Abstract
Telomere length has been hypothesized to be a marker of cumulative exposure to stress, and stress is an established cause of depression and anxiety disorders. The aim of this study was to examine the relationship between depression, anxiety and telomere length, and to assess whether this relationship is moderated by race/ethnicity, gender and/or antidepressant use. Data were from the 1999-2002 National Health and Nutrition Examination Survey. Telomere length was assessed using the quantitative PCR method of telomere length relative to standard reference DNA. Past-year major depression (MD), generalized anxiety disorder (GAD) and panic disorder (PD), as well as depressed affect and anxious affect, were assessed using the Composite International Diagnostic Inventory (N=1290). Multiple linear regression was used to assess the relationship between depression and anxiety disorders and telomere length. Among women, those with GAD or PD had shorter telomeres than those with no anxious affect (β: −0.07, P<0.01), but there was no relationship among men (β: 0.08, P>0.05). Among respondents currently taking an antidepressant, those with MD had shorter telomeres than those without (β: −0.26, P<0.05), but there was no association between MD and telomere length among those not using antidepressants (β: −0.00, P>0.05). Neither depressive nor anxiety disorders were directly associated with telomere length in young adults. There was suggestive evidence that pharmacologically treated MD is associated with shorter telomere length, likely reflecting the more severe nature of MD that has come to clinical attention.
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References
Wulsin LR, Singal BM . Do depressive symptoms increase the risk for the onset of coronary disease? A systematic quantitative review. Psychosom Med 2003; 65: 201–210.
Mezuk B, Eaton WW, Albrecht S, Golden SH . Depression and type 2 diabetes over the lifespan: a meta-analysis. Diabetes Care 2008; 31: 2383–2390.
Mezuk B, Eaton WW, Golden SH . Depression and osteoporosis: epidemiology and potential mediating pathways. Osteoporos Int 2008; 19: 1–12.
Chodosh J, Kado DM, Seeman TE, Karlamangla AS . Depressive symptoms as a predictor of cognitive decline: MacArthur Studies of Successful Aging. Am J Geriatr Psychiatry 2007; 15: 406–415.
Hofmann M, Kohler B, Leichsenring F, Kruse J . Depression as a risk factor for mortality in individuals with diabetes: a meta-analysis of prospective studies. PLoS One 2013; 8: e79809.
Phillips AC, Batty GD, Gale CR, Deary IJ, Osborn D, MacIntyre K, et al. Generalized anxiety disorder, major depressive disorder, and their comorbidity as predictors of all-cause and cardiovascular mortality: the Vietnam experience study. Psychosom Med 2009; 71: 395–403.
Stetler C, Miller GE . Depression and hypothalamic-pituitary-adrenal activation: a quantitative summary of four decades of research. Psychosom Med. 2011; 73: 114–126.
Lamers F, Vogelzangs N, Merikangas KR, de Jonge P, Beekman AT, Penninx BW . Evidence for a differential role of HPA-axis function, inflammation and metabolic syndrome in melancholic versus atypical depression. Mol Psychiatry 2013; 18: 692–699.
Licht CM, de Geus EJ, Zitman FG, Hoogendijk WJ, van Dyck R, Penninx BW . Association between major depressive disorder and heart rate variability in the Netherlands Study of Depression and Anxiety (NESDA). Arch Gen Psychiatry 2008; 65: 1358–1367.
Freeman EW, Sammel MD, Lin H, Nelson DB . Associations of hormones and menopausal status with depressed mood in women with no history of depression. Arch Gen Psychiatry 2006; 63: 375–382.
Amore M, Scarlatti F, Quarta AL, Tagariello P . Partial androgen deficiency, depression and testosterone treatment in aging men. Aging Clin Exp Res 2009; 21: 1–8.
Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, et al. A meta-analysis of cytokines in major depression. Biol Psychiatry. 2010; 67: 446–457.
Franceschi C . Inflammaging as a major characteristic of old people: can it be prevented or cured?. Nutr Rev 2007; 65 (Part 2) S173–S176.
McEwen BS . Mood disorders and allostatic load. Biol Psychiatry 2003; 54: 200–207.
Glei DA, Goldman N, Chuang YL, Weinstein M . Do chronic stressors lead to physiological dysregulation? Testing the theory of allostatic load. Psychosom Med 2007; 69: 769–776.
