Rationale
It has been suggested that corticosteroid-serotonin interactions are central to the pathophysiology of depression. These interactions have been investigated in healthy and depressed humans, primarily using neuroendocrine techniques.

Corticosteroid-serotonin interactions in depression: a review of the human evidence

We measured the growth hormone (GH) response to clonidine (an alpha-2-adrenergic agonist) and to apomorphine (a dopaminergic agonist) in 15 major endogenous and 15 minor depressive in-patients matched for gender and age. Results showed a significantly smaller GH response in the major depressives to both clonidine (P less than 0.01) and apomorphine (P less than 0.001). No significant difference existed between the two groups with regard to changes in blood pressure and pulse rate during either test. While major depressives showed a trend toward smaller sedative side-effects than minor depressives after clonidine, they showed significantly smaller sedative and gastro-intestinal side-effects after apomorphine. No significant correlation was present either in the major depressive or in the minor depressive group between the GH responses following clonidine and apomorphine challenges. These results support the hypothesis of both noradrenergic and dopaminergic neurotransmitter disturbances in major depression, with individual variability with regard to those biochemical anomalies.

/pdf/blunted-response-of-growth-hormone-to-clonidine-and-j0vh39kw5x.pdf

Blunted response of growth hormone to clonidine and apomorphine in endogenous depression.

Functional hypercortisolism (FH) is caused by conditions able to chronically activate hypothalamic-pituitary-adrenal axis and usually occurs in cases of major depression, anorexia nervosa, bulimia nervosa, alcoholism, diabetes mellitus, simple obesity, polycystic ovary syndrome, obstructive sleep apnea syndrome, panic disorder, generalized anxiety disorder, shift work, and end-stage renal disease. Most of these states belong to pseudo-Cushing disease, a condition which is difficult to distinguish from Cushing's syndrome and characterized not only by biochemical findings but also by objective ones that can be attributed to hypercortisolism (e.g., striae rubrae, central obesity, skin atrophy, easy bruising, etc.). This hormonal imbalance, although reversible and generally mild, could mediate some systemic complications, mainly but not only of a metabolic/cardiovascular nature, which are present in these states and are largely the same as those present in Cushing's syndrome. In this review we aim to discuss the evidence suggesting the emerging negative role for FH.

Harmful effects of functional hypercortisolism: a working hypothesis.

Multiple hormone responses to clonidine administration in depressed patients and healthy volunteers.

We have observed a significantly higher growth hormone (GH) response to clonidine administration (150 micrograms i.v.) in 14 patients with a major depressive disorder who had never received antidepressant therapy than in 14 matched depressive patients who had not received tricyclic drugs for at least 15 days. Compared with a control group of eight subjects, untreated depressed patients, as a group, had a normal response, while matched patients had markedly blunted response. Results for the group of untreated depressed patients showed that some patients had a blunted response while others had a response in the normal range. The results suggest that studies on the GH response to clonidine in psychiatric patients need to take into account the confounding and long-lasting effects of tricyclics.

Tricyclic wash-out and growth hormone response to clonidine.

The authors found a significant negative correlation between human growth hormone (HGH) response to clonidine and urinary free cortisol level in 14 depressed patients. The HGH response did not distinguish endogenous depression from nonendogenous depression.

/pdf/the-human-growth-hormone-response-to-clonidine-relationship-539psp8ic4.pdf

Stephen P. Calloway

Papers

The human growth hormone response to clonidine: relationship to clinical and neuroendocrine profile in depression.