Therapeutic effects of methylphenidate for attention-deficit/hyperactivity disorder in children with borderline intellectual functioning or intellectual disability: A systematic review and meta-analysis

Attention-deficit/hyperactivity disorder (ADHD) frequently co-occurs with intellectual disability in children, and may further compromise learning. Methylphenidate is a first-line treatment for ADHD, however no previous meta-analysis has evaluated its overall efficacy for ADHD in children with comorbid intellectual disability (ID) or borderline intellectual functioning. The PubMed/MEDLINE, Cochrane CENTRAL and ScienceDirect databases were systematically searched from inception through 2018/7/15 for clinical studies that investigated the effects of methylphenidate in children with ADHD and ID. A random-effects model meta-analysis was used for data synthesis. Eight studies (average Jadad score = 2.5) enrolling 242 participants receiving methylphenidate and 181 participants receiving placebo were included. The meta-analysis showed that methylphenidate led to a significant improvement in ADHD symptoms relative to placebo (Hedges’ g = 0.878, p < 0.001). Meta-regression analysis pointed to an association between the dose of methylphenidate and overall improvement in ADHD severity (slope = 1.334, p < 0.001). Finally, there was no significant difference in drop-out rate [odds ratio (OR) = 1.679, p = 0.260] or rate of treatment discontinuation due to adverse events (OR = 4.815, p = 0.053) between subjects receiving methylphenidate and those taking placebos. Our study suggests that methylphenidate retains its efficacy in children with ADHD and borderline intellectual functioning or ID

Definitions and clinical guidance on the enteral dependence component of the avoidant/restrictive food intake disorder diagnostic criteria in children

The aim of the current paper is to offer definitive guidance on weaning children who are reliant on nasogastric/gastrostomy feeding tubes. To date, no internationally recognised definitions or principles for interventions exist and clinics have been reliant on creating their own unique intervention criteria. To achieve the aim, two goals are set out within the current paper. The first goal was to definitively define the process of tube weaning. In order to achieve this, both tube dependency and oral eating also required definitions. It is necessary for these two additional definitions to fully understand the process of tube weaning and the transition that the child is making within these clinical interventions. The second goal of this paper was to propose a set of minimum measurement criteria within a tube weaning protocol so that different clinical practices and perspectives may be measured accurately. This would then allow outcomes from different clinical services to be compared for efficacy. The culmination of this paper is a set of five core principles that should govern clinics that adhere to the auspices of evidence-based practice. These principles, if adopted, will provide the basis of a set of internationally recognised criteria within this field of paediatric gastroenterology

Methylphenidate Treatment in Children with Borderline IQ and Mental Retardation: Analysis of Three Aggregated Studies

Objective: To determine response of low-IQ children with attention deficit hyperactivity disorder (ADHD) symptoms to methylphenidate (MPH). Methods: An aggregated analysis was conducted in 90 children with low IQ who received the same dose regimen of MPH in three independent, placebo-controlled studies. Active drug and placebo were given from 2 to 4 weeks each. Outcome measures included teacher and parent ratings on standardized behavior scales (mean n = 84), performance on computer-controlled cognitive-motor tests (n = 62), and measures of cardiovascular response (n = 85). Results: Both teachers and parents rated the children consistently as being improved on subscales assessing attention, overactivity, and conduct problems. Some 44% of the subjects showed at least a 30% reduction compared with placebo on teacher ratings. MPH improved accuracy on several cognitive tests, response speed was increased on some, and seat activity declined for one of three tests; heart rate was mildly increased (3.9 beats/minute) with MPH. Analyses of IQ and mental age as moderator variables suggested that lower functional level (especially lower IQ) may be associated with a less favorable response to MPH. Conclusions: Children with low IQ and ADHD clearly respond to MPH, but their rate of beneficial response appears to be well under that of normal-IQ children and more varied. Different attentional mechanisms may moderate response to psychostimulants

Cognitive Effects of Risperidone in Children with Autism and Irritable Behavior

Objective: The objective of this research was to explore the effects of risperidone on cognitive processes in children with autism and irritable behavior. Method: Thirty-eight children, ages 5-17 years with autism and severe behavioral disturbance, were randomly assigned to risperidone (0.5 to 3.5 mg/day) or placebo for 8 weeks. This sample of 38 was a subset of 101 subjects who participated in the clinical trial; 63 were unable to perform the cognitive tasks. A double-blind placebo-controlled parallel groups design was used. Dependent measures included tests of sustained attention, verbal learning, hand-eye coordination, and spatial memory assessed before, during, and after the 8-week treatment. Changes in performance were compared by repeated measures ANOVA. Results: Twenty-nine boys and 9 girls with autism and severe behavioral disturbance and a mental age ≥18 months completed the cognitive part of the study. No decline in performance occurred with risperidone. Performance on a cancellation task (number of correct detections) and a verbal learning task (word recognition) was better on risperidone than on placebo (without correction for multiplicity). Equivocal improvement also occurred on a spatial memory task. There were no significant differences between treatment conditions on the Purdue Pegboard (hand-eye coordination) task or the Analog Classroom Task (timed math test). Conclusion: Risperidone given to children with autism at doses up to 3.5 mg for up to 8 weeks appears to have no detrimental effect on cognitive performance

Shared heritability of attention-deficit/hyperactivity disorder and autism spectrum disorder

Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are both highly heritable neurodevelopmental disorders. Evidence indicates both disorders co-occur with a high frequency, in 20–50% of children with ADHD meeting criteria for ASD and in 30-80% of ASD children meeting criteria for ADHD. This review will provide an overview on all available studies [family based, twin, candidate gene, linkage, and genome wide association (GWA) studies] shedding light on the role of shared genetic underpinnings of ADHD and ASD. It is concluded that family and twin studies do provide support for the hypothesis that ADHD and ASD originate from partly similar familial/genetic factors. Only a few candidate gene studies, linkage studies and GWA studies have specifically addressed this co-occurrence, pinpointing to some promising pleiotropic genes, loci and single nucleotide polymorphisms (SNPs), but the research field is in urgent need for better designed and powered studies to tackle this complex issue. We propose that future studies examining shared familial etiological factors for ADHD and ASD use a family-based design in which the same phenotypic (ADHD and ASD), candidate endophenotypic, and environmental measurements are obtained from all family members. Multivariate multi-level models are probably best suited for the statistical analysis

A genetic cause of Alzheimer disease: mechanistic insights from Down syndrome

Down syndrome, caused by an extra copy of chromosome 21, is associated with a greatly increased risk of early onset Alzheimer disease. It is thought that this risk is conferred by the presence of three copies of the gene encoding amyloid precursor protein (APP), an Alzheimer risk factor, although the possession of extra copies of other chromosome 21 genes may also play a role. Further study of the mechanisms underlying the development of Alzheimer disease in Down syndrome could provide insights into the mechanisms that cause dementia in the general population