Ellis BJ, Del Giudice M . Beyond allostatic load: rethinking the role of stress in regulating human development. Dev Psychopathol 2013; 26: 1–20.
Wolkowitz OM, Epel ES, Reus VI, Mellon SH . Depression gets old fast: do stress and depression accelerate cell aging? Depress Anxiety 2010; 27: 327–338.
Blackburn E . Telomere states and cell fates. Nature 2000; 408: 53–56.
Blasco M . Telomeres and human disease: ageing, cancer and beyond. Nat Rev Genet 2005; 6: 611–622.
Samani N, Boultby R, Butler R, Thompson J, Goodall A . Telomere shortening in atherosclerosis. Lancet 2001; 358: 472–473.
Brouilette S, Moore J, McMahon A, Thompson J, Ford I, Shepherd J, et al. Telomere length, risk of coronary heart disease, and statin treatment in the West of Scotland Primary Prevention Study: a nested case–control study. Lancet 2007; 369: 107–114.
Fitzpatrick AL, Kronmal RA, Gardner JP, Psaty BM, Jenny NS, Tracy RP, et al. Leukocyte telomere length and cardiovascular disease in the cardiovascular health study. Am J Epidemiol 2007; 165: 14–21.
Willeit P, Willeit J, Brandstatter A, Ehrlenbach S, Mayr A, Gasperi A, et al. Cellular aging reflected by leukocyte telomere length predicts advanced atherosclerosis and cardiovascular disease risk. Arterioscler Thromb Vasc Biol 2010; 30: 1649–1656.
Codd V, Nelson CP, Albrecht E, Mangino M, Deelen J, Buxton JL, et al. Identification of seven loci affecting mean telomere length and their association with disease. Nat Genet 2013; 45: 422–427, 7e1-2.
Zee RY, Castonguay AJ, Barton NS, Germer S, Martin M . Mean leukocyte telomere length shortening and type 2 diabetes mellitus: a case–control study. Transl Res 2010; 155: 166–169.
Salpea KD, Talmud PJ, Cooper JA, Maubaret CG, Stephens JW, Abelak K, et al. Association of telomere length with type 2 diabetes, oxidative stress and UCP2 gene variation. Atherosclerosis 2010; 209: 42–50.
Zhao J, Zhu Y, Lin J, Matsuguchi T, Blackburn E, Zhang Y, et al. Short leukocyte telomere length predicts risk of diabetes in american indians: the strong heart family study. Diabetes 2014; 63: 354–362.
von Zglinicki T, Serra V, Lorenz M, Saretzki G, Lenzen-Grossimlighaus R, Gessner R, et al. Short telomeres in patients with vascular dementia: an indicator of low antioxidative capacity and a possible risk factor? Lab Invest 2000; 80: 1739–1747.
Panossian LA, Porter VR, Valenzuela HF, Zhu X, Reback E, Masterman D, et al. Telomere shortening in T cells correlates with Alzheimer's disease status. Neurobiol Aging 2003; 24: 77–84.
Yaffe K, Lindquist K, Kluse M, Cawthon R, Harris T, Hsueh WC, et al. Telomere length and cognitive function in community-dwelling elders: findings from the Health ABC Study. Neurobiol Aging 2011; 32: 2055–2060.
Honig LS, Kang MS, Schupf N, Lee JH, Mayeux R . Association of shorter leukocyte telomere repeat length with dementia and mortality. Arch Neurol. 2012; 69: 1332–1339.
Willeit P, Willeit J, Mayr A, Weger S, Oberhollenzer F, Brandstatter A, et al. Telomere length and risk of incident cancer and cancer mortality. JAMA 2010; 304: 69–75.
Wentzensen IM, Mirabello L, Pfeiffer RM, Savage SA . The association of telomere length and cancer: a meta-analysis. Cancer Epidemiol Biomarkers Prev 2011; 20: 1238–1250.
Astrup AS, Tarnow L, Jorsal A, Lajer M, Nzietchueng R, Benetos A, et al. Telomere length predicts all-cause mortality in patients with type 1 diabetes. Diabetologia 2010; 53: 45–48.
Cawthon RM, Smith K, O'Brien E, Sivatchenko A, Kerber R . Association between telomere length in blood and mortality in people aged 60 years or older. Lancet 2003; 361: 393–395.
Epel E, Merkin SS, Cawthon R, Blackburn EH, Adler NE, Pletcher MJ, et al. The rate of telomere shortening predicts mortality from cardiovascular disease in elderly men. Aging 2009; 1: 81–88.
