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Neuroendocrine Response to 5-Hydroxy-L-Tryptophan in Prepubertal Children at High Risk of Major Depressive Disorder

Boris Birmaher, MD; Joan Kaufman, PhD; David A. Brent, MD; Ronald E. Dahl, MD; lames M. Perel, PhD; Mayadah Al-Shabbout, MA; Beverly Nelson, RN; Stacey Stull, MS; Uma Rao, MD; G. Scott Waterman, MD; Douglas E. Williamson; Neal D. Ryan, MD
Arch Gen Psychiatry. 1997;54(12):1113-1119. doi:10.1001/archpsyc.1997.01830240073010.
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Background:  Altered serotonergic function has been observed in prepubertal children and adults with an acute episode of major depressive disorder (MDD). However, it is not known whether these alterations are present prior to the onset of MDD.

Methods:  A serotonergic precursor, 5-hydroxy-L-tryptophan (L-5HTP) (oxitriptan) (0.8 mg/kg), was administered 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-risk normal controls (with low family loading for mood disorders and no history of psychopathology). Blood samples for cortisol, prolactin (PRL), and growth hormone were obtained every 15 minutes for 180 minutes, beginning 30 minutes before L-5HTP infusion.

Results:  Children at high risk of MDD and children with MDD had similar hormonal responses following L-5HTP infusion. After controlling for baseline values, both groups secreted significantly less cortisol and more PRL than did the low-risk normal controls, with the PRL finding being limited to girls. There were no between-group differences in baseline cortisol, PRL, or growth hormone secretion measures.

Conclusions:  Before the onset of affective illness, highrisk children had the same pattern of neuroendocrine response to the L-5HTP challenge as did children with MDD. These results extend earlier findings of altered serotonergic regulation in association with early-onset depression and indicate that these alterations may represent a trait marker for depression in children.

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