Psychoneuroendocrinology
Volume 34, Issue 4 , Pages 486-496 , May 2009

Salivary alpha-amylase as a non-invasive biomarker for the sympathetic nervous system: Current state of research

  • U.M. Nater

      Affiliations

    • University of Zurich, Institute of Psychology, Department of Clinical Psychology and Psychotherapy, Zurich, Switzerland
    • Corresponding Author InformationCorresponding author at: University of Zurich, Clinical Psychology & Psychotherapy, Binzmuehlestr. 14/Box 26, 8050 Zurich, Switzerland. Tel.: +41 44 635 7382; fax: +41 44 635 7359.
  • ,
  • N. Rohleder

      Affiliations

    • Brandeis University, Dept. of Psychology, Waltham, MA, USA

Received 13 August 2008 ,Revised 23 January 2009 ,Accepted 27 January 2009.

References 

  1. al’Absi M, Wittmers LE. Enhanced adrenocortical responses to stress in hypertension-prone men and women. Ann. Behav. Med. 2003;25:25–33
  2. Anderson LC, Garrett JR, Johnson DA, Kauffman DL, Keller PJ, Thulin A. Influence of circulating catecholamines on protein secretion into rat parotid saliva during parasympathetic stimulation. J. Physiol. 1984;352:163–171
  3. Arai YC, Sakakibara S, Ito A, Ohshima K, Sakakibara T, Nishi T, et al. Intra-operative natural sound decreases salivary amylase activity of patients undergoing inguinal hernia repair under epidural anesthesia. Acta Anaesthesiol. Scand. 2008;
  4. Asking B. Sympathetic stimulation of amylase secretion during a parasympathetic background activity in the rat parotid gland. Acta Physiol. Scand. 1985;124:535–542
  5. Asking B, Gjorstrup P. Synthesis and secretion of amylase in the rat parotid gland following autonomic nerve stimulation in vivo. Acta Physiol. Scand. 1987;130:439–445
  6. Asking B, Proctor GB. Parasympathetic activation of amylase secretion in the intact and sympathetically denervated rat parotid gland. Q. J. Exp. Physiol. 1989;74:45–52
  7. Batzri S, Selinger Z. Enzyme secretion mediated by the epinephrine-receptor in rat parotid slices. Factors governing efficiency of the process. J. Biol. Chem. 1973;248:356–360
  8. Batzri S, Selinger Z, Schramm M, Robinovitch MR. Potassium release mediated by the epinephrine-receptor in rat parotid slices. Properties and relation to enzyme secretion. J. Biol. Chem. 1973;248:361–368
  9. Baum BJ. Principles of salivary secretion. Ann. N. Y. Acad. Sci. 1993;694:17–23
  10. Bishop NC, Walker GJ, Scanlon GA, Richards S, Rogers E. Salivary IgA responses to prolonged intensive exercise following caffeine ingestion. Med. Sci. Sports Exerc. 2006;38:513–519
  11. Borgeat F, Chagon G, Legault Y. Comparison of the salivary changes associated with a relaxing and with a stressful procedure. Psychophysiology. 1984;21:690–698
  12. Bosch JA, Brand HS, Ligtenberg AJ, Bermond B, Hoogstraten J, Nieuw Amerongen AV. The response of salivary protein levels and S-IgA to an academic examination are associated with daily stress. J. Psychophysiol. 1998;12:384–391
  13. Bosch JA, Brand HS, Ligtenberg TJ, Bermond B, Hoogstraten J, Nieuw Amerongen AV. Psychological stress as a determinant of protein levels and salivary-induced aggregation of Streptococcus gordonii in human whole saliva. Psychosom. Med. 1996;58:374–382
  14. Bosch JA, De Geus EJ, Veerman EC, Hoogstraten J, Nieuw Amerongen AV. Innate secretory immunity in response to laboratory stressors that evoke distinct patterns of cardiac autonomic activity. Psychosom. Med. 2003;65:245–258
