Individual variation in plasma oxytocin and vasopressin levels in relation to the development of combat-related PTSD in a large military cohort Alieke Reijnen a, b, c, * , Elbert Geuze a, b , Eric Vermetten a, b, c, d a Research Centre, Military Mental Healthcare, Utrecht, The Netherlands b Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands c Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands d Arq, Psychotrauma Expert Group, Diemen, The Netherlands article info Article history: Received 9 March 2017 Received in revised form 20 June 2017 Accepted 27 June 2017 Keywords: Oxytocin Arginine vasopressin Posttraumatic stress disorder Military Deployment Susceptibility marker abstract In an attempt to decrease the risk of developing mental health problems after military deployment, it is important to find biological markers to identify those at risk. Oxytocin (OT) and arginine vasopressin (AVP) are potential biomarkers for the development of posttraumatic stress disorder (PTSD) because they are involved in the regulation of stress and anxiety. Therefore, the aim was to examine whether plasma OT (pOT) and AVP (pAVP) levels before and after deployment are biomarkers for the development of posttraumatic stress symptoms over time in addition to other known risk factors. This study is part of a large prospective cohort study on candidate markers for stress-related mental health symptoms and resiliency after deployment to a combat zone; Prospective Research in Stress-related Military Operations (PRISMO; N ¼ 907). Data was collected prior to deployment and follow-ups were performed at 1 and 6 months, and 1, 2, and 5 years post-deployment. Blood samples were collected in the first three assess- ments. The levels of pOT and pAVP were not significantly related to the development of PTSD symptoms over time. The results confirm that age, the experience of early life trauma, combat-related stressors and the presence of depressive symptoms are predictive for the development of PTSD symptoms over time. These findings showed that peripherally measured OT and AVP currently do not qualify as useful sus- ceptibility biomarkers for the development of PTSD symptoms over time in military men after combat. © 2017 Elsevier Ltd. All rights reserved. 1. Introduction Military personnel are at increased risk of developing mental health problems after deployment to a combat zone (Reijnen et al., 2015; Smith et al., 2008). In US combat veterans, a threefold in- crease in posttraumatic stress symptoms was found three years after deployment to Iraq or Afghanistan (Smith et al., 2008). In Dutch military personnel, a high level of posttraumatic stress symptoms was reported by 9% of the participants at six months and 13% at 5 years after deployment to Afghanistan compared to 4% prior to deployment (Eekhout et al., 2016b). Moreover, military personnel with mental health problems place an increased burden on consumption of (mental) health care (Eekhout et al., 2016a). Age, early life trauma and combat-related stressors were reported to be risk factors for the development of PTSD symptoms (Eekhout et al., 2016b). In addition to these factors, it is important to find biological susceptibility markers to identify those at risk for the development of combat-related posttraumatic stress disorder (PTSD). Two potentially useful markers that have been proposed are oxytocin (OT) and arginine vasopressin (AVP; Kang et al., 2015). Both OT and AVP are nonapeptides, which are produced in the hypothalamus and secreted in the bloodstream by the posterior pituitary (Ludwig and Leng, 2006). They are potentially interesting because of their role in social behavior and in the regulation of stress and anxiety (Ditzen et al., 2009; Heinrichs et al., 2003; Neumann and Landgraf, 2012). Moreover, individual differences in the levels of these neuropeptides have been suggested to relate to symptoms of various psychiatric disorders (Meyer-Lindenberg et al., 2011). Oxytocin is often reported to exert anxiolytic effects and to * Corresponding author. Military Mental Healthcare - Research Centre, P.O. Box 90.000, 3509 AA Utrecht, The Netherlands. E-mail address: A.Reijnen@umcutrecht.nl (A. Reijnen). Contents lists available at ScienceDirect Journal of Psychiatric Research journal homepage: www.elsevier.com/locate/psychires http://dx.doi.org/10.1016/j.jpsychires.2017.06.010 0022-3956/© 2017 Elsevier Ltd. All rights reserved. Journal of Psychiatric Research 94 (2017) 88e95