Research Paper Volume 16, Issue 10 pp 8446—8471
Relationships of depression and antidepressant use with epigenetic age acceleration and all-cause mortality among postmenopausal women
- 1 Laboratory of Epidemiology and Population Sciences, National Institute on Aging, NIA/NIH/IRP, Baltimore, MD 21224, USA
- 2 VA National Center on Homelessness Among Veterans, U.S. Department of Veterans Affairs, Washington, DC 20420, USA
- 3 Department of Management, Policy, and Community Health, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX 77030, USA
- 4 Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA
- 5 Department of Biostatistics, School of Public Health, University of California Los Angeles, Los Angeles, CA 90095, USA
- 6 Department of Psychiatry, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
- 7 Herbert Wertheim School of Public Health and Human Longevity Science and Division of Geriatrics, Gerontology, and Palliative Care, Department of Medicine, University of California, San Diego, CA 92093, USA
- 8 Department of Epidemiology, Fielding School of Public Health, Translational Sciences Section, School of Nursing, University of California, Los Angeles, CA 90095, USA
- 9 Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA
- 10 Department of Biostatistics and Data Science, Wake Forest University School of Medicine, Winston-Salem, NC 27101, USA
- 11 Department of Family and Community Medicine (Emeritus), School of Medicine, University of Nevada, Reno, NV 89557, USA
Received: October 30, 2023 Accepted: May 3, 2024 Published: May 27, 2024
https://doi.org/10.18632/aging.205868How to Cite
Copyright: © 2024 Beydoun et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
We investigated relations of depressive symptoms, antidepressant use, and epigenetic age acceleration with all-cause mortality risk among postmenopausal women. Data were analyzed from ≤1,900 participants in the Women's Health Initiative study testing four-way decomposition models. After a median 20.4y follow-up, 1,161 deaths occurred. Approximately 11% had elevated depressive symptoms (EDS+), 7% were taking antidepressant medication at baseline (ANTIDEP+), while 16.5% fell into either category (EDS_ANTIDEP+). Baseline ANTIDEP+, longitudinal transition into ANTIDEP+ and accelerated epigenetic aging directly predicted increased mortality risk. GrimAge DNA methylation age acceleration (AgeAccelGrim) partially mediated total effects of baseline ANTIDEP+ and EDS_ANTIDEP+ on all-cause mortality risk in socio-demographic factors-adjusted models (Pure Indirect Effect >0, P < 0.05; Total Effect >0, P < 0.05). Thus, higher AgeAccelGrim partially explained the relationship between antidepressant use and increased all-cause mortality risk, though only prior to controlling for lifestyle and health-related factors. Antidepressant use and epigenetic age acceleration independently predicted increased all-cause mortality risk. Further studies are needed in varying populations.