Ceramide and Insulin Resistance in Muscle and Endothelial Cells

Abstract

Schizophrenia is a chronic, severe and disabling psychiatric disorder. Although no cure as such, has been developed effective treatment now exists. The first breakthrough in treatment, was the introduction of Chlorpromazine. The typical drugs of which Chlorpromazine was the first, were superseded by Atypical drugs their prototype drug was Clozapine. Clozapine is seen as ‘unique’ as it can be used to treat “treatment-resistant’ patients, who do not benefit from other drugs. However not all the patients who are given Clozapine, experience a response. This variability in response can range from benefit to serious adverse effects. So the aim in this project was to determine what predicts response. There are many factors, which may influence how well an individual responds to a certain drug such as age, dose, gender and genetics. This project will discuss how genetics can influence variability in response. To do this polymorphisms within receptor subtypes were examined for their link to clozapine response. Clinical studies which have investigated the association between polymorphisms within receptor subtypes and the prediction of response to clozapine were identified through systematic searches of various databases. If the inclusion criteria was fulfilled then the studies were retrieved. Relevant data was then extracted from each study, and tabulated, to await qualitative analysis. The majority of the studies involved Dopamine and Serotonin receptor subtypes. Studies involving Adrenaline, Glutamate and Histamine were also retrieved. Findings were very contradictory, this may be due to factors such as ethnic heterogeneity, difficulty in measuring response and an insufficient sample size. Although no firm conclusions could be reached, due to the conflicting findings reported, there may be several potential associations between polymorphisms and clozapine response. These possible links should be investigated further through replication studies. It is hoped that if associations are identified this would go some way to replacing the ‘trial and error’ approach of finding the correct medication for a patient that is currently practiced. Instead patients would get the right drug according to their genotype.