Association between dopamine-related polymorphisms and plasma concentrations of prolactin during risperidone treatment in schizophrenic patients.

Abstract

Hyperprolactinemia is an inevitable consequence of treatment with antipsychotic agents to some extent because prolactin response to antipsychotics is related to dopamine blockade. Recent studies have suggested that polymorphisms of the dopamine receptors are associated with therapeutic response to antipsychotics. Thus, we studied the effects of major polymorphisms of dopamine-related genes on plasma concentration of prolactin. Subjects were 174 schizophrenic patients (68 males, 106 females) receiving 3 mg twice daily of risperidone for at least 4 weeks. Sample collections were conducted 12 h after the bedtime dosing. Five dopamine-related polymorphisms (Taq1A, -141C ins/del for DRD2, Ser9Gly for DRD3, 48 bp VNTR for DRD4, Val158Met for COMT) were identified. The mean (+/-SD) plasma concentration of prolactin in females was significantly higher than males (54.3+/-27.2 ng/ml versus 126.8+/-70.2 ng/ml, p<0.001). No dopamine-related polymorphisms differed the plasma concentration of prolactin in males or females. Multiple regression analyses including plasma drug concentration and age revealed that plasma concentration of prolactin correlated with gender (standardized partial correlation coefficients (beta)=0.551, p<0.001) and negatively with age (standardized beta=-0.202, p<0.01). No correlations were found between prolactin concentration and dopamine-related polymorphisms. These findings suggest that plasma prolactin concentrations in females are much higher than in males but the dopamine-related variants are not predominantly associated with plasma concentration of prolactin.

• Authors: Norio Yasui-Furukori, Manabu Saito, Shoko Tsuchimine, Taku Nakagami, Yasushi Sato, Norio Sugawara, Sunao Kaneko
• Journal: Progress in neuro-psychopharmacology & biological psychiatry (Prog Neuropsychopharmacol Biol Psychiatry) Vol. 32 Issue 6 Pg. 1491-5 (Aug 01 2008) ISSN: 0278-5846 [Print] England
• PMID: 18579277 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antipsychotic Agents
• Receptors, Dopamine D2
• Prolactin
• DNA
• Risperidone
• Dopamine

Topics

• Adult
• Antipsychotic Agents (adverse effects, therapeutic use)
• DNA (genetics)
• Dopamine (genetics)
• Female
• Humans
• Japan (epidemiology)
• Male
• Polymorphism, Genetic (genetics)
• Prolactin (blood)
• Receptors, Dopamine D2 (drug effects, genetics)
• Regression Analysis
• Risperidone (adverse effects, therapeutic use)
• Schizophrenia (drug therapy, epidemiology, genetics)
• Sex Characteristics