Risperidone-related weight gain: genetic and nongenetic predictors.
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.
Lane
Hsien-Yuan
HY
Department of Psychiatry and Institute of Medical Sciences, China Medical University, Taichung, Taiwan. hylane@www.cmuh.org.tw
Liu
Yi-Ching
YC
Huang
Chieh-Liang
CL
Chang
Yue-Cune
YC
Wu
Po-Lun
PL
Lu
Chung-Ta
CT
Chang
Wen-Ho
WH
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
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