Common mental disorders and association with telomere length (Review)

Vakonaki,E.; Tsiminikaki,K.; Plaitis,S.; Fragkiadaki,P.; Tsoukalas,D.; Katsikantami,I.; Vaki,G.; Tzatzarakis,M. N.; Spandidos,D.  A.; Tsatsakis,A. M.

doi:10.3892/br.2018.1040

Common mental disorders and association with telomere length (Review)

Authors:
- E. Vakonaki
- K. Tsiminikaki
- S. Plaitis
- P. Fragkiadaki
- D. Tsoukalas
- I. Katsikantami
- G. Vaki
- M. N. Tzatzarakis
- D. A. Spandidos
- A. M. Tsatsakis
View Affiliations

Affiliations: Laboratory of Toxicology Science and Research, Medical School, University of Crete, 71003 Heraklion, Crete, Greece, Laboratory of Clinical Virology, Medical School, University of Crete, 71409 Heraklion, Crete, Greece
Published online on: January 8, 2018 https://doi.org/10.3892/br.2018.1040
Pages: 111-116
Copyright: © Vakonaki et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Telomeres are repeated 5'-TTAGGG-3' sequences at the end of chromosomes, which maintain genomic stability. Their length is related to a number of diseases that affect humans. Apart from cancer, cardiovascular diseases, diabetes and other, telomere length has been associated with chronic diseases. Chronic mental illness includes various types of mental disorders with the most common being depression, schizophrenia and stress‑anxiety. The aim of this review is to summarize the current state of knowledge on the role of telomeres in these disorders and to compare telomere length variations in patients receiving medication and patients not taking treatment. Most studies report reduced telomere length in patients suffering from mental disorders, compared to the general population. Since the factors that can affect telomere length are various, more experiments and investigations are required to understand the general impact of different factors on telomere length.

View Figures

View References

1	Aubert G and Lansdorp PM: Telomeres and aging. Physiol Rev. 88:557–579. 2008. View Article : Google Scholar : PubMed/NCBI
2	Swanson MJ, Baribault ME, Israel JN and Bae NS: Telomere protein RAP1 levels are affected by cellular aging and oxidative stress. Biomed Rep. 5:181–187. 2016. View Article : Google Scholar : PubMed/NCBI
3	de Lange T: Shelterin: The protein complex that shapes and safeguards human telomeres. Genes Dev. 19:2100–2110. 2005. View Article : Google Scholar : PubMed/NCBI
4	Collins K and Mitchell JR: Telomerase in the human organism. Oncogene. 21:564–579. 2002. View Article : Google Scholar : PubMed/NCBI
5	Harley CB, Futcher AB and Greider CW: Telomeres shorten during ageing of human fibroblasts. Nature. 345:458–460. 1990. View Article : Google Scholar : PubMed/NCBI
6	Blasco MA: Telomere length, stem cells and aging. Nat Chem Biol. 3:640–649. 2007. View Article : Google Scholar : PubMed/NCBI
7	Hemann MT, Strong MA, Hao LY and Greider CW: The shortest telomere, not average telomere length, is critical for cell viability and chromosome stability. Cell. 107:67–77. 2001. View Article : Google Scholar : PubMed/NCBI
8	Samper E, Flores JM and Blasco MA: Restoration of telomerase activity rescues chromosomal instability and premature aging in Terc^−/− mice with short telomeres. EMBO Rep. 2:800–807. 2001. View Article : Google Scholar : PubMed/NCBI
9	Blasco MA: Telomeres and human disease: Ageing, cancer and beyond. Nat Rev Genet. 6:611–622. 2005. View Article : Google Scholar : PubMed/NCBI
10	Collado M, Blasco MA and Serrano M: Cellular senescence in cancer and aging. Cell. 130:223–233. 2007. View Article : Google Scholar : PubMed/NCBI
11	Willeit P, Willeit J, Brandstätter A, Ehrlenbach S, Mayr A, Gasperi A, Weger S, Oberhollenzer F, Reindl M, Kronenberg F and Kiechl S: Cellular aging reflected by leukocyte telomere length predicts advanced atherosclerosis and cardiovascular disease risk. Arterioscler Thromb Vasc Biol. 30:1649–1656. 2010. View Article : Google Scholar : PubMed/NCBI
