Cognitive deficit in schizophrenia and its neurochemical basis.
Cognitive impairment is a central feature of schizophrenia and has been correlated with negative symptoms and impaired social functioning. There is a growing body of data suggesting that the so-called atypical antipsychotic drugs (e.g. clozapine, risperidone, and olanzapine) are better at enhancing cognitive function than traditional neuroleptics. Preclinical studies of information processing using a pre-pulse inhibition model show that the mechanism of action of both olanzapine and clozapine for cognitive enhancement may involve glutamatergic/N-methyl-D-aspartate (NMDA) antagonism. Using positron emission tomography, we have described the metabolic and neurochemical correlates of cognitive impairment induced by glutamatergic/NMDA antagonism. A better understanding of the underlying causes of cognitive impairment may contribute to elucidating the pathophysiology of schizophrenia and the development of more efficacious treatments for this disorder.
Breier
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Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA.
D014150:Antipsychotic Agents / Q000627:therapeutic use; D001569:Benzodiazepines; D003024:Clozapine / Q000627:therapeutic use; D003072:Cognition Disorders / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism; D018698:Glutamic Acid / Q000502:physiology; D006220:Haloperidol / Q000627:therapeutic use; D006801:Humans; D016202:N-Methylaspartate / Q000378:metabolism; D000077152:Olanzapine; D010890:Pirenzepine / Q000031:analogs & derivatives / Q000627:therapeutic use; D018967:Risperidone / Q000627:therapeutic use; D012559:Schizophrenia / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism; D012565:Schizophrenic Psychology
D014150:Antipsychotic Agents; D001569:Benzodiazepines; D010890:Pirenzepine; D018698:Glutamic Acid; D016202:N-Methylaspartate; D003024:Clozapine; D006220:Haloperidol; D018967:Risperidone; D000077152:Olanzapine