Calarge Chadi A, Ellingrod Vicki L, Zimmerman Bridget, Acion Laura, Sivitz William I, Schlechte Janet A
Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.
Psychiatr Genet. 2009 Dec;19(6):320-7. doi: 10.1097/ypg.0b013e3283328e06.
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.
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 .
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.
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.
随着非典型抗精神病药物在儿童和青少年中的使用增加，人们对其长期安全性产生了担忧。我们旨在研究利培酮引起的体重增加、瘦素浓度与青少年瘦素基因（LEP）-2548G/A变异之间的关联。
通过儿科精神病诊所招募了接受利培酮长期自然治疗的7至17岁身体健康的儿童和青少年。进行了人体测量和实验室检测。从病历中获取生长和用药史。研究了LEP基因型对瘦素浓度以及利培酮治疗开始前后体重和体重指数（BMI）Z评分曲线斜率的影响。
在74名长期接受利培酮治疗的个体中，A等位基因与低体重和BMI Z评分时较高的瘦素浓度相关。在开始使用利培酮之前，LEP基因型对体重或BMI Z评分没有影响。然而，之后，A等位基因携带者的体重和BMI Z评分增加速率更快。结果，GG基因型携带者超重/肥胖（即BMI高于第85百分位数）的可能性降低了2.5倍。这种对利培酮相关体重增加的遗传效应并未扩展到与精神兴奋剂相关的体重减轻。
LEP - 2548G/A变异似乎会调节利培酮的体重改变作用，但不会调节精神兴奋剂的作用。这可能与组织对瘦素的敏感性存在遗传差异有关，从而导致身体成分不同。
