Risperidone or Aripiprazole Can Resolve Autism Core Signs and Symptoms in Young Children: Case Study.
Ontology highlight
ABSTRACT:
SUBMITTER: Alsayouf HA
PROVIDER: S-EPMC8143447 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description: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.
| S-EPMC4851735 | biostudies-literature
Project description:The human gut microbiome has increasingly been associated with autism spectrum disorder (ASD), which is a neurological developmental disorder, characterized by impairments to social interaction. The ability of the gut microbiota to signal across the gut-brain-microbiota axis with metabolites, including short-chain fatty acids, impacts brain health and has been identified to play a role in the gastrointestinal and developmental symptoms affecting autistic children. The fecal microbiome of older children with ASD has repeatedly shown particular shifts in the bacterial and fungal microbial community, which are significantly different from age-matched neurotypical controls, but it is still unclear whether these characteristic shifts are detectable before diagnosis. Early microbial colonization patterns can have long-lasting effects on human health, and pre-emptive intervention may be an important mediator to more severe autism. In this study, we characterized both the microbiome and short-chain fatty acid concentrations of fecal samples from young children between 21 and 40 months who were showing early behavioral signs of ASD. The fungal richness and acetic acid concentrations were observed to be higher with increasing autism severity, and the abundance of several bacterial taxa also changed due to the severity of ASD. Bacterial diversity and SCFA concentrations were also associated with stool form, and some bacterial families were found with differential abundance according to stool firmness. An exploratory analysis of the microbiome associated with pre-emptive treatment also showed significant differences at multiple taxonomic levels. These differences may impact the microbial signaling across the gut-brain-microbiota axis and the neurological development of the children.
| S-EPMC9371947 | biostudies-literature
Project description:BackgroundAtypical antipsychotics decrease irritability in autism. They also affect the cytokine network. Psychological stress, depression, and, possibly, autism spectrum disorder (ASD) are associated with the production of pro-inflammatory cytokines. We sought to determine if risperidone treatment led to changes in plasma cytokine levels.MethodsForty-five subjects from an open-label study of risperidone treatment of children and adolescents with ASD, ages 4-18 years, had an analysis of 27 different cytokines at baseline and after 8 weeks of treatment using multiplex assays (Millipore) and read on the Luminex 100(™) platform. We examined changes in each of the cytokine levels in the entire group, and also compared changes in cytokines in responders versus nonresponders.ResultsAfter 8 weeks of risperidone treatment, 2 of the 27 plasma cytokines showed statistically significant decreases in median levels: Eotaxin (p=0.0003) and monocyte chemoattractant protein-1 (MCP-1) (p=0.0024). Six of the 48 subjects met two criteria for responders to risperidone, and the median values of interleukin (IL)-5 were significantly higher (p=0.005) in the overall responder group than in nonresponders.ConclusionsTwo cytokines, eotaxin and MCP-1, which have previously been identified as abnormally elevated in children with autism, decreased during treatment with risperidone. This suggests a possible mechanism of action of risperidone treatment and a balancing of the immune system in affected subjects in this very preliminary study.
| S-EPMC4268580 | biostudies-literature
Project description:ObjectiveThe purpose of this study was to investigate the course of autistic symptoms, using a quantitative measure of core autistic traits, among risperidone-treated children who participated in a 10 year life course longitudinal study.MethodsParents completed surveys of intervention history, as well as serial symptom severity measurements using the Social Responsiveness Scale (SRS), on their autism spectrum disorder (ASD)-affected children. Fifty participants (out of a total of 184 with full intervention histories) were reported to have been treated with risperidone during the course of the study. Serial SRS scores during risperidone treatment were available for a majority of children whose parents reported a positive effect from risperidone.ResultsTwo thirds of risperidone-treated children (n=33) were reported by parents to have improved by taking the medication, with the principal effects described being that children were calmer, better focused, and less aggressive. SRS scores of children reported to have responded positively to risperidone did not improve over time.ConclusionsRisperidone's beneficial effect on aggression and other elements of adaptive functioning were not necessarily accompanied by reduction in core ASD symptoms, as serially assessed by the same caregivers who reported improvement in their children. These results reflect the distinction between reduction in core symptom burden and improvement in adaptive functioning. Given the cumulative risks of atypical neuroleptics, the findings underscore the importance of periodic re-evaluation of medication benefit for children with ASD receiving neuroleptic treatment.
