Association study of serotonergic gene variants with antipsychotic-induced adverse reactions

Ismail Al-Janabi, Maria J. Arranz, Alexandra I.F. Blakemore, Pilar A. Saiz, Margaret T. Susce, Paul E.A. Glaser, Daniel Clark, Jose De Leon

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


Introduction: The products of the serotonin receptor genes are important targets for conventional and atypical antipsychotics, and may be relevant for antipsychotic activity and associated adverse reactions. It has been shown that the high potency at 5-HT2 receptors may also be associated with the production of moderate extrapyramidal side effects (EPS). In addition, serotonin neurotransmitter systems in the central nervous system play an important role in eating behaviours, and are involved in the symptomatology related to the metabolic syndrome, including obesity, diabetes and hyperlipidemia. Materials and Methods: This study was designed to investigate the hypothesis that serotonin pathway genes play a part in mediating antipsychotic-induced adverse reactions, including EPS, tardive dyskinesia, obesity and diabetes. Polymorphisms in the 5-HT2A (102 (T/C), His452Tyr), 5-HT2C (Cys23Ser, -759 (C/T), -995 (G/A), TPH2 (-366 (C/T), -8933 (A/G) and 5-HTT (LPR, -15370 (A/G)) genes were investigated in a cohort of 427 US Caucasian patients undergoing antipsychotic treatment, using automated genotyping techniques. Results: 5-HTT (LPR) and 5-HT2A (102 (T/C) polymorphisms were found to be associated with BMI (P=0.05 and 0.005, respectively). The genotype distribution of the TPH2-366 (T/C) polymorphism was found to be significantly associated with the presence of diabetes (P=0.01). A trend towards an association (P=0.07) between the 5-HT2C Cys23Ser polymorphism and tardive dyskinesia was found when age, duration of treatment, dose and sex were considered. Genotype distributions of the 5-HT2C -995 (G/A), 5-HT2C -759 (C/T) and 5-HT2A His452Tyr polymorphisms differed among patients presenting EPS and those without (P=0.08, 0.06 and 0.08, respectively). No other statistically significant associations were observed. Conclusion Serotonergic polymorphism may play a moderate role in the development of side effects associated with antipsychotic treatment.

Original languageEnglish
Pages (from-to)305-311
Number of pages7
JournalPsychiatric Genetics
Issue number6
StatePublished - Dec 2009


  • 5-HT2A
  • 5-HT2C
  • 5-HTT
  • Adverse reaction
  • Antipsychotic
  • Gene
  • TPH2

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Psychiatry and Mental health
  • Biological Psychiatry


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