  15. Brown CC. The parotid puzzle: a review of the literature on human salivation and its applications to psychophysiology. Psychophysiology. 1970;7:65–85
  16. Busch L, Sterin-Borda L, Borda E. Differences in the regulatory mechanism of amylase release by rat parotid and submandibular glands. Arch. Oral Biol. 2002;47:717–722
  17. Calvo F, Chicharro JL, Bandres F, Lucia A, Perez M, Alvarez J, et al. Anaerobic threshold determination with analysis of salivary amylase. Can. J. Appl. Physiol. 1997;22:553–561
  18. Castle D, Castle A. Intracellular transport and secretion of salivary proteins. Crit. Rev. Oral Biol. Med. 1998;9:4–22
  19. Chatterton RT, Vogelsong KM, Lu YC, Ellman AB, Hudgens GA. Salivary alpha-amylase as a measure of endogenous adrenergic activity. Clin. Physiol. 1996;16:433–448
  20. Chatterton RT, Vogelsong KM, Lu YC, Hudgens GA. Hormonal responses to psychological stress in men preparing for skydiving. J. Clin. Endocrinol. Metab. 1997;82:2503–2509
  21. Cole SW, Naliboff BD, Kemeny ME, Griswold MP, Fahey JL, Zack JA. Impaired response to HAART in HIV-infected individuals with high autonomic nervous system activity. Proc. Natl. Acad. Sci. U.S.A. 2001;98:12695–12700
  22. Coupland NJ, Wilson SJ, Potokar JP, Bell C, Nutt DJ. Increased sympathetic response to standing in panic disorder. Psychiatry Res. 2003;118:69–79
  23. Crespi H, Armando I, Tumilasci O, Levin G, Massimo J, Barontini M, et al. Catecholamines levels and parotid secretion in children with chronic atopic dermatitis. J. Invest. Dermatol. 1982;78:493–497
  24. Edgar WM. Saliva: its secretion, composition and functions. Br. Dent. J. 1992;172:305–312
  25. Ehlert U, Erni K, Hebisch G, Nater U. Salivary alpha-amylase levels after yohimbine challenge in healthy men. J. Clin. Endocrinol. Metab. 2006;91:5130–5133
  26. El-Sheikh M, Erath SA, Buckhalt JA, Granger DA, Mize J. Cortisol and children's adjustment: the moderating role of sympathetic nervous system activity. J. Abnorm. Child Psychol. 2008;36:601–611
  27. Emmelin N. Nerve interactions in salivary glands. J. Dent. Res. 1987;66:509–517
  28. Fortunato CK, Dribin AE, Granger DA, Buss KA. Salivary alpha-amylase and cortisol in toddlers: differential relations to affective behaviors. Dev. Psychobiol. 2008;
  29. Fredrickson M, Tuomisto M, Bergman-Losman B. Neuroendocrine and cardiovascular stress reactivity in middle-aged normotensive adults with parental history of cardiovascular disease. Psychophysiology. 1991;28:656–664
  30. Friedman BH, Thayer JF, Borkovec TD, Tyrrell RA, Johnson BH, Columbo R. Autonomic characteristics of nonclinical panic and blood phobia. Biol. Psychiatry. 1993;34:298–310
  31. Gaab J, Blattler N, Menzi T, Pabst B, Stoyer S, Ehlert U. Randomized controlled evaluation of the effects of cognitive-behavioral stress management on cortisol responses to acute stress in healthy subjects. Psychoneuroendocrinology. 2003;28:767–779
  32. Gilman SC, Fischer GJ, Biersner RJ, Thornton RD, Miller DA. Human parotid alpha-amylase secretion as a function of chronic hyperbaric exposure. Undersea Biomed. Res. 1979;6:303–307
  33. Gilman SC, Thornton R, Miller D, Biersner R. Effects of exercise stress on parotid gland secretion. Horm. Metab. Res. 1979;11:454
  34. Goi N, Hirai Y, Harada H, Ikari A, Ono T, Kinae N, et al. Comparison of peroxidase response to mental arithmetic stress in saliva of smokers and non-smokers. J. Toxicol. Sci. 2007;32:121–127
  35. Goldstein DS. Catecholamines in the periphery. Overview. Adv. Pharmacol. 1998;42:529–539
