The 5-HT hypothesis of schizophrenia.

Schizophrenia is a serious psychiatric illness that is responsible for a substantial proportion of mental illness worldwide. Symptoms include hallucination, delusions, thought disorder and negative symptoms, including poverty of thought and emotion, and social withdrawal. Early theories of schizophrenia implicated disturbed serotonin (5-HT) neurotransmission, but these were largely overshadowed by the dopamine theory of schizophrenia, which became established after the introduction of chlorpromazine. However, the importance of 5-HT in CNS function is once again being recognized. The ability of antipsychotic drugs to diminish positive symptoms has been correlated with their ability to block dopamine D(2) receptors, although negative symptoms are not as effectively treated by typical neuroleptics. There is increasing interest in the correlation between negative symptoms of schizophrenia and 5-HT(2) receptors. The rationale for these studies is the hypothesis that abnormal neurotransmission at 5-HT(2) receptors may be involved in the pathophysiology of schizophrenia. This review highlights recent pharmacological and clinical advances in the understanding of the potential use of serotonin 5-HT(2) receptor antagonists in the treatment of schizophrenia.