title: Role of dopamine D3 receptor (DRD3) and dopamine transporter (DAT) polymorphism in cognitive dysfunctions and therapeutic response to atypical antipsychotics in patients with schizophrenia.
abstract: Molecular components of the dopaminergic system may play an important role in the pathophysiology of schizophrenia. In this study, we investigated the relationship of the Ser9Gly (S/G) polymorphism of the dopamine D3 receptor (DRD3) and the variable number of tandem repeats (VNTR) polymorphism of the dopamine transporter (DAT) with therapeutic response to atypical antipsychotics (clozapine, olanzapine, quetiapine, risperidone) and cognitive functions. No associations were found between the DRD3 and DAT polymorphisms and schizophrenia. The S/S genotype and the S allele were more frequent in the non-responder patients (n = 28) than in the group of responders (n = 47) (cut-off: >20-point improvement in Global Assessment of Functioning (GAF) scale). The patients with S/S genotype completed fewer categories and had more perseverative errors in the Wisconsin Card Sorting Test (WCST) compared with the S/G patients. The S/S and S/G patients did not differ in positive and negative symptoms, GAF scores, WCST failure to maintain set, and verbal learning. No differences in symptoms or WCST measures were observed in the patients with different DAT genotypes. These results suggest that the S/S genotype of the DRD3 is associated with worse therapeutic response and more severe executive dysfunctions in patients with schizophrenia.
authors.affiliation: Department of Psychiatry, University of Szeged, Szeged, Hungary. szeri@phys.szote.u-szeged.hu
authors.forename: György
authors.initials: G
authors.lastname: Szekeres
authors.forename: Szabolcs
authors.initials: S
authors.lastname: Kéri
authors.forename: Anna
authors.initials: A
authors.lastname: Juhász
authors.forename: Agnes
authors.initials: A
authors.lastname: Rimanóczy
authors.forename: István
authors.initials: I
authors.lastname: Szendi
authors.forename: Csongor
authors.initials: C
authors.lastname: Czimmer
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Janka
mesh_terms: D000328:Adult; D000483:Alleles; D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use; D003024:Clozapine / Q000627:therapeutic use; D003072:Cognition Disorders / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D003987:Dibenzothiazepines / Q000627:therapeutic use; D050483:Dopamine Plasma Membrane Transport Proteins; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D018598:Minisatellite Repeats / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics*; D000077152:Olanzapine; D011110:Polymorphism, Genetic; D000069348:Quetiapine Fumarate; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D050637:Receptors, Dopamine D3; D018967:Risperidone / Q000627:therapeutic use; D012559:Schizophrenia / Q000150:complications / Q000188:drug therapy* / Q000235:genetics
chemical_list: D014150:Antipsychotic Agents; C493593:DRD3 protein, human; D003987:Dibenzothiazepines; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; C493214:SLC6A3 protein, human; D001569:Benzodiazepines; D000069348:Quetiapine Fumarate; D003024:Clozapine; D018967:Risperidone; D000077152:Olanzapine