  36. Gordis EB, Granger DA, Susman EJ, Trickett PK. Asymmetry between salivary cortisol and alpha-amylase reactivity to stress: relation to aggressive behavior in adolescents. Psychoneuroendocrinology. 2006;31:976–987
  37. Gordis EB, Granger DA, Susman EJ, Trickett PK. Salivary alpha amylase-cortisol asymmetry in maltreated youth. Horm. Behav. 2008;53:96–103
  38. Granger DA, Kivlighan KT, Blair C, El-Sheikh M, Mize J, Lisonbee JA, et al. Integrating the measurement of salivary alpha-amylase into studies of child health, development, and social relationships. J. Pers. Soc. Relat. 2006;23:267–290
  39. Granger DA, Kivlighan KT, el-Sheikh M, Gordis EB, Stroud LR. Salivary alpha-amylase in biobehavioral research: recent developments and applications. Ann. N. Y. Acad. Sci. 2007;1098:122–144
  40. Grassi G, Esler M. How to assess sympathetic activity in humans. J. Hypertens. 1999;17:719–734
  41. Grillon C, Duncko R, Covington MF, Kopperman L, Kling MA. Acute stress potentiates anxiety in humans. Biol. Psychiatry. 2007;62:1183–1186
  42. Hamilton LD, Fogle EA, Meston CM. The roles of testosterone and alpha-amylase in exercise-induced sexual arousal in women. J. Sex. Med. 2008;5:845–853
  43. Het S, Wolf OT. Mood changes in response to psychosocial stress in healthy young women: effects of pretreatment with cortisol. Behav. Neurosci. 2007;121:11–20
  44. Hill-Soderlund AL, Mills-Koonce WR, Propper C, Calkins SD, Granger DA, Moore GA, et al. Parasympathetic and sympathetic responses to the strange situation in infants and mothers from avoidant and securely attached dyads. Dev. Psychobiol. 2008;50:361–376
  45. Hodgson NA, Andersen S. The clinical efficacy of reflexology in nursing home residents with dementia. J. Altern. Complement. Med. 2008;14:269–275
  46. Humphrey SP, Williamson RT. A review of saliva: normal composition, flow, and function. J. Prosthet. Dent. 2001;85:162–169
  47. Kalman DS, Feldman S, Feldman R, Schwartz HI, Krieger DR, Garrison R. Effect of a proprietary Magnolia and Phellodendron extract on stress levels in healthy women: a pilot, double-blind, placebo-controlled clinical trial. Nutr. J. 2008;7:11
  48. Kaufman E, Lamster IB. The diagnostic applications of saliva—a review. Crit. Rev. Oral. Biol. Med. 2002;13:197–212
  49. Kirschbaum C, Hellhammer DH. Salivary cortisol in psychobiological research: an overview. Neuropsychobiology. 1989;22:150–169
  50. Kirschbaum C, Hellhammer DH. Salivary cortisol in psychoneuroendocrine research: recent developments and applications. Psychoneuroendocrinology. 1994;19:313–333
  51. Kirschbaum C, Pirke KM, Hellhammer DH. The ‘Trier Social Stress Test’—a tool for investigating psychobiological stress responses in a laboratory setting. Neuropsychobiology. 1993;28:76–81
  52. Kivlighan KT, Granger DA. Salivary alpha-amylase response to competition: relation to gender, previous experience, and attitudes. Psychoneuroendocrinology. 2006;31:703–714
  53. Labudda K, Wolf OT, Markowitsch HJ, Brand M. Decision-making and neuroendocrine responses in pathological gamblers. Psychiatry Res. 2007;153:233–243
  54. Laederach-Hofmann K, Mussgay L, Buchel B, Widler P, Ruddel H. Patients with erythrophobia (fear of blushing) show abnormal autonomic regulation in mental stress conditions. Psychosom. Med. 2002;64:358–365
  55. Lang PJ, Davis M, Ohman A. Fear and anxiety: animal models and human cognitive psychophysiology. J. Affect. Disord. 2000;61:137–159