12	Aviv A: Telomeres and human aging: Facts and fibs. Sci Aging Knowledge Environ 2004. pe432004.
13	Demissie S, Levy D, Benjamin EJ, Cupples LA, Gardner JP, Herbert A, Kimura M, Larson MG, Meigs JB, Keaney JF and Aviv A: Insulin resistance, oxidative stress, hypertension, and leukocyte telomere length in men from the Framingham Heart Study. Aging Cell. 5:325–330. 2006. View Article : Google Scholar : PubMed/NCBI
14	Fitzpatrick AL, Kronmal RA, Gardner JP, Psaty BM, Jenny NS, Tracy RP, Walston J, Kimura M and Aviv A: Leukocyte telomere length and cardiovascular disease in the cardiovascular health study. Am J Epidemiol. 165:14–21. 2007. View Article : Google Scholar : PubMed/NCBI
15	Astrup AS, Tarnow L, Jorsal A, Lajer M, Nzietchueng R, Benetos A, Rossing P and Parving HH: Telomere length predicts all-cause mortality in patients with type 1 diabetes. Diabetologia. 53:45–48. 2010. View Article : Google Scholar : PubMed/NCBI
16	Olivieri F, Lorenzi M, Antonicelli R, Testa R, Sirolla C, Cardelli M, Mariotti S, Marchegiani F, Marra M, Spazzafumo L, et al: Leukocyte telomere shortening in elderly Type2DM patients with previous myocardial infarction. Atherosclerosis. 206:588–593. 2009. View Article : Google Scholar : PubMed/NCBI
17	Karabatsiakis A, Kolassa IT, Kolassa S, Rudolph KL and Dietrich DE: Telomere shortening in leukocyte subpopulations in depression. BMC Psychiatry. 14:1922014. View Article : Google Scholar : PubMed/NCBI
18	Ladwig KH, Brockhaus AC, Baumert J, Lukaschek K, Emeny RT, Kruse J, Codd V, Häfner S, Albrecht E, Illig T, et al: Posttraumatic stress disorder and not depression is associated with shorter leukocyte telomere length: Findings from 3,000 participants in the population-based KORA F4 study. PLoS One. 8:e647622013. View Article : Google Scholar : PubMed/NCBI
19	Fernandez-Egea E, Bernardo M, Heaphy CM, Griffith JK, Parellada E, Esmatjes E, Conget I, Nguyen L, George V, Stöppler H and Kirkpatrick B: Telomere length and pulse pressure in newly diagnosed, antipsychotic-naive patients with nonaffective psychosis. Schizophr Bull. 35:437–442. 2009. View Article : Google Scholar : PubMed/NCBI
20	Yang Z, Ye J, Li C, Zhou D, Shen Q, Wu J, Cao L, Wang T, Cui D, He S, et al: Drug addiction is associated with leukocyte telomere length. Sci Rep. 3:15422013. View Article : Google Scholar : PubMed/NCBI
21	Thomas P, O' Callaghan NJ and Fenech M: Telomere length in white blood cells, buccal cells and brain tissue and its variation with ageing and Alzheimer's disease. Mech Ageing Dev. 129:183–190. 2008. View Article : Google Scholar : PubMed/NCBI
22	Wolkowitz OM, Epel ES, Reus VI and Mellon SH: Depression gets old fast: Do stress and depression accelerate cell aging? Depress Anxiety. 27:327–338. 2010. View Article : Google Scholar : PubMed/NCBI
23	Hammen C: Stress and depression. Annu Rev Clin Psychol. 1:293–319. 2005. View Article : Google Scholar : PubMed/NCBI
24	Alloy LB, Liu RT and Bender RE: Stress generation research in depression: A commentary. Int J Cogn Ther. 3:380–388. 2010. View Article : Google Scholar : PubMed/NCBI
25	McEwen BS and McEwen BS: Mood disorders and allostatic load. Biol Psychiatry. 54:200–207. 2003. View Article : Google Scholar : PubMed/NCBI
