Tryptophan depletion during continuous CSF sampling in healthy human subjects

Neuropsychopharmacology. 1998 Jul;19(1):26-35. doi: 10.1016/S0893-133X(97)00198-X.


The tryptophan (TRP) depletion paradigm has been employed to investigate mood and behavioral effects of acutely lowering plasma TRP, and presumably brain serotonin (5-hydroxytryptamine [5-HT]) levels through administration of a special diet and/or amino acid drink. Our goal was to test the assumption that a corresponding fall in central levels of TRP and 5-HT (measured by its major metabolite, 5-hydroxyindoleacetic acid [5-HIAA]) occurs during the standard execution of this method in healthy adult subjects. Three males and two females completed the protocol, which included a one-day low-TRP diet and a TRP-free amino acid drink. Lumbar puncture was performed, with placement of an indwelling catheter connected to a peristaltic pump and fraction collector. Cerebrospinal fluid (CSF) was sampled continuously for a 13.5-hour period (before, during, and after the drink), with fractions removed every 15 minutes. Plasma samples were simultaneously obtained. CSF TRP levels and plasma TRP levels were highly correlated, falling a mean of 92% and 85% from baseline, respectively. CSF nadirs were reached several hours after plasma nadirs. CSF 5-HIAA decreased modestly (24% to 40%, mean 31% change from baseline), with lowest concentrations observed 8-12 hours after the amino acid drink. These data suggest that TRP depletion results in substantial declines in central 5-HT turnover.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Affect / drug effects
  • Brain / metabolism
  • Catheters, Indwelling
  • Diet
  • Drinking
  • Female
  • Humans
  • Hydroxyindoleacetic Acid / cerebrospinal fluid
  • Male
  • Serotonin / metabolism
  • Tryptophan / administration & dosage
  • Tryptophan / blood
  • Tryptophan / cerebrospinal fluid*
  • Tryptophan / deficiency*
  • Tyrosine / administration & dosage
  • Tyrosine / blood
  • Tyrosine / cerebrospinal fluid


  • Serotonin
  • Tyrosine
  • Hydroxyindoleacetic Acid
  • Tryptophan