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J Neuropsychiatry Clin Neurosci 1997; 9:1-17
Copyright © 1997 by American Neuropsychiatric Association
The role of serotonin in the pathophysiology and treatment of schizophrenia
A Abi-Dargham, M Laruelle, GK Aghajanian, D Charney and J Krystal
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA.
The concept of "balanced serotonergic/dopaminergic antagonists" reflects
renewed interest in the role of serotonin (5-HT) in schizophrenia.
Postmortem brain tissue analysis, cerebrospinal fluid studies, and
pharmacological challenges suggest a deficit in 5-HT function in the cortex
of patients with schizophrenia. In contrast, however, 5-HT2 antagonism is
claimed to have beneficial effects on both positive and negative symptoms
of the illness. The authors attempt to resolve this paradox with a model
that takes into account the suggestion of a cortical serotonergic
hypofunction and a beneficial effect of 5-HT2 antagonism via modulation of
subcortical dopamine activity. Although involvement of 5-HT in
schizophrenia is supported by compelling evidence, more research is needed
to better define its role in pathophysiology and treatment of this illness.
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