Association Study between 5-HT2A Receptor and DRD3 Receptor Gene Polymorphism and Clinical Response to Atypical Antipsychotics in Patients with Schizophrenia / 신경정신의학

OBJECTIVES: This study was performed based on the hypothesis that the interindividual differences in clinical response to atypical antipsychotics might be associated with serotonin 2A receptor(5-HT2A) gene and(or) dopamine D3 receptor(DRD3) gene polymorphisms. METHODS: Seventy-five patients(39 men, 36 women) who met DSM-IV criteria for Schizophrenia at the Asan Medical Center were selected for the analysis of the medical records and subsequent interview. A written informed consent was obtained prior to the study and the privacy protection was kept throughout the course. Clinical Global Impression(CGI) Scale was applied after 4 weeks of treatment to assess the response to atypical antipsychotics. All patients in this study were administered olanzapine(n=39), risperidone(n=52) or clozapine(n=4). According to CGI scale, the patients were classified in 7 groups ; very much improvement ; much improvement ; minimal improvement ; no change ; minimal worsening ; much worsening ; very much worsening. The first and second groups were regarded as responders while the other groups were non-responders. Patients were genotyped for 5-HT2A by PCR(Msp I) for detection of T102 and C102 alleles. And they were also genotyped for DRD3 Ser9Gly polymorphism by PCR(Bal I). We conducted the statistical analyses to detect association between responders and non responders with chi-square tests. RESULTS: The patients who were shown no or minimally improved patients were sorted to non-responders(n=42, men 24, women 18) and the other patients shown much or very much improved were grouped as responders(n=33, men 15, women 18). The differences in demographic variables(age, sex), age of onset, and duration of illness were not statistically significant between the two groups. T102 allele is more frequent in non-responders(56.0%) than responders(45.5%), however, this difference is not statistically significant(p=0.20). Gly9 allele is near equal between non-responders and responders (65.5%, 65.2%). Genotype frequencies of the two groups also is not a statistically significant for 5-HT2A T102C(p=0.28) and DRD3 Ser9Gly(p=0.90). CONCLUSION:These results do not show significant associations among 5-HT2A gene, DRD3 gene and clinical response to atypical antipsychotics. On the assumption that responses to atypical antipsychotics are mediated by these two receptors, we can draw two possibilities. First, 5-HT2A and DRD3 genes may not be the functional variants related with responses to atypical antipsychotics. Second possibility is that the unknown variations which might be in linkage disequilibrium with the 5-HT2A T102C polymorphism and DRD3 Ser9Gly polymorphism may be associated with the response to atypical antipsychotics in schizophrenia. However, it is possible that the small number of subjects and ethnic difference of allele frequency of marker polymorphism could induce false negative results.

The Association between Polymorphism of the Dopamine D3 Receptors and Concentrations of Plasma Homovanillic and 5-hydroxyindoleacetic Acid, and Therapeutic Response of chronic Schizophrenic Patients

OBJECTIVES: Schizophrenia manifests a variety of interindividual differences in therapeutic response to antipsychotics. This might be attributable to dopamine and serotonin receptors that a important target for various antipsychotics, and the D3 receptor(DRD3) alleles they carry. The purpose of our study was to investigate whether the plasma levels of homovanillic acid(HVA) and 5-hydroxyindoleacetic acid(HIAA), and the polymorphism of DRD3 can be held as a predictor of treatment response ni chronic schizophrenic patients. METHODS: Therapeutic response for 16 korean schizophrenia patient treated during 48 weeks were assessed by PANSS used as the clinical symptom rating scales. The levels of concentration of HVA and 5-HIAA were examined by HPLC at baseline and at 48 weeks. We classified the polymorphism of DRD3 receptor using amplifying by polymerase chain reaction(PCR). RESULTS: Neither concentrations of HVA and 5-HIAA nor genotype of dopamine 3 receptor were not significantly associated with the therapeutic response. But, the patients who has A1 alleles of DRD3 gene showed poor therapeutic responses. CONCLUSION: A1 allele of DRD3 gene is associated with poor prognosis of chronic schizophrenia.