+ Models PNEC-1715; No of Pages 10 Please cite this article in press as: Pesonen, A.-K., et al., Childhood separation experience predicts HPA axis hormonal responses in late adulthood: A natural experiment of World War II. Psychoneuroendocrinology (2009), doi:10.1016/j.psyneuen.2009.10.017 Childhood separation experience predicts HPA axis hormonal responses in late adulthood: A natural experiment of World War II Anu-Katriina Pesonen a,b , Katri Ra ¨ikko ¨nen b, * , Kimmo Feldt b , Kati Heinonen b , Clive Osmond c , David I.W. Phillips c , David J.P. Barker c,d , Johan G. Eriksson e,f,g,h , Eero Kajantie a,i a Department of Clinical Medicine, Hospital for Children and Adolescents, Helsinki University Central Hospital and University of Helsinki, Finland b Department of Psychology, University of Helsinki, Helsinki, Finland c MRC Epidemiology Resource Centre, and Developmental Origins of Health and Disease Division, University of Southampton, Southampton, UK d Heart Research Center, Department of Medicine, Oregon Health & Sciences University, Portland, USA e Department of Public Health, University of Helsinki, Helsinki, Finland f Vasa Central Hospital, Vasa, Finland g Helsinki University Central Hospital, Unit of General Practice, Helsinki, Finland h Folkha¨lsan Research Centre, Helsinki, Finland i National Institute for Health and Welfare, Department of Chronic Disease Prevention, Helsinki, Finland Received 15 April 2009; received in revised form 28 October 2009; accepted 29 October 2009 Psychoneuroendocrinology (2009) xxx, xxx—xxx KEYWORDS ACTH; Child; Cortisol; ELS; HPA; Old age; Psychological trauma; Stress Summary Background: Animal models have linked early maternal separation with lifelong changes in hypothalamic—pituitary—adrenocortical (HPA) axis activity. Although this is paralleled in human studies, this is often in the context of other life adversities, for example, divorce or adoption, and it is not known whether early separation in the absence of these factors has long term effects on the HPA axis. Aims: The Finnish experience in World War II created a natural experiment to test whether separation from a father serving in the armed forces or from both parents due to war evacuation are associated with alterations in HPA axis response to psychosocial stress in late adulthood. Method: 282 subjects (M = 63.5 years, SD = 2.5), of whom 85 were non-separated, 129 were separated from their father, and 68 were separated from both their caregivers during WWII, were enlisted to participate in a Trier Social Stress Test (TSST), during which we measured salivary cortisol and, for 215 individuals, plasma cortisol and ACTH concentrations. We used mixed models * Corresponding author at: Department of Psychology, Siltavuorenpenger 20d, PO Box 9, 00014 University of Helsinki, Finland. E-mail address: katri.raikkonen@helsinki.fi (K. Ra ¨ikko ¨nen). available at www.sciencedirect.com journal homepage: www.elsevier.com/locate/psyneuen 0306-4530/$ — see front matter # 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.psyneuen.2009.10.017