The hyporeactivity of salivary cortisol at stress test (TSST-C) in children with internalizing or externalizing disorders is contrastively associated with α-amylase

•Significant group-differences in TSST-C responses but not in circadian activity.•Hyporeactivity in cortisol at TSST-C in internalizing or externalizing disorders.•Cortisol percentage increase during TSST-C differentiates diagnostic groups well.•Negative association between cortisol and α-amylase in internalizing disorders.•Positive association between cortisol and α-amylase in externalizing disorders.

BackgroundStress biomarkers of the autonomic nervous system and hypothalamic-pituitary-adrenal axis (HPA-axis) can be measured via alpha-amylase (AA) and cortisol and cortisone in saliva. Objectives were to determine 1) the response patterns of cortisol, cortisone, and AA under both circadian conditions and the Trier Social Stress Test for Children (TSST-C), 2) which reactivity index is most suitable to differentiate internalizing or externalizing disorders from controls, and to explore 3) the interaction between AA and cortisol in the presence of internalizing or externalizing disorders.MethodsSaliva samples (n = 2893) from children with internalizing (n = 55) or externalizing disorders (n = 33) and healthy children (n = 81) were analyzed for cortisol, cortisone, and AA under circadian conditions and TSST-C.ResultsCircadian rhythm of three biomarkers did not differ between diagnostic groups. Age and gender were significant predictors for cortisol and awakening time influenced all three biomarkers significantly. TSST-C responses appeared sequentially in the order of AA, cortisol, and cortisone. Trajectories of cortisol and cortisone responses, not in AA, were significantly lower in children with internalizing or externalizing disorders than in healthy children. Cortisol percentage increase appeared to be the most suitable reactivity index to detect the difference between the diagnostic groups. Internalizing disorders had a negative association between AA decrease and cortisol increase (β = −.199, p < .05, R2 = .304). Externalizing disorders had a positive association between AA baseline and cortisol increase (β = .229, p < .05, R2 = .304).ConclusionAn altered HPA-axis response during stress might result from chronic allostatic load in internalizing disorders and underaroused stress response system in externalizing disorders.

Graphical abstractA. Negative moderation effect of internalizing disorders twisted the surface of the interaction between AA percentage decrease and cortisol percentage increase: in children with internalizing disorders, cortisol percentage increase on the y-axis declined when AA percentage decrease on the x-axis inclined, whereas, in controls and to a lesser extent in externalizing disorders, cortisol percentage increase tended to incline along with the increasing amount of AA percentage decrease., B. Positive moderation effect of externalizing disorders bent the surface of the association between AA baseline and cortisol percentage increase: at the same AA baseline levels, cortisol percentage increase was much lower in externalizing disorders than other two diagnostic groups. A gradual increase in cortisol percentage increase against AA baseline in externalizing disorders resulted in a positive effect. (Int.: Children with internalizing disorders (N = 55), Ext.: Children with externalizing disorders (N = 33), Cont.: Healthy children (N = 81); cortisol percentage increase and AA indices were log-transformed).Figure optionsDownload full-size imageDownload as PowerPoint slide