title: Association study of serotonergic gene variants with antipsychotic-induced adverse reactions.
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  CONCLUSIONS
  Serotonergic polymorphism may play a moderate role in the development of side effects associated with antipsychotic treatment.
authors.affiliation: Section of Genomic Medicine, Imperial College London, Hammersmith Hospital Campus, London, UK.
authors.forename: Ismail
authors.initials: I
authors.lastname: Al-Janabi
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Arranz
authors.forename: Alexandra I F
authors.initials: AI
authors.lastname: Blakemore
authors.forename: Pilar A
authors.initials: PA
authors.lastname: Saiz
authors.forename: Margaret T
authors.initials: MT
authors.lastname: Susce
authors.forename: Paul E A
authors.initials: PE
authors.lastname: Glaser
authors.forename: Daniel
authors.initials: D
authors.lastname: Clark
authors.forename: Jose
authors.initials: J
authors.lastname: de Leon
mesh_terms: D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects*; D005260:Female; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D044348:Receptors, Serotonin, 5-HT2 / Q000235:genetics*; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D044348:Receptors, Serotonin, 5-HT2