Research Article Cytomegalovirus Antibody Elevation in Bipolar Disorder: Relation to Elevated Mood States A. R. Prossin, 1,2 R. H. Yolken, 3 M. Kamali, 4 M. M. Heitzeg, 4 J. B. Kaplow, 1 W. H. Coryell, 5 and M. G. McInnis 4 1 Department of Psychiatry, University of Texas Health Science Center at Houston, 1941 East Road, No. 2308, Houston, TX 77054, USA 2 Department of Symptom Research, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA 3 Stanley Laboratory of Developmental Neurovirology, Johns Hopkins University Medical Center, Baltimore, MD 21287, USA 4 Department of Psychiatry, University of Michigan Medical School, Ann Arbor, MI 48109, USA 5 Department of Psychiatry, University of Iowa School of Medicine, Iowa City, IA 52242, USA Correspondence should be addressed to A. R. Prossin; alan.prossin@uth.tmc.edu Received 11 September 2014; Accepted 23 October 2014 Academic Editor: Jo˜ ao Quevedo Copyright © A. R. Prossin et al. his is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. he neurobiology of mood states is complicated by exposure to everyday stressors (e.g., psychosocial, ubiquitous environmental infections like CMV), each luctuating between latency and reactivation. CMV reactivation induces proinlammatory cytokines (e.g., TNF-) associated with induction of neurotoxic metabolites and the presence of mood states in bipolar disorder (BD). Whether CMV reactivation is associated with bipolar diagnoses (trait) or speciic mood states is unclear. We investigated 139BD type I and 99 healthy controls to determine if concentrations of IgG antibodies to Herpesviridae (e.g., CMV, HSV-1, and HSV- 2) were associated with BD-I diagnosis and speciic mood states. We found higher CMV antibody concentration in BD-I than in healthy controls (T 234 = 3.1,  uncorr = 0.002;  corr = 0.006) but no diference in HSV-1 ( > 0.10) or HSV-2 ( > 0.10). Compared to euthymic BD-I volunteers, CMV IgG was higher in BD-I volunteers with elevated moods ( < 0.03) but not diferent in depressed moods ( > 0.10). While relationships presented between BD-I diagnosis, mood states, and CMV antibodies are encouraging, they are limited by the study’s cross sectional nature. Nevertheless, further testing is warranted to replicate indings and determine whether reactivation of CMV infection exacerbates elevated mood states in BD-I. 1. Introduction Bipolar disorder (BD) a mood disorder characterized by the presence of elevated, irritable, or mixed mood episodes frequently interspersed with episodes of depression afects approximately 2-3% of the population [1–3]. Despite sub- stantial individual and societal impact, knowledge of the biological processes underlying and driving mood states in BD is limited. Revealing associations between biological factors and both mood traits and states will set a trajectory for understanding the pathophysiology of moods and in developing novel, more eicacious intervention strategies in BD. Ubiquitous environmental infections (e.g., Herpesviridae including cytomegalovirus; CMV) and associated human immune responses luctuate between latency and reactivation in humans, potentially triggered by psychosocial stressors [4– 6]. Viruses may facilitate exacerbation of psychiatric disease pathology through various mechanisms, including induction of inlammatory factors (e.g., TNF-, IL-6, etc.) [7] or via direct interactions with speciic illness susceptibility genes. A recent preliminary fMRI study of pediatric bipolar disorder may suggest a mechanism whereby alterations in TNF- related processes could impact some of the symptoms in BD-I. In this study, Barzman et al. identiied correlations between 11 TNF- related gene expressions and activation within the amygdala or anterior cingulate cortex during the afective Posner task [8]. Evidence from recent studies in BD also shows that TNF- is higher in BD volunteers compared to healthy control volunteers [9, 10]. Further, as outlined in Hindawi Publishing Corporation Neural Plasticity Article ID 939780