Background: Effects of the hypothalamic-pituitary-adrenal (HPA) axis on cen
tral dopaminergic systems have been proposed to underlie the development of
psychotic symptoms in depression, This study examined HPA axis hormone eff
ects on plasma levels of homovanillic acid (HVA), the dopamine metabolite,
in healthy volunteers, using a placebo-controlled double-blind, random-assi
gnment, crossover design, On the basis of preliminary studies, we hypothesi
zed that HPA axis hormones would produce delayed effects on plasma HVA leve
ls measured in the afternoon;
Methods: Ten healthy subjects underwent a standard protocol an four occasio
ns and each time received ovine corticotropin-releasing hormone, synthetic
adrenocorticotropic hormone (ACTH), cortisol, or placebo. Plasma HVA was me
asured at 9 AM and 4 PM an Day 1, immediately prior to administration of th
e test substance at 7 PM, then at 30-60-min intervals until 11 PM. Plasma H
VA levels were subsequently obtained at 9 AM and 4 PM on Days 2 and 3.
Results: As predicted, there were significant differences between test subs
tances in delayed effects on afternoon HVA levels measured on Days 2 and 3,
with cortisol and ACTH producing greater increases in HVA than placebo. Ac
ute effects of HPA axis hormones on HVA were not found, while differences b
etween test substances in delayed effects on morning HVA levels approached
significance,
Conclusions:HPA axis hormones exert delayed effects an plasma HVA levels in
healthy humans. (C) 1999 Society of Biological Psychiatry.