Fitzpatrick AL, Kronmal RA, Kimura M, Gardner JP, Psaty BM, Jenny NS, et al. Leukocyte telomere length and mortality in the Cardiovascular Health Study. J Gerontol A Biol Sci Med Sci 2011; 66: 421–429.
Honig LS, Kang MS, Schupf N, Lee JH, Mayeux R . Association of shorter leukocyte telomere repeat length with dementia and mortality. Arch Neurol 2012; 69: 1–8.
Kimura M, Hjelmborg J, Gardner J, Bathum L, Brimacombe M, Lu X, et al. Short leukocyte telomeres forecast mortality: a study in elderly Danish twins. Am J Epidemiol 2008; 167: 799–806.
Lee J, Sandford AJ, Connett JE, Yan J, Mui T, Li Y, et al. The relationship between telomere length and mortality in chronic obstructive pulmonary disease (COPD). PLoS One 2012; 7: e35567.
Martin-Ruiz C, Dickinson HO, Keys B, Rowan E, Kenny RA, Von Zglinicki T . Telomere length predicts poststroke mortality, dementia, and cognitive decline. Ann Neurol. 2006; 60: 174–180.
Weischer M, Bojesen SE, Cawthon RM, Freiberg JJ, Tybjaerg-Hansen A, Nordestgaard BG . Short telomere length, myocardial infarction, ischemic heart disease, and early death. Arterioscler Thromb Vasc Biol 2012; 32: 822–829.
Bakaysa S, Mucci L, Slagbloom P, Boomsma D, McClearn G, Johansson B, et al. Telomere length predicts survival independent of genetic influences. Aging Cell 2007; 6: 769–774.
Farzaneh-Far R, Cawthon RM, Na B, Browner WS, Schiller NB, Whooley MA . Prognostic value of leukocyte telomere length in patients with stable coronary artery disease: data from the Heart and Soul Study. Arterioscler Thromb Vasc Biol 2008; 28: 1379–1384.
Deelen J, Beekman M, Codd V, Trompet S, Broer L, Hagg S, et al. Leukocyte telomere length associates with prospective mortality independent of immune-related parameters and known genetic markers. Int J Epidemiol 2014; 43: 878–886.
Verhoeven JE, Revesz D, Epel ES, Lin J, Wolkowitz OM, Penninx BW . Major depressive disorder and accelerated cellular aging: results from a large psychiatric cohort study. Mol Psychiatry 2014; 19: 895–901.
Phillips AC, Robertson T, Carroll D, Der G, Shiels PG, McGlynn L, et al. Do symptoms of depression predict telomere length? Evidence from the West of Scotland Twenty-07 study. Psychosom Med 2013; 75: 288–296.
Hoen PW, Rosmalen JG, Schoevers RA, Huzen J, van der Harst P, de Jonge P . Association between anxiety but not depressive disorders and leukocyte telomere length after 2 years of follow-up in a population-based sample. Psychol Med 2013; 43: 689–697.
Kessler RC, Berglund P, Demler O, Jin R, Koretz D, Merikangas KR, et al. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA 2003; 289: 3095–3105.
Lin J, Epel E, Cheon J, Kroenke C, Sinclair E, Bigos M, et al. Analyses and comparisons of telomerase activity and telomere length in human T and B cells: insights for epidemiology of telomere maintenance. J Immunol Methods 2010; 352: 71–80.
Cawthon RM . Telomere measurement by quantitative PCR. Nucleic Acids Res 2002; 30: e47.
Kessler RC, Andrews G, Mroczek D, Ustun B, Wittchen H-U . The World Health Organization Composite International Diagnostic Interview short-form (CIDI-SF). Int J Methods Psychiatr Res 1998; 7: 171–185.
Wittchen HU . Reliability and validity studies of the WHO—Composite International Diagnostic Interview (CIDI): a critical review. J Psychiatr Res 1994; 28: 57–84.
Lexicon Plus: All you need in one easy-to-read database: Cerner Multum; 2013. Available from: http://www.multum.com/lexicon.html (last accessed 18 February 2014).
Wang PS, Lane M, Olfson M, Pincus HA, Wells KB, Kessler RC . Twelve-month use of mental health services in the United States: results from the National Comorbidity Survey Replication. Arch Gen Psychiatry 2005; 62: 629–640.
