An Effective Method to Facilitate Personalized and Precise Medicine for Schizophrenia Treatment Based on Pharmacogenomics

Abstract

Background: Schizophrenia is a serious mental illness affecting 0.3% - 0.7% of people in the whole world. It is a classic quantitative genetic disease and is affected by a variety of common and rare genetic variants. Methods: To facilitate personalized and precise medicine for schizophrenia treatment, we designed a program by genotyping a panel of related genes, including cytochrome P450 genes CYP1A2, CYP2D6, CYP3A4, dopamine 2 receptor gene (DRD2), 5-Hydroxytryptamine Receptor 1A and 2C genes (HTR1A and HTR2C) as well as melanocortin4 receptor (MC4R) gene, for the schizophrenia patients using MassArray time-of-flight mass spectrometry. Results: The program is tested in an observational clinical study conducted at the Hulunbuir Mental Health Center of China. In the study, a total of 254 patients diagnosed with schizophrenia were recruited and genotyped. The genotyping results were used to generate reports listing where the 16 included antipsychotics should be placed: 'Use as directed', 'Use with caution' or 'Use with caution and with frequent blood concentration monitoring' columns. However, the medication would not change regardless. 72 of the patients completed the 24-week follow-up observation, during which their PANSS scores were assessed at eight time points. For all of them, the PANSS scores dropped significantly, showing the effectiveness of the treatments. The treatments for those cohorts initially in the 'Use with caution' or 'Use with caution and with frequent blood concentration monitoring' categories were more effective than those in the 'Use as directed' category in a shorter term sense, up to three months. However, in the longer term, it was still those who were initially in the 'Use as directed' column fared better, whose PANSS scores dropped more significantly. Conclusions: This research indicated that our pharmacogenomic-based program could be a suitable and effective tool to facilitate precise medicine in schizophrenia treatment.