Dataset Information

Weight Gain and Metabolic Consequences of Risperidone in Young Children With Autism Spectrum Disorder.

ABSTRACT: We examine weight gain and metabolic consequences of risperidone monotherapy in children with autism spectrum disorder (ASD).This was a 24-week, multisite, randomized trial of risperidone only versus risperidone plus parent training in 124 children (mean age 6.9 ± 2.35 years; 105 boys and 19 girls) with ASD and serious behavioral problems. We monitored height, weight, waist circumference, and adverse effects during the trial. Fasting blood samples were obtained before treatment and at week 16.In 97 children with a mean of 22.9 ± 2.8 weeks of risperidone exposure, there was a 5.4 ± 3.4 kg weight gain over 24 weeks (p < .0001); waist circumference increased from 60.7 ± 10.4 cm to 66.8 ± 11.3 cm (p < .0001). At baseline, 59 of 97 children (60.8%) were classified as having normal weight; by week 24, only 25 of 85 (29.4%) remained in that group. Growth curve analysis showed a significant change in body mass index (BMI) z scores from pretreatment to week 24 (p < .0001). This effect was significantly greater for children with reported increased appetite in the first 8 weeks. From before treatment to week 16, there were significant increases in glucose (p = .02), hemoglobin A1c (p = .01), insulin (p <.0001), homeostatic model assessment-insulin resistance (HOMA-IR; p < .001), alanine aminotransferase (p = .01), and leptin (p < .0001). Adiponectin declined (p = .003). At baseline, 7 children met conventional criteria for metabolic syndrome; by week 16, 12 additional children were so classified.Rapid weight gain with risperidone treatment may promote the cascade of biochemical indices associated with insulin resistance and metabolic syndrome. Appetite, weight, waist circumference, liver function tests, blood lipids, and glucose warrant monitoring. Clinical trial registration information-Drug and Behavioral Therapy for Children With Pervasive Developmental Disorders; http://clinicaltrials.gov/; NCT00080145.

SUBMITTER: Scahill L

PROVIDER: S-EPMC4851735 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Weight Gain and Metabolic Consequences of Risperidone in Young Children With Autism Spectrum Disorder.

Scahill Lawrence L Jeon Sangchoon S Boorin Susan J SJ McDougle Christopher J CJ Aman Michael G MG Dziura James J McCracken James T JT Caprio Sonia S Arnold L Eugene LE Nicol Ginger G Deng Yanhong Y Challa Saankari A SA Vitiello Benedetto B

Journal of the American Academy of Child and Adolescent Psychiatry 20160307 5

<h4>Objective</h4>We examine weight gain and metabolic consequences of risperidone monotherapy in children with autism spectrum disorder (ASD).<h4>Method</h4>This was a 24-week, multisite, randomized trial of risperidone only versus risperidone plus parent training in 124 children (mean age 6.9 ± 2.35 years; 105 boys and 19 girls) with ASD and serious behavioral problems. We monitored height, weight, waist circumference, and adverse effects during the trial. Fasting blood samples were obtained b ...[more]

PMID: 27126856

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Project description:Autism spectrum disorder is associated with an altered early brain development. However, the specific cortical structure abnormalities underlying this disorder remain largely unknown. Nonetheless, atypical cortical folding provides lingering evidence of early disruptions in neurodevelopmental processes and identifying changes in the geometry of cortical sulci is of primary interest for characterizing these structural abnormalities in autism and their evolution over the first stages of brain development. Here, we applied state-of-the-art sulcus-based morphometry methods to a large highly-selective cohort of 73 young male children of age spanning from 18 to 108 months. Moreover, such large cohort was selected through extensive behavioral assessments and stringent inclusion criteria for the group of 59 children with autism. After manual labeling of 59 different sulci in each hemisphere, we computed multiple shape descriptors for each single sulcus element, hereby separating the folding measurement into distinct factors such as the length and depth of the sulcus. We demonstrated that the central, intraparietal and frontal medial sulci showed a significant and consistent pattern of abnormalities across our different geometrical indices. We also found that autistic and control children exhibited strikingly different relationships between age and structural changes in brain morphology. Lastly, the different measures of sulcus shapes were correlated with the CARS and ADOS scores that are specific to the autistic pathology and indices of symptom severity. Inherently, these structural abnormalities are confined to regions that are functionally relevant with respect to cognitive disorders in ASD. In contrast to those previously reported in adults, it is very unlikely that these abnormalities originate from general compensatory mechanisms unrelated to the primary pathology. Rather, they most probably reflect an early disruption on developmental trajectory that could be part of the primary pathology.

Project description:Aims: Obesity is a significant problem for patients taking atypical antipsychotics. There were two aims of our study. The first aim was to compare the prevalence of overweight and obesity between children and adolescents with autism spectrum disorder (ASD) treated with risperidone with the general pediatric population. The second aim was to investigate the association of the HTR2C -759C>T, ABCB1 1236C>T, ABCB1 2677G>T/A, and ABCB1 3435C>T polymorphisms with risperidone-induced overweight and obesity in children and adolescents with ASD. Methods: Body weight and height were measured in 134 subjects. Overweight and obesity in children and adolescents were classified using the International Obesity Task Force (IOTF) criteria. Genotyping was performed by TaqMan real-time polymerase chain reaction (PCR). Results: Our study found that the prevalence of overweight and obesity was significantly higher in children and adolescents with ASD treated with risperidone compared with healthy individuals (p = 0.01 and p = 0.002). The genetic polymorphisms of HTR2C -759C>T, ABCB1 1236C>T, ABCB1 2677G>T/A, and ABCB1 3435C>T were not associated with overweight/obesity in children and adolescents with ASD treated with risperidone after adjustment for multiple comparisons by the method of Bonferroni. Additionally, haplotype analysis revealed that there was no significant association between ABCB1 3435T-2677T/A-1236T haplotype and overweight/obesity. In multivariate logistic regression, after adjustment by the Bonferroni correction, there was only the duration of risperidone treatment that was significantly associated with overweight/obesity in children and adolescents with ASD. Conclusions: The findings suggest that children and adolescents with ASD treated with risperidone are at a higher risk of obesity, especially patients with extended treatment with risperidone. For the pharmacogenetic factors, -759C>T polymorphism of HTR2C gene and 1236C>T, 2677G>T/A, and 3435C>T polymorphisms of ABCB1 gene were not likely to be associated with the susceptibility to overweight/obesity in children and adolescents treated with risperidone. Due to the small sample size, further studies with a larger independent group are needed to confirm these findings.

Dataset Information

Weight Gain and Metabolic Consequences of Risperidone in Young Children With Autism Spectrum Disorder.

Publications

Weight Gain and Metabolic Consequences of Risperidone in Young Children With Autism Spectrum Disorder.

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