Association of HTR1A Gene Polymorphisms with Efficacy and Plasma Concentrations of Atypical Antipsychotics in the Treatment of Male Patients with Schizophrenia

Abstract

Purpose

We investigate the association of HTR1A rs10042486 and rs6295 with efficacy and plasma concentrations of atypical antipsychotics in the treatment of male patients with schizophrenia.

Patients and Methods

A total of 140 male patients diagnosed with schizophrenia who were treated with any single atypical antipsychotic between May 2020 and May 2022 were retrospectively included. Clinical symptoms were assessed using Positive and Negative Syndrome Scale (PANSS). All SNPs were typed using Agena Bioscience MassARRAY DNA mass spectrometry. Plasma concentrations of antipsychotics at week 3, 6 and 12 after treatment commence were analyzed using mass spectrometry.

Results

For efficacy of atypical antipsychotics, we observed no significant difference between HTR1A rs10042486, rs6295 and positive symptom improvement, where the patients with heterozygous mutant at the rs10042486 and rs6295 locus were superior to those with wild-type or homozygous mutant genotypes on negative symptom improvement, especially at 12 weeks of follow-up when the difference between genotypes at the rs6295 locus have statistical significance (P = 0.037). For plasma concentration, we found that quetiapine plasma concentrations were significantly lower in patients with mutation-heterozygous types than in wild-type and homozygous mutation genotypes at week 6. In contrast, higher plasma concentrations were found for mutant heterozygous than wild genotypes in the risperidone monotherapy analysis, and the difference among genotypes at the rs6295 locus was statistically significant at 6 weeks of follow-up.

Conclusion

The assessment of the correlation of genetic polymorphisms of HTR1A rs6295 and rs10042486 in male patients with schizophrenia with the monitoring of therapeutic drug concentrations and therapeutic efficacy provides a constructive foundation for the clinical individualization of antipsychotics, such as quetiapine and risperidone, which is important in selecting the dose of the medication and improving the improvement of negative symptoms.

Keywords:

• schizophrenia
• HTR1A
• polymorphism
• plasma concentration
• atypical antipsychotics
• asian male patients

Abbreviations

PANSS, The Positive and Negative Syndrome Scale; ICD-11, The International Classification of Diseases 11th Revision; MALDI-TOF MS, Matrix-assisted laser desorption ionization-time-of-light mass spectrometry; TDM, Therapeutical drug monitoring; LC-MS, Liquid chromatography and mass spectrometry instrument; CI, Confidence intervals.

Data Sharing Statement

The datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Ethical Statement

The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was conducted in accordance with the Declaration of Helsinki (as revised in 2013) and was approved by the ethics committee of clinical trial ethics committee of the Second People’s Hospital of Guizhou Province. Written informed consent was obtained from all individuals included in the study.

Acknowledgments

The authors wish to thank Shanghai Conlight Medical Co., Ltd. for technical support.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

Jingfeng Tong and Chengchen Huang are affiliated with Shanghai Conlight Medical Co., Ltd. The authors declare no other conflicts of interest in this work.

Additional information

Funding

The study was supported by Science and Technology Fund Project of Guizhou Provincial Health Committee gzwkj 2022-066 and Guizhou Provincial Key Technology R&D Program [2020]4Y064.