Risperidone: An Example of the Antipsychotic Treatment According to the Susceptibility Genes
Received Date: Feb 19, 2019 / Accepted Date: Feb 25, 2019 / Published Date: Feb 28, 2019
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 . 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 . 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 .
In the mesolimbic system, the neural network is pointed out, as seen in Figure 1, dopaminergic neurons, which have a high activity according to genes (e.g., COMT, MAO), apply a postsynaptic excitatory potential via D2 receptor to GABAergic neurons, which according to the genes dysbindin-1 or neuregulin-1 exert a weak presynaptic inhibitory potential, via NMDA receptors, upon serotonergic neurons. The serotonergic neurons exert a strong activating potential via 5-HT2A receptors upon GABAergic neurons, which apply a weak presynaptic inhibitory potential upon dopaminergic neurons, which is encoded in the GAD 67 gene [2,3,5]. In the VTA, dopaminergic neurons transmit a postsynaptic excitatory potential to other dopaminergic neurons (A10 cell group) and serotonergic neurons apply an activating potential to other serotonergic neurons. Both neurons send an activating potential to each other and thus they increase dopamine and 5-HT release .
Figure 1: Neural network in the brain areas involved in schizophrenia. 5-HT: serotonin; DA: dopamine; GABA: gammaaminobutyric acid; Glu: glutamate. 5-HT2A: 5-HT2A receptor of the serotonin (5-HT) receptor; D2: D2 receptor of the dopamine (DA) receptor; GABAA: GABAA receptor of the GABA receptor; NMDA: N-methyl-D-aspartate receptor.
The second-generation antipsychotic drug risperidone blocks dopaminergic and serotonergic receptors and has a specific affinity for the D2 receptor . In an explorative study, 690 schizophrenic patients and 430 healthy subjects received a risperidone treatment for 8 weeks. Blood samples were taken and single nucleotide polymorphisms of the COMT risk gene and of the dopamine receptors were examined by the polymerase chain reaction. A correlation analysis was conducted between the schizophrenia related genes and the improvement of positive and negative schizophrenic total score scale. A single nucleotide polymorphism referring to the COMT enzyme was related with a significantly better improvement of positive and negative symptoms in schizophrenia .
Does efficacy of the different antipsychotic drugs depend on the risk genes in schizophrenic patients?
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Citation: Werner FM, Coveñas R (2019) Risperidone: An Example of the Antipsychotic Treatment According to the Susceptibility Genes. J Cytol Histol 10: e121. DOI: 10.4172/2157-7099.1000e122
Copyright: © 2019 Werner FM, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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