Leukocyte telomere length and depression, anxiety and stress and adjustment disorders in primary health care patients

Xiao Wang, Kristina Sundquist, Anna Hedelius, Karolina Palmér, Ashfaque A Memon, Jan Sundquist, Xiao Wang, Kristina Sundquist, Anna Hedelius, Karolina Palmér, Ashfaque A Memon, Jan Sundquist

Abstract

Background: The primary aim was to examine possible differences in telomere length between primary health care patients, with depression, anxiety or stress and adjustment disorders, and healthy controls. The second aim was to examine the association between telomere length and baseline characteristics in the patients. The third aim was to examine the potential effects of the 8-week treatments (mindfulness-based group therapy or treatment as usual, i.e. mostly cognitive-based therapy) on telomere length, and to examine whether there was a difference in the potential effect on telomere length between the two groups.

Methods: A total of 501 individuals including 181 patients (aged 20-64 years), with depression, anxiety and stress and adjustment disorders, and 320 healthy controls (aged 19-70 years) were recruited in the study. Patient data were collected from a randomized controlled trial comparing mindfulness-based group therapy with treatment as usual. We isolated genomic DNA from blood samples, collected at baseline and after the 8-week follow-up. Telomere length was measured by quantitative real-time (qRT)-PCR.

Results: Telomere length was significantly shorter in the patients (mean = 0.77 ± 0.12,), compared to the controls (mean = 0.81 ± 0.14) (p = 0.006). The difference in telomere length remained significant after controlling for age and sex. Old age, male sex and being overweight were associated with shorter telomere length. There was no significant difference in telomere length between baseline and at the 8-week follow-up in any of the treatment groups and no difference between the two groups.

Conclusion: Our findings confirm that telomere length, as compared with healthy controls, is shortened in patients with depression, anxiety and stress and adjustment disorders. In both groups (mindfulness-based group therapy or treatment as usual), the telomere length remained unchanged after the 8-week treatment/follow-up and there was no difference between the two groups.

Trial registration: (ClinicalTrials.gov ID: NCT01476371 ) Registered November 11, 2011.

Keywords: Anxiety; Depression; Stress and adjustment disorders; Telomere length.

Figures

Fig. 1
Fig. 1
Mean values and 95% confidence intervals of telomere length for patients and control subjects (at baseline and follow-up) together with p-values (n = 501). All analyses are adjusted for age. aDifference tested by independent sample t-test. bDifference tested by paired t-test