26	Kapczinski F, Dal-Pizzol F, Teixeira AL, Magalhaes PV, Kauer-Sant'Anna M, Klamt F, Moreira JC, de Bittencourt Pasquali MA, Fries GR, Quevedo J, et al: Peripheral biomarkers and illness activity in bipolar disorder. J Psychiatr Res. 45:156–161. 2011. View Article : Google Scholar : PubMed/NCBI
27	Kinser PA and Lyon DE: Major depressive disorder and measures of cellular aging: An integrative review. Nurs Res Pract. 2013:4690702013.PubMed/NCBI
28	Epel ES, Blackburn EH, Lin J, Dhabhar FS, Adler NE, Morrow JD and Cawthon RM: Accelerated telomere shortening in response to life stress. Proc Natl Acad Sci USA. 101:pp. 17312–17315. 2004; View Article : Google Scholar : PubMed/NCBI
29	Berk M, Kapczinski F, Andreazza AC, Dean OM, Giorlando F, Maes M, Yücel M, Gama CS, Dodd S, Dean B, et al: Pathways underlying neuroprogression in bipolar disorder: Focus on inflammation, oxidative stress and neurotrophic factors. Neurosci Biobehav Rev. 35:804–817. 2011. View Article : Google Scholar : PubMed/NCBI
30	Monteleone P, Serritella C, Martiadis V and Maj M: Decreased levels of serum brain-derived neurotrophic factor in both depressed and euthymic patients with unipolar depression and in euthymic patients with bipolar I and II disorders. Bipolar Disord. 10:95–100. 2008. View Article : Google Scholar : PubMed/NCBI
31	Ferrón SR, Marqués-Torrejón MA, Mira H, Flores I, Taylor K, Blasco MA and Fariñas I: Telomere shortening in neural stem cells disrupts neuronal differentiation and neuritogenesis. J Neurosci. 29:14394–14407. 2009. View Article : Google Scholar : PubMed/NCBI
32	Kendler KS, Karkowski LM and Prescott CA: Fears and phobias: Reliability and heritability. Psychol Med. 29:539–553. 1999. View Article : Google Scholar : PubMed/NCBI
33	Fyhrquist F and Saijonmaa O: Telomere length and cardiovascular aging. Ann Med. 44 Suppl 1:138–142. 2012. View Article : Google Scholar
34	Simon NM, Smoller JW, McNamara KL, Maser RS, Zalta AK, Pollack MH, Nierenberg AA, Fava M and Wong KK: Telomere shortening and mood disorders: Preliminary support for a chronic stress model of accelerated aging. Biol Psychiatry. 60:432–435. 2006. View Article : Google Scholar : PubMed/NCBI
35	Brieger K, Schiavone S, Miller FJ Jr and Krause KH: Reactive oxygen species: From health to disease. Swiss Med Wkly. 142:w136592012.PubMed/NCBI
36	von Zglinicki T: Oxidative stress shortens telomeres. Trends Biochem Sci. 27:339–344. 2002. View Article : Google Scholar : PubMed/NCBI
37	Verhoeven JE, Révész D, Epel ES, Lin J, Wolkowitz OM and Penninx BW: Major depressive disorder and accelerated cellular aging: Results from a large psychiatric cohort study. Mol Psychiatry. 19:895–901. 2014. View Article : Google Scholar : PubMed/NCBI
38	Elvsåshagen T, Vera E, Bøen E, Bratlie J, Andreassen OA, Josefsen D, Malt UF, Blasco MA and Boye B: The load of short telomeres is increased and associated with lifetime number of depressive episodes in bipolar II disorder. J Affect Disord. 135:43–50. 2011. View Article : Google Scholar : PubMed/NCBI
39	Needham BL, Mezuk B, Bareis N, Lin J, Blackburn EH and Epel ES: Depression, anxiety and telomere length in young adults: Evidence from the National Health and Nutrition Examination Survey. Mol Psychiatry. 20:520–528. 2015. View Article : Google Scholar : PubMed/NCBI
40	Lung FW, Chen NC and Shu BC: Genetic pathway of major depressive disorder in shortening telomeric length. Psychiatr Genet. 17:195–199. 2007. View Article : Google Scholar : PubMed/NCBI
