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.