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Risperidone-induced weight gain in referred children with autism spectrum disorders is associated with a common polymorphism in the 5-hydroxytryptamine 2C receptor gene.

ABSTRACT: Weight gain is an important adverse effect of risperidone, but predictors of significant weight gain have yet to be identified in pediatric patients. Here, we investigated differences between age- and gender-normed body mass index-standardized z scores at baseline and after 8 weeks of open-label, flexible-dose risperidone treatment (mean dose: 1.70? mg/day) in 32 youths with pervasive developmental disorder (mean age?=?8.74, range?=?5-16 years) in relation to -759C/T 5-hydroxytryptamine 2C receptor (HTR2C) promoter and rs1414334 HTR2C intragenic C/G alleles, along with gender, age, and risperidone dose, using repeated measures analyses of variance. Carriers of the HTR2C promoter T allele gained an average of 0.043?±?0.017 body mass index-standardized z scores (1.84?±?1.51? kg) versus 0.64?±?0.35 z (3.23?±?1.47? kg) for non-T-allele carriers (p?

SUBMITTER: Hoekstra PJ

PROVIDER: S-EPMC3003450 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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Risperidone-induced weight gain in referred children with autism spectrum disorders is associated with a common polymorphism in the 5-hydroxytryptamine 2C receptor gene.

Hoekstra Pieter J PJ Troost Pieter W PW Lahuis Bertine E BE Mulder Hans H Mulder Erik J EJ Franke Barbara B Buitelaar Jan K JK Anderson George M GM Scahill Lawrence L Minderaa Ruud B RB

Journal of child and adolescent psychopharmacology 20101201 6

Weight gain is an important adverse effect of risperidone, but predictors of significant weight gain have yet to be identified in pediatric patients. Here, we investigated differences between age- and gender-normed body mass index-standardized z scores at baseline and after 8 weeks of open-label, flexible-dose risperidone treatment (mean dose: 1.70 mg/day) in 32 youths with pervasive developmental disorder (mean age = 8.74, range = 5-16 years) in relation to -759C/T 5-hydroxytryptamine 2C recep ...[more]

PMID: 21186965

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Project description:Iron deficiency disrupts dopaminergic signaling in rodents, resulting in cognitive deficits that may be reversed with psychostimulants. In humans, iron deficiency with or without anemia has similarly been found to cause neuropsychological and behavioral impairments. However, the clinical effects of low body iron stores in antipsychotic-treated children have not been examined.Medically healthy, 5- to 17-year-old boys treated with risperidone for at least 1 year were enrolled between February 2009 and November 2013 in a multiphase study, examining the skeletal effects of calcium and vitamin D supplementation in risperidone-induced hyperprolactinemia. Anthropometric measures were collected and medical and pharmacy records were reviewed to obtain treatment history. Psychiatric diagnoses were based on clinical interviews, structured interviews, rating scales, and a review of their medical records. Extrapyramidal symptoms were assessed, and a food frequency questionnaire was completed in a subsample. Laboratory tests, including ferritin concentration (a marker of body iron status), were obtained upon study entry.A total of 114 participants (mean age: 11.0?±?2.6 years) were included, the vast majority (>90%) having attention-deficit/hyperactivity disorder and/or disruptive behavior disorder. They had taken risperidone for an average 3.1?±?2.0 years. Their serum ferritin concentration was 37.3?±?25.6??g/L with 21% of the sample having a level <20??g/L, despite appropriate daily dietary iron intake. Ferritin concentration was inversely associated with weight gain following risperidone treatment onset but was not significantly associated with prolactin. After adjusting for the weight-adjusted dose of psychostimulants and risperidone and the daily dose of selective serotonin reuptake inhibitors, ferritin was inversely associated with the severity of disruptive behavior and positively associated (albeit marginally) with prosocial behavior. No association was found between ferritin concentration and extrapyramidal symptoms.Body iron stores are inversely related to risperidone-induced weight gain, even after extended treatment and despite adequate iron intake. Low iron stores are associated with poorer treatment response. Future research should examine iron absorption during antipsychotic treatment and whether repleting iron stores would facilitate clinical response.

Dataset Information

Risperidone-induced weight gain in referred children with autism spectrum disorders is associated with a common polymorphism in the 5-hydroxytryptamine 2C receptor gene.

Publications

Risperidone-induced weight gain in referred children with autism spectrum disorders is associated with a common polymorphism in the 5-hydroxytryptamine 2C receptor gene.

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