Behavioral Response to Catecholamine Depletion in Individuals With Schizophrenia and Healthy Volunteers.

Background and Hypothesis: Dysfunction of the dopamine system is the leading neurobiological hypothesis of schizophrenia. In this study, we tested this hypothesis in the context of aberrance salience theory of delusions using catecholamine depletion. We hypothesized that acute dopamine depletion improves both positive symptoms and salience attribution in individuals with schizophrenia. Study Design: Catecholamine depletion was achieved by oral administration of alpha-methyl-para-tyrosine (AMPT) in 15 individuals with schizophrenia and 15 healthy volunteers. The study design consisted of a randomized, double-blind, placebo-controlled crossover, single-site experimental trial. The main outcome measures were the Scale for the Assessment of Positive Symptoms and the Salience Attribution Test. Study Results: Catecholamine depletion transiently reduced specific psychotic symptoms in symptomatic individuals with schizophrenia, namely delusions and positive formal thought disorder (interaction treatment-by-timepoint, Conclusions: This study suggests that the relationship between dopamine hyperactivity and delusional symptoms in schizophrenia is mediated by impaired attribution of salience to reward-predicting stimuli.