Darryn M. Sikora

Prevalence and risk factors of maladaptive behaviour in young children with Autistic Disorder

BACKGROUND Children with Autistic Disorder (AD) evidence more co-occurring maladaptive behaviours than their typically developing peers and peers with intellectual disability because of other aetiologies. The present study investigated the prevalence of Clinically Significant maladaptive behaviours during early childhood and identified at-risk subgroups of young children with AD. METHOD Parents rated their childs maladaptive behaviours on the Child Behaviour Checklist (CBCL) in 169 children with AD aged 1.5 to 5.8 years. RESULTS One-third of young children with AD had a CBCL Total Problems score in the Clinically Significant range. The highest percentage of Clinically Significant scores were in the Withdrawal, Attention, and Aggression CBCL syndrome scales. There was a high degree of co-morbidity of Clinically Significant maladaptive behaviours. Several subject characteristic risk factors for maladaptive behaviours were identified. CONCLUSIONS Findings highlight the need to include behavioural management strategies aimed at increasing social engagement, sustained attention and decreasing aggressive behaviour in comprehensive intervention programmes for young children with AD.

The Near Universal Presence of Autism Spectrum Disorders in Children With Smith-Lemli-Opitz Syndrome

Smith–Lemli–Opitz syndrome (SLOS) is an autosomal recessive condition caused by a defect in cholesterol synthesis. Affected children often have malformations and mental retardation. Autistic behaviors also are evident. The purpose of the present study was to determine the prevalence of autism spectrum disorders (ASDs) in children with SLOS. Fourteen children, 3–16 years old, were evaluated using three different methods to document autistic symptoms: (a) parent interview, (b) direct observation, and (c) a behavior checklist. Blood sterols were also measured at regular intervals. Each subject was determined to have Autistic Disorder, Pervasive Developmental Disorder, not otherwise specified (PDD NOS), or no diagnosis on the autism spectrum, based on DSM‐IV criteria. Correlations among variables were calculated, and blood sterol levels were compared between diagnostic groups. Approximately three‐fourths of the children with SLOS (71–86% depending on the evaluation method) had an ASD, about 50% diagnosed with Autistic Disorder and the rest with PDD NOS. The childrens baseline cholesterol, 7‐dehydrocholesterol (7‐DHC), and 8‐dehydrocholesterol (8‐DHC) levels, and cholesterol levels following supplementation did not correlate with the presence or severity of autistic symptoms. These results suggest that most children with SLOS have some variant of autism. SLOS appears to have the most consistent relationship with autism of any single gene disorder. Therefore, a link between cholesterol metabolism and autism is suggested. With further study, these findings, together with knowledge of the genetic and biochemical defects in SLOS, will likely provide valuable insights into the causes of autism in general.

Health-Related Quality of Life in Children with Autism Spectrum Disorders: Results from the Autism Treatment Network

We examined data collected as a part of the Autism Treatment Network, a group of 15 autism centers across the United States and Canada. Mean Health-Related Quality of Life (HRQoL) scores of the 286 children assessed were significantly lower than those of healthy populations (according to published norms). When compared to normative data from children with chronic conditions, children with ASD demonstrated worse HRQoL for total, psychosocial, emotional and social functioning, but did not demonstrate differing scores for physical and school functioning. HRQoL was not consistently related to ASD diagnosis or intellectual ability. However, it was consistently related to internalizing and externalizing problems as well as repetitive behaviors, social responsiveness, and adaptive behaviors. Associations among HRQoL and behavioral characteristics suggest that treatments aimed at improvements in these behaviors may improve HRQoL.

Central nervous system stem cell transplantation for children with neuronal ceroid lipofuscinosis

OBJECT Infantile and late-infantile neuronal ceroid lipofuscinoses (NCLs) are invariably fatal lysosomal storage diseases associated with defects in lysosomal enzyme palmitoyl-protein thioesterase 1 (PPT-1) or tripeptidyl peptidase 1 (TPP1) activity. Previous preclinical studies have demonstrated that human CNS stem cells (HuCNS-SCs) produce both PPT-1 and TPP1 and result in donor cell engraftment and reduced accumulation of storage material in the brain when tested in an NCL mouse model. METHODS HuCNS-SC transplantation was tested in an open-label dose-escalation Phase I clinical trial as a potential treatment for infantile and late-infantile NCL. Study design included direct neurosurgical transplantation of allogeneic HuCNS-SCs into the cerebral hemispheres and lateral ventricles accompanied by 12 months of immunosuppression. RESULTS Six children with either the infantile or late-infantile forms of NCL underwent low- (3 patients) and high- (3 patients) dose transplantation of HuCNS-SCs followed by immunosuppression. The surgery, immunosuppression, and cell transplantation were well tolerated. Adverse events following transplantation were consistent with the underlying disease, and none were directly attributed to the donor cells. Observations regarding efficacy of the intervention were limited by the enrollment criteria requiring that patients be in advanced stages of disease. CONCLUSIONS This study represents the first-in-human clinical trial involving transplantation of a purified population of human neural stem cells for a neurodegenerative disorder. The feasibility of this approach and absence of transplantation-related serious adverse events support further exploration of HuCNS-SC transplantation as a potential treatment for select subtypes of NCL, and possibly for other neurodegenerative disorders.

The Effects of a Developmental, Social-Pragmatic Language Intervention on Rate of Expressive Language Production in Young Children with Autistic Spectrum Disorders.

