The effects of d-amphetamine on working memory and language deficits in schizophrenia

Abstract

It has been hypothesized that language deficits in schizophrenia reflect a working memory dysfunction. More specifically, such deficits may be associated with a disturbance in the ability to generate and maintain discourse plans that guide and constrain subsequent language production. Such working memory deficits in schizophrenia may be related to reduced dopamine effects in prefrontal cortex. To test this hypothesis, healthy controls and schizophrenic patients performed language and working memory tasks on each of two days, following administration of either d-amphetamine (0.25 rug/kg) or placebo (double-blind, randomized order). All schizophrenic patients were medicated with low dose « 250 mg CPZ equivalents) high potency neuroleptics. On each day, participants completed structured interviews to assess language function, our modified version of the Continuous Performance Test, and a spatial working memory task. Among controls, amphetamine significantly increased the amount and complexity of speech, and decreased pausing. Among patients, amphetamine increased verbosity and decreased pausing, while significantly reducing formal thought disorder and unclear references. These findings are consistent with the hypothesis that language deficits in schizophrenia are associated with decreased dopamine effects in prefrontal cortex.