title: Hyperprolactinemia in Children and Adolescents with Use of Risperidone: Clinical and Molecular Genetics Aspects.
abstract: OBJECTIVE
  In children and adolescents treated with risperidone, hyperprolactinemia is a frequent complication that may have clinical repercussions. Several genes have been associated with this occurrence. The aim of this study was to evaluate the frequency of hyperprolactinemia in children and adolescents treated with risperidone, and its associations with clinical and pharmacological data and certain polymorphisms of the following genes: Dopamine receptor D2 (DRD2), 5-hydroxytryptamine (serotonin) receptor 2C (HTR2C), cytochrome P450, family 2, subfamily D, polypeptide 6 (CYP2D6), leptin (LEP), leptin receptor (LEPR), melanocortin 4 receptor (MC4R), and scavenger receptor class B, member 2 (SCARB2).
  
  
  METHODS
  The study included patients using risperidone (8-20 years old) and healthy subjects not exposed to the medication. Psychopathological symptoms, doses, and duration of treatment with risperidone, sex, skin color, body mass index (BMI), use of other psychotropic drugs, and polymorphisms of DRD2, HTR2C, CYP2D6, LEP, LEPR, MC4R, and SCARB2 genes were evaluated.
  
  
  RESULTS
  There were 120 patients and 197 individuals not exposed to risperidone who were evaluated. Among patients, hyperprolactinemia was found in 79 (65.8%) cases, with no differences regarding sex, skin color, or being in monotherapy with risperidone (26.7% of total patients) or not. The level of prolactin was not correlated, either in case or control groups, with chronological age, bone age, prescribed dose of risperidone, weight-adjusted dose of risperidone, or BMI (p > 0.05), but was negatively correlated with the treatment duration (r = -0.352, p = 0.001 among cases; and r = -0.324, p = 0.039 among controls). There were significant differences in use of risperidone between patients and healthy subjects without the medication in the frequency of the polymorphisms of the DRD2, HTR2C, and LEP genes. Considering both sexes together and also specifically among females, the occurrence of hyperprolactinemia was higher in the presence of the C allele of the rs6318 single nucleotide polymorphisms (SNP) of the HTR2C gene.
  
  
  CONCLUSIONS
  This group of children and adolescents with or without isolated use of risperidone presented with a high frequency of hyperprolactinemia, although asymptomatic, and associated, when considering only females or both sexes together, with being a carrier of the C allele of the rs6318 SNP of the HTR2C gene.
authors.affiliation: 1 Department of Psychiatry, School of Medical Sciences (FCM), State University of Campinas (Unicamp) , Campinas, SP, Brazil .
authors.forename: Amilton
authors.initials: A
authors.lastname: dos Santos Júnior
authors.affiliation: 2 Laboratory of Human Genetics, Center for Molecular Biology and Genetic Engineering (CBMEG) , Unicamp, Campinas, SP, Brazil .
authors.forename: Taciane Barbosa
authors.initials: TB
authors.lastname: Henriques
authors.affiliation: 2 Laboratory of Human Genetics, Center for Molecular Biology and Genetic Engineering (CBMEG) , Unicamp, Campinas, SP, Brazil .
authors.forename: Maricilda Palandi
authors.initials: MP
authors.lastname: de Mello
authors.affiliation: 1 Department of Psychiatry, School of Medical Sciences (FCM), State University of Campinas (Unicamp) , Campinas, SP, Brazil .
authors.forename: Adriana Perez
authors.initials: AP
authors.lastname: Ferreira Neto
authors.affiliation: 1 Department of Psychiatry, School of Medical Sciences (FCM), State University of Campinas (Unicamp) , Campinas, SP, Brazil .
authors.forename: Lúcia Arisaka
authors.initials: LA
authors.lastname: Paes
authors.affiliation: 1 Department of Psychiatry, School of Medical Sciences (FCM), State University of Campinas (Unicamp) , Campinas, SP, Brazil .
authors.forename: Osmar Henrique
authors.initials: OH
authors.lastname: Della Torre
authors.affiliation: 3 Growth and Development Laboratory, Center for Investigation in Pediatrics (CIPED) , FCM, Unicamp, Campinas, SP, Brazil .
authors.forename: Letícia Esposito
authors.initials: LE
authors.lastname: Sewaybricker
authors.affiliation: 1 Department of Psychiatry, School of Medical Sciences (FCM), State University of Campinas (Unicamp) , Campinas, SP, Brazil .
authors.forename: Thiago Salum
authors.initials: TS
authors.lastname: Fontana
authors.affiliation: 1 Department of Psychiatry, School of Medical Sciences (FCM), State University of Campinas (Unicamp) , Campinas, SP, Brazil .
authors.forename: Eloisa Helena Rubello Valler
authors.initials: EH
authors.lastname: Celeri
authors.affiliation: 3 Growth and Development Laboratory, Center for Investigation in Pediatrics (CIPED) , FCM, Unicamp, Campinas, SP, Brazil .|4 Department of Pediatrics, Pediatric Endocrinology Unit , FCM, Unicamp, Campinas, SP, Brazil .
authors.forename: Gil
authors.initials: G
authors.lastname: Guerra Júnior
authors.affiliation: 1 Department of Psychiatry, School of Medical Sciences (FCM), State University of Campinas (Unicamp) , Campinas, SP, Brazil .
authors.forename: Paulo
authors.initials: P
authors.lastname: Dalgalarrondo
mesh_terms: D000293:Adolescent; D000483:Alleles; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002648:Child; D003430:Cross-Sectional Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D006966:Hyperprolactinemia / Q000139:chemically induced / Q000235:genetics*; D008297:Male; D065886:Neurodevelopmental Disorders / Q000188:drug therapy / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011388:Prolactin / Q000097:blood; D044405:Receptor, Serotonin, 5-HT2C / Q000235:genetics*; D018967:Risperidone / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D014150:Antipsychotic Agents; D044405:Receptor, Serotonin, 5-HT2C; D011388:Prolactin; D018967:Risperidone