References

    1. Vazquez-Barquero JL, Garcia J, Simon JA, Iglesias C, Montejo J, Herran A, Dunn G. Mental health in primary care. An epidemiological study of morbidity and use of health resources. Br J Psychiatry. 1997;170:529–535. doi: 10.1192/bjp.170.6.529.
    1. Nordstrom A, Bodlund O. Every third patient in primary care suffers from depression, anxiety or alcohol problems. Nord J Psychiatry. 2008;62(3):250–255. doi: 10.1080/08039480802141129.
    1. Irwin MR, Miller AH. Depressive disorders and immunity: 20 years of progress and discovery. Brain Behav Immun. 2007;21(4):374–383. doi: 10.1016/j.bbi.2007.01.010.
    1. Lindqvist D, Epel ES, Mellon SH, Penninx BW, Revesz 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. 2015;55:333–364. doi: 10.1016/j.neubiorev.2015.05.007.
    1. Nemeroff CB, Musselman DL, Evans DL. Depression and cardiac disease. Depress Anxiety. 1998;8(Suppl 1):71–79. doi: 10.1002/(SICI)1520-6394(1998)8:1+<71::AID-DA11>;2-X.
    1. Evans DL, Charney DS, Lewis L, Golden RN, Gorman JM, Krishnan KR, Nemeroff CB, Bremner JD, Carney RM, Coyne JC, et al. Mood disorders in the medically ill: scientific review and recommendations. Biol Psychiatry. 2005;58(3):175–189. doi: 10.1016/j.biopsych.2005.05.001.
    1. Kyrou I, Kollia N, Panagiotakos D, Georgousopoulou E, Chrysohoou C, Tsigos C, Randeva HS, Yannakoulia M, Stefanadis C, Papageorgiou C, et al. Association of depression and anxiety status with 10-year cardiovascular disease incidence among apparently healthy Greek adults: the ATTICA study. Eur J Prev Cardiol. 2017;24(2):145–52.
    1. Svensson E, Farkas DK, Gradus JL, Lash TL, Sorensen HT. Adjustment disorder and risk of Parkinson's disease. Eur J Neurol. 2016;23(4):751–756. doi: 10.1111/ene.12933.
    1. Roy S, Chakraborty A, Ghosh C, Banerjee B. Systematic analysis of integrated Gene functional network of four chronic stress-related lifestyle disorders. Genome Integrity. 2015;6:1. doi: 10.4103/2041-9414.155952.
    1. Gradus JL, Farkas DK, Svensson E, Ehrenstein V, Lash TL, Milstein A, Adler N, Sorensen HT. Associations between stress disorders and cardiovascular disease events in the Danish population. BMJ Open. 2015;5(12):e009334. doi: 10.1136/bmjopen-2015-009334.
    1. Wolkowitz OM, Mellon SH, Epel ES, Lin J, Dhabhar FS, Su Y, Reus VI, Rosser R, Burke HM, Kupferman E, et al. Leukocyte telomere length in major depression: correlations with chronicity, inflammation and oxidative stress--preliminary findings. PLoS One. 2011;6(3):e17837. doi: 10.1371/journal.pone.0017837.
    1. 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(8):895–901. doi: 10.1038/mp.2013.151.
    1. 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(12):1111–1116. doi: 10.1002/da.20749.
    1. Epel ES, Blackburn EH, Lin J, Dhabhar FS, Adler NE, Morrow JD, Cawthon RM. Accelerated telomere shortening in response to life stress. Proc Natl Acad Sci U S A. 2004;101(49):17312–17315. doi: 10.1073/pnas.0407162101.
    1. Blackburn EH. Switching and signaling at the telomere. Cell. 2001;106(6):661–673. doi: 10.1016/S0092-8674(01)00492-5.
    1. de Lange T. Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev. 2005;19(18):2100–2110. doi: 10.1101/gad.1346005.
    1. Blackburn EH. Telomere states and cell fates. Nature. 2000;408(6808):53–56. doi: 10.1038/35040500.
    1. Beyne-Rauzy O, Prade-Houdellier N, Demur C, Recher C, Ayel J, Laurent G, Mansat-De Mas V. Tumor necrosis factor-alpha inhibits hTERT gene expression in human myeloid normal and leukemic cells. Blood. 2005;106(9):3200–3205. doi: 10.1182/blood-2005-04-1386.
    1. Shay JW, Wright WE. Hallmarks of telomeres in ageing research. J Pathol. 2007;211(2):114–123. doi: 10.1002/path.2090.
    1. De Meyer T, Rietzschel ER, De Buyzere ML, Van Criekinge W, Bekaert S. Studying telomeres in a longitudinal population based study. Front Biosci. 2008;13:2960–2970. doi: 10.2741/2901.
    1. von Zglinicki T. Oxidative stress shortens telomeres. Trends Biochem Sci. 2002;27(7):339–344. doi: 10.1016/S0968-0004(02)02110-2.
