Salivary cortisol: a tool for biobehavioral research in children

Measurement of salivary cortisol has been widely used in pediatric research for more than 20 years as a biomarker of hypothalamic pituitary adrenal (HPA) axis activity during normal activity and in response to stress. McCarthy et al. (2010) recently reported cognitive-behavioral interventions that were effective in reducing pain and distress in children undergoing intravenous needle insertion and salivary cortisol measurement was a useful marker of biological response to compare the effect of interventions in conjunction with other physiological and/or behavioral outcome measures. The inclusion of salivary cortisol as an outcome measure would provide a useful biological marker with future research to investigate: stress in children undergoing painful procedures, weight loss, sleep problems, as well as caregiver stress. The use of salivary cortisol in pediatric biobehavioral research has revealed important information about the pattern of cortisol secretion during childhood, the response to stressors in a non-clinical environment, the response to therapeutic interventions, and the identification of dysfunctional patterns of secretion in children. Salivary cortisol is a reliable non-invasive method to assess HPA function, however collection and measurement of specimens with infants and children requires special consideration. This paper will summarize pertinent issues related to salivary cortisol collection to encourage “broader employment” of this method in pediatric biobehavioral research. Various psychological and physical stressors can activate the HPA axis such that corticotrophin releasing hormone (CRH) and adrenocorticotropin hormones (ACTH) are released with subsequent rise in cortisol levels. Once the HPA axis is activated, it takes approximately 15–30 minutes for the cortisol levels to peak. Cortisol secretion has a circadian pattern, peaking in the early morning (approximately 20–30 minutes after awakening) with the nadir around midnight (Stratakis, Gold, & Chrousos, 1995), and short bursts of secretion over the course of the day. The diurnal pattern of cortisol secretion is typically established in early infancy (Price, Close, & Fielding, 1983). HPA axis function and regulation has been shown to have a significant impact on growth and development. Poor regulation of the cortisol response to emotional stress correlates with detrimental effects on cognitive and emotional functioning (Lupien, 2009). Salivary cortisol is a measure of unbound, or “free” cortisol that is biologically relevant with the ease of sampling in clinical and field settings. Saliva sampling is reliable, non-invasive method to measure biologically active, unbound plasma of cortisol in infants and children. Salivary testing offers advantages over venipuncture since it is noninvasive and less likely to confound results. Also, multiple samples can be obtained without increasing ethical concerns. This method is extensively used in psychoneuroendocrinological research (Kirschbaum & Hellhammer, 1994). For example, studies of naturalistic life events that are considered stressful, such as starting school for a child, have incorporated salivary cortisol as an outcome measure to investigate normal versus mal-adaptive responses (Boyce et al., 1995). Also, studies of diurnal salivary cortisol patterns provide insight regarding the role of early environmental factors on cortisol regulation, cognition, and growth (Gutman & Nemeroff, 2003). In addition, salivary cortisol is a useful diagnostic test in the evaluation of suspected cortisol dysregulation (Gafni, Papanicolaou, & Nieman, 2000). For excellent reviews see: Hanrahan, 2006; Jessop & Turner-Cobb, 2006; Kirschbaum & Hellhammer, 1994; and Schmidt, 1997.