  56. Laurikainen K, Laurikainen E, Tenovuo J, Kaila T, Vilja P. Effects of a beta-blocking agent, timolol maleate, on saliva in healthy volunteers. Scand. J. Dent. Res. 1988;96:121–127
  57. Ljungberg G, Ericson T, Ekblom B, Birkhed D. Saliva and marathon running. Scand. J. Med. Sci. Sports. 1997;7:214–219
  58. Makinen KK. Salivary enzymes. In:  Tenovuo JO editors. Human Saliva: Clinical Chemistry and Microbiology. vol. 2:Boca Raton: CRC Press; 1989;p. 93–119
  59. Morrison WE, Haas EC, Shaffner DH, Garrett ES, Fackler JC. Noise, stress, and annoyance in a pediatric intensive care unit. Crit. Care Med. 2003;31:113–119
  60. Morse DR, Schacterle GR, Esposito JV, Chod SD, Furst ML, DiPonziano J, et al. Stress, meditation and saliva: a study of separate salivary gland secretions in endodontic patients. J. Oral Med. 1983;38:150–160
  61. Morse DR, Schacterle GR, Zaydenberg M, Furst ML, Pollack RL, Moskow A, et al. Salivary volume and amylase activity. I. Relaxation versus relaxed chewing. J. Am. Soc. Psychosom. Dent. Med. 1983;30:85–96
  62. Nater UM. The Role of Salivary Alpha-Amylase in Stress Research. Göttingen: Cuvillier; 2004;
  63. Nater UM, Abbruzzese E, Krebs M, Ehlert U. Sex differences in emotional and psychophysiological responses to musical stimuli. Int. J. Psychophysiol. 2006;62:300–308
  64. Nater UM, La Marca R, Florin L, Moses A, Langhans W, Koller MM, et al. Stress-induced changes in human salivary alpha-amylase activity—associations with adrenergic activity. Psychoneuroendocrinology. 2006;31:49–58
  65. Nater UM, Rohleder N, Gaab J, Berger S, Jud A, Kirschbaum C, et al. Human salivary alpha-amylase reactivity in a psychosocial stress paradigm. Int. J. Psychophysiol. 2005;55:333–342
  66. Nater UM, Rohleder N, Schlotz W, Ehlert U, Kirschbaum C. Determinants of the diurnal course of salivary alpha-amylase. Psychoneuroendocrinology. 2007;32:392–401
  67. Nederfors T, Dahlof C. Effects on salivary flow rate and composition of withdrawal of and re-exposure to the beta 1-selective antagonist metoprolol in a hypertensive patient population. Eur. J. Oral Sci. 1996;104:262–268
  68. Nederfors T, Ericsson T, Twetman S, Dahlof C. Effects of the beta-adrenoceptor antagonists atenolol and propranolol on human parotid and submandibular–sublingual salivary secretion. J. Dent. Res. 1994;73:5–10
  69. Nexo E, Hansen MR, Konradsen L. Human salivary epidermal growth factor, haptocorrin and amylase before and after prolonged exercise. Scand. J. Clin. Lab. Invest. 1988;48:269–273
  70. Nierop A, Bratsikas A, Klinkenberg A, Nater UM, Zimmermann R, Ehlert U. Prolonged salivary cortisol recovery in second-trimester pregnant women and attenuated salivary {alpha}-amylase responses to psychosocial stress in human pregnancy. J. Clin. Endocrinol. Metab. 2006;91:1329–1335
  71. Noto Y, Sato T, Kudo M, Kurata K, Hirota K. The relationship between salivary biomarkers and state-trait anxiety inventory score under mental arithmetic stress: a pilot study. Anesth. Analg. 2005;101:1873–1876
  72. Payne JD, Jackson ED, Hoscheidt S, Ryan L, Jacobs WJ, Nadel L. Stress administered prior to encoding impairs neutral but enhances emotional long-term episodic memories. Learn. Mem. 2007;14:861–868
  73. Rohleder N, Chen E, Wolf JM, Miller GE. The psychobiology of trait shame in young women: extending the social self preservation theory. Health Psychol. 2008;27:523–532
  74. Rohleder N, Nater UM. Determinants of salivary alpha-amylase in humans and methodological considerations. Psychoneuroendocrinology. 2009;this issue
