title: Pharmacogenetic study focused on fluoxetine pharmacodynamics in children and adolescent patients: impact of the serotonin pathway.
abstract: OBJECTIVE
  Pharmacogenetic studies of fluoxetine in children and adolescents are scarce. After reporting the effect of genetic variants in genes related to the fluoxetine pharmacokinetics on clinical response in a pediatric population, we now evaluate the impact of genetic markers involved in its pharmacodynamics.
  
  
  METHODS
  The assessment was performed in 83 patients after 12 weeks of fluoxetine treatment. The genetic association analysis included a total of 316 validated single nucleotide polymorphisms in 45 candidate genes involved in six different pathways.
  
  
  RESULTS
  Clinical improvement after treatment with fluoxetine in our pediatric population was associated significantly with two polymorphisms located in genes related to the serotonergic system: the 5-hydroxytryptamine receptor 1B (HTR1B) and the tryptophan 5-hydroxylase 2 (TPH2).
  
  
  CONCLUSIONS
  Although a wide range of candidate genes related to different pathways were assessed, the results show that genetic markers directly related to serotonin have an important effect on fluoxetine response.
authors.affiliation: Departments of aPathological Anatomy, Pharmacology and Microbiology bPsychiatry and Clinical Psychobiology, University of Barcelona cDepartment of Child and Adolescent Psychiatry and Psychology, Institute of Neurosciences dDepartment of Clinical Pharmacology, Hospital Clinic de Barcelona eAugust Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona fMental Health Networking Biomedical Research Centre (CIBERSAM), Madrid, Spain.
authors.forename: Sergi
authors.initials: S
authors.lastname: Mas
authors.forename: Ana
authors.initials: A
authors.lastname: Blázquez
authors.forename: Natalia
authors.initials: N
authors.lastname: Rodríguez
authors.forename: Daniel
authors.initials: D
authors.lastname: Boloc
authors.forename: Amalia
authors.initials: A
authors.lastname: Lafuente
authors.forename: Joan A
authors.initials: JA
authors.lastname: Arnaiz
authors.forename: Luisa
authors.initials: L
authors.lastname: Lázaro
authors.forename: Patricia
authors.initials: P
authors.lastname: Gassó
mesh_terms: D000293:Adolescent; D001008:Anxiety Disorders / Q000188:drug therapy; D002648:Child; D003866:Depressive Disorder / Q000188:drug therapy; D005260:Female; D005473:Fluoxetine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000188:drug therapy*; D009771:Obsessive-Compulsive Disorder / Q000188:drug therapy; D000071185:Pharmacogenomic Testing / Q000379:methods; D000071184:Pharmacogenomic Variants; D044302:Receptor, Serotonin, 5-HT1B / Q000235:genetics*; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016896:Treatment Outcome; D014365:Tryptophan Hydroxylase / Q000235:genetics*
chemical_list: D005473:Fluoxetine; D044302:Receptor, Serotonin, 5-HT1B; D017367:Selective Serotonin Reuptake Inhibitors; D014365:Tryptophan Hydroxylase; C470302:HTR1B protein, human; C494784:TPH2 protein, human