Risperidone: An Example of the Antipsychotic Treatment According to the Susceptibility Genes

Abstract

Schizophrenia is a chronic psychiatric illness which affects about 1% of the population. In the prodromal phase, symptoms such as depression, social withdrawal and mutism occur during about 7 years, till an acute manifestion with symptoms as hallucinations, illusions and paranoia appears [1]. Since the proposal of the dopamine hypothesis, a multi-neurotransmitter system in different brain regions has been suggested. An increased dopamine release, via the dopaminergic D2 receptor, and an augmented serotonin release via the serotonergic 5-HT2A receptor occur in in the involved brain areas, e.g. ventral tegmental area. In preclinical studies, ketamine, an antagonist of the NMDA (N-methyl-D-aspartate) receptor can cause schizophrenia-like symptoms, which can be ameliorated with 5-HT2A antagonists, but not by first-generation antipsychotic drugs which block D2 receptors. The search for susceptibility genes has been developed, and some risk genes are known [2,3]. In most cases, schizophrenic patients are treated with first-generation antipsychotic drugs and more often with newer antipsychotic drugs which block, with different affinities, the dopaminergic D2 receptor and the serotonergic 5-HT2A receptor [4]. In schizophrenia, the current discovered susceptibility genes are the following: COMT (catechol-Omethyl-transferase), which is an enzyme that shows a decreased activity and catalyses the catabolism of dopamine; MAO (monoamine oxidase), which is also an enzyme with a reduced activity and catalyses the breakdown of dopamine; GAD 67 (glutamate decarboxylase), which indicates a diminished activity of GABAergic neurons, and the genes dysbindin and neuregulin, which refer to a declined activity of NMDA glutamatergic neurons [2].