Schizophrenia is a severe mental disorder which affects about 1% of the population, and that has a profound social and economical cost. Treatment of schizophrenia requires antipsychotic drugs which bind a wide range of neurotransmitter receptors. However, which receptors are important for the therapeutic action of antipsychotics is still not clear. In a previous study it was hypothesized that genetic variation in neurotransmitter receptors could influence response to antipsychotics targeting them. In this way, alterations in genes coding for receptor proteins may affect their function, expression or binding affinities for antipsychotic drugs which may in turn alter the drug's therapeutic action. This hypothesis was supported by the finding, made by researchers at The Institute of Psychiatry, University of London, England, of an association between a silent polymorphism in the serotonin-2A (5-HT2A) receptor gene and response to clozapine, a drug which displays high affinity for 5-HT receptors. Further evidence supporting this hypothesis is provided by new findings of association between polymorphisms in the promoter and coding regions of the 5-HT2A receptor and clozapine response. These results suggest that 5-HT receptors are important for the therapeutic action of those antipsychotic drugs targeting them. Genetic variation in dopaminergic, histaminergic, muscarinic and adrenergic receptors should be investigated on appropriated samples of subjects treated with antipsychotics targeting them to investigate their relevance in the drug therapeutic action. This work is published in the January 1988 issue of Molecular Psychiatry.
For information on this Molecular Psychiatry article, please contact the author:
Dr. Maria J. Arranz
Clinical Neuropharmacology, Institute of Psychiatry, University of London,
tel: +44 171 919 3343