Association of serotonin 2C receptor polymorphisms with antipsychotic drug response in schizophrenia

Jiang Li, Hitoshi Hashimoto, Herbert Y Meltzer*

*Corresponding author for this work

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number58
JournalFrontiers in Psychiatry
Volume10
Issue numberFEB
DOIs
StatePublished - Jan 1 2019

Fingerprint

Receptor, Serotonin, 5-HT2C
Antipsychotic Agents
Schizophrenia
pamidronate
Clozapine
Genetic Polymorphisms
Haplotypes
Meta-Analysis
Serotonin
Therapeutics
Logistic Models
Odds Ratio
Prospective Studies

Keywords

  • Antipsychotic agents
  • Clozapine
  • Genetic
  • Meta-analysis
  • Polymorphism
  • Schizophrenia
  • Serotonin2C
  • Treatment response

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

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title = "Association of serotonin 2C receptor polymorphisms with antipsychotic drug response in schizophrenia",
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.",
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Association of serotonin 2C receptor polymorphisms with antipsychotic drug response in schizophrenia . / Li, Jiang; Hashimoto, Hitoshi; Meltzer, Herbert Y.

In: Frontiers in Psychiatry, Vol. 10, No. FEB, 58, 01.01.2019.

Research output: Contribution to journalArticle

TY - JOUR

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AU - Hashimoto, Hitoshi

AU - Meltzer, Herbert Y

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N2 - 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.

AB - 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.

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