  75. Rohleder N, Nater UM, Wolf JM, Ehlert U, Kirschbaum C. Psychosocial stress-induced activation of salivary alpha-amylase: an indicator of sympathetic activity?. Ann. N. Y. Acad. Sci. 2004;1032:258–263
  76. Rohleder N, Wolf JM, Herpfer I, Fiebich BL, Kirschbaum C, Lieb K. No response of plasma substance P, but delayed increase of interleukin-1 receptor antagonist to acute psychosocial stress. Life Sci. 2006;78:3082–3089
  77. Rohleder N, Wolf JM, Maldonado EF, Kirschbaum C. The psychosocial stress-induced increase in salivary alpha-amylase is independent of saliva flow rate. Psychophysiology. 2006;43:645–652
  78. Scannapieco FA, Torres G, Levine MJ. Salivary alpha-amylase: role in dental plaque and caries formation. Crit. Rev. Oral Biol. Med. 1993;4:301–307
  79. Schaffer L, Burkhardt T, Muller-Vizentini D, Rauh M, Tomaske M, Mieth RA, et al. Cardiac autonomic balance in small-for-gestational-age neonates. Am. J. Physiol. Heart Circ. Physiol. 2008;294:H884–890
  80. Schoofs D, Hartmann R, Wolf OT. Neuroendocrine stress responses to an oral academic examination: no strong influence of sex, repeated participation and personality traits. Stress. 2007;1
  81. Schoofs D, Preuss D, Wolf OT. Psychosocial stress induces working memory impairments in an n-back paradigm. Psychoneuroendocrinology. 2008;33:643–653
  82. Selinger Z, Batzri S, Eimerl S, Schramm M. Calcium and energy requirements for K+ release mediated by the epinephrine-receptor in rat parotid slices. J. Biol. Chem. 1973;248:369–372
  83. Seugnet L, Boero J, Gottschalk L, Duntley SP, Shaw PJ. Identification of a biomarker for sleep drive in flies and humans. Proc. Natl. Acad. Sci. U.S.A. 2006;103:19913–19918
  84. Shalev AY, Rogel-Fuchs Y. Psychophysiology of the posttraumatic stress disorder: from sulfur fumes to behavioral genetics. Psychosom. Med. 1993;55:413–423
  85. Shea AK, Steiner M, Brennan P, Walker E, Newport DJ, Stowe ZN. Maternal depression and salivary alpha-amylase response to stress in their infants—abstract. Psychosom. Med. 2006;68:A5
  86. Shirasaki S, Fujii H, Takahashi M, Sato T, Ebina M, Noto Y, et al. Correlation between salivary alpha-amylase activity and pain scale in patients with chronic pain. Reg. Anesth. Pain Med. 2007;32:120–123
  87. Skosnik PD, Chatterton RT, Swisher T, Park S. Modulation of attentional inhibition by norepinephrine and cortisol after psychological stress. Int. J. Psychophysiol. 2000;36:59–68
  88. Skov Olsen P, Kirkegaard P, Rasmussen T, Magid E, Poulsen SS, Nexo E. Adrenergic effects on secretion of amylase from the rat salivary glands. Digestion. 1988;41:34–38
  89. Smith PM. Mechanisms of secretion by salivary glands. In:  Edgar WM,  O’Mullane DM editor. Saliva and Oral Health. London: British Dental Association; 1996;p. 9–25
  90. Southwick SM, Krystal JH, Morgan CA, Johnson D, Nagy LM, Nicolaou A, et al. Abnormal noradrenergic function in posttraumatic stress disorder. Arch. Gen. Psychiatry. 1993;50:266–274
  91. Speirs RL, Herring J, Cooper WD, Hardy CC, Hind CR. The influence of sympathetic activity and isoprenaline on the secretion of amylase from the human parotid gland. Arch. Oral Biol. 1974;19:747–752
  92. Sreebny LM. Saliva in health and disease: an appraisal and update. Int. Dent. J. 2000;50:140–161
  93. Steerenberg PA, van Asperen IA, Van Nieuw Amerongen A, Biewenga J, Mol D, Medema G. Salivary levels of immunoglobulin A in triathletes. Eur. J. Oral Sci. 1997;105:305–309
