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 antipsych otic drugs. By the method of acute tryptophan depletion (ATD) 5-HT can be s electively 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 subje ct, double-blind, placebo-controlled counterbalanced cross-over study. Pati ents with a concurrent DSM-IV axis I diagnosis were excluded. Symptoms, moo d and cognitive function were evaluated following ATD or ingestion of a con trol drink. Results. The depleting drink significantly reduced plasma total and free tr yptophan. Tryptophan/LNAA ratios did not alter with the administration of t he control drink, but differed significantly with ATD; however there was no significant change in tyrosine/LNAA ratio. ATD led to impairment in execut ive function that was dependent upon the order of administration. Tests of sustained attention, speed of processing, and everyday memory were not affe cted. No effects were observed on subjective mood ratings, movement disorde rs or PANSS scores. Conclusions. Acute tryptophan depletion selectively alters cognition in sch izophrenia, but has no effect on symptoms, mood ratings or movement disorde rs.