Genetic contributions to acute autonomic stress responsiveness in children Anett Mueller a, ⁎ , 1 , Jana Strahler b, 1 , Diana Armbruster c , Klaus-Peter Lesch d , Burkhard Brocke e , Clemens Kirschbaum d a Department of Psychology, Stony Brook University, Stony Brook, NY, USA b Clinical Biopsychology, Philipps-University Marburg, Marburg, Germany c Differential and Personality Psychology, Dresden University of Technology, Dresden, Germany d Molecular Psychiatry, Laboratory of Translational Neuroscience, Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany e Biological Psychology, Dresden University of Technology, Dresden, Germany abstract article info Article history: Received 8 June 2011 Received in revised form 28 October 2011 Accepted 15 November 2011 Available online 28 November 2011 Keywords: Salivary alpha-amylase Heart rate variability COMT 5-HTTLPR Gene polymorphism Identification of genetic factors that influence stress reactivity is important in order to link environmental de- mands, particularly adversity to disease outcome. There is ample literature on genetic contribution to the en- docrine stress response, while evidence for genetic contribution to individual differences in autonomic nervous system function is sparse and produced conflicting results. Here, we investigated the influence of two polymorphisms in the Catechol-o-methyltransferase (COMT) and serotonin transporter (5-HTT; SCL6A4) gene. We examined the autonomic stress response to the Trier Social Stress Test for Children in 115 children. Salivary α-amylase (sAA) was obtained prior to the stressor and repeatedly during recovery as a marker of autonomic reactivity. Furthermore, heart rate (HR) and heart rate variability (HRV) were mon- itored continuously. We found differences in ANS stress response associated with each polymorphism (all p b .05). Children with the L variant of 5-HTTLPR showed a higher increase and sharper recovery of sAA in re- sponse to stress than those with S variants. For HR, we found differences associated with COMT, i.e. children carrying at least one met allele showed lower mean HR increase and slower HR recovery in response to the stressor compared to those with two val alleles (p b .001) as well as a significant decrease in heart rate vari- ability (p b .05). Our findings indicate that these two polymorphisms do indeed influence the ANS response to stress. This study provides further evidence for the crucial role of genetic factors in the modulation of differ- ences in the acute stress response during childhood. © 2011 Elsevier B.V. All rights reserved. 1. Introduction Organisms need to respond appropriately to both internal and ex- ternal stressors. A diminished ability to mount a functional “adaptive stress response” can contribute to the development of pathologic dis- ease states (Chrousos, 2007). It has been well established that both ge- netic and environmental factors, such as age, gender, nutrition and personality factors, influence the endocrine stress response (Federenko et al., 2004; Gomez et al., 1998; Kirschbaum et al., 1992; Kudielka et al., 2009; Linkowski et al., 1993). The identification of genes is therefore of vital importance (Wu et al., 2010; Yusuf et al., 2004) and helps to as- sess psychobiological mechanisms of stress regulation and causes of ill- ness. In addition to the hypothalamus–pituitary–adrenal (HPA) axis, the autonomic nervous system (ANS) is an important part of the adaptive stress response. Typically, assessing the ANS response to acute stress re- lies on peripheral ANS markers such as heart rate (HR), heart rate variability (HRV) and catecholamines (De Geus et al., 2007; Wu et al., 2010). The ANS also elicits salivary α-amylase (sAA) production, which has been suggested to reflect stress-related autonomic changes in the body (e.g. Granger et al., 2007; Nater and Rohleder, 2009). To date, there are numerous reports of acute sAA changes in response to different psychologically stressful conditions, with highest increases immediately after the stressor (for a review see Nater and Rohleder, 2009). Basal and stress-induced sAA values are affected by parasympa- thetic activity which mediates salivary flow but also contributes, to a lesser extent, to protein release. Further, amylase is also affected by sympathetic innervations which primarily influence protein concentra- tion. However, it should be mentioned that stress-induced changes of sAA seem to be independent of salivary flow rate (Rohleder et al., 2006). Current literature provides knowledge of various factors contrib- uting to individual heterogeneity in sAA levels while there is still a lack of evidence for genetic influences (Out et al., 2011). Allelic variations in several genes have been identified that influence differences in adaptive stress response to the environment, such as the serotonin transporter (5-HTT) and Catechol-o-methyltransferase, COMT (Conway et al., 2010; Lovallo and Thomas, 2000; Xu et al., 2006). The transcriptional ac- tivity of the 5-HTT gene is significantly modulated by a length International Journal of Psychophysiology 83 (2012) 302–308 ⁎ Corresponding author at: Stony Brook University, Stony Brook, NY, USA. Tel.: + 1 631 632 4209. E-mail address: anmuller@notes.cc.sunysb.edu (A. Mueller). 1 These authors contributed equally to the work. 0167-8760/$ – see front matter © 2011 Elsevier B.V. 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