SHORT COMMUNICATION Tryptophan depletion affects the autonomic stress response in generalized social anxiety disorder J. Frederieke van Veen a, * , Irene M. van Vliet a , Roel H. de Rijk b , Johannes van Pelt c , Bart Mertens d , Durk Fekkes e , Frans G. Zitman a a Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands b Division of Medical Pharmacology, LACDR/LUMC, Gorlaeus Laboratories, Leiden, The Netherlands c Department of Clinical Chemistry, Leiden University Medical Center, Leiden, The Netherlands d Department of Medical Statistics, Leiden University Medical Center, Leiden, The Netherlands e Departments of Neuroscience and Psychiatry, Erasmus Medical Center, Rotterdam, The Netherlands Received 6 January 2009; received in revised form 12 May 2009; accepted 13 May 2009 1. Introduction Several biological systems behave differently in generalized social anxiety disorder (gSAD). With respect to the seroto- nergic system higher binding potentials for the serotonin transporter in the thalamus and reduced 5-HT1A receptors levels have been found (see among others Van der Wee et al., 2008). In addition, challenges with various serotonergic Psychoneuroendocrinology (2009) 34, 1590—1594 KEYWORDS Phobic disorders; Serotonin; alpha-Amylase; Autonomic nervous system; Hydrocortisone; Hypothalamic pituitary adrenal axis Summary In generalized social anxiety disorder (gSAD), serotonergic dysfunctions are found, as well as abnormalities of the autonomic nervous system (ANS) in basal conditions and of the hypothalamic pituitary adrenal (HPA) axis in response to psychological challenges. These findings raise the question whether these phenomena are interrelated. Therefore we designed a study in which two groups with nine pair wise age and gender matched gSAD patients (total of 10 men and 8 women), who were successfully treated with a selective serotonin reuptake inhibitor (SSRI), underwent a tryptophan depletion challenge (TD) or a placebo condition. A TD procedure temporarily decreases serotonergic neurotransmission. In order to activate the stress system the TD/placebo challenge was combined with a public speaking task. We assessed ANS responses, as measured with the promising new marker salivary alpha-amylase (sAA), and HPA-axis responses, as measured with salivary cortisol. The most important result was that the TD group showed a significant larger sAA response to the public speaking task as compared to the placebo group, reflecting hyperresponsivity of the ANS in this group, whereas no differences were seen in cortisol responses. This suggests that in gSAD there is a vulnerability of the ANS more than the HPA-axis. # 2009 Elsevier Ltd. All rights reserved. * Corresponding author at: Department of Psychiatry B1-P, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands. Tel.: +31 71 5263785; fax: +31 71 5248156. E-mail address: j.f.van_veen@lumc.nl (J.F. van Veen). 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.2009.05.007