41	Phillips AC, Robertson T, Carroll D, Der G, Shiels PG, McGlynn L and Benzeval M: Do symptoms of depression predict telomere length? Evidence from the west of Scotland twenty-07 study. Psychosom Med. 75:288–296. 2013. View Article : Google Scholar : PubMed/NCBI
42	Wikgren M, Maripuu M, Karlsson T, Nordfjäll K, Bergdahl J, Hultdin J, Del-Favero J, Roos G, Nilsson LG, Adolfsson R and Norrback KF: Short telomeres in depression and the general population are associated with a hypocortisolemic state. Biol Psychiatry. 71:294–300. 2012. View Article : Google Scholar : PubMed/NCBI
43	Hartmann N, Boehner M, Groenen F and Kalb R: Telomere length of patients with major depression is shortened but independent from therapy and severity of the disease. Depress Anxiety. 27:1111–1116. 2010. View Article : Google Scholar : PubMed/NCBI
44	Simon NM, Walton ZE, Bui E, Prescott J, Hoge E, Keshaviah A, Schwarz N, Dryman T, Ojserkis RA, Kovachy B, et al: Telomere length and telomerase in a well-characterized sample of individuals with major depressive disorder compared to controls. Psychoneuroendocrinology. 58:9–22. 2015. View Article : Google Scholar : PubMed/NCBI
45	Puterman E and Epel E: An intricate dance: Life experience, multisystem resiliency, and rate of telomere decline throughout the lifespan. Soc Personal Psychol Compass. 6:807–825. 2012. View Article : Google Scholar : PubMed/NCBI
46	Czepielewski LS, Massuda R, Panizzutti B, da Rosa ED, de Lucena D, Macêdo D, Grun LK, Barbé-Tuana FM and Gama CS: Telomere length in subjects with schizophrenia, their unaffected siblings and healthy controls: Evidence of accelerated aging. Schizophr Res. 174:39–42. 2016. View Article : Google Scholar : PubMed/NCBI
47	Shastry BS: Schizophrenia: A genetic perspective (Review). Int J Mol Med. 9:207–212. 2002.PubMed/NCBI
48	Rao S, Ye N, Hu H, Shen Y and Xu Q: Variants in TERT influencing telomere length are associated with paranoid schizophrenia risk. Am J Med Genet B Neuropsychiatr Genet. 171B:1–324. 2016.
49	Yu WY, Chang HW, Lin CH and Cho CL: Short telomeres in patients with chronic schizophrenia who show a poor response to treatment. J Psychiatry Neurosci. 33:244–247. 2008.PubMed/NCBI
50	Wolkowitz OM, Jeste DV, Martin AS, Lin J, Daly RE, Reuter C and Kraemer H: Leukocyte telomere length: Effects of schizophrenia, age, and gender. J Psychiatr Res. 85:42–48. 2017. View Article : Google Scholar : PubMed/NCBI
51	Leykin I, Mayer R and Shinitzky M: Short and long-term immunosuppressive effects of clozapine and haloperidol. Immunopharmacology. 37:75–86. 1997. View Article : Google Scholar : PubMed/NCBI
52	Müller N, Myint AM and Schwarz MJ: Inflammation in schizophrenia. Adv Protein Chem Struct Biol. 88:49–68. 2012. View Article : Google Scholar : PubMed/NCBI
53	Porton B, Delisi LE, Bertisch HC, Ji F, Gordon D, Li P, Benedict MM, Greenberg WM and Kao HT: Telomerase levels in schizophrenia: A preliminary study. Schizophr Res. 106:242–247. 2008. View Article : Google Scholar : PubMed/NCBI
54	Rao S, Kota LN, Li Z, Yao Y, Tang J, Mao C, Jain S, Xu Y and Xu Q: Accelerated leukocyte telomere erosion in schizophrenia: Evidence from the present study and a meta-analysis. J Psychiatr Res. 79:50–56. 2016. View Article : Google Scholar : PubMed/NCBI
