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Major depressive disorder and accelerated cellular aging: results from a large psychiatric cohort study

Abstract

Patients with major depressive disorder (MDD) have an increased onset risk of aging-related somatic diseases such as heart disease, diabetes, obesity and cancer. This suggests mechanisms of accelerated biological aging among the depressed, which can be indicated by a shorter length of telomeres. We examine whether MDD is associated with accelerated biological aging, and whether depression characteristics such as severity, duration, and psychoactive medication do further impact on biological aging. Data are from the Netherlands Study of Depression and Anxiety, including 1095 current MDD patients, 802 remitted MDD patients and 510 control subjects. Telomere length (TL) was assessed as the telomere sequence copy number (T) compared to a single-copy gene copy number (S) using quantitative polymerase chain reaction. This resulted in a T/S ratio and was converted to base pairs (bp). MDD diagnosis and MDD characteristics were determined by self-report questionnaires and structured psychiatric interviews. Compared with control subjects (mean bp=5541), sociodemographic-adjusted TL was shorter among remitted MDD patients (mean bp=5459; P=0.014) and current MDD patients (mean bp=5461; P=0.012). Adjustment for health and lifestyle variables did not reduce the associations. Within the current MDD patients, separate analyses showed that both higher depression severity (P<0.01) and longer symptom duration in the past 4 years (P=0.01) were associated with shorter TL. Our results demonstrate that depressed patients show accelerated cellular aging according to a ‘dose–response’ gradient: those with the most severe and chronic MDD showed the shortest TL. We also confirmed the imprint of past exposure to depression, as those with remitted MDD had shorter TL than controls.

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Acknowledgements

The infrastructure for the NESDA study (www.nesda.nl) is funded through the Geestkracht program of the Netherlands Organization for Health Research and Development (Zon-Mw, grant number 10-000-1002) and is supported by participating universities and mental health-care organizations (VU University Medical Center, GGZ inGeest, Arkin, Leiden University Medical Center, GGZ Rivierduinen, University Medical Center Groningen, Lentis, GGZ Friesland, GGZ Drenthe, Institute for Quality of Health Care (IQ Healthcare), Netherlands Institute for Health Services Research (NIVEL) and Netherlands Institute of Mental Health and Addiction (Trimbos)). BP, JV, DR and telomere length assaying were supported through a NWO-VICI grant (number 91811602).

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Correspondence to J E Verhoeven.

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EE is a co-founder of Telome Health, Inc, a telomere measurement company. JL is an Associate Research Biochemist in the Department of Biochemistry and Biophysics at UCSF. The other authors declare no conflict of interest.

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Verhoeven, J., Révész, D., Epel, E. et al. Major depressive disorder and accelerated cellular aging: results from a large psychiatric cohort study. Mol Psychiatry 19, 895–901 (2014). https://doi.org/10.1038/mp.2013.151

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Keywords

  • cell aging
  • depression
  • mood disorders
  • telomere shortening

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