Neuroendocrine effects of citalopram, a selective serotonine re-uptake inhibitor, during life span in humans

Objective Serotonergic system contributes to the regulation of hypothalamus-pituitary-adrenal axis (HPA). In humans, serotonergic agonists increase prolactin (PRL), adrenocorticotropin hormone (ACTH) and cortisol while serotonin (5HT) influence on growth hormone (GH) is controversial. Central serotonin activity and neuroendocrine function change during lifespan. Design To clarify the neuroendocrine response to 5HT across lifespan, we assessed ACTH, cortisol, dehydroepiandrosterone (DHEA), PRL and GH responses to citalopram (CT) in young adults (12 YA, 29.2+/-1.7 yrs MEAN+/-SEM), middle aged (12 MA, 54.3+/-0.9 yrs) and elderly (12 ES, 69.3+/-0.9 yrs) males. All the subjects received placebo (saline i.v. over 120 min) or CT (20 mg i.v. over 120 min). Blood samples were taken every 15 min up to 240. Results During placebo, ACTH, cortisol, GH and PRL were similar in all groups while DHEA showed an age-dependent reduction from middle age (p<0.001). During CT, ACTH and cortisol were higher than during placebo in YA (p<0.05) and even more in MA (p<0.01 vs placebo, p<0.05 vs YA); in ES, the increase of both ACTH and cortisol (p<0.05 vs placebo) was lower than in MA (p<0.05) and higher than in YA (p<0.05 for cortisol only). No changes were observed for DHEA, GH and PRL in any group. Conclusions Corticotrope response to citalopram is age-dependent in normal men, being amplified starting from middle age, suggesting precocious changes in the serotonergic neuroendocrine control during lifespan. Citalopram is a useful tool to evaluate the age-dependent serotonergic function in humans.