Consistent associations between measures of psychological stress and CMV antibody levels in a large occupational sample Jerrald L. Rector a,b , Jennifer B. Dowd c , Adrian Loerbroks b,d , Victoria E. Burns a , Paul A. Moss e , Marc N. Jarczok b , Tobias Stalder f , Kristina Hoffman b , Joachim E. Fischer b , Jos A. Bosch b,g,h,⇑ a School of Sport, Exercise, and Rehabilitation Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom b Mannheim Institute of Public Health, Social and Preventive Medicine (MIPH), Mannheim Medical Faculty, University of Heidelberg, Ludolf-Krehl-Str. 7-11, D-68167 Mannheim, Germany c CUNY School of Public Health and CUNY Institute for Demographic Research (CIDR), One Bernard Baruch Way, New York, NY 10010, USA d Institute of Occupational and Social Medicine, Centre for Health and Society, Faculty of Medicine, University of Düsseldorf, Universitätsstrasse 1, 40225 Düsseldorf, Germany e Cancer Research UK Centre, University of Birmingham, Edgbaston, Birmingham B152TT, United Kingdom f Department of Psychology, Technische Universität Dresden, 01069 Dresden, Germany g Department of Psychology, University of Amsterdam, Weesperplein 4, 1018 XA Amsterdam, The Netherlands h Laboratory of Integrated Physiology, Department of Health and Human Performance, University of Houston, Houston, TX, USA article info Article history: Received 1 November 2013 Received in revised form 16 January 2014 Accepted 17 January 2014 Available online 26 January 2014 Keywords: Anxiety CMV Cytomegalovirus Depression Herpes virus Mental health Psychological stress Psychoneuroimmunology Reactivation Socioeconomic status Vital exhaustion abstract Cytomegalovirus (CMV) is a herpes virus that has been implicated in biological aging and impaired health. Evidence, largely accrued from small-scale studies involving select populations, suggests that stress may promote non-clinical reactivation of this virus. However, absent is evidence from larger stud- ies, which allow better statistical adjustment for confounding and mediating factors, in more represen- tative samples. The present study involved a large occupational cohort (N = 887, mean age = 44, 88% male). Question- naires assessed psychological (i.e., depression, anxiety, vital exhaustion, SF-12 mental health), demo- graphic, socioeconomic (SES), and lifestyle variables. Plasma samples were analyzed for both the presence and level of CMV-specific IgG antibodies (CMV-IgG), used as markers for infection status and viral reactivation, respectively. Also assessed were potential biological mediators of stress-induced reac- tivation, such as inflammation (C-reactive protein) and HPA function (awakening and diurnal cortisol). Predictors of CMV infection and CMV-IgG among the infected individuals were analyzed using logistic and linear regression analyses, respectively. Confirming prior reports, lower SES (education and job status) was positively associated with infection status. Among those infected (N = 329), higher CMV-IgG were associated with increased anxiety (b = .14, p < .05), depression (b = .11, p = .06), vital exhaustion (b = .14, p < .05), and decreased SF-12 mental health (b = À.14, p < .05), adjusting for a range of potential confounders. Exploratory analyses showed that these associations were generally stronger in low SES individuals. We found no evidence that elevated inflam- mation or HPA-function mediated any of the associations. In the largest study to date, we established associations between CMV-IgG levels and multiple indica- tors of psychological stress. These results demonstrate the robustness of prior findings, and extend these to a general working population. We propose that stress-induced CMV replication warrants further research as a psychobiological mechanism linking stress, aging and health. Ó 2014 Published by Elsevier Inc. 1. Introduction There is convincing evidence that psychological stress impacts health, with the immune system likely playing an important mediating role (Miller et al., 2009; Segerstrom and Miller, 2004). An elegant in vivo paradigm to study the impact of stress on the immune system is the reactivation of latent herpes viruses, such as herpes simplex virus (HSV), Epstein-Barr virus (EBV), varicella zoster virus (VZV), or cytomegalovirus (CMV) (Glaser and Kiecolt-Glaser, 1997, 2005). These infections are distinctive because the host is unable to completely eliminate the virus, establishing a life-long competition between the pathogen and the host immune system (Sinclair, 2008). In immune competent http://dx.doi.org/10.1016/j.bbi.2014.01.012 0889-1591/Ó 2014 Published by Elsevier Inc. ⇑ Corresponding author at: Department of Psychology, University of Amsterdam, Weesperplein 4, 1018 XA Amsterdam, The Netherlands. Tel.: +31 (0) 20 525 6819; fax: +31 (0) 20 639 1369. E-mail address: j.a.bosch@uva.nl (J.A. Bosch). Brain, Behavior, and Immunity 38 (2014) 133–141 Contents lists available at ScienceDirect Brain, Behavior, and Immunity journal homepage: www.elsevier.com/locate/ybrbi