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Cognitive deficit in schizophrenia and its neurochemical basis

Published online by Cambridge University Press:  06 August 2018

Alan Breier
Alan Breier*
Affiliation:
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA
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Abstract

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.

Type
Research Article
Information
The British Journal of Psychiatry , Volume 174 , Issue S37: Focus on schizophrenia , February 1999 , pp. 16 - 18
Copyright
Copyright © The Royal College of Psychiatrists, 1999 

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References

Bakshi, V. P. & Geyer, M. A. (1995) Antagonism of phencyclidine-induced deficits in pre-pulse inhibition by the putative atypical antipsychotic olanzapine. Psychopharmacology, 122, 198–201.CrossRefGoogle ScholarPubMed
Breier, A., Schreiber, J. L., Dyer, J., et al (1991) National Institute of Mental Health longitudinal study of chronic schizophrenia: prognosis and prediction of outcome. Archives of General Psychiatry, 48, 239–246.Google Scholar
Breier, A., Buchanan, R. W., Kirkpatrick, B., et al (1994) Effects of clozapine on positive and negative symptoms in outpatients with schizophrenia. American Journal of Psychiatry, 151, 20–26.Google Scholar
Breier, A., Su, T.-R., Saunders, R., et al (1997) Schizophrenia is associated with elevated amphetamine-induced synaptic dopamine concentrations: evidence from a novel positron emission tomography method. Proceedings of the National Academy of Sciences of the United States of America, 94, 2569–2574.Google Scholar
Breier, A., Adler, C. M., Weisenfeld, N. L., et al (1998) Effects of NMDA antagonism on striatal dopamine release in healthy subjects: application of a novel PET approach. Synapse, 29, 142–147.3.0.CO;2-7>CrossRefGoogle ScholarPubMed
Green, M. F. (1996) What are the functional consequences of neurocognitive deficits in schizophrenia? American Journal of Psychiatry, 153, 321–330.Google Scholar
Green, M. F., Marshall, B. D. J., Wirshing, W. C., et al (1997) Does risperidone improve verbal working memory in treatment-resistant schizophrenia? American Journal of Psychiatry, 154, 799–804.Google Scholar
Hagger, C., Buckley, P., Kenny, J. T., et al (1993) Improvement in cognitive functions and psychiatric symptoms in treatment-refractory schizophrenic patients receiving clozapine. Biological Psychiatry, 34, 702–712.CrossRefGoogle ScholarPubMed
Hoff, A. L., Faustman, W. O., Wieneke, M., et al (1996) The effects of clozapine on symptom reduction, neurocognitive function, and clinical management in treatment-refractory state hospital schizophrenic inpatients. Neuropsychopharmacology, 15, 361–369.CrossRefGoogle ScholarPubMed
Krystal, J. H., Karper, L. P., Seibyl, J. P., et al (1994) Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans: psychotomimetic, perceptual, cognitive, and neuroendocrine responses. Archives of General Psychiatry, 51, 199–214.Google Scholar
Lahti, A. C., Koffel, B., LaPorte, D., et al (1995) Subanesthetic doses of ketamine stimulate psychosis in schizophrenia. Neuropsychopharmacology, 13, 9–19.CrossRefGoogle ScholarPubMed
Malhotra, A. K., Adler, C. M., Kennison, S. D., et al (l997a) Clozapine blunts NMDA antagonist-induced psychosis: a study with ketamine. Biological Psychiatry, 42, 664–668.Google Scholar
Malhotra, A. K., Pinals, D. A., Adler, C. M., et al (1997b) Ketamine-induced exacerbation of psychotic symptoms and cognitive impairment in neuroleptic-free schizophrenics. Implications for NMDA receptor function. Neuropsychopharmacology, 17, 141–150.Google Scholar
Park, S., Holzman, P. S. & Goldman-Rakic, P. S. (1995) Spatial working memory deficits in the relatives of schizophrenic patients. Archives of General Psychiatry, 52, 821–828.Google Scholar
Purdon, S. E., Jones, B. D. W., Chouinard, G., et al (1998) Neuropsychological change in early phase schizophrenia over twelve months of treatment with olanzapine, risperidone, or haloperidol. Schizophrenia Research, 29, 152–153.Google Scholar
Rupp, A. & Keith, S. J. (1993) The costs of schizophrenia: assessing the burden. Psychiatric Clinics of North America, 16, 413–423.Google Scholar
Saykin, A. J., Shtasel, D. L., Gur, R. E., et al (1994) Neuropsychological deficits in neuroleptic naive patients with first-episode schizophrenia. Archives of General Psychiatry, 51, 124–131.Google Scholar
Siegel, C., Waldo, M., Mizner, G., et al (1984) Deficits in sensory gating in schizophrenic patients and their relatives. Archives of General Psychiatry, 41, 607–612.Google Scholar
Waldo, M. C., Carey, G., Myles-Worsley, M., et al (1991) Codistribution of a sensory gating deficit and schizophrenia in multi-affected families. Psychiatry Research, 39, 257–268.Google Scholar
Waldo, M. C., Cawthra, E., Adler, L. E., et al (1994) Auditory sensory gating, hippocampal volume, and catecholamine metabolism in schizophrenics and their siblings. Schizophrenia Research, 12, 93–106.CrossRefGoogle ScholarPubMed
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