Paternoster R, Brame R, Mazerolle P, Piquero A . Using the correct statistical test for the quality of regression coefficients. Criminology 1998; 36: 859–866.
National Center for Health Statistics. Analytic and Reporting Guidelines: The National Health and Nutrition Examination Survey (NHANES). National Center for Health Statistics, Centers for Disease Control and Prevention: Hyattsville, MD, USA, 2006.
Zhang D, Cheng L, Craig DW, Redman M, Liu C . Cerebellar telomere length and psychiatric disorders. Behav Genet 2010; 40: 250–254.
Simon NM, Smoller JW, McNamara KL, Maser RS, Zalta AK, Pollack MH, et al. Telomere shortening and mood disorders: preliminary support for a chronic stress model of accelerated aging. Biol Psychiatry 2006; 60: 432–435.
Hartmann N, Boehner M, Groenen F, Kalb R . Telomere length of patients with major depression is shortened but independent from therapy and severity of the disease. Depress Anxiety 2010; 27: 1111–1116.
Wikgren M, Maripuu M, Karlsson T, Nordfjall K, Bergdahl J, Hultdin J, et al. Short telomeres in depression and the general population are associated with a hypocortisolemic state. Biol Psychiatry 2012; 71: 294–300.
Elvsashagen T, Vera E, Boen E, Bratlie J, Andreassen OA, Josefsen D, et al. The load of short telomeres is increased and associated with lifetime number of depressive episodes in bipolar II disorder. J Affect Disord 2011; 135: 43–50.
Hoen PW, de Jonge P, Na BY, Farzaneh-Far R, Epel E, Lin J, et al. Depression and leukocyte telomere length in patients with coronary heart disease: data from the Heart and Soul Study. Psychosom Med 2011; 73: 541–547.
Puterman E, Epel ES, Lin J, Blackburn EH, Gross JJ, Whooley MA, et al. Multisystem resiliency moderates the major depression-telomere length association: findings from the Heart and Soul Study. Brain Behav Immun 2013; 33: 65–73.
Teyssier JR, Chauvet-Gelinier JC, Ragot S, Bonin B . Up-regulation of leucocytes genes implicated in telomere dysfunction and cellular senescence correlates with depression and anxiety severity scores. PLoS One 2012; 7: e49677.
Garcia-Rizo C, Fernandez-Egea E, Miller BJ, Oliveira C, Justicia A, Griffith JK, et al. Abnormal glucose tolerance, white blood cell count, and telomere length in newly diagnosed, antidepressant-naive patients with depression. Brain Behav Immun 2013; 28: 49–53.
Shalev I, Moffitt TE, Braithwaite AW, Danese A, Fleming NI, Goldman-Mellor S, et al. Internalizing disorders and leukocyte telomere erosion: a prospective study of depression, generalized anxiety disorder and post-traumatic stress disorder. Mol Psychiatry advance online publication, 14 January 2014; doi:10.1038/mp.2013.183 (e-pub ahead of print).
Breslau J, Aguilar-Gaxiola S, Kendler KS, Su M, Williams D, Kessler RC . Specifying race–ethnic differences in risk for psychiatric disorder in a USA national sample. Psychol Med 2006; 36: 57–68.
Needham BL, Adler N, Gregorich S, Rehkopf D, Lin J, Blackburn EH, et al. Socioeconomic status, health behavior, and leukocyte telomere length in the National Health and Nutrition Examination Survey, 1999–2002. Soc Sci Med 2013; 85: 1–8.
Diez Roux AV, Ranjit N, Jenny NS, Shea S, Cushman M, Fitzpatrick A, et al. Race/ethnicity and telomere length in the Multi-Ethnic Study of Atherosclerosis. Aging Cell 2009; 8: 251–257.
Geronimus AT, Hicken MT, Pearson JA, Seashols SJ, Brown KL, Cruz TD . Do US black women experience stress-related accelerated biological aging?: A novel theory and first population-based test of black-white differences in telomere length. Hum Nat 2010; 21: 19–38.
Aviv A, Chen W, Gardner JP, Kimura M, Brimacombe M, Cao X, et al. Leukocyte telomere dynamics: longitudinal findings among young adults in the Bogalusa Heart Study. Am J Epidemiol 2009; 169: 323–329.
