depressive symptoms (years 15, 20, 25) were assessed with the Center for Epidemiologic Studies Depression (CES-D) scale; LTL (years 15, 20, 25) and mtDNAcn (years 15, 25) were measured in whole blood by quantitative PCR. With mixed-model analyses, we explored between- and within-person associations between CES-D scores and cellular aging markers. Results showed that high levels of depressive symptomatology throughout the 10-year time span was associated with shorter average LTL over 10 years (B=−4.2; P=0.014) after covarying for age, sex, race and education. However, no within-person association was found between depressive symptoms and LTL at each year (B=−0.8; P=0.548). Further, we found no between-person (B=−0.2; P=0.744) or within-person (B=0.4; P=0.497) associations between depressive symptomatology and mtDNAcn. Our results provide evidence for a long-term, between-person relationship of depressive symptoms with LTL, rather than a dynamic and direct within-person relationship. In this study, we found no evidence for an association between depressive symptoms and mtDNAcn.

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Acknowledgements

The CARDIA study is supported by contracts HHSN268201300025C, HHSN268201300026C, HHSN268201300027C, HHSN268201300028C, HHSN268201300029C and HHSN268200900041C from the National Heart, Lung, and Blood Institute (NHLBI), the Intramural Research Program of the National Institute on Aging (NIA) and an intra-agency agreement between NIA and NHLBI (AG0005). Cell aging assays were supported by grants to EP and EE by the John & Catherine MacArthur Foundation Research Network on Socioeconomic Status and Health and by the National Heart, Lung and Blood Institute of the National Institutes of Health under award number K99/R00 HL 109247. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies, including the National Institutes of Health. JV, DR and BP were supported through a NWO-VICI grant (number 91811602). This manuscript has been reviewed by CARDIA for scientific content.

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Verhoeven, J., Révész, D., Picard, M. et al. Depression, telomeres and mitochondrial DNA: between- and within-person associations from a 10-year longitudinal study. Mol Psychiatry 23, 850–857 (2018). https://doi.org/10.1038/mp.2017.48

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