55	Savolainen K, Räikkönen K, Kananen L, Kajantie E, Hovatta I, Lahti M, Lahti J, Pesonen AK, Heinonen K and Eriksson JG: History of mental disorders and leukocyte telomere length in late adulthood: The Helsinki Birth Cohort Study (HBCS). J Psychiatr Res. 46:1346–1353. 2012. View Article : Google Scholar : PubMed/NCBI
56	Beaulieu JM and Gainetdinov RR: The physiology, signaling, and pharmacology of dopamine receptors. Pharmacol Rev. 63:182–217. 2011. View Article : Google Scholar : PubMed/NCBI
57	Hoffmeyer K, Raggioli A, Rudloff S, Anton R, Hierholzer A, Del Valle I, Hein K, Vogt R and Kemler R: Wnt/β-catenin signaling regulates telomerase in stem cells and cancer cells. Science. 336:1549–1554. 2012. View Article : Google Scholar : PubMed/NCBI
58	Schizophrenia Working Group of the Psychiatric Genomics Consortium, . Biological insights from 108 schizophrenia-associated genetic loci. Nature. 511:421–427. 2014. View Article : Google Scholar : PubMed/NCBI
59	Okusaga OO: Accelerated aging in schizophrenia patients: The potential role of oxidative stress. Aging Dis. 5:256–262. 2013.PubMed/NCBI
60	Okusaga O, Hamilton RG, Can A, Igbide A, Giegling I, Hartmann AM, Konte B, Friedl M, Reeves GM, Rujescu D and Postolache TT: Phadiatop seropositivity in schizophrenia patients and controls: A preliminary study. AIMS Public Health. 1:43–50. 2014. View Article : Google Scholar : PubMed/NCBI
61	Kirkpatrick B and Galderisi S: Deficit schizophrenia: An update. World Psychiatry. 7:143–147. 2008. View Article : Google Scholar : PubMed/NCBI
62	Kao HT, Cawthon RM, Delisi LE, Bertisch HC, Ji F, Gordon D, Li P, Benedict MM, Greenberg WM and Porton B: Rapid telomere erosion in schizophrenia. Mol Psychiatry. 13:118–119. 2008. View Article : Google Scholar : PubMed/NCBI
63	Polho GB, De-Paula VJ, Cardillo G, dos Santos B and Kerr DS: Leukocyte telomere length in patients with schizophrenia: A meta-analysis. Schizophr Res. 165:195–200. 2015. View Article : Google Scholar : PubMed/NCBI
64	Prabakaran S, Swatton JE, Ryan MM, Huffaker SJ, Huang JT, Griffin JL, Wayland M, Freeman T, Dudbridge F, Lilley KS, et al: Mitochondrial dysfunction in schizophrenia: Evidence for compromised brain metabolism and oxidative stress. Mol Psychiatry. 9:684–697. 2004. View Article : Google Scholar : PubMed/NCBI
65	Nishioka N and Arnold SE: Evidence for oxidative DNA damage in the hippocampus of elderly patients with chronic schizophrenia. Am J Geriatr Psychiatry. 12:167–175. 2004. View Article : Google Scholar : PubMed/NCBI
66	Yao JK, Reddy R, McElhinny LG and van Kammen DP: Reduced status of plasma total antioxidant capacity in schizophrenia. Schizophr Res. 32:1–8. 1998. View Article : Google Scholar : PubMed/NCBI
67	Khan MM, Evans DR, Gunna V, Scheffer RE, Parikh VV and Mahadik SP: Reduced erythrocyte membrane essential fatty acids and increased lipid peroxides in schizophrenia at the never-medicated first-episode of psychosis and after years of treatment with antipsychotics. Schizophr Res. 58:1–10. 2002. View Article : Google Scholar : PubMed/NCBI
68	Ranjekar PK, Hinge A, Hegde MV, Ghate M, Kale A, Sitasawad S, Wagh UV, Debsikdar VB and Mahadik SP: Decreased antioxidant enzymes and membrane essential polyunsaturated fatty acids in schizophrenic and bipolar mood disorder patients. Psychiatry Res. 121:109–122. 2003. View Article : Google Scholar : PubMed/NCBI
69	Epel ES: Psychological and metabolic stress: A recipe for accelerated cellular aging? Hormones (Athens). 8:7–22. 2009. View Article : Google Scholar : PubMed/NCBI
