Polymorphisms in dopamine receptor DRD1 and DRD2 genes and psychopathological and extrapyramidal symptoms in patients on long‐term antipsychotic treatment

Abstract

DRD(1) and DRD(2) receptor gene variants have been associated with clinical aspects of schizophrenia; however only specific features were analyzed in different samples. To assess the complex interaction between genetic and clinical factors, we studied the possible cross-interactions between DRD1 and DRD2 dopamine receptor gene polymorphisms, symptomatology of schizophrenia and schizoaffective disorders, and the occurrence of treatment induced side effects taking into consideration possible clinical confounding variables. One hundred thirty one outpatients in stable remission meeting the DSMIV criteria for schizophrenia spectrum disorders and receiving long-term maintenance therapy with haloperidol, fluphenazine, zuclopenthixole, or risperidone were genotyped for DRD1 A-48G, DRD2 Ins-141CDel, and DRD2 Ser311Cys polymorphisms. Psychopathological symptoms were assessed with the positive and negative syndrome scale for schizophrenia (PANSS). Extrapyramidal side effects were assessed with the Simpson-Angus extrapyramidal side effects scale (EPS), the Barnes Akathisia scale (BARS), and the abnormal involuntary movement scale (AIMS). Drug dosage was included as covariant because it was associated with the severity of symptomatology, akathisia, and parkinsonism. No association was observed for DRD1 and DRD2 polymorphisms and extrapyramidal side effects, or with the other clinical variables considered. Our study suggests that DRD1 and DRD2 variants are not liability factors for tardive dyskinesia.

Sexually dimorphic interaction between the DRD1 and COMT genes in schizophrenia

“…Nevertheless, case-control genetic association studies analyzing the role of DRD1 in schizophrenia have revealed negative results [Campion et al, 1994;Cichon et al, 1996;Kojima et al, 1999;Iwata et al, 2003;Hoogendoorn et al, 2005;Dmitrzak-Weglarz et al, 2006;Dolzan et al, 2007;Talkowski et al, 2008].…”

Genome-wide association study of antipsychotic-induced parkinsonism severity among schizophrenia patients

“…Using the candidate gene approach, several polymorphisms within genes encoding receptors for dopamine and serotonin have been studied for association with AIP, but findings are not conclusive (Gunes et al 2008;Kaiser et al 2002;Nakazono et al 2005;Güzey et al 2007;Dolzan et al 2007;Al Hadithy et al 2008). Associations have been reported for the VNTR polymorphism in DAT1 (Güzey et al 2007), Taq1, and141CIns/Del variants in DRD2 (Guzey et al 2007;Al Hadithy et al 2008), and the HTR2C polymorphism Cys23Ser (Gunes et al 2008;Al Hadithy et al 2008).…”

Antipsychotic-induced tardive dyskinesia and polymorphic variations in COMT, DRD2, CYP1A2 and MnSOD genes: a meta-analysis of pharmacogenetic interactions

“…For both polymorphisms, the search yielded nine studies. Five studies could not be included either because categorical data were not used 61,69 or data were not reported. 56,59,60 No large or significant pooled OR was found for the alleles or genotypes for Ser311Cys 58,[66][67][68] or for À141C Ins/Del 27,66-68 (results available upon request).…”