Isabel M. Smith

Executive Function in Preschoolers: A Review Using an Integrative Framework.

During the last 2 decades, major advances have been made in understanding the development of executive functions (EFs) in early childhood. This article reviews the EF literature during the preschool period using an integrative framework. The framework adopted considers EF to be a unitary construct with partially dissociable components (A. Miyake et al., 2000). The authors focus on 3 EF components: working memory, response inhibition, and shifting. For the present purposes, the central executive is conceived of as a central attention system that is involved in all EF component operations. Research to date suggests that elementary forms of the core EF components are present early during the preschool period. Changes in EF during the latter half of the preschool period appear to be due to the development of attention and integration of component EFs. Finally, the review outlines a number of areas that warrant further investigation if researchers are to move forward in understanding early EF development.

Risperidone in the Treatment of Disruptive Behavioral Symptoms in Children With Autistic and Other Pervasive Developmental Disorders

Objective. To investigate the efficacy and safety of risperidone for the treatment of disruptive behavioral symptoms in children with autism and other pervasive developmental disorders (PDD). Methods. In this 8-week, randomized, double-blind, placebo-controlled trial, risperidone/placebo solution (0.01–0.06 mg/kg/day) was administered to 79 children who were aged 5 to 12 years and had PDD. Behavioral symptoms were assessed using the Aberrant Behavior Checklist (ABC), Nisonger Child Behavior Rating Form, and Clinical Global Impression-Change. Safety assessments included vital signs, electrocardiogram, extrapyramidal symptoms, adverse events, and laboratory tests. Results. Subjects who were taking risperidone (mean dosage: 0.04 mg/kg/day; 1.17 mg/day) experienced a significantly greater mean decrease on the irritability subscale of the ABC (primary endpoint) compared with those who were taking placebo. By study endpoint, risperidone-treated subjects exhibited a 64% improvement over baseline in the irritability score almost double that of placebo-treated subjects (31%). Risperidone-treated subjects also exhibited significantly greater decreases on the other 4 subscales of the ABC; on the conduct problem, insecure/anxious, hyperactive, and overly sensitive subscales of the Nisonger Child Behavior Rating Form (parent version); and on the Visual Analog Scale of the most troublesome symptom. More risperidone-treated subjects (87%) showed global improvement in their condition compared with the placebo group (40%). Somnolence, the most frequently reported adverse event, was noted in 72.5% versus 7.7% of subjects (risperidone vs placebo) and seemed manageable with dose/dose-schedule modification. Risperidone-treated subjects experienced statistically significantly greater increases in weight (2.7 vs 1.0 kg), pulse rate, and systolic blood pressure. Extrapyramidal symptoms scores were comparable between groups. Conclusions. Risperidone was well tolerated and efficacious in treating behavioral symptoms associated with PDD in children.

Imitation and action in autism: A critical review.

This article considers the evidence for an imitative deficit in autism and for the possible role of deficiencies in the representation of actions. An argument is developed for the claim that the imitation problem is diagnostic of a basic information-processing rather than a social dysfunction. Reviews are offered of the empirical literature on gestural imitation in autism (and other developmental disorders) and the more anecdotal evidence for problems in the domain of action development in autism. An account that may help to integrate these areas is suggested, as are directions for future research.

An epidemiological analysis of CHARGE syndrome: Preliminary results from a Canadian study

CHARGE syndrome is a well‐characterized clinical diagnosis with recent data supporting a genetic etiology. A 3‐year national surveillance coordinated by the Canadian Pediatric Surveillance Program (CPSP) was started in September 2001. Physicians notified the CPSP if they had cared for individuals with CHARGE syndrome within their practice, and then completed a detailed reporting form. To date, there are 77 confirmed cases of CHARGE syndrome. The highest provincial prevalence of CHARGE syndrome in Canada was estimated at 1 in 8,500 live births. Subgroups of cases with particular clusters of anomalies were identified. In older individuals, bilateral posterior choanal atresia (BPCA) was predictive of the presence of the three other major criteria and of aortic arch anomalies. Individuals with CHARGE syndrome who demonstrated a less extensive phenotype (≤3 major criteria) were more likely to present with minor cardiovascular malformations, including small atrial or ventricular septal defects (VSD) or patent ductus arteriosus (PDA). A significant cause of morbidity was severe feeding difficulty, including problems with chewing, swallowing, and gastroesophageal reflux, which were prevalent throughout childhood. Infant mortality is high in individuals with CHARGE syndrome. However, life expectancy has improved for those surviving their first year. Increased mortality was associated with distinct cardiovascular malformations or ventriculomegaly combined with brainstem or cerebellar anomalies. From this study, revised diagnostic criteria are proposed for infants, children, and adolescents to help identify a group of individuals who represent CHARGE syndrome with more of the classical features as apposed to the boarder association.

