Hostname: page-component-78c5997874-s2hrs Total loading time: 0 Render date: 2024-11-17T04:21:09.614Z Has data issue: false hasContentIssue false

Decreased leucocyte telomere length in male patients with chronic bipolar disorder: lack of effect of long-term lithium treatment

Published online by Cambridge University Press:  09 August 2021

Ewa Ferensztajn-Rochowiak*
Affiliation:
Department of Adult Psychiatry, Poznan University of Medical Sciences, Poznan, Poland
Ewa Kurczewska
Affiliation:
Department of Adult Psychiatry, Poznan University of Medical Sciences, Poznan, Poland
Błażej Rubiś
Affiliation:
Department of Clinical Chemistry and Molecular Diagnostics, Poznan University of Medical Sciences, Poznan, Poland
Michalina Lulkiewicz
Affiliation:
Department of Clinical Chemistry and Molecular Diagnostics, Poznan University of Medical Sciences, Poznan, Poland
Hanna Hołysz
Affiliation:
Department of Clinical Chemistry and Molecular Diagnostics, Poznan University of Medical Sciences, Poznan, Poland
Filip Rybakowski
Affiliation:
Department of Adult Psychiatry, Poznan University of Medical Sciences, Poznan, Poland
Janusz K. Rybakowski
Affiliation:
Department of Adult Psychiatry, Poznan University of Medical Sciences, Poznan, Poland
*
Author for correspondence: Ewa Ferensztajn-Rochowiak, Email: [email protected]

Abstract

Objectives:

Bipolar disorder (BD) may be connected with accelerated aging, the marker of this can be shorter telomere length (TL). Some data suggest that lithium may exert a protective effect against telomere shortening. The study aimed to compare the TL between patients with BD and control subjects. The effect of long-term lithium treatment was also assessed.

Methods:

The study group comprised 41 patients with BD, including 29 patients treated longitudinally with lithium (mean 16.5 years) and 20 healthy people. TL was assessed by the quantitative polymerase chain reaction (qPCR).

Results:

In the control group, the TL was significantly longer in males than in females. Male bipolar patients had significantly shorter TL compared with the control male group. In bipolar patients, there was no correlation between TL and duration of treatment. The TL was negatively correlated with age in male bipolar patients.

Conclusions:

The study did not confirm the lithium effect on TL in bipolar patients. TL showed gender differences, being shorter in BD males, compared to control males, and longer in healthy males, compared to control females.

Type
Original Article
Copyright
© The Author(s), 2021. Published by Cambridge University Press in association with Scandinavian College of Neuropsychopharmacology

