Corrigendum to "Pharmacogenetics of Risperidone and Cardiovascular Risk in Children and Adolescents".
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ABSTRACT:
SUBMITTER: Dos Santos-Junior A
PROVIDER: S-EPMC5448052 | biostudies-literature | 2017
REPOSITORIES: biostudies-literature
Publications
Corrigendum to "Pharmacogenetics of Risperidone and Cardiovascular Risk in Children and Adolescents".
Dos Santos-Júnior Amilton A Henriques Taciane Barbosa TB de Mello Maricilda Palandi MP Della Torre Osmar Henrique OH Paes Lúcia Arisaka LA Ferreira-Neto Adriana Perez AP Sewaybricker Letícia Esposito LE Fontana Thiago Salum TS Celeri Eloisa Helena Rubello Valler EHRV Guerra-Júnior Gil G Dalgalarrondo Paulo P
International journal of endocrinology 20170503
[This corrects the article DOI: 10.1155/2016/5872423.]. ...[more]
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Project description:Objective. To identify the frequency of obesity and metabolic complications in child and adolescent users of risperidone. Potential associations with clinical parameters and SNPs of the HTR2C, DRD2, LEP, LEPR, MC4R, and CYP2D6 genes were analyzed. Methods. Samples from 120 risperidone users (8-20 years old) were collected and SNPs were analyzed, alongside assessment of chronological and bone ages, prescribed and weight-adjusted doses, use of other psychotropic drugs, waist circumference, BMI z-scores, blood pressure, HOMA-IR index, fasting levels of serum glucose, insulin, cholesterol, triglycerides, transaminases, and leptin. Results. Thirty-two (26.7%) patients were overweight and 5 (4.2%) obese. Hypertension was recorded in 8 patients (6.7%), metabolic syndrome in 6 (5%), and increased waist circumference in 20 (16.7%). The HOMA-IR was high for 22 patients (18.3%), while total cholesterol and triglycerides were high in 20 (16.7%) and 41 (34.2%) patients, respectively. SNP associations were found for LEP, HTR2C, and CYP2D6 with BMI; CYP2D6 with blood pressure, ALT, and HOMA-IR; HTR2C and LEPR with leptin levels; MC4R and DRD2 with HOMA-IR; HTR2C with WC; and LEP with ALT. Conclusions. Although not higher than in the general pediatric population, a high frequency of patients was overweight/obese, with abnormalities in metabolic parameters and some pharmacogenetic associations.
| S-EPMC4736591 | biostudies-literature
Project description:ObjectivePrevious cross-sectional evidence has linked antipsychotic-related weight gain to reduced body iron concentration. Using longitudinal data, we examined the association between changes in weight following risperidone initiation or discontinuation and ferritin concentration.MethodStudy 1: Between April 2004 and September 2007, participants were enrolled from outpatient settings in a prospective randomized clinical trial comparing the efficacy of risperidone monotherapy to the combination of risperidone and behavior therapy in targeting disruptive behavior in 4- to 13-year-old children with DSM-IV-TR-based autism spectrum disorder. Study 2: Medically healthy 7- to 17-year-old participants in long-term open-label risperidone treatment at study entry returned for follow-up 1.5 years later, between July 2007 and July 2011. Available blood samples were used to measure ferritin. Linear multivariable regression analysis tested the association between ferritin concentration and change in age-sex-specific body mass index (BMI) z score between study entry and endpoint, adjusting for relevant confounders.ResultsStudy 1 sample consisted of 73 participants (85% males, mean age: 7.7 ± 2.4 years). After 18.0 ± 2.0 weeks on risperidone, their BMI z score increased by 0.93 ± 0.70 points and ferritin concentration declined by 6.8 ± 13.3 μg/L. After adjusting for age and sex, change in BMI z score was inversely correlated with percent change in ferritin concentration (β = -18.3, P < .003). Study 2 participants had all been receiving risperidone at study entry. At follow-up, 1.5 ± 0.3 years later, risperidone was discontinued in 26 of the 96 who were included in the analysis. Neither change in BMI z score nor in ferritin concentration was different between those who continued versus discontinued risperidone. However, a reduction in BMI z score between study entry and follow-up was associated with higher ferritin concentration at follow-up in participants who discontinued risperidone compared to those who continued it (P = .01).ConclusionsRisperidone-related weight gain is associated with a reduction in body iron reserves, which appears to improve with weight loss following risperidone discontinuation. Preliminary evidence suggests that risperidone may also directly inhibit iron absorption.Trial registrationClinicalTrials.gov Identifier: NCT00080145.
