HPA Axis Dysfunction in Major Depression: Relationship to 5-HT_1A Receptor Activity

Abstract

Major depression is associated with a dysfunction of the serotonergic activity and the hypothalamic-pituitary- adrenal (HPA) axis. Moreover, a reciprocal relationship between the serotonergic and HPA axis systems has been hypothesized. The purpose of the present study was to assess the relationship between sensitivity of 5-HT_1A receptors as measured by hormonal (ACTH, cortisol and PRL) and temperature responses to flesinoxan and HPA axis activity as measured by the dexamethasone suppression test. The sample included 21 inpatients with major depression. Dexamethasone nonsuppressors exhibited lower ACTH responses to flesinoxan as compared with dexamethasone suppressors. The results showed that a dysfunction in 5-HT_1A receptor activity could be due to a hypersecretion of cortisol.

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

“…Responses to 5-HT 1A receptor agonists Pichot (2001) used neuroendocrine challenge with the specific 5-HT 1A receptor agonist flesinoxan, in 21 depressed in-patients. There was no relationship between cortisol, ACTH, PRL and hypothermic responses and post-dexamethasone cortisol.…”

CSF neurochemicals during tryptophan depletion in individuals with remitted depression and healthy controls

“…These CSF neurochemicals included: 3-methoxy-4-hydroxy-phenylglycol (MHPG), homovanillic acid (HVA), neuropeptide “Y” (NPY), and corticotrophin releasing hormone (CRH). CRH (Dinan, 1996; Pitchot et al, 2001) and NPY (Mathé et al, 1996; Mathé, 1999; Jiménez et al, 2001; Husum et al, 2003) have also been implicated in the pathophysiology of depression. Research has shown that NPY concentrations are reduced and CRH concentrations are increased in individuals with depression.…”

The effects of sub-chronic administration of hydrocortisone on hormonal and psychological responses to L-tryptophan in normal male volunteers

“…Abnormalities of the hypothalamic-pituitary-adrenal (HPA) axis are also well documented in depressive illness (Holsboer 1995), and it has been suggested that serotonergic dysfunction may be secondary to glucocorticoid hypersecretion (Dinan 1994;Pitchot et al 2001). Previous studies have investigated the relationship between hypercortisolaemia and 5-HT function by examining the effects of administration of glucocorticoids to healthy volunteers.…”