Salivary cortisol and alpha-amylase diurnal profiles and stress reactivity in children with Attention Deficit Hyperactivity Disorder

Psychoneuroendocrinology. 2018 Apr:90:174-181. doi: 10.1016/j.psyneuen.2018.02.026. Epub 2018 Feb 23.


There is growing evidence for dysregulation of the stress system in individuals with Attention Deficit Hyperactivity Disorder (ADHD). The stress system includes neuroanatomical and functional components that function in concert to maintain homeostasis and its main effectors are the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic/adrenomedullary nervous system (SNS). As stress system activity demonstrates a distinct circadian variation, we aimed to describe simultaneously, diurnal rhythms of both the HPA axis and the SNS in children with ADHD and a comparison group. Moreover, we attempted to investigate stress responses to a physical stressor, venipuncture, in both groups. Sixty-two prepubertal children with ADHD combined (ADHD-C) or inattentive (ADHD-I) type and 40 typically developing children provided saliva samples at six specific time points during a day, as well as before and 10 min after a scheduled morning venipuncture. Salivary cortisol and α- amylase were selected as reliable noninvasive biomarkers for HPA axis and SNS function and were measured in the samples obtained. Results revealed that children with ADHD-C had lower mean cortisol values both 30 min after awakening and at 18:00 h than controls (p = 0.002 and p = 0.018 respectively), as well as lower mean Cortisol Awakening Response (CAR) and Area Under the Curve for "wake to bed" period (AUCi) values of cortisol (p = 0.004 and p = 0.001, respectively). Also, mean CAR and cortisol AUCi were lower in children with ADHD-I than the control group (p = 0.034 and p = 0.038 respectively). Alpha-amylase measurements showed an increase over time (p < 0.001), which was similar in all three groups. Interestingly, α-amylase changes over time were correlated with the corresponding cortisol changes (p < 0.001). Venipuncture, elicited a significant increase only in α-amylase levels and more so in the control group (p = 0.003). These findings suggest a partial hypofunction of the stress system in children with ADHD.

Keywords: ADHD; Cortisol; Diurnal rhythms; Stress response; Stress system; α-amylase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Attention Deficit Disorder with Hyperactivity / enzymology
  • Attention Deficit Disorder with Hyperactivity / genetics
  • Attention Deficit Disorder with Hyperactivity / metabolism*
  • Biomarkers / metabolism
  • Child
  • Circadian Rhythm / physiology
  • Female
  • Humans
  • Hydrocortisone / metabolism*
  • Hypothalamo-Hypophyseal System / metabolism
  • Male
  • Pituitary-Adrenal System / metabolism
  • Saliva / metabolism*
  • Stress, Psychological / enzymology
  • Stress, Psychological / metabolism*
  • alpha-Amylases / metabolism*


  • Biomarkers
  • alpha-Amylases
  • Hydrocortisone