70	Grahame TJ and Schlesinger RB: Oxidative stress-induced telomeric erosion as a mechanism underlying airborne particulate matter-related cardiovascular disease. Part Fibre Toxicol. 9:212012. View Article : Google Scholar : PubMed/NCBI
71	von Zglinicki T, Bürkle A and Kirkwood TB: Stress, DNA damage and ageing - an integrative approach. Exp Gerontol. 36:1049–1062. 2001. View Article : Google Scholar : PubMed/NCBI
72	Huzen J, Wong LS, van Veldhuisen DJ, Samani NJ, Zwinderman AH, Codd V, Cawthon RM, Benus GF, van der Horst IC, Navis G, et al: Telomere length loss due to smoking and metabolic traits. J Intern Med. 275:155–163. 2014. View Article : Google Scholar : PubMed/NCBI
73	Broer L, Codd V, Nyholt DR, Deelen J, Mangino M, Willemsen G, Albrecht E, Amin N, Beekman M, de Geus EJ, et al: Meta-analysis of telomere length in 19,713 subjects reveals high heritability, stronger maternal inheritance and a paternal age effect. Eur J Hum Genet. 21:1163–1168. 2013. View Article : Google Scholar : PubMed/NCBI
74	Lindqvist D, Epel ES, Mellon SH, Penninx BW, Révész D, Verhoeven JE, Reus VI, Lin J, Mahan L, Hough CM, et al: Psychiatric disorders and leukocyte telomere length: Underlying mechanisms linking mental illness with cellular aging. Neurosci Biobehav Rev. 55:333–364. 2015. View Article : Google Scholar : PubMed/NCBI
75	Verhoeven JE, van Oppen P, Puterman E, Elzinga B and Penninx BW: The association of early and recent psychosocial life stress with leukocyte telomere length. Psychosom Med. 77:882–891. 2015. View Article : Google Scholar : PubMed/NCBI
76	Hoen PW, Rosmalen JG, Schoevers RA, Huzen J, van der Harst P and 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. 43:689–697. 2013. View Article : Google Scholar : PubMed/NCBI
77	Malouff JM and Schutte NS: A meta-analysis of the relationship between anxiety and telomere length. Anxiety Stress Coping. 30:264–272. 2017. View Article : Google Scholar : PubMed/NCBI
78	Mathur MB, Epel E, Kind S, Desai M, Parks CG, Sandler DP and Khazeni N: Perceived stress and telomere length: A systematic review, meta-analysis, and methodologic considerations for advancing the field. Brain Behav Immun. 54:158–169. 2016. View Article : Google Scholar : PubMed/NCBI
79	Wang X, Sundquist K, Hedelius A, Palmér K, Memon AA and Sundquist J: Leukocyte telomere length and depression, anxiety and stress and adjustment disorders in primary health care patients. BMC Psychiatry. 17:1482017. View Article : Google Scholar : PubMed/NCBI
80	Weischer M, Bojesen SE, Cawthon RM, Freiberg JJ, Tybjærg-Hansen A and Nordestgaard BG: Short telomere length, myocardial infarction, ischemic heart disease, and early death. Arterioscler Thromb Vasc Biol. 32:822–829. 2012. View Article : Google Scholar : PubMed/NCBI
81	Wentzensen IM, Mirabello L, Pfeiffer RM and Savage SA: The association of telomere length and cancer: A meta-analysis. Cancer Epidemiol Biomarkers Prev. 20:1238–1250. 2011. View Article : Google Scholar : PubMed/NCBI
82	Willeit P, Raschenberger J, Heydon EE, Tsimikas S, Haun M, Mayr A, Weger S, Witztum JL, Butterworth AS, Willeit J, et al: Leucocyte telomere length and risk of type 2 diabetes mellitus: New prospective cohort study and literature-based meta-analysis. PLoS One. 9:e1124832014. View Article : Google Scholar : PubMed/NCBI