Polymorphisms of serotonin neurotransmission and their effects on antipsychotic drug action

The receptor pharmacology of many antipsychotic drugs includes actions at various serotonin (5-hydroxytryptamine [5-HT]) receptors. The 5-HT neurotransmitter system is thought to be involved in many of the consequences of treatment with antipsychotic drugs, including both symptom response, primarily of negative and depressive symptoms, and adverse effects, notably extrapyramidal side effects and weight gain. There is substantial interindividual variability in these drug effects, to which genetic variability contributes. We review here the influence of functional polymorphisms in genes associated with 5-HT function, including the various processes of neurotransmitter synthesis, receptors, transporters and metabolism, on the clinical response to, and adverse effects of, antipsychotic drugs. The relatively young field of epigenetics also contributes to the variability of 5-HT-related genes in influencing drug response. Several of these findings inform our understanding of the mechanisms of antipsychotic drug action, and also provide the opportunity for the development of genetic testing for personalized medicine.