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Adams, J, Martin-Ruiz, C, Pearce, MS, White, M, Parker, L and von Zglinicki, T (2007) No association between socio economic status and white blood cell telomere length. Aging Cell 6, 125128.CrossRefGoogle ScholarPubMed
Alonso-Alvarez, C, Bertrand, S, Faivre, B, Chastel, O and Sorci, G (2007) Testosterone and oxidative stress: the oxidation handicap hypothesis. Proceedings. Biological Sciences 274, 819.Google Scholar
Aviv, A, Shay, JW, Karre, C and Wright, WE (2005) The longevity gender gap: are telomeres the explanation? Science of Aging Knowledge Environment 2005, e16.CrossRefGoogle ScholarPubMed
Barbé-Tuana, FM, Parisi, MM, Panizzutti, BS, Fries, GR, Grun, LK, Guma, FT, Kapczinski, F, Berk, M, Gama, CS and Rosa, AR (2016) Shortened telomere length in bipolar disorder: a comparison of the early and late stages of disease. Brazilian Journal of Psychiatry 38, 281286.CrossRefGoogle ScholarPubMed
Barczak, W, Rozwadowska, N, Romaniuk, A, Lipińska, N, Lisiak, N, Grodecka-Gazdecka, S, Książek, K and Rubiś, B (2016) Telomere length assessment in leukocytes presents potential diagnostic value in patients with breast cancer. Oncology Letters 11, 23052309.CrossRefGoogle ScholarPubMed
Barrett, EL and Richardson, DS (2011) Sex differences in telomeres and lifespan. Aging Cell 10, 913921.CrossRefGoogle ScholarPubMed
Benetos, A, Okuda, K, Lajemi, M, Kimura, M, Thomas, F, Skurnick, J, Labat, C, Bean, K and Aviv, A (2001) Telomere length as an indicator of biological aging: the gender effect and relation with pulse pressure and pulse wave velocity. Hypertension 37, 381385.CrossRefGoogle ScholarPubMed
Cawthon, RM (2009) Telomere length measurement by a novel monochrome multiplex quantitative PCR method. Nucleic Acids Research 37, e21.CrossRefGoogle ScholarPubMed
Colpo, GD, Leffa, DD, Köhler, CA, Kapczinski, F, Quevedo, J and Carvalho, AF (2015) Is bipolar disorder associated with accelerating aging? A meta-analysis of telomere length studies. Journal of Affective Disorders 186, 241248.CrossRefGoogle ScholarPubMed
Coutts, F, Palmos, AB, Duarte, RRR, de Jong, S, Lewis, CM, Dima, D and Powell, TR (2019) The polygenic nature of telomere length and the anti-ageing properties of lithium. Neuropsychopharmacology 44, 757765.CrossRefGoogle ScholarPubMed
de Melo, LGP, Nunes, SOV, Anderson, G, Vargas, HO, Barbosa, DS, Galecki, P, Carvalho, AF and Maes, M (2017) Shared metabolic and immune-inflammatory, oxidative and nitrosative stress pathways in the metabolic syndrome and mood disorders. Progress in Neuro-psychopharmacology & Biological Psychiatry 78, 3450.CrossRefGoogle Scholar
Elvsåshagen, T, Vera, E, Bøen, E, Bratlie, J, Andreassen, O, Josefsen, D, Malt, U, Blasco, M and Boye, B (2011) The load of short telomeres is increased and associated with lifetime number of depressive episodes in bipolar II disorder. Journal of Affective Disorders 135, 4350.CrossRefGoogle ScholarPubMed
Fries, GR, Bauer, IE Scaini, G, Wu, MJ, Kazimi, IF, Valvassori, SS, Zunta-Soares, G, Walss-Bass, C, Soares, JC and Quevedo, J (2017) Accelerated epigenetic aging and mitochondrial DNA copy number in bipolar disorder. Translational Psychiatry 7, 1283.CrossRefGoogle ScholarPubMed
Fries, GR, Zamzow, MJ, Andrews, T, Pink, O, Scaini, G and Quevedo, J (2020a) Accelerated aging in bipolar disorder: a comprehensive review of molecular findings and their clinical implications. Neuroscience and Biobehavioral Reviews 112, 107116.CrossRefGoogle ScholarPubMed
Fries, GR, Zamzow, MJ, Colpo, GD, Monroy-Jaramillo, N, Quevedo, J, Arnold, JG, Bowden, CL and Walss-Bass, C (2020b) The anti-aging effects of lithium in lymphoblastoid cell lines from patients with bipolar disorder and controls. Journal of Psychiatric Research 128, 3842.CrossRefGoogle ScholarPubMed
Gardner, M, Bann, D, Wiley, L, Cooper, R, Hardy, R, Nitsch, D, Martin-Ruiz, C, Shiels, P, Sayer, AA, Barbieri, M, Bekaert, S, Bischoff, C, Brooks-Wilson, A, Chen, W, Cooper, C, Christensen, K, De Meyer, T, Deary, I, Der, G, Diez Roux, A, Fitzpatrick, A, Hajat, A, Halaschek-Wiener, J, Harris, S, Hunt, SC, Jagger, C, Jeon, HS, Kaplan, R, Kimura, M, Lansdorp, P, Li, C, Maeda, T, Mangino, M, Nawrot, TS, Nilsson, P, Nordfjall, K, Paolisso, G, Ren, F, Riabowol, K, Robertson, T, Roos, G, Staessen, JA, Spector, T, Tang, N, Unryn, B, van der Harst, P, Woo, J, Xing, C, Yadegarfar, ME, Park, JY, Young, N, Kuh, D, von Zglinicki, T and Ben-Shlomo, Y (2014) Halcyon study team. Gender and telomere length: systematic review and meta-analysis. Experimental Gerontology 51, 1527.CrossRefGoogle Scholar