Hunt SC, Chen W, Gardner JP, Kimura M, Srinivasan SR, Eckfeldt JH, et al. Leukocyte telomeres are longer in African Americans than in whites: the National Heart, Lung, and Blood Institute Family Heart Study and the Bogalusa Heart Study. Aging Cell 2008; 7: 451–458.
Berkson J . Limitations of the application of fourfold table analysis to hospital data. Biometrics 1946; 2: 47–53.
Eaton WW, Hall AL, Macdonald R, McKibben J . Case identification in psychiatric epidemiology: a review. Int Rev Psychiatry 2007; 19: 497–507.
Friedrich U, Griese E, Schwab M, Fritz P, Thon K, Klotz U . Telomere length in different tissues of elderly patients. Mech Ageing Dev 2000; 119: 89–99.
Daniali L, Benetos A, Susser E, Kark JD, Labat C, Kimura M, et al. Telomeres shorten at equivalent rates in somatic tissues of adults. Nat Commun 2013; 4: 1597.
Lukens JN, Van Deerlin V, Clark CM, Xie SX, Johnson FB . Comparisons of telomere lengths in peripheral blood and cerebellum in Alzheimer's disease. Alzheimers Dement 2009; 5: 463–469.
Wolkowitz OM, Mellon SH, Epel ES, Lin J, Reus VI, Rosser R, et al. Resting leukocyte telomerase activity is elevated in major depression and predicts treatment response. Mol Psychiatry 2012; 17: 164–172.
Zalli A, Carvalho LA, Lin J, Hamer M, Erusalimsky JD, Blackburn EH, et al. Shorter telomeres with high telomerase activity are associated with raised allostatic load and impoverished psychosocial resources. Proc Natl Acad Sci USA 2014; 111: 4519–4524.
Wolkowitz OM, Mellon SH, Epel ES, Lin J, Dhabhar FS, Su Y, et al. Leukocyte telomere length in major depression: correlations with chronicity, inflammation and oxidative stress—preliminary findings. PLoS One 2011; 6: e17837.
Rius-Ottenheim N, Houben JM, Kromhout D, Kafatos A, van der Mast RC, Zitman FG, et al. Telomere length and mental well-being in elderly men from the Netherlands and Greece. Behav Genet 2012; 42: 278–286.
Shaffer JA, Epel E, Kang MS, Ye S, Schwartz JE, Davidson KW, et al. Depressive symptoms are not associated with leukocyte telomere length: findings from the Nova Scotia Health Survey (NSHS95), a population-based study. PLoS One 2012; 7: e48318.
Okereke OI, Prescott J, Wong JY, Han J, Rexrode KM, De Vivo I . High phobic anxiety is related to lower leukocyte telomere length in women. PLoS One 2012; 7: e40516.
Ladwig KH, Brockhaus AC, Baumert J, Lukaschek K, Emeny RT, Kruse J, et al. Posttraumatic stress disorder and not depression is associated with shorter leukocyte telomere length: findings from 3000 participants in the population-based KORA F4 study. PLoS One 2013; 8: e64762.
Georgin-Lavialle S, Moura DS, Bruneau J, Chauvet-Gelinier JC, Damaj G, Soucie E, et al. Leukocyte telomere length in mastocytosis: Correlations with depression and perceived stress. Brain Behav Immun 2014; 35: 51–57.
Acknowledgements
This work is supported by a grant from the National Institute on Aging (Elissa Epel, PI; R01AG033592-01A1). We thank Carolyn Neal, PhD, and Ajay Yesupriya, MPH, for their assistance. B Mezuk is supported by a career development award from the National Institute of Mental Health (K01-MH093642-A1) and the University of Michigan Center for Integrative Approaches to Health Disparities (2P60-MD002249). The sponsors had no role in the design, analysis or interpretation of the findings.
Author Contributions
BN and BM conceptualized the study and drafted the manuscript. BN conducted the data analysis. NB conducted the literature review and provided feedback on the analysis plan. JL and EB developed, executed and oversaw the laboratory portion of the study and provided criteria feedback on the manuscript draft. EE provided criteria feedback on the manuscript draft.
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JL, EB and EE were co-founders of Telome Health.
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Needham, B., Mezuk, B., Bareis, N. et al. Depression, anxiety and telomere length in young adults: evidence from the National Health and Nutrition Examination Survey. Mol Psychiatry 20, 520–528 (2015). https://doi.org/10.1038/mp.2014.89
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DOI: https://doi.org/10.1038/mp.2014.89
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