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• W2924158582 abstract "Background Schizophrenia is a severe and disabling mental disorder, characterized by the psychotic symptoms. The delay in providing a proper treatment, the duration of the First Episode of Psychosis (FEP) and the low response to the initial treatment are among the main factors of poor prognosis. In a previous study, our group evaluated the transcriptome in blood of antipsychotic-naive FEP patients before and after risperidone treatment, identifying 15 genes that may be directly related to this antipsychotic drug. The aim of the present study is to identify genetic polymorphisms related to risperidone response. Methods A total of 53 FEP patients with genetic data and two clinical evaluations (baseline and 2 months follow-up) were included. At first, SNPs genotypes from genes differentially expressed between case and healthy controls found in a previous study of our group, went through a quality control step in order to exclude SNPs and individuals below the cutoff limits. The remaining SNPs were extracted from microarray Infinium PsychArray using Plink 1.9 and RStudio softwares. Subsequently we performed the analysis of association between the groups of responders and non-responders to the treatment and the SNPs most associated with the response were analyzed in silico by the GTEx database. Risperidone response was assessed using the Positive And Negative Syndrome Scale (PANSS) total score from the two timepoints, considering as responders those with a decrease of at least 30% in PANSS. With this criterion, 27 patients were considered responders and 26 were non-responders. Results We analyzed a total of 69 independent SNPs within 14 of the 15 differentially expressed gene and observed a statistically significant association between rs1812923 SNP and risperidone response (χ2(2)=6.536, p=0.038). In addition, considering a dominant model, alternative A-allele carriers were associated with a better response to treatment (χ2(1)= 4.775, p= 0.029). An in silico analysis in the GTEx database further showed that this SNP is an eQTL of the SNCA gene in tissues of the tibial artery and left ventricle of the heart where the A allele is upregulated and an eQTL of the RP11-67M1.1 gene (located in the reverse strand) into the cerebellum, tissue in which the A allele is downregulated. Discussion In this study, we found suggestive association between the rs1812923 SNP (A/C) and the response to treatment. This SNP is located intronic region of the SNCA gene which has been associated with Parkinson disease and was downregulated in FEP patients after risperidone treatment, the next step of this study will be to replicate these results in another cohort of FEP patients (N=60) and in chronic schizophrenia patients (N=254)." @default.
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• W2924158582 date "2019-01-01" @default.
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• W2924158582 title "INVESTIGATION OF THE RISPERIDONE TREATMENT RESPONSE: A PHARMACOGENETICS STUDY IN A COHORT OF FIRST EPISODE OF PSYCHOSIS PATIENTS" @default.
• W2924158582 doi "https://doi.org/10.1016/j.euroneuro.2017.08.285" @default.
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