Relation between biochemical severity and intelligence in early treated congenital hypothyroidism: a threshold effect

Abstract Objectives : To assess whether early treatment of congenital hypothyroidism fully prevents intellectual impairment. Design : A national register of children with congenital hypothyroidism who were compared with unaffected children from the same school classes and matched for age, sex, social class, and first language. Setting - First three years (1982-4) of a neonatal screening programme in England, Wales, and Northern Ireland. Subjects : 361 children with congenital hypothyroidism given early treatment and 315 control children. Main outcome measures : Intelligence quotient (IQ) measured at school entry at 5 years of age with the Wechsler preschool and primary scale of intelligence. Results : There was a discontinuous relation between IQ and plasma thyroxine concentration at diagnosis, with a threshold at 42.8 nmol/l (95% confidence interval 35.2 to 47.1 nmol/l). Hypothyroid children with thyroxine values below 42.8 nmol/l had a mean IQ 10.3 points (6.9 to 13.7 points) lower than those with higher values and than controls. None of the measures of quality of treatment (age at start of treatment (range 1 -173 days), average thyroxine dose (12.76 mug in the first year), average thyroxine concentration during treatment (79-234 nmol/l in the first year), and thyroxine concentration less than 103 nmol/l at least once during the first year) influenced IQ at age 5. Conclusions : Despite early treatment in congenital hypothyroidism the disease severity has a threshhold effect on brain development, probably determined prenatally. The 55% of infants with more severe disease continue to show clinically significant intellectual impairment; infants with milder disease show no such impairment. The findings predict that 10% of early treated infants with severe hypothyroidism, compared with around 40% of those who presented with symptoms in the period before screening began, are likely to require special education.

Clinical assessment of autism in high-risk 18-month-olds

Earlier intervention improves outcomes for children with autism spectrum disorders (ASDs), but existing identification tools are at the limits of standardization with 18-month-olds. We assessed potential behavioural markers of ASD at 18 months in a high-risk cohort of infant siblings of children with ASD. Prospective data were collected using the Autism Diagnostic Observation Schedule (ADOS) and Autism Observation Scale for Infants (AOSI) on 155 infant siblings and 73 low-risk controls at 18 months. Infants were classified into three groups (ASD sibs, non-ASD sibs, controls) based on blind best-estimate diagnosis at age 3. Fishers exact tests, followed by discriminant function analyses, revealed that the majority of informative ADOS items came from the social and behavioural domains, and AOSI items measuring behavioural reactivity and motor control contributed additional information. Findings highlight the importance of considering not only social-communication deficits, but also basic dimensions of temperament including state regulation and motor control when assessing toddlers with suspected ASD.

Effect of stopping low-phenylalanine diet on intellectual progress of children with phenylketonuria.

Forty-seven patients at the Hospital for Sick Children, London, who had phenylketonuria and were on a low-phenylalanine diet (21 early-treated--that is, treatment started before the age of 4 months--and 26 late-treated) were placed on a normal diet between the ages of 5 and 15 years. They showed significant falls in mean IQ of about six points after the diet was withdrawn. Twenty-two similar patients (five early-treated and 17 late-treated) at the Universitäts-Kinderklinik, Heidelberg, who were placed on a relaxed low-phenylalanine rather than a normal diet, showed smaller and non-significant falls in mean IQ. During the period of strict diet none of the patients in London or Heidelberg showed any consistent falls in IQ. These results suggest that complete withdrawal of the low-phenylalanine diet during childhood leads to a fall in intellectual progress in many patients.

Epidemiology of autism: Prevalence, associated characteristics, and implications for research and service delivery

We provide an overview of research on the epidemiology of autism and related pervasive developmental disorders (PDDs). First, we provide data on the prevalence of autism, which now is estimated to be considerably higher than previously documented. Next, we focus on characteristics associated with autism, including psychosocial correlates, as well as associated physical and medical/psychiatric conditions. In this context, special consideration is given to the coexistence of autism and mental retardation, and to associated conditions that might be the most informative in advancing our understanding of the neurobiology and neuropsychology of autism. Data on outcome are also discussed, with special reference to early intervention and to empirically supported methods. We end by identifying potentially fruitful directions for future epidemiological research on autism/PDD, and by outlining implications of what already is known for the planning and delivery of services for this unique population. MRDD Research Reviews 1998;4:97–103.

New variant of phenylketonuria with progressive neurological illness unresponsive to phenylalanine restriction.

Three children, two of them siblings, with an unusual type of phenylketonuria are described. The three patients, two of them observed from the neonatal period, had a progressive neurological illness which was unlike that of classical phenylketonuria, and which did not respond to a low phenylalanine diet. The biochemical features suggested that the block in the conversion of phenylalanine to tyrosine was less severe than in the classical disease, and phenylalanine rho-hydroxylase activity, measured in one patient was normal. It is suggested that the patients have a disorder of biopterin metabolism possibly due to a defect of the enzyme dihydropteridine reductase.

Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder

We are performing whole-genome sequencing of families with autism spectrum disorder (ASD) to build a resource (MSSNG) for subcategorizing the phenotypes and underlying genetic factors involved. Here we report sequencing of 5,205 samples from families with ASD, accompanied by clinical information, creating a database accessible on a cloud platform and through a controlled-access internet portal. We found an average of 73.8 de novo single nucleotide variants and 12.6 de novo insertions and deletions or copy number variations per ASD subject. We identified 18 new candidate ASD-risk genes and found that participants bearing mutations in susceptibility genes had significantly lower adaptive ability (P = 6 × 10−4). In 294 of 2,620 (11.2%) of ASD cases, a molecular basis could be determined and 7.2% of these carried copy number variations and/or chromosomal abnormalities, emphasizing the importance of detecting all forms of genetic variation as diagnostic and therapeutic targets in ASD.