Role of Dopamine D3 Receptor (DRD3) and Dopamine Transporter (DAT) Polymorphism in Cognitive Dysfunctions and Therapeutic Response to Atypical Antipsychotics in Patients with Schizophrenia

G. Szekeres, S. Kéri, A. Juhász, A. Rimanóczy, István Szendi, Csongor Czimmer, Z. Janka

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102 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1-5
Number of pages5
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume124 B
Issue number1
Publication statusPublished - Jan 1 2004

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Dopamine D3 Receptors
Dopamine Plasma Membrane Transport Proteins
Antipsychotic Agents
Schizophrenia
Genotype
olanzapine
Therapeutics
Verbal Learning
Minisatellite Repeats
Risperidone
Symptom Assessment
Clozapine
Cognition
Cognitive Dysfunction
Alleles

Keywords

  • Dopamine D3 receptor
  • Dopamine transporter
  • Executive functions
  • Polymorphism
  • Schizophrenia
  • Verbal memory
  • Wisconsin Card Sorting Test

ASJC Scopus subject areas

  • Genetics(clinical)
  • Neuropsychology and Physiological Psychology
  • Neuroscience(all)

Cite this

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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.",
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AU - Kéri, S.

AU - Juhász, A.

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AU - Szendi, István

AU - Czimmer, Csongor

AU - Janka, Z.

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