| S-EPMC4238250 | biostudies-literature
Project description:BackgroundBoth the US FDA and the European Medicines Agency (EMA) have approved aripiprazole for use in adolescents for specific indications. Given the assumed favorable side-effect profile of aripiprazole, its use in children and adolescents has increased for both official and off-label indications (anxiety disorders, eating disorders, personality disorders). However, several cases of children and adolescents with new-onset extrapyramidal symptoms (EPS) after commencing treatment with aripiprazole have been reported, and a more systematic appraisal of this possible risk is lacking.ObjectiveWe conducted a systematic review and a meta-analysis to assess the evidence for acute EPS (acute dystonia, akathisia, Parkinsonism) associated with the use of aripiprazole in children and adolescents.MethodWe searched the MEDLINE and Embase databases (2003-10 April 2016) for clinical trials in pediatric patients (aged 0-18 years) using the keywords 'aripiprazole' (regardless of the formulation) and 'extrapyramidal symptoms'. We evaluated the abstracts of papers using the following exclusion criteria: (1) study design: case report, letter to the editor, editorial, or poster presentation data; (2) unrelated PICOS (population, intervention, comparators, outcomes, study) structure. We performed a meta-analysis, in which we used effect sizes with 95 % confidence intervals (CIs). To examine the homogeneity of the effect size distribution, we used a Q-statistic. When we observed heterogeneity in effect sizes, we assessed the possible influence of moderator variables (age and sex, mean dose, study duration, and method of measuring EPS incidence) and evaluated the suitability of either a fixed or a random model. Finally, we assessed the incidence of EPS in children and adolescents treated with aripiprazole compared with placebo.ResultsAn initial search via PubMed and Embase yielded 328 hits. A manual search of the reference lists of review papers revealed seven additional relevant articles. We included 41 studies, with 2114 pediatric patients, in the meta-analysis. For the analysis of the mean incidence of EPS, data were provided by 24 studies, with a total of 1446 pediatric patients. Meta-analysis revealed a mean EPS incidence of 17.1 % (95 % CI 0.128-0.223). In terms of the incidence of various extrapyramidal side effects, overall, no significant effects of age, sex, mean dose, study duration, or measuring method could be demonstrated. The side effects 'EPS', 'parkinsonism', and 'tremor' were significantly more common in children and adolescents treated with aripiprazole than in those treated with placebo.ConclusionOur meta-analysis provides evidence for a non-negligible incidence of acute EPS in children and adolescents treated with aripiprazole. Although the study has several limitations and further investigation is needed, these findings may help clinicians make more balanced treatment choices and more closely monitor the use of this drug in youth.
| S-EPMC4996892 | biostudies-literature
Project description:Hyperprolactinaemia is a troublesome side-effect of treatment with antipsychotics.This double-blind, placebo-controlled study aimed at examining the effect of adjunctive treatment with 10?mg aripiprazole on prolactin levels and sexual side-effects in patients with schizophrenia symptomatically maintained on risperidone.Thirty patients taking risperidone were enrolled into the trial (CTRI/2012/11/003114). Aripiprazole was administered at a fixed daily dose of 10?mg/day for 8 weeks. Serum prolactin was measured at baseline and at 8 weeks. Hyperprolactinaemia-related problems, psychopathology and side-effects were evaluated every 2 weeks.Prolactin levels decreased by 58% in the aripiprazole group compared with an increase by 22% in the placebo group. Prolactin levels normalised in 46% of patients in the aripiprazole group (number needed to treat, NNT=2). Aripiprazole improved erectile dysfunction in five out of six patients. There were no significant differences in change in psychopathology or side-effects between groups.Adjunctive aripiprazole reduced prolactin levels in those treated with risperidone, with no effect on psychopathology and extrapyramidal symptoms. This is a potential treatment for hyperprolactinaemia observed during treatment with second-generation antipsychotics.None.© The Royal College of Psychiatrists 2015. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.
