NEUROENDOCRINE RESPONSE TO 5-HYDROXY-L-TRYPTOPHAN IN PREPUBERTAL CHILDREN AT HIGH-RISK OF MAJOR DEPRESSIVE DISORDER

Background: Altered serotonergic function has been observed in prepube rtal children and adults with an acute episode of major depressive dis order (MDD). However, it is not known whether these alterations are pr esent prior to the onset of MDD. Methods: A serotonergic precursor, 5- hydroxy-L-tryptophan (L-5HTP) (oxitriptan) (0.8 mg/kg), was administer ed through an indwelling catheter to 36 children at high risk of MDD ( with high family loading for MDD), 31 children with MDD, and 23 low-ri sk normal controls (with low family loading for mood disorders and no history of psychopathology). Blood samples for cortisol, prolactin (PR L), and growth hormone were obtained every 15 minutes for 180 minutes, beginning 30 minutes before L-5HTP infusion. Results: Children at hig h risk of MDD and children with MDD had similar hormonal responses fol lowing L-5HTP infusion. After controlling for baseline values, both gr oups secreted significantly less cortisol and more PRL than did the lo w-risk normal controls, with the PRL finding being limited to girls. T here were no between-group differences in baseline cortisol, PRI, or g rowth hormone secretion measures. Conclusions: Before the onset of aff ective illness, highrisk children had the same pattern of neuroendocri ne response to the L-5HTP challenge as did children with MDD. These re sults extend earlier findings of altered serotonergic regulation in as sociation with early-onset depresssion and indicate that these alterat ions may represent a trait mark:er for depression in children.