Association of Serotonin2c Receptor Polymorphisms With Antipsychotic Drug Response in Schizophrenia

Jiang Li; Hitoshi Hashimoto; Herbert Y Meltzer

doi:10.3389/fpsyt.2019.00058

Association of Serotonin_2c Receptor Polymorphisms With Antipsychotic Drug Response in Schizophrenia

Front Psychiatry. 2019 Feb 15:10:58. doi: 10.3389/fpsyt.2019.00058. eCollection 2019.

Authors

Jiang Li¹, Hitoshi Hashimoto^{1

2

3

4

5

6}, Herbert Y Meltzer¹

Affiliations

¹ Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Evanston, IL, United States.
² Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Japan.
³ Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, Osaka University, Suita, Japan.
⁴ iPS Cell-based Research Project on Brain Neuropharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Japan.
⁵ Division of Bioscience, Institute for Datability Science, Osaka University, Suita, Japan.
⁶ Transdimensional Life Imaging Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Suita, Japan.

Abstract

There is conflicting evidence for the association between genetic polymorphisms in the serotonin (5-HT)_2C receptor (HTR2C) and response to antipsychotic drugs (APD) in schizophrenic patients. We tested the association between the HTR2C polymorphisms, Cys23Ser, -759C/T, and -697G/C, and response to APDs (mainly clozapine) in a 6 month prospective study in 171 patients with schizophrenia. Ser23 was significantly associated with treatment response (positive symptoms, X ² = 7.540, p = 0.01; negative symptoms, X ² = 4.796, p = 0.03) in male patients only. A -759C-Ser23 haplotype was similar associated with positive (X ² = 6.648, p = 0.01) and negative (X ² = 6.702, p = 0.01) symptom improvement. Logistic regression, after controlling for covariates, also showed significant haplotypic associations. A meta-analysis of six studies for Ser23 and treatment response showed an overall odds ratio of 2.00 (95%CI, 1.38-2.91, p = 0.0003) or 1.94 (95%CI, 1.27-2.99, p = 0.0024) under fixed or random effect models. These results provide additional evidence that HTR2C polymorphisms are associated with treatment response to APD with HTR2C antagonism or inverse agonism, in male schizophrenic patients.

Keywords: antipsychotic agents; clozapine; genetic; meta-analysis; polymorphism; schizophrenia; serotonin2C; treatment response.