    1. Wu X, Amos CI, Zhu Y, Zhao H, Grossman BH, Shay JW, Luo S, Hong WK, Spitz MR. Telomere dysfunction: a potential cancer predisposition factor. J Natl Cancer Inst. 2003;95(16):1211–1218. doi: 10.1093/jnci/djg011.
    1. Willeit P, Willeit J, Mayr A, Weger S, Oberhollenzer F, Brandstatter A, Kronenberg F, Kiechl S. Telomere length and risk of incident cancer and cancer mortality. JAMA. 2010;304(1):69–75. doi: 10.1001/jama.2010.897.
    1. Calado RT, Young NS. Telomere diseases. N Engl J Med. 2009;361(24):2353–2365. doi: 10.1056/NEJMra0903373.
    1. Brouilette SW, Moore JS, McMahon AD, Thompson JR, Ford I, Shepherd J, Packard CJ, Samani NJ. 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(9556):107–114. doi: 10.1016/S0140-6736(07)60071-3.
    1. Zhao J, Zhu Y, Lin J, Matsuguchi T, Blackburn E, Zhang Y, Cole SA, Best LG, Lee ET, Howard BV. Short leukocyte telomere length predicts risk of diabetes in american indians: the strong heart family study. Diabetes. 2014;63(1):354–362. doi: 10.2337/db13-0744.
    1. Garcia-Rizo C, Fernandez-Egea E, Miller BJ, Oliveira C, Justicia A, Griffith JK, Heaphy CM, Bernardo M, Kirkpatrick B. 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. doi: 10.1016/j.bbi.2012.11.009.
    1. Hoen PW, de Jonge P, Na BY, Farzaneh-Far R, Epel E, Lin J, Blackburn E, Whooley MA. Depression and leukocyte telomere length in patients with coronary heart disease: data from the heart and soul study. Psychosom Med. 2011;73(7):541–547. doi: 10.1097/PSY.0b013e31821b1f6e.
    1. Lung FW, Chen NC, Shu BC. Genetic pathway of major depressive disorder in shortening telomeric length. Psychiatr Genet. 2007;17(3):195–199. doi: 10.1097/YPG.0b013e32808374f6.
    1. Simon NM, Smoller JW, McNamara KL, Maser RS, Zalta AK, Pollack MH, Nierenberg AA, Fava M, Wong KK. Telomere shortening and mood disorders: preliminary support for a chronic stress model of accelerated aging. Biol Psychiatry. 2006;60(5):432–435. doi: 10.1016/j.biopsych.2006.02.004.
    1. Cai N, Chang S, Li Y, Li Q, Hu J, Liang J, Song L, Kretzschmar W, Gan X, Nicod J, et al. Molecular signatures of major depression. Curr Biol. 2015;25(9):1146–1156. doi: 10.1016/j.cub.2015.03.008.
    1. Karabatsiakis A, Kolassa IT, Kolassa S, Rudolph KL, Dietrich DE. Telomere shortening in leukocyte subpopulations in depression. BMC Psychiatry. 2014;14:192. doi: 10.1186/1471-244X-14-192.
    1. Martinsson L, Wei Y, Xu D, Melas PA, Mathe AA, Schalling M, Lavebratt C, Backlund L. Long-term lithium treatment in bipolar disorder is associated with longer leukocyte telomeres. Transl Psychiatry. 2013;3 doi: 10.1038/tp.2013.37.
    1. Epel E, Daubenmier J, Moskowitz JT, Folkman S, Blackburn E. Can meditation slow rate of cellular aging? Cognitive stress, mindfulness, and telomeres. Ann N Y Acad Sci. 2009;1172:34–53. doi: 10.1111/j.1749-6632.2009.04414.x.
    1. Oei TP, Bullbeck K, Campbell JM. Cognitive change process during group cognitive behaviour therapy for depression. J Affect Disord. 2006;92(2–3):231–241. doi: 10.1016/j.jad.2006.02.004.
    1. Basu N, Skinner HG, Litzelman K, Vanderboom R, Baichoo E, Boardman LA. Telomeres and telomere dynamics: relevance to cancers of the GI tract. Expert Rev Gastroenterol Hepatol. 2013;7(8):733–748. doi: 10.1586/17474124.2013.848790.
    1. Carlson LE, Beattie TL, Giese-Davis J, Faris P, Tamagawa R, Fick LJ, Degelman ES, Speca M. Mindfulness-based cancer recovery and supportive-expressive therapy maintain telomere length relative to controls in distressed breast cancer survivors. Cancer. 2015;121(3):476–484. doi: 10.1002/cncr.29063.
    1. Schutte NS, Malouff JM. A meta-analytic review of the effects of mindfulness meditation on telomerase activity. Psychoneuroendocrinology. 2014;42:45–48. doi: 10.1016/j.psyneuen.2013.12.017.
    1. Daubenmier J, Lin J, Blackburn E, Hecht FM, Kristeller J, Maninger N, Kuwata M, Bacchetti P, Havel PJ, Epel E. Changes in stress, eating, and metabolic factors are related to changes in telomerase activity in a randomized mindfulness intervention pilot study. Psychoneuroendocrinology. 2012;37(7):917–928. doi: 10.1016/j.psyneuen.2011.10.008.
