THE EFFECTS OF CANDIDATE GENE IN PKPD PATHWAY ON ANTIPSYCHOTICS-INDUCED AMENORRHEA IN FEMALE SCHIZOPHRENIA PATIENTS

Abstract

Background: Amenorrhea frequently occurs in female patients taking under antipsychotic drugs (APs).It may affect drug compliance resulting treatment failure. The aim of this study was to explore the genetic effects of candidate single nucleotide polymorphisms (SNPs) in pharmacokinetics and pharmacodynamics (PKPD) pathway of APon AP-induced amenorrhea in female schizophrenia patients. Method(s): Eighty-nine female schizophrenic patients (age range from 18 to 40) taking the same AP for more than 3 months were enrolled. Amenorrhea was defned as the absence of menses for three months or three periods in a row. The serum levelsof prolactin, estradiol (E2), Follicle-stimulating hormone (FSH), Luteinizing hormone (LH), and thyroid-stimulating hormone (TSH) were measured. Cytochrome P450 2D6 (CYP2D6), dopamine receptor D2 (DRD2) and estrogen receptor 1 (ESR1) were genotyped. Result(s): Compared to the patients without amenorrhea (n= 67), pro-lactin level was higher (71.5 vs. 94.1 ng/mL; p= 0.044) and E2 was lower (46.7 vs. 27.0ng/mL; p= 0.007) inthe patients with amenor-rhea (n= 22). There was no difference in other hormonesand baseline characteristics between the patients with and without amenorrhea. Amisulpiride, chlorpromazine, haloperidol, paliperidone, and risperidone were observed to highly increase prolactin level and categorized to drugs increasing prolactin level. DRD2-141insC (OR= 0.59, 95% CI= 0.34-0.99; p= 0.049) and drugs increasing prolactin level (OR= 6.17, 95% CI= 1.28-29.64; p= 0.023) were identifed as predictors for AP-induced amenorrhea using multiple logistic regression analysis identifed. Conclusion(s): This fnding is the frst evidence suggesting that DRD2-141insC might be a possible protective biomarker for AP-induced amenorrhea. Further studies to confrm the DRD2-141insC as a biomarker for AP-induced amenorrhea are needed in larger female antipsychotic patients.