Veera Manikandan, R (2014) Polymorphisms in the dopamine receptor 4 gene: is there an association with clinical response to clozapine in patients with treatment-resistant schizophrenia? Masters thesis, Christian Medical College, Vellore.
|
Text
201301114veera_manikandan.pdf Download (3MB) | Preview |
Abstract
BACKGROUND: Clozapine is the treatment of choice for treatment-resistant schizophrenia (TRS). Its use is, however, often associated with variable clinical outcomes. It acts as an antagonist of dopamine receptors, with a high affinity for dopamine receptor 4 (DRD4). Polymorphisms in the DRD4 gene have been suggested to contribute to variable drug responses seen. OBJECTIVES: The aim of this study was to determine whether a 120 base-pair duplication polymorphism in the DRD4 gene affects response to clozapine. METHODS: Patients diagnosed to have TRS, on stable doses of clozapine were the subjects of the study. Genomic DNA was isolated from peripheral venous blood from the patients, and genotyped for the polymorphism. Serum clozapine levels were also measured. Participants’ socio-demographic and clinical profiles were recorded. Standard assessment schedules were used to assess premorbid adjustments, response to traumatic events, cognitive status and disability. Clozapine response was defined a priori; allelic and genotypic frequencies were determined and correlated with the clinical responses. RESULTS: No genotypic association was found between the polymorphism and serum clozapine levels or response to treatment with clozapine in patients with TRS. However, among the adverse effects, hyper-salivation is significantly associated with the polymorphism of interest (p=0.0009). Presence of the 120-bp duplication in DRD4 appears to confer risk for sialorrhea in response to clozapine therapy. These results suggest that routine screening for DRD4 120-bp repeat polymorphism before clozapine therapy may not be useful as a predictor for clinical response to clozapine. It may, however, help to identify those at high risk for clozapine-induced hyper-salivation.
| Item Type: | Thesis (Masters) |
|---|---|
| Uncontrolled Keywords: | Schizophrenia, clozapine, sialorrhea, adverse effects, DRD4, dopamine D4 receptor, polymorphism, pharmacogenetics, drug resistance, brief psychiatric rating scale, antipsychotic agents, tandem repeat sequences, genetic association studies. |
| Subjects: | MEDICAL > Biochemistry |
| Depositing User: | Subramani R |
| Date Deposited: | 09 Jul 2020 16:31 |
| Last Modified: | 09 Jul 2020 16:31 |
| URI: | http://repository-tnmgrmu.ac.in/id/eprint/12517 |
Actions (login required)
 |
View Item |