    1. Lavretsky H, Epel ES, Siddarth P, Nazarian N, Cyr NS, Khalsa DS, Lin J, Blackburn E, Irwin MR. A pilot study of yogic meditation for family dementia caregivers with depressive symptoms: effects on mental health, cognition, and telomerase activity. Int J Geriatr Psychiatry. 2013;28(1):57–65. doi: 10.1002/gps.3790.
    1. Sundquist J, Lilja A, Palmer K, Memon AA, Wang X, Johansson LM, Sundquist K. Mindfulness group therapy in primary care patients with depression, anxiety and stress and adjustment disorders: randomised controlled trial. Br J Psychiatry. 2015;206(2):128–135. doi: 10.1192/bjp.bp.114.150243.
    1. Wang X, Sundquist K, Hedelius A, Palmer K, Memon AA, Sundquist J. Circulating microRNA-144-5p is associated with depressive disorders. Clin Epigenetics. 2015;7(1):69. doi: 10.1186/s13148-015-0099-8.
    1. Blood donation in Sweden https://geblodnu/english-engelska/.
    1. Cawthon RM. Telomere measurement by quantitative PCR. Nucleic Acids Res. 2002;30(10) doi: 10.1093/nar/30.10.e47.
    1. Cawthon RM, Smith KR, O'Brien E, Sivatchenko A, Kerber RA. Association between telomere length in blood and mortality in people aged 60 years or older. Lancet. 2003;361(9355):393–395. doi: 10.1016/S0140-6736(03)12384-7.
    1. Nordfjall K, Osterman P, Melander O, Nilsson P, Roos G. hTERT (−1327)T/C polymorphism is not associated with age-related telomere attrition in peripheral blood. Biochem Biophys Res Commun. 2007;358(1):215–218. doi: 10.1016/j.bbrc.2007.04.099.
    1. Bojesen SE. Telomeres and human health. J Intern Med. 2013;274(5):399–413. doi: 10.1111/joim.12083.
    1. Rode L, Nordestgaard BG, Bojesen SE. Peripheral blood leukocyte telomere length and mortality among 64,637 individuals from the general population. J Natl Cancer Inst. 2015;107(6):djv074. doi: 10.1093/jnci/djv074.
    1. Lin J, Epel E, Cheon J, Kroenke C, Sinclair E, Bigos M, Wolkowitz O, Mellon S, Blackburn E. 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(1–2):71–80. doi: 10.1016/j.jim.2009.09.012.
    1. Wolkowitz OM, Epel ES, Reus VI, Mellon SH. Depression gets old fast: do stress and depression accelerate cell aging? Depress Anxiety. 2010;27(4):327–338. doi: 10.1002/da.20686.
    1. Gururajan A, Clarke G, Dinan TG, Cryan JF. Molecular biomarkers of depression. Neurosci Biobehav Rev. 2016;64:101–133. doi: 10.1016/j.neubiorev.2016.02.011.
    1. Szebeni A, Szebeni K, DiPeri T, Chandley MJ, Crawford JD, Stockmeier CA, Ordway GA. Shortened telomere length in white matter oligodendrocytes in major depression: potential role of oxidative stress. Int J Neuropsychopharmacol. 2014;17(10):1579–1589. doi: 10.1017/S1461145714000698.
    1. Kawanishi S, Oikawa S. Mechanism of telomere shortening by oxidative stress. Ann N Y Acad Sci. 2004;1019:278–284. doi: 10.1196/annals.1297.047.
    1. von Zglinicki T, Saretzki G, Ladhoff J, d'Adda di Fagagna F, Jackson SP. Human cell senescence as a DNA damage response. Mech Ageing Dev. 2005;126(1):111–117. doi: 10.1016/j.mad.2004.09.034.
    1. Hoge EA, Chen MM, Orr E, Metcalf CA, Fischer LE, Pollack MH, De Vivo I, Simon NM. Loving-kindness meditation practice associated with longer telomeres in women. Brain Behav Immun. 2013;32:159–163. doi: 10.1016/j.bbi.2013.04.005.
    1. Weischer M, Bojesen SE, Nordestgaard BG. Telomere shortening unrelated to smoking, body weight, physical activity, and alcohol intake: 4,576 general population individuals with repeat measurements 10 years apart. PLoS Genet. 2014;10(3):e1004191. doi: 10.1371/journal.pgen.1004191.
    1. Lynch SM, Peek MK, Mitra N, Ravichandran K, Branas C, Spangler E, Zhou W, Paskett ED, Gehlert S, DeGraffinreid C, et al. Race, ethnicity, psychosocial factors, and telomere length in a multicenter setting. PLoS One. 2016;11(1):e0146723. doi: 10.1371/journal.pone.0146723.
    1. Revesz D, Verhoeven JE, Milaneschi Y, Penninx BW. Depressive and anxiety disorders and short leukocyte telomere length: mediating effects of metabolic stress and lifestyle factors. Psychol Med. 2016;46(11):2337–2349. doi: 10.1017/S0033291716000891.
    1. Folkhälsorapport FHS. , 2012.

Source: PubMed

Szponzorok és közreműködők

Egészségi állapot

Kábítószer-beavatkozások

3
Iratkozz fel