| S-EPMC6728911 | biostudies-literature
Project description:The global prevalence of overweight and obesity in children and adolescents has increased substantially over the past several decades. These trends are also visible in developing economies like India. Childhood obesity impacts all the major organ systems of the body and is well known to result in significant morbidity and mortality. Obesity in childhood and adolescence is associated with established risk factors for cardiovascular diseases and accelerated atherosclerotic processes, including elevated blood pressure (BP), atherogenic dyslipidemia, atherosclerosis, metabolic syndrome, type II diabetes mellitus, cardiac structural and functional changes and obstructive sleep apnea. Probable mechanisms of obesity-related hypertension include insulin resistance, sodium retention, increased sympathetic nervous system activity, activation of the renin-angiotensin-aldosterone system and altered vascular function. Adiposity promotes cardiovascular risk clustering during childhood and adolescence. Insulin resistance has a strong association with childhood obesity. A variety of proinflammatory mediators that are associated with cardiometabolic dysfunction are also known to be influenced by obesity levels. Obesity in early life promotes atherosclerotic disease in vascular structures such as the aorta and the coronary arteries. Childhood and adolescent adiposity has strong influences on the structure and function of the heart, predominantly of the left ventricle. Obesity compromises pulmonary function and increases the risk of sleep-disordered breathing and obstructive sleep apnea. Neglecting childhood and adolescent obesity will compromise the cardiovascular health of the pediatric population and is likely to result in a serious public health crisis in future.
| S-EPMC3263181 | biostudies-literature
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.
| S-EPMC7677569 | biostudies-literature
Project description:ObjectiveAggression is among the most common indications for referral to child and adolescent mental health services and is often challenging to treat. Understanding the biological underpinnings of aggression could help optimize treatment efficacy. Neuronal nicotinic acetylcholine receptors (nAChRs), specifically the α7 nAChR, encoded by the gene CHRNA7, have been implicated in aggressive behaviors in animal models as well as humans. Copy number variants (CNVs) of CHRNA7 are found in individuals with neuropsychiatric disorders, often with comorbid aggression. In this study, we aimed to determine the prevalence of CHRNA7 CNVs among individuals treated with risperidone, predominantly for irritability and aggression.MethodsRisperidone-treated children and adolescents were assessed for CHRNA7 copy number state using droplet digital PCR and genomic quantitative PCR. Demographic, anthropometric, and clinical data, including the Child Behavior Checklist (CBCL), were collected and compared across individuals with and without the CHRNA7 deletion.ResultsOf 218 individuals (90% males, mean age: 12.3 ± 2.3 years), 7 (3.2%) were found to carry a CHRNA7 deletion and one proband carried a CHRNA7 duplication (0.46%). T-scores for rule breaking, aggression, and externalizing behavior factors of the CBCL were higher in the deletion group, despite taking 58% higher dose of risperidone.ConclusionsCHRNA7 loss may contribute to a phenotype of severe aggression. Given the high prevalence of the deletion among risperidone-treated youth, future studies should examine the therapeutic potential of α7 nAChR-targeting drugs to target aggression associated with CHRNA7 deletions.
