Central serotoninergic activity (CSA) is known to influence the hypothalamuspituitaryadrenal (HPA) axis, and a CSA loss seems to play a role in human brain aging and in etiology of functional hypercortisolism and depression, whose incidence increase with advancing age. Citalopram (CT), a SSRI, has been considered a good tool to evaluate CSA in humans. Aim of this study was to evaluate the neuroendocrine response to CT in healthy adult subjects during lifespan. We evaluated ACTH, cortisol (F), DHEA, PRL and GH secretion following placebo or acute i.v. CT infusion (20 mg over 120 min) in 12 young (YA, age: 29.2±1.7 years), 10 middle aged (MA, 53.2±1.3 years) and 12 elderly subjects (ES, 69.3±0.9 years). Blood samples were taken every 15′ for 240′. During placebo, ACTH, F, PRL, and GH levels were not different in the three groups, while DHEA secretion showed a clear age-dependent reduction, starting from middle age (AUC, mean±SEM, YA: 2420.7±205, MA: 938.3±94.4 μg/l per min, P<0.01 versus YA; ES: 674.5±62.5, P<0.03 versus MA). In YA, CT infusion was followed by significant increase in ACTH and F (P<0.05 versus placebo), while no significant hormonal changes were observed for DHEA, PRL and GH. In MA, CT increased both ACTH and F (P<0.03 versus placebo) and the hormonal responses were higher than in YA (P<0.05); no significant effect on DHEA, PRL or GH was reported. In ES, ACTH and F response to CT were lower than in MA and similar to that in YA, while DHEA, PRL and GH were not modified. These preliminary findings indicate that the corticotrope response to citalopram is amplified in middle age but not in aging, a described condition of HPA hyperactivity. This suggests that the neuroendocrine effects of citalopram are clearly age-related, showing a transient hypersensitivity to SSRI during middle age.
03 - 07 May 2008
European Society of Endocrinology