5. Diagnosis of stress system damage

5.1. The dexamethasone suppression test (DST)

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

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

Another strong indication that the HPA axis, and cortisol in particular, plays a central role in ADHD is provided by a study in which dexamethasone (as a drug) was able to significantly reduce ADHD symptoms in rats. Dexamethasone increased dopamine and noradrenaline levels and reduced DAT expression.⁴ The SHR rats used represent ADHD-HI and ADHD-C, not the ADHD-I subtype.

No further evidence of its use for analysis in ADHD has been found to date. It should be noted that the cortisol response to acute stressors in people with ADHD varies depending on the subtype. In people with ADHD-HI (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 response of the HPA axis to cortisol administration may also be altered depending on the stress phenotype (ADHD subtype). We expect a deficient deactivation of the HPA axis in ADHD-HI and ADHD-C in particular.

In a test of people with ADHD, the DST showed an excessive cortisol response.⁵
The DST showed an increased ACTH response in borderline people without comorbid PTSD, and a significantly attenuated ACTH response in borderline people with comorbid PTSD⁶

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