Hartmann, N, Boehner, M, Groenen, F and Kalb, R (2010) Telomere length of patients with major depression is shortened but independent from therapy and severity of the disease. Depression and Anxiety 27, 11111116.CrossRefGoogle ScholarPubMed
Huang, YC, Wang, LJ, Tseng, PT, Hung, CF and Lin, PY (2018) Leukocyte telomere length in patients with bipolar disorder: an updated meta-analysis and subgroup analysis by mood status. Psychiatry Research 270, 4149.CrossRefGoogle ScholarPubMed
Kahl, VFS, Allen, JAM, Nelson, CB, Sobinoff, AP, Lee, M, Kilo, T, Vasireddy, RS and Pickett, HA (2020) Telomere length measurement by molecular combing. Frontiers in Cell and Developmental Biology 8, 493.CrossRefGoogle ScholarPubMed
Kessing, LV, Vradi, E, McIntyre, RS and Andersen, PK (2015) Causes of decreased life expectancy over the life span in bipolar disorder. Journal of Affective Disorders 180, 142147.CrossRefGoogle Scholar
Kimura, M, Stone, RC, Hunt, SC, Skurnick, J, Lu, X, Cao, X, Harley, CB and Aviv, A (2010) Measurement of telomere length by the Southern blot analysis of terminal restriction fragment lengths. Nature Protocols 5, 15961607.CrossRefGoogle ScholarPubMed
Köse Çinar, R (2018) Telomere length and hTERT in mania and subsequent remission. Brazilian Journal of Psychiatry 40, 1925.CrossRefGoogle ScholarPubMed
Lai, TP, Wright, WE and Shay, JW (2018) Comparison of telomere length measurement methods. Philosophical Transactions of the Royal Society of London, Series B: Biological Sciences 373, 20160451.CrossRefGoogle ScholarPubMed
Lai, TP, Zhang, N, Noh, J, Mender, I, Tedone, E, Huang, E, Wright, WE, Danuser, G and Shay, JW (2017) A method for measuring the distribution of the shortest telomeres in cells and tissues. Nature Communications 8, 1356.CrossRefGoogle Scholar
Leboyer, M, Oliveira, J and Tamouza, R (2016) Is it time for immunopsychiatry in psychotic disorders? Psychopharmacology (Berlin) 233, 16511660.CrossRefGoogle Scholar
Lima, IMM, Barros, A, Rosa, DV, Albuquerque, M, Malloy-Diniz, L, Neves, FS, Romano-Silva, MA and de Miranda, DM (2015) Analysis of telomere attrition in bipolar disorder. Journal of Affective Disorders 172, 4347.CrossRefGoogle ScholarPubMed
Liu, L, Trimarchi, JR, Smith, PJS and Keefe, DL (2002) Mitochondrial dysfunction leads to telomere attrition and genomic instability. Aging Cell 1, 4046.CrossRefGoogle ScholarPubMed
Maes, M and Carvalho, AF (2018) The compensatory immune-regulatory reflex system (CIRS) in depression and bipolar disorder. Molecular Neurobiology 55, 88858903.CrossRefGoogle ScholarPubMed
Martinsson, L, Wei, Y, Xu, D, Melas, PA, Mathé, AA, Schalling, M, Lavebratt, C and Backlund, L (2013) Long-term lithium treatment in bipolar disorder is associated with longer leukocyte telomeres. Translational Psychiatry 3, e261.CrossRefGoogle Scholar
Muneer, A and Minhas, FA (2019) Telomere biology in mood disorders: an updated, comprehensive review of the literature. Clinical Psychopharmacology and Neuroscience: The Official Scientific Journal of the Korean College of Neuropsychopharmacology 17, 343363.CrossRefGoogle ScholarPubMed
Muneer, A (2019) Interventions addressing the telomere-telomerase system. Advances in Experimental Medicine and Biology 1192, 521544.CrossRefGoogle ScholarPubMed
O’Callaghan, NJ and Fenech, M (2011) A quantitative PCR method for measuring absolute telomere length. Biological Procedures Online 13, 3.CrossRefGoogle ScholarPubMed
Okazaki, S, Numata, S, Otsuka, I, Horai, T, Kinoshita, M, Sora, I, Ohmori, T and Hishimoto, A (2020) Decelerated epigenetic aging associated with mood stabilizers in the blood of patients with bipolar disorder. Translational Psychiatry 10, 129.CrossRefGoogle ScholarPubMed
Palmos, AB, Duarte, RRR, Smeeth, DM, Hedges, EC, Nixon, DF, Thuret, S and Powell, TR (2020) Telomere length and human hippocampal neurogenesis. Neuropsychopharmacology 45, 22392247.CrossRefGoogle ScholarPubMed