| S-EPMC5725633 | biostudies-literature
Project description:BackgroundThere are few and conflicting data on the role of cytochrome P450 2D6 (CYP2D6) polymorphisms in relation to risperidone adverse events (AEs) in children. This study assessed the association between CYP2D6 metabolizer status and risk for risperidone AEs in children.MethodsChildren ≤18 years with at least 4 weeks of risperidone exposure were identified using BioVU, a de-identified DNA biobank linked to electronic health record data. The primary outcome of this study was AEs. After DNA sequencing, individuals were classified as CYP2D6 poor, intermediate, normal, or ultrarapid CYP2D6 metabolizers.ResultsFor analysis, the 257 individuals were grouped as poor/intermediate metabolizers (n = 33, 13%) and normal/ultrarapid metabolizers (n = 224, 87%). AEs were more common in poor/intermediate vs. normal/ultrarapid metabolizers (15/33, 46% vs. 61/224, 27%, P = 0.04). In multivariate analysis adjusting for age, sex, race, and initial dose, poor/intermediate metabolizers had increased AE risk (adjusted odds ratio 2.4, 95% confidence interval 1.1-5.1, P = 0.03).ConclusionChildren with CYP2D6 poor or intermediate metabolizer phenotypes are at greater risk for risperidone AEs. Pre-prescription genotyping could identify this high-risk subset for an alternate therapy, risperidone dose reduction, and/or increased monitoring for AEs.
| S-EPMC6435416 | biostudies-literature
Project description: Not available
| S-EPMC3751579 | biostudies-literature
Project description:[This corrects the article DOI: 10.1093/pch/pxx204.].
| S-EPMC7395314 | biostudies-literature
Project description:Objective:Therapeutic drug monitoring helps clinicians in choosing the right drug and adjust its dose in specific patients. To this end, we aimed to assess time patterns of risperidone and its metabolite, 9-hydroxyrisperidone, in children and adolescents with oppositional defiant and/or conduct disorder. Methods:We measured plasma concentrations of risperidone and 9-hydroxyrisperidone, their sum (active moiety, AM) and ratio, as well as plasma concentrations corrected for daily dose (C/D), from 140 children/adolescents with the above-mentioned disorders. We used Student's t test to compare females versus males, patients under versus over 16-year-old, patients with lower versus higher than the median body weight, and patients with lower versus higher than the median body mass index (BMI). Two mixed-effects logistic regression models were fitted for risperidone/9- hydroxyrisperidone ratio and AM, respectively, by considering risperidone daily dose and patients' demographic characteristics. Results:Females had higher 9-hydroxyrisperidone and AM plasma concentrations than males (p = 0.004 and p = 0.034). Younger patients had lower risperidone plasma concentration and risperidone/9-hydroxyrisperidone ratio (p = 0.02 and p = 0.021), but higher C/D 9-hydroxyrisperidone and AM than older patients (p = 0.013 and p = 0.043). Lower-weight patients had lower plasma risperidone and risperidone/9-hydroxyrisperidone ratio (p = 0.014 and p = 0.019), but higher C/D 9-hydroxyrisperidone concentration than heavier patients (p = 0.03). All these results could be accounted for by daily dose. Patients with lower and higher BMI did not differ significantly. Regression analyses showed that only risperidone daily dose predicted risperidone/9-hydroxyrisperidone ratio, whereas risperidone daily dose, sex, and age predicted AM. Conclusion:Clinicians prescribing risperidone need to consider sex, age, and weight, but not BMI when adjusting daily doses.
| S-EPMC7006987 | biostudies-literature
Project description:Cardiovascular risk factors develop in childhood and adolescence. This enumerative review addresses whether sleep characteristics, including sleep duration, continuity, quality, and daytime sleepiness, are associated with cardiovascular risk factors in young people. Thirty-nine studies were identified, which examined the following risk factors: metabolic syndrome, glucose and insulin, lipids, blood pressure, and cardiovascular responses to psychological stressors. Due to the availability of other reviews, 16 longitudinal studies of obesity published in 2011 and later were also included in this report. Excluded from the review were studies of participants with suspected or diagnosed sleep disorders and reports from sleep deprivation experiments. Combining studies, evidence was strongest for obesity, followed by glucose, insulin, blood pressure (especially ambulatory blood pressure), and parasympathetic responses to psychological stressors. There was little evidence for metabolic syndrome cluster, lipids, and blood pressure responses to psychological stressors. The more positive associations were obtained for studies that incorporated objective measures of sleep and that included adolescents. The foundational evidence is almost entirely cross-sectional, except for work on obesity. In summary, available evidence suggests that the associations between sleep characteristics and cardiovascular risk vary by risk factor. It is time to conduct studies to determine antecedent and consequent relationships, and to expand risk factors to include markers of inflammation.
| S-EPMC4689674 | biostudies-literature