Variants of the dopamine D2 receptor gene and risperidone-induced hyperprolactinemia in children and adolescents

Chadi A Calarge; Vicki L Ellingrod; Laura Acion; Del D Miller; Jessica Moline; Michael J Tansey; Janet A Schlechte

doi:10.1097/FPC.0b013e328329a60f

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Variants of the dopamine D2 receptor gene and risperidone-induced hyperprolactinemia in children and adolescents

Journal article

Peer reviewed

Variants of the dopamine D2 receptor gene and risperidone-induced hyperprolactinemia in children and adolescents

Chadi A Calarge, Vicki L Ellingrod, Laura Acion, Del D Miller, Jessica Moline, Michael J Tansey and Janet A Schlechte

Pharmacogenetics and genomics, Vol.19(5), pp.373-382

05/2009

DOI: 10.1097/FPC.0b013e328329a60f

PMCID: PMC2699901

PMID: 19339912

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https://www.ncbi.nlm.nih.gov/pmc/articles/2699901View

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Abstract

To investigate the association between hyperprolactinemia and variants of the dopamine D2 receptor (DRD2) gene in children and adolescents in long-term treatment with risperidone. Medically healthy 7 to 17-year-old patients chronically treated with risperidone but receiving no other antipsychotics were recruited in a cross-sectional study. Four DRD2 variants were genotyped and prolactin concentration was measured. Medication history was obtained from the medical records. The effect of the TaqIA variants of the DRD2 on the risk of risperidone-induced hyperprolactinemia was the primary outcome measure. Hyperprolactinemia was present in 50% of 107 patients (87% males) treated with risperidone for an average of 2.9 years. Age, stage of sexual development, and the dose of risperidone independently predicted a higher prolactin concentration, whereas the dose of psychostimulants was negatively correlated with it. However, these four predictors became nonsignificant when risperidone serum concentration was entered into the model. Adverse events potentially related to hyperprolactinemia were more common in participants with elevated prolactin concentration and in girls (45%) compared with boys (10%). After controlling for risperidone concentration and the dose of psychostimulants, the TaqIA A1 and the A-241G alleles were associated with higher prolactin concentration, whereas the -141C Ins/Del and C957T variants had no significant effect. In addition, adverse events potentially related to hyperprolactinemia were four times more common in TaqIA A1 allele carriers. Prolactin concentration is closely related to central DRD2 blockade, as reflected by risperidone serum concentration. Furthermore, the TaqIA and A-241G variants of the DRD2 gene could be useful in predicting the emergence of hyperprolactinemia and its potential adverse events.

Genetic Predisposition to Disease

Child Behavior Disorders - drug therapy

Antipsychotic Agents - adverse effects

Gene Frequency

Humans

Male

Tic Disorders - genetics

Hyperprolactinemia - chemically induced

Receptors, Dopamine D2 - genetics

Linkage Disequilibrium

Hyperprolactinemia - genetics

Prolactin - blood

Obsessive-Compulsive Disorder - genetics

Obsessive-Compulsive Disorder - drug therapy

Polymorphism, Genetic - physiology

Risperidone - therapeutic use

Antipsychotic Agents - therapeutic use

Adolescent

Risperidone - adverse effects

Female

Retrospective Studies

Child Behavior Disorders - genetics

Tic Disorders - drug therapy

Child

Details

Title: Subtitle: Variants of the dopamine D2 receptor gene and risperidone-induced hyperprolactinemia in children and adolescents
Creators: Chadi A Calarge - The University of Iowa Carver College of Medicine, Iowa, USA. chadi-calarge@uiowa.edu
Vicki L Ellingrod
Laura Acion
Del D Miller
Jessica Moline
Michael J Tansey
Janet A Schlechte
Resource Type: Journal article
Publication Details: Pharmacogenetics and genomics, Vol.19(5), pp.373-382
DOI: 10.1097/FPC.0b013e328329a60f
PMID: 19339912
PMCID: PMC2699901
NLM abbreviation: Pharmacogenet Genomics
ISSN: 1744-6872
eISSN: 1744-6880
Publisher: United States
Grant note: UL1 RR024979 / NCRR NIH HHS M01 RR000059-466771 / NCRR NIH HHS K23 MH085005 / NIMH NIH HHS M01 RR000059 / NCRR NIH HHS RR00059 / NCRR NIH HHS
Language: English
Date published: 05/2009
Academic Unit: Endocrinology and Diabetes; Psychiatry; Stead Family Department of Pediatrics; Internal Medicine
Record Identifier: 9984003430002771

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