Leptin gene -2548G/A variants predict risperidone-associated weight gain in children and adolescents.
OBJECTIVE
As the use of atypical antipsychotics in children and adolescents has increased, concerns have been raised about their long-term safety. We aimed to investigate the association between risperidone-induced weight gain, leptin concentration, and the leptin gene (LEP) -2548G/A variants in youths.


METHODS
Medically healthy 7- to 17-year-old children and adolescents, in extended naturalistic treatment with risperidone, were recruited through pediatric psychiatry clinics. Anthropometric measures and laboratory testing were conducted. Growth and medication history was obtained from the medical record. The effect of the LEP genotypes on leptin concentration and on the slopes of the weight and body mass index (BMI) Z-score curves before and after the onset of risperidone treatment was investigated .


RESULTS
In 74 individuals, chronically treated with risperidone, the A allele was associated with higher leptin concentration at low weight and BMI Z-scores. There was no effect of the LEP genotypes on weight or BMI Z-scores before risperidone was started. Afterwards, however, the A-allele carriers showed a steeper rate of increase in weight and BMI Z-scores. As a result, the GG-genotype carriers were 2.5 times less likely to be overweight/obese (i.e. having a BMI above the 85th percentile). This genetic effect on risperidone-associated weight gain did not extend to weight loss related to psychostimulants.


CONCLUSIONS
The LEP - 2548G/A variants seem to moderate the weight-altering effect of risperidone but not psychostimulants. This may be related to genetic differences in tissue sensitivity to leptin, resulting in differential body composition.
Calarge
Chadi A
CA
Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA. chadi-calarge@uiowa.edu
Ellingrod
Vicki L
VL
Zimmerman
Bridget
B
Acion
Laura
L
Sivitz
William I
WI
Schlechte
Janet A
JA
D000293:Adolescent; D014150:Antipsychotic Agents / Q000009:adverse effects*; D001483:Base Sequence; D002648:Child; D017931:DNA Primers; D005260:Female; D006801:Humans; D020738:Leptin / Q000235:genetics*; D008297:Male; D016133:Polymerase Chain Reaction; D018967:Risperidone / Q000009:adverse effects*; D015430:Weight Gain / Q000187:drug effects*
D014150:Antipsychotic Agents; D017931:DNA Primers; D020738:Leptin; D018967:Risperidone