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

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Summary

Development of new biomarkers is a constantly evolving field of research endeavor in psychoneuroendocrinology. Salivary biomarkers have received special attention since they are readily accessible and easily obtained. Salivary alpha-amylase (sAA) has been proposed as a sensitive biomarker for stress-related changes in the body that reflect the activity of the sympathetic nervous system (SNS), and a growing body of research is accumulating to support the validity and reliability of this parameter. However, questions remain to be answered before sAA can be accepted as an index of SNS activity. This review describes sAA as an emerging biomarker for stress and provides an overview of the current literature on stress-related alterations in sAA. It critically discusses how sAA might reflect changes in the autonomic nervous system. Finally, current and future fields for the application of sAA measurement are outlined.

Introduction

In recent years, salivary measures have become increasingly important in psychoneuroendocrinological research. In the early 1970s, Brown suggested that changes in saliva parameters could be regarded as an “index of specific states of psychopathology” (Brown, 1970, p. 66). While research is not yet quite at the point to use salivary measures in the way Brown suggested, the scientific understanding of various salivary parameters is progressing rapidly. However, apart from the analysis of hormones such as cortisol and DHEA (see, e.g. Vining and McGinley, 1987; see, e.g. Kirschbaum and Hellhammer, 1994), few other salivary components have been taken into consideration as meaningful physiological markers in psychoneuroendocrinological research. A specific focus of interest within this field of research is on stress. In stress research, subjects might be examined either in the field or in the laboratory. Whichever setting is chosen, valid and reliable measures of changes associated with stress must be applied. Moreover, the simple handling and easy sampling of a stress measure is of utmost importance. A wide array of possible parameters indicating stress-related changes has been proposed over the years. Some have disappeared into oblivion; others have endured for decades and are still being used. Since stress is a multi-faceted phenomenon, it requires a multidimensional measurement approach. As a consequence, research can gain from additions to the canon of psychobiological parameters. One parameter that has been suggested to reflect stress-related changes in the body is the salivary enzyme alpha-amylase (Chatterton et al., 1996, Nater, 2004, Rohleder et al., 2004, Granger et al., 2007). Salivary alpha-amylase (sAA) release is known to be elicited by activation of the autonomic nervous system (ANS) which controls the salivary glands.

The aim of this review is to assess whether sAA should be incorporated in the canon of psychoneuroendocrinological parameters measuring stress. The accompanying review by Rohleder and Nater (2009) provides a detailed account of methodological issues that arise when measuring sAA.

Section snippets

What is salivary alpha-amylase?

sAA (α-1,4-α-d-glucan 4-glucanohydrolase; EC 3.2.1.1) is one of the most important enzymes in saliva. The enzyme was first described in saliva by Leuchs in 1831 (Zakowski and Bruns, 1985). It consists of two families of isoenzymes, of which one set is glycosylated and the other contains no carbohydrate. The molecular weight of the glycosylated form is about 57,000; that of the non-glycosylated form is about 54,000. sAA accounts for 40% to 50% of the total salivary gland-produced protein, most

Stress-induced salivary alpha-amylase secretion

As outlined in the previous sections of this review, the release of sAA is governed by activation of the ANS. Thus, an increase in sAA may be expected during psychological stress, when autonomic activation is high. The following section reviews findings on sAA responses due to psychological stress.

Applications of salivary alpha-amylase measurement

The findings on the association of sAA and the sympathetic nervous system summarized above indicate that sAA can function as a useful biomarker in acute and chronic stress studies. An overview of previous and potential applications in stress research is given below.

Conclusion

The aim of this review was to evaluate the role of sAA activity as a potential indicator for sympathetic activation in response to stress. Although first findings on the role of sAA in stress processes were published almost three decades ago, no attempts were made to scientifically elucidate this relationship until the mid-1990s. Numerous studies have since shown that changes in sAA are indeed dependent on stressful stimuli, either physiological or psychological in nature. The biological

Role of the funding source

NR was supported by personal (salary) fellowships by the German Research Association (DFG; Ro 2353/4-1) and the Michael Smith Foundation for Health Research. UMN has no funding source to report.

Conflicts of interest

The authors have no conflicts of interest and declare no financial interests.

Acknowledgments

The authors would like to thank Ulrike Ehlert and Clemens Kirschbaum for their support and theoretical input. Furthermore, NR acknowledges the support of the German Research Foundation (DFG; grant no. Ro 2353/4-1) and the Michael Smith Foundation for Health Research.

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