title: Tryptophan depletion during continuous CSF sampling in healthy human subjects.
abstract: 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.
authors.affiliation: Butler Hospital, Department of Psychiatry and Human Behavior, Brown University School of Medicine, Providence, RI 02906, USA.
authors.forename: L L
authors.initials: LL
authors.lastname: Carpenter
authors.forename: G M
authors.initials: GM
authors.lastname: Anderson
authors.forename: G H
authors.initials: GH
authors.lastname: Pelton
authors.forename: J A
authors.initials: JA
authors.lastname: Gudin
authors.forename: P D
authors.initials: PD
authors.lastname: Kirwin
authors.forename: L H
authors.initials: LH
authors.lastname: Price
authors.forename: G R
authors.initials: GR
authors.lastname: Heninger
authors.forename: C J
authors.initials: CJ
authors.lastname: McDougle
mesh_terms: D000328:Adult; D000339:Affect / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D002408:Catheters, Indwelling; D004032:Diet; D004326:Drinking; D005260:Female; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid; D008297:Male; D012701:Serotonin / Q000378:metabolism; D014364:Tryptophan / Q000008:administration & dosage / Q000097:blood / Q000134:cerebrospinal fluid* / Q000172:deficiency*; D014443:Tyrosine / Q000008:administration & dosage / Q000097:blood / Q000134:cerebrospinal fluid
chemical_list: D012701:Serotonin; D014443:Tyrosine; D006897:Hydroxyindoleacetic Acid; D014364:Tryptophan