5. Diagnosis of stress system damage

5.1. The Dexamethasone Suppression Test (DST)

Damage to the HPA axis can be determined by, among other things, the dexamethasone suppression test (DST). Oral or intravenous administration of a low dose of dexamethasone (a synthetically produced cortisol derivative) causes a significant decrease in CRH, ACTH and cortisol levels in healthy individuals. If, on the other hand, the levels increase, this indicates a disturbance of the HPA axis, e.g., due to a reduced glucocorticoid (cortisol) receptor effect.¹ The DST is used primarily to diagnose Cushing’s syndrome in which there is no decrease in blood cortisol levels. In depression and other HPA stress axis disorders, the response to cortisol is also altered.²

One study tested ADHD sufferers with the DST. In more than half of all ADHD sufferers, the dexamethasone test did not show the drop in cortisol levels expected in a healthy HPA axis.³ The proportion of ADHD-affected children who did not have a normal daily cortisol course was even higher (43%).

Another strong indication that the HPA axis, and cortisol in particular, plays a central role in ADHD comes from a study that found dexamethasone (as a drug) significantly reduced ADHD symptoms in rats. Dexamethasone increased domapamine and norepinephrine levels and a reduction in DAT expression.⁴ The SHR rats used represent ADHD-HI and ADHD-C, not the ADHD-I subtype.

Further evidence of use for analysis in ADHD has not yet been found on this side. It will be important to note that in ADHD sufferers the cortisol response to acute stressors varies according to subtype. In ADHD-HI sufferers (with hyperactivity), the cortisol response to an acute stressor is usually reduced (flattened), whereas in ADHD-I (without hyperactivity) it is often increased. Therefore, the HPA axis response to cortisol administration is also likely to be altered depending on the stress phenotype (ADHD subtype). We expect a deficient HPA axis shutdown especially in ADHD-HI and ADHD-C.

In those affected by early childhood stress, the DST showed an exaggerated cortisol response in one test.⁵
In borderline sufferers without comorbid PTSD, the DST showed an increased ACTH response; in borderline sufferers with comorbid PTSD, the DST showed a significantly attenuated ACTH response⁶

For specific differences in changes in cortisol, ACTH, and CRH responses to acute stressors in various mental disorders, see ⇒ The HPA axis/stress regulatory axis.