Leukocyte telomere length positively correlates with duration of lithium treatment in bipolar disorder patients

被引:58
作者
Squassina, Alessio [1 ]
Pisanu, Claudia [1 ]
Congiu, Donatella [1 ]
Caria, Paola [2 ]
Frau, Daniela [2 ]
Niola, Paola
Melis, Carla [1 ]
Baggiani, Gioia [3 ]
Lopez, Juan Pablo [4 ]
Cruceanu, Cristiana [4 ]
Turecki, Gustavo [4 ]
Severino, Giovanni [1 ]
Bocchetta, Alberto [3 ]
Vanni, Roberta [2 ]
Chillotti, Caterina [3 ]
Del Zompo, Maria [1 ,3 ]
机构
[1] Univ Cagliari, Sect Neurosci & Clin Pharmacol, Dept Biomed Sci, Cittadella Univ Monserrato,Sp 6,Km 0-700, I-09042 Cagliari, Italy
[2] Univ Cagliari, Unit Biol & Genet, Dept Biomed Sci, Cagliari, Italy
[3] Univ Hosp Cagliari, Unit Clin Pharmacol, Cagliari, Italy
[4] McGill Univ, Douglas Mental Hlth Univ Inst, McGill Grp Suicide Studies, Montreal, PQ, Canada
关键词
Leukocyte telomere length; Bipolar disorder; Lithium; Tetomerase; Quantitative real time PCR; Neural progenitor cells; LYMPHOBLASTOID CELL-LINES; GROWTH-FACTOR; BRAIN; EXPRESSION; LIFETIME; CANCER; MODEL; MICE;
D O I
10.1016/j.euroneuro.2016.03.020
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Bipolar disorder (BD) has been suggested to be associated with accelerated aging and premature cell senescence. While findings on shorter telomeres in BD are controversial, a recent study showed that long-term lithium treatment correlates with longer telomeres in BD. In our study, we sought to investigate the correlation between leukocyte telomere length (LTL) and long-term lithium treatment in a sample of 200 BD patients characterized for lithium response. We also compared data from two different methods commonly used to measure telomere length, quantitative PCR (qPCR) and quantitative fluorescence in situ hybridization (Q-FISH). We also measured, for the first time, the effect of lithium in vitro on the expression of the telomerase gene in human-derived neural progenitor cells (NPCs). Our findings showed that LTL correlated negatively with age (p=0.0002) and was independent of sex, diagnosis, age at onset, suicidal behavior, number of mood episodes, response to lithium and use of other psychotropic medications. After correcting for age, LTL was positively correlated with lithium treatment duration in patients treated for more than two years (n=150, R=0.17, p=0.037). There was a significant correlation between data measured with qPCR and Q-FISH (p=0.012, R=0.826). Lithium treatment increased telomerase expression in NPCs, though this effect was not statistically significant. Our data support previous findings showing that long-term lithium treatment associates with longer telomeres in BD, though this effect appeared to be independent from clinical response to the treatment. Moreover, we suggested for the first time that lithium increases the expression of telomerase gene in human neural progenitor cells. (C) 2016 Elsevier B.V. and ECNP. All rights reserved.
引用
收藏
页码:1241 / 1247
页数:7
相关论文
共 46 条
[1]   Lithium treatment alters brain concentrations of nerve growth factor, brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor in a rat model of depression [J].
Angelucci, F ;
Aloe, L ;
Jiménez-Vasquez, P ;
Mathé, AA .
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY, 2003, 6 (03) :225-231
[2]   Genetic variation in human telomerase is associated with telomere length in Ashkenazi centenarians [J].
Atzmon, Gil ;
Cho, Miook ;
Cawthon, Richard M. ;
Budagov, Temuri ;
Katz, Micol ;
Yang, Xiaoman ;
Siegel, Glenn ;
Bergman, Aviv ;
Huffman, Derek M. ;
Schechter, Clyde B. ;
Wright, Woodring E. ;
Shay, Jerry W. ;
Barzilai, Nir ;
Govindaraju, Diddahally R. ;
Suh, Yousin .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 :1710-1717
[3]   Telomeres and endocrine dysfunction of the adrenal and GH/IGF-1 axes [J].
Aulinas, Anna ;
Jose Ramirez, Maria ;
Jose Barahona, Maria ;
Mato, Eugenia ;
Bell, Olga ;
Surralles, Jordi ;
Webb, Susan M. .
CLINICAL ENDOCRINOLOGY, 2013, 79 (06) :751-759
[4]   Impartial comparative analysis of measurement of leukocyte telomere length/DNA content by Southern blots and qPCR [J].
Aviv, Abraham ;
Hunt, Steven C. ;
Lin, Jue ;
Cao, Xiaojian ;
Kimura, Masayuki ;
Blackburn, Elizabeth .
NUCLEIC ACIDS RESEARCH, 2011, 39 (20)
[5]   Telomere length predicts survival independent of genetic influences [J].
Bakaysa, Stephanie L. ;
Mucci, Lorelei A. ;
Slagboom, P. Eline ;
Boomsma, Dorret I. ;
McClearn, Gerald E. ;
Johansson, Boo ;
Pedersen, Nancy L. .
AGING CELL, 2007, 6 (06) :769-774
[6]   Higher circulating levels of IGF-1 are associated with longer leukocyte telomere length in healthy subjects [J].
Barbieri, Michelangela ;
Paolisso, Giuseppe ;
Kimura, Masayuki ;
Gardner, Jeffrey P. ;
Boccardi, Virginia ;
Papa, Michela ;
Hjelmborg, Jacob V. ;
Christensen, Kaare ;
Brimacombe, Michael ;
Nawrot, Tim S. ;
Staessen, Jan A. ;
Pollak, Michael N. ;
Aviv, Abraham .
MECHANISMS OF AGEING AND DEVELOPMENT, 2009, 130 (11-12) :771-776
[7]   The paradoxical pro- and anti-apoptotic actions of GSK3 in the intrinsic and extrinsic apoptosis signaling pathways [J].
Beurel, Eleonore ;
Jope, Richard S. .
PROGRESS IN NEUROBIOLOGY, 2006, 79 (04) :173-189
[8]   Telomeres and telomerase:: the path from maize, Tetrahymena and yeast to human cancer and aging [J].
Blackburn, Elizabeth H. ;
Greider, Carol W. ;
Szostak, Jack W. .
NATURE MEDICINE, 2006, 12 (10) :1133-1138
[9]   Telomeres in Molecular Epidemiology Studies [J].
Bodelon, Clara ;
Savage, Sharon A. ;
Gadalla, Shahinaz M. .
TELOMERES IN HEALTH AND DISEASE, 2014, 125 :113-131
[10]   Properties of a fetal multipotent neural stem cell (NEP cell) [J].
Cai, JL ;
Wu, YY ;
Mirua, T ;
Pierce, JL ;
Lucero, MT ;
Albertine, KH ;
Spangrude, GJ ;
Rao, MS .
DEVELOPMENTAL BIOLOGY, 2002, 251 (02) :221-240