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


OBJECTIVE
To review the evidence regarding the nature of these interactions in healthy and depressed humans.


METHODS
Electronic searches were performed for relevant papers, employing MEDLINE and Web of Science. To focus the review, we selected only those articles involving (i) assessment of serotonergic function following experimental manipulation of the HPA axis in healthy volunteers; and (ii) assessment of both serotonergic and HPA axis function in clinically depressed subjects.


RESULTS
Pre-treatment with hydrocortisone, both acutely and sub-acutely attenuates the GH response to GHRH in healthy subjects. This complicates the interpretation of 5-HT neuroendocrine studies employing GH output as a measure. In depression there is evidence that reduced availability of l-tryptophan impairs HPA axis feedback. There is also evidence that depressed and healthy subjects may adapt differently both to low tryptophan and hypercortisolaemic challenges. There is no consistent evidence of a simple relationship between HPA axis function and 5-HT function in depression.


CONCLUSIONS
The putative reduction in central 5-HT function has not been shown to be a direct consequence of hypercortisolaemia. Rather, the 5-HT system and HPA axis have complex inter-relationships. Challenges to either system, such as stress or reduced dietary tryptophan, may perturb the other and subjects vulnerable to depression may fail to adapt to such challenges.
Porter
Richard J
RJ
Department of Psychological Medicine, Christchurch School of Medicine, Christchurch, New Zealand. richard.porter@chmeds.ac.nz
Gallagher
Peter
P
Watson
Stuart
S
Young
Allan H
AH
D000305:Adrenal Cortex Hormones / Q000378:metabolism*; D000818:Animals; D003863:Depression / Q000378:metabolism* / Q000503:physiopathology; D019317:Evidence-Based Medicine; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D016239:MEDLINE; D010913:Pituitary-Adrenal System / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*
D000305:Adrenal Cortex Hormones; D012701:Serotonin