Pharmacogenetics of antipsychotics using an animal model

Abstract

One major problem of the therapy with neuroleptics is the lack of efficacy in many of the patients and the occurrence of extrapyramidal side effects that can both limit the therapy and the compliance. Thus, the availability of a predictive tool for the response to psychopharmacologic agents in the therapy of psychiatric disorders is desirable. To search for genes associated with e.g. response to neuroleptics or extrapyramidal symptoms (EPS) a hypothesis free approach was used including animal models, neuronal cell cultures, and differenzial gene expression analyses. Immunohistochemical analyses were performed in rats that received an agent mimicking aspects of psychosis (MK-801), or haloperidol, or a combination of these agents, or saline. Genes differenzially expressed between the different groups had been genotyped in our clinical sample on pharmacogenetics including 104 patients with acute psychosis (schizophrenia, schizoaffective, brief psychotic, and substance-induced psychotic disorder) treated with haloperidol for up to 28 days. Diagnosis was established by applying the SCID I and II interview. Patients were assessed at baseline and on days 3, 7, 14, 21and 28. Improvement and response were measured by using the Positive and Negative Syndrome Scale. We will present novel data on this ongoing large-scale association study on response to haloperidol.