| S-EPMC4998932 | biostudies-other
Project description:Children with autism spectrum disorders (ASDs) often have severe behavioral problems. Not all children with these problems respond to atypical antipsychotic medications; therefore, we investigated whether peripheral blood gene expression before treatment with risperidone, an atypical antipsychotic, was associated with improvements in severe behavioral disturbances 8 weeks following risperidone treatment in 42 ASD subjects (age 112.7±51.2 months). Exon expression levels in blood before risperidone treatment were compared with pre-post risperidone change in Aberrant Behavior Checklist-Irritability (ABC-I) scores. Expression of exons within five genes was correlated with change in ABC-I scores across all risperidone-treated subjects: GBP6, RABL5, RNF213, NFKBID and RNF40 (?<0.001). RNF40 is located at 16p11.2, a region implicated in autism and schizophrenia. Thus, these genes expressed before treatment were associated with subsequent clinical response. Future studies will be needed to confirm these results and determine whether this expression profile is associated with risperidone response in other disorders, or alternative antipsychotic response within ASD.
| S-EPMC3175502 | biostudies-other
Project description:Gut Microbiota Features in Young Children with Autism Spectrum Disorders
| PRJEB29421 | ENA
Project description:BackgroundPrevious research studies have demonstrated abnormalities in the metabolism of mothers of young children with autism.MethodsMetabolic analysis was performed on blood samples from 30 mothers of young children with Autism Spectrum Disorder (ASD-M) and from 29 mothers of young typically-developing children (TD-M). Targeted metabolic analysis focusing on the folate one-carbon metabolism (FOCM) and the transsulfuration pathway (TS) as well as broad metabolic analysis were performed. Statistical analysis of the data involved both univariate and multivariate statistical methods.ResultsUnivariate analysis revealed significant differences in 5 metabolites from the folate one-carbon metabolism and the transsulfuration pathway and differences in an additional 48 metabolites identified by broad metabolic analysis, including lower levels of many carnitine-conjugated molecules. Multivariate analysis with leave-one-out cross-validation allowed classification of samples as belonging to one of the two groups of mothers with 93% sensitivity and 97% specificity with five metabolites. Furthermore, each of these five metabolites correlated with 8-15 other metabolites indicating that there are five clusters of correlated metabolites. In fact, all but 5 of the 50 metabolites with the highest area under the receiver operating characteristic curve were associated with the five identified groups. Many of the abnormalities appear linked to low levels of folate, vitamin B12, and carnitine-conjugated molecules.ConclusionsMothers of children with ASD have many significantly different metabolite levels compared to mothers of typically developing children at 2-5 years after birth.
| S-EPMC7734806 | biostudies-literature
Project description:BackgroundThe objective of this study is to gain new insights into the relationship between clinical signs and age at diagnosis.MethodWe utilize a new, large, online survey of 1743 parents of children diagnosed with ASD, and use multiple statistical approaches. These include regression analysis, factor analysis, and machine learning (regression tree).ResultsWe find that clinical signs that most strongly predict early diagnosis are not necessarily specific to autism, but rather those that initiate the process that eventually leads to an ASD diagnosis. Given the high correlations between symptoms, only a few signs are found to be important in predicting early diagnosis. For several clinical signs we find that their presence and intensity are positively correlated with delayed diagnosis (e.g., tantrums and aggression). Even though our data are drawn from parents' retrospective accounts, we provide evidence that parental recall bias and/or hindsight bias did not play a significant role in shaping our results.ConclusionIn the subset of children without early deficits in communication, diagnosis is delayed, and this might be improved if more attention will be given to clinical signs that are not necessarily considered as ASD symptoms. Our findings also suggest that careful attention should be paid to children showing excessive tantrums or aggression, as these behaviors may interfere with an early ASD diagnoses.
| S-EPMC7905573 | biostudies-literature