Psychoneuroendocrinology (2015) 51, 135—150 Available online at www.sciencedirect.com ScienceDirect j ourna l h om epa ge : www.elsevier.com/locate/psyneuen Alterations in HPA-axis and autonomic nervous system functioning in childhood anxiety disorders point to a chronic stress hypothesis Gwendolyn C. Dieleman a,* , Anja C. Huizink b , Joke H.M. Tulen c , Elisabeth M.W.J. Utens a , Hanneke E. Creemers d , Jan van der Ende a , Frank C. Verhulst a a Department of Child and Adolescent Psychiatry/Psychology, Erasmus Medical Center Rotterdam/Sophia Children’s Hospital, Rotterdam, The Netherlands b Department of Child Development, Faculty of Psychology and Education, Vrije Universiteit, Amsterdam, The Netherlands c Department of Psychiatry, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands d Faculty of Social and Behavioral Science, University of Amsterdam, Amsterdam, The Netherlands Received 11 April 2014; received in revised form 14 August 2014; accepted 3 September 2014 KEYWORDS Anxiety disorder; Autonomic nervous system; Cortisol; Child; HPA-axis; Psychophysiology; Stress, Perceived arousal; Comorbidity, Severity Summary Background: It is of debate whether or not childhood anxiety disorders (AD) can be captured by one taxonomic construct. This study examined whether perceived arousal (PA), autonomic nervous system (ANS) and hypothalamic—pituitary—adrenal (HPA) axis measures can distinguish children with different primary diagnoses of clinical anxiety disorders (AD) from each other, and from a general population reference group (GP). Methods: The study sample consisted of 152 AD children (comparing separation anxiety disorder, generalized anxiety disorder, social phobia and specific phobia), aged 8- to 12-years, and 200 same-aged reference children. HPA-axis functioning was measured by a diurnal cortisol profile. ANS functioning was measured by continuous measures of skin conductance level in rest and during a mental arithmetic task and high frequency heart rate variability in rest. PA was assessed by a questionnaire. ∗ Corresponding author at: Erasmus Medical Center Rotterdam/Sophia Children’s Hospital, Department of Child and Adolescent Psychia- try/Psychology,Wytemaweg 80, 3015 CN Rotterdam, The Netherlands. Tel.: +31 10 7040209; fax: +31 10 7036803. E-mail address: g.dieleman@erasmusmc.nl (G.C. Dieleman). http://dx.doi.org/10.1016/j.psyneuen.2014.09.002 0306-4530/© 2014 Elsevier Ltd. All rights reserved.