Pisanu, C, Congiu, D, Manchia, M, Caria, P, Cocco, C, Dettori, T, Frau, DV, Manca, E, Meloni, A, Nieddu, M, Noli, B, Pinna, F, Robledo, R, Sogos, V, Ferri, GL, Carpiniello, B, Vanni, R, Bocchetta, A, Severino, G, Ardau, R, Chillotti, C, Zompo, MD and Squassina, A (2020) Differences in telomere length between patients with bipolar disorder and controls are influenced by lithium treatment. Pharmacogenomics 21, 533540.CrossRefGoogle ScholarPubMed
Powell, TR, Dima, D, Frangou, S and Breen, G (2018) Telomere length and bipolar disorder. Neuropsychopharmacology 43, 454.CrossRefGoogle ScholarPubMed
Rizzo, LB, Do Prado, CH, Grassi-Oliveira, R, Wieck, A, Correa, BL, Teixeira, AL and Bauer, ME (2013) Immunosenescence is associated with human cytomegalovirus and shortened telomeres in type I bipolar disorder. Bipolar Disorders 15, 832838.CrossRefGoogle ScholarPubMed
Rubiś, B, Hołysz, H, Barczak, W, Gryczka, R, Łaciński, M, Jagielski, P, Czernikiewicz, A, Półrolniczak, A, Wojewoda, A, Perz, K, Białek, P, Morze, K, Kanduła, Z, Lisiak, N, Mrozikiewicz, PM, Grodecka-Gazdecka, S and Rybczyńska, M (2012) Study of ABCB1 polymorphism frequency in breast cancer patients from Poland. Pharmacological Reports 64, 15601566.CrossRefGoogle ScholarPubMed
Rybakowski, JK and Suwalska, A (2010) Excellent lithium responders have normal cognitive functions and plasma BDNF levels. International Journal of Neuropsychopharmacology 13, 617622.CrossRefGoogle ScholarPubMed
Simon, NM, Smoller, JW, McNamara, KL, Maser, RS, Zalta, AK, Pollack, MH, Nierenberg, AA, Fava, M and Wong, KK (2006) Telomere shortening and mood disorders: preliminary support for a chronic stress model of accelerated aging. Biological Psychiatry 60, 432435.CrossRefGoogle ScholarPubMed
Squassina, A, Manchia, M, Pisanu, C, Ardau, R, Arzedi, C, Bocchetta, A, Caria, P, Cocco, C, Congiu, D, Cossu, E, Dettori, T, Frau, DV, Garzilli, M, Manca, E, Meloni, A, Montis, MA, Mura, A, Nieddu, M, Noli, B, Paribello, P, Pinna, F, Robledo, R, Severino, G, Sogos, V, Del Zompo, M, Ferri, GL, Chillotti, C, Vanni, R and Carpiniello, B (2020) Telomere attrition and inflammatory load in severe psychiatric disorders and in response to psychotropic medications. Neuropsychopharmacology 45, 22292238.CrossRefGoogle ScholarPubMed
Squassina, A, Pisanu, C, Congiu, D, Caria, P, Frau, D, Niola, P, Melis, C, Baggiani, G, Lopez, JP, Cruceanu, C, Turecki, G, Severino, G, Bocchetta, A, Vanni, R, Chillotti, C and Del Zompo, M (2016) Leukocyte telomere length positively correlates with duration of lithium treatment in bipolar disorder patients. European Neuropsychopharmacology 26, 12411247.CrossRefGoogle ScholarPubMed
Squassina, A, Pisanu, C and Vanni, R (2019) Mood disorders, accelerated aging, and inflammation: is the link hidden in telomeres? Cells 8, 52.CrossRefGoogle ScholarPubMed
Squassina, A, Pisanu, C, Corbett, N and Alda, M (2017) Telomere length in bipolar disorder and lithium response. European Neuropsychopharmacology 27, 560567.CrossRefGoogle ScholarPubMed
Vaiserman, A and Krasnienkov, D (2020) Telomere length as a marker of biological age: state-of-the-art, open issues, and future perspectives. Frontiers in Genetics 11, 630186.CrossRefGoogle ScholarPubMed
Vasconcelos-Moreno, MP, Fries, GR, Gubert, C, Dos Santos, BTMQ, Fijtman, A, Sartori, J, Ferrari, P, Grun, LK, Parisi, MM, Guma, FTCR, Barbé-Tuana, FM, Kapczinski, F, Rosa, AR, Yatham, LN and Kauer-Sant’Anna, M (2017) Telomere length, oxidative stress, inflammation and BDNF levels in siblings of patients with bipolar disorder: implications for accelerated cellular aging. Int J Neuropsychopharmacology 20, 445454.CrossRefGoogle ScholarPubMed
Velosa, J, Delgado, A, Finger, E, Berk, M, Kapczinski, F and de Azevedo Cardoso, T (2020) Risk of dementia in bipolar disorder and the interplay of lithium: a systematic review and meta-analyses. Acta Psychiatrica Scandinavica 141, 510521.CrossRefGoogle ScholarPubMed
Verhoeven, JE, Révész, D, Epel, ES, Lin, J, Wolkowitz, OM and Penninx, BW (2014) Major depressive disorder and accelerated cellular aging: results from a large psychiatric cohort study. Molecular Psychiatry 19, 895901.CrossRefGoogle ScholarPubMed