Original Article Immunosenescence is associated with human cytomegalovirus and shortened telomeres in type I bipolar disorder Rizzo LB, Do Prado CH, Grassi-Oliveira R, Wieck A, Correa BL, Teixeira AL, Bauer ME. Immunosenescence is associated with human cytomegalovirus and shortened telomeres in type I bipolar disorder. Bipolar Disord 2013: 15: 832–838. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. Objective: Bipolar disorder (BD) has been associated with persistent low-grade inflammation and premature cell senescence, as shown by reduced telomere length (TL). The human cytomegalovirus (CMV) has increasingly been implicated in accelerated immunosenescence in aging studies. Here, we compared CMV serology and its relationships with cell senescence markers, including TL and lymphocyte subsets, in patients with type I BD and healthy controls. Methods: Twenty-two euthymic female patients with BD type I and 17 age-matched healthy controls were selected for the study. A sample of blood was collected and mononuclear cells and DNA were isolated and TL measured. CMV immunoglobulin M (IgM) and IgG titers were measured using chemiluminescent assays. Lymphocyte subsets [T, natural killer (NK) and NKT] were phenotyped by flow cytometry. Results: Individuals with BD had shorter TLs but higher CMV IgG levels than controls (both p < 0.01). CMV IgG level was inversely correlated with TL. None of the subjects showed IgM reactivity for CMV, excluding acute viral infection. CMV IgG level was associated with expansion of senescent CD8+CD28À T cells and NK cells, which are involved in viral control. Conclusions: These data support the hypothesis of accelerated aging in BD, as shown by shortened telomeres, higher seropositivity for CMV, and expansion of senescent T cells. Lucas Bortolotto Rizzo a, *, Carine Hartmann Do Prado a, *, Rodrigo Grassi-Oliveira a,b , Andr  ea Wieck a , Bruna Luz Correa a , Antonio Lucio Teixeira c and Mois  es Evandro Bauer a,b a Laboratory of Immunosenescence, Institute of Biomedical Research, Pontifical Catholic University of the Rio Grande do Sul (PUCRS), Porto Alegre, b Faculty of Psychology, Center of Studies and Research in Traumatic Stress (NEPTE), PUCRS, Porto Alegre, c Translational Psychoneuroimmunology Group, UFMG, Belo Horizonte, Brazil *These authors contributed equally to this work. doi: 10.1111/bdi.12121 Key words: bipolar disorder – cytomegalovirus – immunosenescence – lymphocytes – telomeres Received 8 October 2012, revised and accepted for publication 26 April 2013 Corresponding author: Dr. Mois es E. Bauer Faculty of Biosciences Instituto de Pesquisas Biom edicas Hospital S~ ao Lucas da PUCRS Av. Ipiranga 6690, 2 º andar P.O. Box 1429 Porto Alegre RS 90.610-000 Brazil Fax: +55 51 33203312 E-mail: mebauer@pucrs.br Bipolar disorder (BD) has been associated with immunologic imbalance—as shown by increased plasma inflammatory markers (1–4)—and acceler- ated cell aging (5, 6). Shortened telomeres are good correlates of replicative senescence, oxidative stress and aging and have been previously documented in major depression (7), in BD type II (8), and in a pool of patients with BD types I and II (5). The accelerated cell senescence in BD can be demon- strated by changes in specific lymphocyte subsets. We have reported an increased number of late-dif- ferentiated CD8+ T cells that lack CD28 expres- sion (CD8+CD28À) in euthymic patients with type I BD (9). These cells are expanded during aging, 832 Bipolar Disorders 2013: 15: 832–838 © 2013 John Wiley & Sons A/S Published by John Wiley & Sons Ltd. BIPOLAR DISORDERS