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Does ketamine mimic aspects of schizophrenic speech?

CASPR, Artificial Intelligence Center, University of Georgia, Athens, Georgia, USA, mc{at}uga.edu

Wim J. Riedel

GlaxoSmithKline Research & Development Ltd., Addenbrooke's Hospital, Cambridge, UK

Cati Brown

CASPR, Artificial Intelligence Center, University of Georgia, Athens, Georgia, USA

Congzhou He

CASPR, Artificial Intelligence Center, University of Georgia, Athens, Georgia, USA

Eric Morris

CASPR, Artificial Intelligence Center, University of Georgia, Athens, Georgia, USA

Sara Weinstein

Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada

James SempLe

GlaxoSmithKline Research & Development Ltd., Addenbrooke's Hospital, Cambridge, UK

John Brown

GlaxoSmithKline Research & Development Ltd., Addenbrooke's Hospital, Cambridge, UK

Speech disturbances are well-known symptoms contributing to the diagnosis of schizophrenia. Subanesthetic doses of the N-methyl-D-aspartate (NMDA) antagonist ketamine have been reported to produce positive and negative symptoms and cognitive impairments consistent with those seen in schizophrenia. Insofar as this is true, it constitutes evidence that the NMDA system is involved in schizophrenia. It is therefore of interest to know whether ketamine produces speech disturbances like those of schizophrenia.

Quantitative computer-aided analysis of apparently normal speech can detect clinically relevant changes and differences that are not noticeable to the human observer.

Accordingly, in this study, speech samples were analysed for repetitiousness, idea density, and verb density using software developed by the authors. The samples came from two experiments, a within-subjects study of healthy volunteers given intravenous ketamine versus placebo, and a between-groups study of patients diagnosed with schizophrenia and comparable healthy controls.

Our primary hypothesis was that in both schizophrenia and ketamine, repetitiousness wouLd increase, since perserverative speech is a well-known symptom of schizophrenia. Our secondary hypotheses were that in both schizophrenia and ketamine, idea density and verb density would decrease as indicators of cognitive impairment.

The primary hypothesis was confirmed in the schizophrenia experiment (between groups) and the ketamine experiment (within subjects).

The secondary hypotheses were disconfirmed except that in the ketamine experiment, verb density was significantly lowered. Reduced use of verbs apparently reflects a cognitive impairment of a different type than repetitiousness, and further investigation is needed to determine whether this impairment occurs in psychosis.

Key Words: ketamine • schizophrenia • N-methyl-D-aspartate (NMDA) • speech • Language • verbal behavior • perseveration • verbs • idea density

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