To observe the association between adverse effects of long-term use of antipsychotic drugs in female schizophrenic patients and dopamine D2 receptor (DRD2), cytochrome P450 (CYP) 2D6, estrogen receptor-α gene (ESR1).

The subjects were 89 female schizophrenic patients (age range from 18 to 40) who had been taking the same medication for more than 3 months. The adverse effects with regard to hyperprolactinemia were studied through the blood collection at one point of the subjects. Furthermore, the effect of DRD2, CYP2D6, ESR1 on serum prolactin level and amenorrhea was analyzed.

There was a lower concentration of E2 in patients with amenorrhea. In addition, an inverse correlation was found between prolactin level and E2 level. Hyperprolactinemia (HPRL) was commonly found in patients who had been using risperidone, amisulpride and paliperidone; in contrast, HPRL was found less in those who had been taking aripiprazole, olanzapine, ziprasidone, clozapine and quetiapine. Moreover, female schizophrenic patients who had DRD2 Taq1 A1 allele had twice the chance of developing amenorrhea than those who did not have A1 allele. Female schizophrenic patients who had Taq1 A1 allele also had 48% higher concentration level of prolactin than those who did not have A1 allele. There was no association found between prolactin and CYP2D6 or ESR1.

Female schizophrenic patients who had DRD2 Taq1 A1 allele showed high prolactin level and high-frequency of HPRL. Therefore, reducing the use of prolactin-elevating antipsychotics for female schizophrenic patients with DRD2 Taq1 A1 allele would be one method minimizing the adverse effects of drug-induced hyperprolactinemia.