Evening salivary alpha-amylase, major depressive disorder, and antidepressant use in the Netherlands Study of Depression and Anxiety (NESDA) Gerthe Veen a,b,n , Erik J. Giltay b , Carmilla M.M. Licht a , Sophie A. Vreeburg a , Christa M. Cobbaert c , Brenda W.J.H. Penninx a,b,d , Frans G. Zitman b a Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands b Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands c Department of Clinical Chemistry, Leiden University Medical Center, Leiden, The Netherlands d Department of Psychiatry, University Medical Center Groningen, Groningen, The Netherlands article info Article history: Received 28 January 2012 Received in revised form 11 March 2013 Accepted 17 March 2013 Keywords: Autonomic nervous system Stress Catecholamines Heart rate Heart rate variability abstract Salivary alpha-amylase (sAA) may be a suitable index for sympathetic activity and dysregulation of the autonomic nervous system. The relationship between antidepressants and depression with sAA levels was studied, since antidepressants were previously shown to have a profound impact on heart rate variability as an ANS indicator. Data are from 1692 participants of the Netherlands Study of Depression and Anxiety (NESDA) who were recruited from the community, general practice, and specialized mental health care. Differences in evening sAA levels were examined between patient groups (i.e., 752 current major depressive disorder [MDD], 611 remitted MDD, and 329 healthy controls) and between 46 tricyclic antidepressant (TCA) users, 307 selective serotonin reuptake inhibitor (SSRI) users, 97 users of another antidepressant, and 1242 non-users. Each participant sampled twice at 22.00h and 23.00h. In multivariable analysis, there was a trend over the three groups with increasing sAA levels from controls to remitted MDD to current MDD that approached significance. Furthermore, in comparison to non-users of antidepressants, TCA rather than SSRI users showed higher sAA levels, that persisted after multivariable adjustment. The present study shows that higher evening sAA levels in depressed patients, indicative of an increased sympathetic activity, may be induced by TCAs. & 2013 Elsevier Ireland Ltd. All rights reserved. 1. Introduction There is a central belief that a dysregulated autonomic nervous system (ANS) plays a role in the pathophysiology of depression. In previous cross-sectional studies, diverse methods of measuring ANS tone and reactivity have been used, including plasma levels of catecholamines (i.e. (nor)epinephrine), heart rate, and heart rate variability (HRV). Recently, salivary alpha-amylase (sAA) assess- ments have been proposed as another noninvasive technique for the measurement of the sympathetic tone of ANS (Chatterton Jr. et al., 1996; Granger et al., 2007). Summarizing the existing literature, early studies suggested sAA as a noninvasive marker of adrenergic activity in humans (Chatterton et al., 1996; Skosnik et al., 2000; Nater and Rohleder, 2009). Activation of the autonomic nervous system results in norepinephrine release that may subsequently elicit the release of alpha-amylase by the salivary glands. The underlying function of the norepinephrine is to balance vigilance/scanning behavior with focused attention on novel environmental stimuli and the state of arousal. Norepi- nephrine is involved intrinsically with the stress response system, and high levels of norepinephrine have been implicated in the pathogenesis of depressive disorders (Goddard et al., 2010). Under basal conditions in healthy volunteers, sAA activity shows a diurnal profile with a decrease during the first 30 min after awakening and an increase during the rest of the day (Nater et al., 2007; Rohleder et al., 2004a, 2004b). Diurnal sAA levels were relatively independent of several possible confounders like age, gender, body mass index (BMI), activity level, smoking, eating and drinking but significantly associated with chronic stress and stress reactivity in healthy volunteers (Nater et al., 2007). With regard to evening sAA levels, only age and alcohol intake were found to be significant determinants (Veen et al., 2012). Different types of psychological and physiological challenges were followed by Contents lists available at SciVerse ScienceDirect journal homepage: www.elsevier.com/locate/psychres Psychiatry Research 0165-1781/$ - see front matter & 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.psychres.2013.03.012 n Corresponding author at: Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands. Tel.: þ31 20 7884666; fax: þ31 20 7884677. E-mail address: G.Veen@ggzingeest.nl (G. Veen). Psychiatry Research 208 (2013) 41–46