title: Leukocyte telomere length positively correlates with duration of lithium treatment in bipolar disorder patients.
abstract: 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.
authors.affiliation: Department of Biomedical Sciences, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, Italy. Electronic address: squassina@unica.it.
authors.forename: Alessio
authors.initials: A
authors.lastname: Squassina
authors.affiliation: Department of Biomedical Sciences, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Pisanu
authors.affiliation: Department of Biomedical Sciences, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Congiu
authors.affiliation: Department of Biomedical Sciences, Unit of Biology and Genetics, University of Cagliari, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Caria
authors.affiliation: Department of Biomedical Sciences, Unit of Biology and Genetics, University of Cagliari, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Frau
authors.affiliation: Department of Biomedical Sciences, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Niola
authors.affiliation: Department of Biomedical Sciences, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Melis
authors.affiliation: Unit of Clinical Pharmacology of the University Hospital of Cagliari, Italy.
authors.forename: Gioia
authors.initials: G
authors.lastname: Baggiani
authors.affiliation: McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada.
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Lopez
authors.affiliation: McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada.
authors.forename: Cristiana
authors.initials: C
authors.lastname: Cruceanu
authors.affiliation: McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Turecki
authors.affiliation: Department of Biomedical Sciences, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Severino
authors.affiliation: Unit of Clinical Pharmacology of the University Hospital of Cagliari, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Bocchetta
authors.affiliation: Department of Biomedical Sciences, Unit of Biology and Genetics, University of Cagliari, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Vanni
authors.affiliation: Unit of Clinical Pharmacology of the University Hospital of Cagliari, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Chillotti
authors.affiliation: Department of Biomedical Sciences, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, Italy; Unit of Clinical Pharmacology of the University Hospital of Cagliari, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Del Zompo
mesh_terms: D000328:Adult; D000367:Age Factors; D018692:Antimanic Agents / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D018020:Lithium Compounds / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D058953:Neural Stem Cells / Q000187:drug effects / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012737:Sex Factors; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000187:drug effects* / Q000378:metabolism*; D059506:Telomere Shortening / Q000187:drug effects; D013997:Time Factors
chemical_list: D018692:Antimanic Agents; D018020:Lithium Compounds; C509186:TERT protein, human; D019098:Telomerase
keywords: Bipolar disorder; Leukocyte telomere length; Lithium; Neural progenitor cells; Quantitative real time PCR; Telomerase