title: Risperidone-related weight gain: genetic and nongenetic predictors.
abstract: OBJECTIVE
  A serious side effect of atypical antipsychotics is increased body weight, which leads to further morbidity and nonadherence to medication. It has been suggested that both genetic and nongenetic variables may influence antipsychotics-related weight gain. This study aimed to simultaneously explore the effects of multiple candidate genes and environment factors on body weight of schizophrenia patients who received risperidone, a commonly used atypical antipsychotic agent.
  
  
  METHODS
  One hundred twenty-three ethnically Han Chinese inpatients with acutely exacerbated schizophrenia were given risperidone monotherapy for up to 42 days. Body weight and clinical manifestations were assessed biweekly. Drug efficacy was measured by the Positive and Negative Syndrome Scale (PANSS), and safety was evaluated by the Extrapyramidal Symptom Rating Scale (ESRS) and the UKU Side Effect Rating Scale. We collected body weight as the response value. Potential prognostic factors were baseline body weight, age, sex, diagnosis subtypes, risperidone dosage, PANSS total scores, treatment duration (weeks 0-6), and 15 genetic variants [across 10 candidate genes: 5-HT1A, 5-HT2A, 5-HT2C, 5-HT6, D1, D2, D3, and alpha1-adrenergic receptors, brain-derived neurotrophic factor (BDNF), and cytochrome P450 2D6 (CYP2D6)]. Because there were repeated assessments, multiple linear regression with the generalized estimating equation (GEE) method was used to adjust the within-subject dependence.
  
  
  RESULTS
  Of 15 genetic polymorphisms examined, 5-HT2A 102-T/C, 5-HT2C -759-C/T, 5-HT6 267-C/T, BDNF 66-Val/Met, and CYP2D6 188-C/T significantly influenced body weight, and so did baseline body weight, age, gender, schizophrenia subtype, and treatment duration and efficacy.
  
  
  CONCLUSIONS
  These results suggest that numerous genetic and nongenetic factors affect antipsychotics-related weight gain.
authors.affiliation: Department of Psychiatry and Institute of Medical Sciences, China Medical University, Taichung, Taiwan. hylane@www.cmuh.org.tw
authors.forename: Hsien-Yuan
authors.initials: HY
authors.lastname: Lane
authors.forename: Yi-Ching
authors.initials: YC
authors.lastname: Liu
authors.forename: Chieh-Liang
authors.initials: CL
authors.lastname: Huang
authors.forename: Yue-Cune
authors.initials: YC
authors.lastname: Chang
authors.forename: Po-Lun
authors.initials: PL
authors.lastname: Wu
authors.forename: Chung-Ta
authors.initials: CT
authors.lastname: Lu
authors.forename: Wen-Ho
authors.initials: WH
authors.lastname: Chang
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D002681:China; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics; D044405:Receptor, Serotonin, 5-HT2C / Q000235:genetics; D011985:Receptors, Serotonin / Q000235:genetics; D018967:Risperidone / Q000008:administration & dosage / Q000627:therapeutic use*; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics; D012737:Sex Factors; D015430:Weight Gain / Q000187:drug effects* / Q000235:genetics
chemical_list: D014150:Antipsychotic Agents; D019208:Brain-Derived Neurotrophic Factor; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin; C097216:serotonin 6 receptor; D019389:Cytochrome P-450 CYP2D6; D018967:Risperidone