01:830:364 Lecture Notes - Lecture 17: Tyrosine Hydroxylase, Intellectual Disability, Drug Withdrawal
Document Summary
Chronic exposure to excessive stress induces depression: Stress reduces the activity of tyrosine hydroxylase, which is the rate-limiting enzyme in the synthesis of ne. Acute stress stimulates hpa to release cortisol. Cortisol release is terminated by cortisol binding to glucocorticoid receptors on the hypothalamus. Chronic stress damages the glucocorticoid receptors rendering them insensitive to cortisol. Stress damages the off-switch resulting in continuous secretion of cortisol. The continuous release of the stress hormone cortisol results in hypervigilance, sleep disorders, anhedonia, and exhaustion. Dexamethasone is a synthetic glucocorticoid or cortisol-like compound. In normals, administration of dexamethasone inhibits the release of acth. One hour after dexamethasone administration, acth levels are low. In approximately 50% of patients diagnosed as suffering from melancholic depression, administration of dexamethasone fails to inhibit the release of acth. One hour after dexamethasone administration, acth levels are high. Upwards of 85% of these patients show positive treatment response to tricyclic anti-
