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author:("Xie, dilong")
1.  Rate of Weight Gain and Cardiometabolic Abnormalities in Children and Adolescents 
The Journal of pediatrics  2012;161(6):1010-1015.e1.
To investigate whether the rate of weight gain is associated with cardiometabolic risk, independent of weight measured concurrently.
Study design
Healthy 7–17 year-old risperidone-treated patients (n=105, 88% male) had blood pressure, anthropometry, and laboratory tests performed. Growth history was extracted from medical records. The rate of change in age-sex-adjusted weight and body mass index (BMI) z-score after the initiation of risperidone was individually modeled. Multivariable linear regression analyses explored the association of the rate of weight (BMI) z score change with cardiometabolic outcomes, independent of last measured weight (BMI) z score.
Following a mean of 1.9 years (sd=1.0) of risperidone treatment, the absolute increase in weight and BMI z-scores was 0.61 (sd=0.61) and 0.62 (sd=0.73), respectively. After controlling for the final weight z-score, the rate of change in weight z-score was significantly associated with final glucose (p<0.04), C-peptide (p<0.004), HOMA-IR (p<0.02), HDL cholesterol (p<0.0001), a metabolic syndrome score (p<0.005), adiponectin (p<0.04), and hsCRP (p<0.04). After controlling for the final BMI z-score, the rate of change in BMI z-score was associated with final HDL cholesterol (p<0.04), leptin (p<0.03), and adiponectin (p<0.04), with a suggestion of an association with final HOMA-IR (p<0.08).
The rate of weight gain in risperidone-treated children explains equally or more of the variance in certain cardiometabolic outcomes (e.g., HDL cholesterol: ΔR2= 11% vs. ΔR2= 8% and hsCRP: ΔR2= 9% vs. ΔR2= 5%) than the weight measured concurrently, and may serve as a treatment target.
PMCID: PMC3461238  PMID: 22738944
Antipsychotics; Risperidone; Weight Gain; Cardiometabolic Abnormalities; Children; Adolescents
2.  Iron Status in Toddlerhood Predicts Sensitivity to Psychostimulants in Children 
Journal of attention disorders  2010;16(4):295-303.
Iron deficiency is associated with impaired dopaminergic signaling and externalizing behavior. However, whether iron stores in toddlerhood influence later response to psychostimulants is unknown.
Youths participating in a study monitoring the long-term safety of risperidone were included in this analysis if they had received psychostimulant monotherapy for at least 3 weeks and had a complete blood count obtained prior to psychostimulant treatment. Sensitivity to psychostimulants was defined based on the weight-adjusted dose during the first year of treatment. Regression analysis examined whether the hematological tests based on the characteristics of red blood cells were associated with sensitivity to psychostimulants.
Twenty nine participants (93% males, 76% Caucasians), primarily with ADHD (93%), comprised the current sample. The hematological tests were obtained, on average, 3 years before the initiation of psychostimulants monotherapy which occurred at 5.8 years of age and continued for a median of 0.85 years, at an average daily dose of 0.98 mg/kg (SD=0.38) in methylphenidate-equivalent. Compared to those that were poorly sensitive to psychostimulants, after adjusting for age, mean corpuscular volume was significantly higher in the highly and moderately sensitive groups.
If replicated, our findings suggest that more attention should be paid to optimizing body iron in early childhood.
PMCID: PMC3556512  PMID: 20978274
3.  Correlates of weight gain during long-term risperidone treatment in children and adolescents 
Most clinical trials of antipsychotics in children are brief, failing to address their long-term safety, particularly when taken concurrently with other psychotropics. This hypothesis-generating analysis evaluates potential correlates of weight gain in children receiving extended risperidone treatment.
Medically healthy 7–17 year-old patients treated with risperidone for six months or more were enrolled. Anthropometric measurements were conducted. Developmental and medication history was obtained from the medical record. Information related to birth weight, dietary intake, physical activity, and parental weight was collected. Mixed regression analyses explored the contribution of various demographic and clinical factors to age- and sex-adjusted weight and body mass index (BMI) z scores over the treatment period.
The sample consisted of 110 patients (89% males) with a mean age of 11.8 years (sd = 2.9) upon enrollment. The majority had an externalizing disorder and received 0.03 mg/kg/day (sd = 0.02) of risperidone, for 2.5 years (sd = 1.7), to primarily target irritability and aggression (81%). Polypharmacy was common with 71% receiving psychostimulants, 50% selective serotonin reuptake inhibitors (SSRIs), and 32% α2-agonists. Weight and BMI z score were positively correlated with baseline weight at the start of risperidone, treatment duration, and the weight-adjusted dose of risperidone but inversely associated with the weight-adjusted dose of psychostimulants and the concurrent use of SSRIs and α2-agonists. The effect of risperidone dose appeared to attenuate as treatment extended while that of psychostimulants became more significant. The rate of change in weight (or BMI) z score prior to and within the first 12 weeks of risperidone treatment did not independently predict future changes neither did birth weight, postnatal growth, dietary intake, physical activity, or parental weight.
This comprehensive analysis exploring correlates of long-term weight (or BMI) change in risperidone-treated youths revealed that pharmacotherapy exerts significant but complex effects.
Trial Registration
Not applicable.
PMCID: PMC3489823  PMID: 22643087
Child; Adolescent; Weight gain; Obesity; Antipsychotics; Risperidone; Predictors
4.  A Cross-sectional Evaluation of the Effect of Risperidone and Selective Serotonin Reuptake Inhibitors on Bone Mineral Density in Boys 
The aim of the present study was to investigate the effect of risperidone-induced hyperprolactinemia on trabecular bone mineral density (BMD) in children and adolescents.
Medically healthy 7–17yo males chronically treated, in a naturalistic setting, with risperidone were recruited through child psychiatry outpatient clinics between November 2005 and June 2007. Anthropometric measurements and laboratory testing were conducted. Developmental and treatment history was obtained from the medical record. Volumetric BMD of the ultra-distal radius was measured using peripheral quantitative computerized tomography and areal BMD of the lumbar spine was estimated using dual energy X-ray absorptiometry.
Hyperprolactinemia was present in 49% of 83 boys (n=41) treated with risperidone for an average of 2.9 years. Serum testosterone concentration increased with pubertal status but was not affected by hyperprolactinemia. As expected, bone mineral content and BMD increased with sexual maturity. After adjusting for the stage of sexual development, height and BMI Z-scores, serum prolactin was negatively associated with trabecular volumetric BMD at the ultra-distal radius (p<0.03). Controlling for relevant covariates, we also found treatment with selective serotonin reuptake inhibitors (SSRIs) to be associated with lower trabecular BMD at the radius (p=0.03) and BMD Z-score at the lumbar spine (p<0.05). These findings became more marked when the analysis was restricted to non-Hispanic Caucasians. Of 13 documented fractures, only two occurred after risperidone and SSRIs were started and none in patients with hyperprolactinemia.
This is the first study to link risperidone-induced hyperprolactinemia and SSRI treatment to lower BMD in children and adolescents. Future research should evaluate the longitudinal course of this adverse event to determine its temporal stability and whether a higher fracture rate ensues.
PMCID: PMC2845988  PMID: 20331935

Results 1-4 (4)