Pharmacogenetics of psychotropic drug response.
OBJECTIVE
Molecular genetic approaches provide a novel method of dissecting the heterogeneity of psychotropic drug response. These pharmacogenetic strategies offer the prospect of identifying biological predictors of psychotropic drug response and could provide the means of determining the molecular substrates of drug efficacy and drug-induced adverse events.


METHODS
The authors discuss methods issues in executing pharmacogenetic studies, review the first generation of pharmacogenetic studies of psychotropic drug response, and consider future directions for this rapidly evolving field.


RESULTS
Pharmacogenetics has been most commonly used in studies of antipsychotic drug efficacy, antidepressant drug response, and drug-induced adverse effects. Data from antipsychotic drug studies indicate that polymorphisms within the serotonin 2A and dopamine receptor 2 genes may influence drug efficacy in schizophrenia. Moreover, a growing body of data suggests a relationship between the serotonin transporter gene and clinical effects of the selective serotonin reuptake inhibitors used to treat depression. A significant relationship between genetic variation in the cytochrome P450 system and drug-induced adverse effects may exist for certain medications. Finally, a number of independent studies point to a significant effect of a dopamine D(3) receptor polymorphism on susceptibility to tardive dyskinesia.


CONCLUSIONS
Initial research into the pharmacogenetics of psychotropic drug response suggests that specific genes may influence phenotypes associated with psychotropic drug administration. These results remain preliminary and will require further replication and validation. New developments in molecular biology, human genomic information, statistical methods, and bioinformatics are ongoing and could pave the way for the next generation of pharmacogenetic studies in psychiatry.
Malhotra
Anil K
AK
Department of Psychiatry Research, Zucker Hillside Hospital, 75-59 263rd St., Glen Oaks, NY 11004, USA. malhotra@lij.edu
Murphy
Greer M
GM
Kennedy
James L
JL
D000928:Antidepressive Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D003866:Depressive Disorder / Q000188:drug therapy / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D006801:Humans; D001523:Mental Disorders / Q000188:drug therapy* / Q000235:genetics*; D010597:Pharmacogenetics / Q000379:methods; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics; D011618:Psychotic Disorders / Q000188:drug therapy / Q000235:genetics; D011619:Psychotropic Drugs / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D012559:Schizophrenia / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D016896:Treatment Outcome
D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D011619:Psychotropic Drugs; D003577:Cytochrome P-450 Enzyme System