Acute tryptophan depletion in schizophrenia.
BACKGROUND
Brain 5-hydroxytryptamine (5-HT) function is implicated in the pathophysiology of schizophrenia and the action of new generation antipsychotic drugs. By the method of acute tryptophan depletion (ATD) 5-HT can be selectively manipulated. The aim of this study was to examine the effects of ATD on symptoms, mood and cognition in schizophrenic patients.


METHODS
Twenty-eight schizophrenic patients participated in a within subject, double-blind, placebo-controlled counterbalanced cross-over study. Patients with a concurrent DSM-IV axis I diagnosis were excluded. Symptoms, mood and cognitive function were evaluated following ATD or ingestion of a control drink.


RESULTS
The depleting drink significantly reduced plasma total and free tryptophan. Tryptophan/LNAA ratios did not alter with the administration of the control drink, but differed significantly with ATD; however there was no significant change in tyrosine/LNAA ratio. ATD led to impairment in executive function that was dependent upon the order of administration. Tests of sustained attention, speed of processing, and everyday memory were not affected. No effects were observed on subjective mood ratings, movement disorders or PANSS scores.


CONCLUSIONS
Acute tryptophan depletion selectively alters cognition in schizophrenia, but has no effect on symptoms, mood ratings or movement disorders.
Golightly
K L
KL
School of Neurosciences, Division of Psychiatry, University of Newcastle-upon-Tyne.
Lloyd
J A
JA
Hobson
J E
JE
Gallagher
P
P
Mercer
G
G
Young
A H
AH
D000284:Administration, Oral; D000328:Adult; D000339:Affect; D000596:Amino Acids / Q000008:administration & dosage; D001812:Blood-Brain Barrier; D003071:Cognition; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D014176:Protein Biosynthesis; D012559:Schizophrenia / Q000188:drug therapy* / Q000503:physiopathology; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014364:Tryptophan / Q000097:blood / Q000378:metabolism*
D000596:Amino Acids; D014364:Tryptophan