  94. Stroud LR, Foster E, Papandonatos GD, Handwerger K, Granger DA, Kivlighan KT, et al. Stress response and the adolescent transition: performance versus peer rejection stressors. Dev. Psychopathol. 2009;21(1):47–68
  95. Stroud LR, Handwerger K, Granger DA, Kivlighan KT. Salivary alpha-amylase stress reactivity in children and adolescents: validity, associations with cortisol, and links to behavior—abstract. Psychosom. Med. 2006;68:A5
  96. Takai N, Yamaguchi M, Aragaki T, Eto K, Uchihashi K, Nishikawa Y. Effect of psychological stress on the salivary cortisol and amylase levels in healthy young adults. Arch. Oral Biol. 2004;49:963–968
  97. Takai N, Yamaguchi M, Aragaki T, Eto K, Uchihashi K, Nishikawa Y. Gender-specific differences in salivary biomarker responses to acute psychological stress. Ann. N. Y. Acad. Sci. 2007;1098:510–515
  98. Tenovuo J. Antimicrobial function of human saliva—how important is it for oral health?. Acta Odontol. Scand. 1998;56:250–256
  99. Tu MT, Lupien SJ, Walker CD. Multiparity reveals the blunting effect of breastfeeding on physiological reactivity to psychological stress. J. Neuroendocrinol. 2006;18:494–503
  100. van Stegeren A, Rohleder N, Everaerd W, Wolf OT. Salivary alpha amylase as marker for adrenergic activity during stress: effect of betablockade. Psychoneuroendocrinology. 2006;31:137–141
  101. van Stegeren AH, Wolf OT, Kindt M. Salivary alpha amylase and cortisol responses to different stress tasks: impact of sex. Int. J. Psychophysiol. 2008;69:33–40
  102. Vigil, J.M., Flinn, M.V., Granger, D.A., Geary, D.C., in press. Sex differences in stress responses following Hurricane Katrina. Child Dev.
  103. Vining RF, McGinley RA. The measurement of hormones in saliva: possibilities and pitfalls. J. Steroid. Biochem. 1987;27:81–94
  104. Walsh NP, Blannin AK, Clark AM, Cook L, Robson PJ, Gleeson M. The effects of high-intensity intermittent exercise on saliva IgA, total protein and alpha-amylase. J. Sports Sci. 1999;17:129–134
  105. West SG, Granger DA, Kivlighan KT, Hurston KL. Salivary alpha-amylase response to the cold pressor is corralled with cardiac markers of sympathetic activation—abstract. Psychosom. Med. 2006;68:A4–A5
  106. Wetherell MA, Crown AL, Lightman SL, Miles JN, Kaye J, Vedhara K. The four-dimensional stress test: psychological, sympathetic–adrenal–medullary, parasympathetic and hypothalamic–pituitary–adrenal responses following inhalation of 35% CO2. Psychoneuroendocrinology. 2006;31:736–747
  107. Wolf JM, Nicholls E, Chen E. Chronic stress, salivary cortisol, and alpha-amylase in children with asthma and healthy children. Biol. Psychol. 2008;78:20–28
  108. Yamaguchi M, Takeda K, Onishi M, Deguchi M, Higashi T. Non-verbal communication method based on a biochemical marker for people with severe motor and intellectual disabilities. J. Int. Med. Res. 2006;34:30–41
  109. Yamaguchi M, Wakasugi J, Sakakima J. Evaluation of driver stress using biomarker in motor-vehicle driving simulator. Conf. Proc. IEEE Eng. Med. Biol. Soc. 2006;1:1834–1837
  110. Yamakage M, Hayase T, Satoh JI, Namiki A. Work stress in medical anaesthesiology trainees. Eur. J. Anaesthesiol. 2007;24:809–811
  111. Zakowski JJ, Bruns DE. Biochemistry of human alpha amylase isoenzymes. Crit. Rev. Clin. Lab. Sci. 1985;21:283–322

PII: S0306-4530(09)00032-8

doi: 10.1016/j.psyneuen.2009.01.014

Psychoneuroendocrinology
Volume 34, Issue 4 , Pages 486-496 , May 2009