Developmental, social—pragmatic (DSP) interventions are based on the study of interactions betWeen typically developing infants and their mothers. Despite the fact that DSP approaches are firmly grounded in developmental theory, there is limited research on the efficacy of these interventions for promoting social-communicative behavior in young children With autism. This study used a single-subject, multiple-baseline design to examine the effectiveness of a DSP language intervention on three children With autistic spectrum disorders (ASD). Results indicate the children exhibited increases in their use of spontaneous speech With the therapist as Well as With their parents, Who had not been trained in the intervention. These findings provide preliminary support for the effectiveness of language therapy using a developmental, social—pragmatic approach With young children With ASD.

The relationship between sleep problems and daytime behavior in children of different ages with autism spectrum disorders.

BACKGROUND The purpose of the current study was to evaluate the relationships among sleep problems and daytime behaviors in a large, well-defined cohort of children with autism spectrum disorder (ASD). METHODS Out of a registry population of 3452 children with ASDs, a subset of 1193 children aged 4 to 10 years of age from 14 centers across the country was used to evaluate the relationship between varying levels of sleep problems and daytime behavior. Measures included Children’s Sleep Habits Questionnaire, Vineland Adaptive Behavior Scales, Survey Interview Form, Second Edition, and Child Behavior Checklist. Multiple analysis of covariance was used to assess the association between sleep and behavior. RESULTS Results suggest that sleep problems, as identified by parent report by use of the Children’s Sleep Habits Questionnaire, have a negative relationship with daytime behavior. More specifically, children with ASDs and sleep problems had more internalizing and externalizing behavior problems, as measured by the Child Behavior Checklist, and poorer adaptive skill development, as measured by the Vineland Adaptive Behavior Scales, than children with ASDs and no sleep problems. Children with moderate to severe sleep problems had greater behavior difficulties, but not necessarily poorer adaptive functioning, than children with mild to moderate sleep problems. Both preschool- and school-aged children demonstrated a negative relationship between behavior and sleep, whereas the relationship between sleep and adaptive functioning was much more variable. CONCLUSIONS These results suggest that, although sleep has a negative relationship with internalizing and externalizing behavior, it may have a different relationship with the acquisition of adaptive skills.

Attention-Deficit/Hyperactivity Disorder Symptoms, Adaptive Functioning, and Quality of Life in Children With Autism Spectrum Disorder

OBJECTIVE The purpose of the current study was to evaluate the frequency of co-occurring attention-deficit/hyperactivity disorder (ADHD) symptoms in a well-defined cohort of children with autism spectrum disorders (ASDs) and to examine the relationship between ADHD symptoms and both adaptive functioning and health-related quality of life as reported by parents or other primary caregivers. METHODS T scores on 2 ADHD-related scales from the Child Behavior Checklist were used to indicate the presence of ADHD symptoms. Participants were divided into groups based on whether their parents/caregivers rated them as having clinically significant T scores on the Attention Problem and Attention Deficit Hyperactivity Problem subscales. Standard scores from the Vineland Adaptive Behavior Scales, Second Edition and raw scores from the Pediatric Quality of Life Inventory were then compared between groups with the use of multivariate analyses. RESULTS Approximately 40% of participants had 1 elevated T score, and 19% had both ADHD-related T scores elevated on the Child Behavior Checklist. The ASD + ADHD group had lower scores on the Vineland Adaptive Behavior Scales, Second Edition and the Pediatric Quality of Life Inventory in comparison with the ASD alone group. CONCLUSIONS Results suggest greater impairment in adaptive functioning and a poorer health-related quality of life for children with ASDs and clinically significant ADHD symptoms in comparison with children with ASDs and fewer ADHD symptoms. Physicians are encouraged to evaluate for the presence of ADHD symptoms in their patients with ASDs and, if present, include symptom treatment in the overall care plan.

Which DSM-IV-TR criteria best differentiate high-functioning autism spectrum disorder from ADHD and anxiety disorders in older children?

Diagnosis of autism spectrum disorder (ASD) is often delayed in high-functioning children with milder and more varied forms of ASD. The substantial overlap between ASD and other psychiatric disorders is thought to contribute to this delay. This study examined the endorsement of DSM-IV-TR diagnostic criteria for ASD based on semi-structured parent interviews across three groups of older children referred to an ASD clinic: 55 children diagnosed with high-functioning ASD, 27 children diagnosed with attention-deficit/hyperactivity disorder (ADHD), and 23 children diagnosed with anxiety disorder. Results indicate that the criteria within the domains of communication and social relatedness were largely able to discriminate the high-functioning ASD group from the ADHD and anxiety disorder groups, but criteria within the domain of restricted/repetitive/stereotyped patterns were not.

Detecting Autism Spectrum Disorder in Children With Intellectual Disability: Which DSM-IV-TR Criteria Are Most Useful?

The diagnosis of autism spectrum disorders (ASDs) in older children with intellectual disabilities (IDs) is challenging because of overlap in symptomatology and the high comorbidity of these disorders. On the basis of a sample of 89 older children with IDs (aged 6—15 years) referred to an ASD clinic, semistructured parent interviews were used to investigate the Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.) diagnostic criteria that differentiated children with ASDs from those without ASDs. Diagnostic criteria related to impaired social interactions, stereotyped or idiosyncratic language, poor conversational skills, lack of pretend and imitative play, and restricted or narrowed interests were related to ASD diagnoses. The findings of this study have implications for improving ASD diagnostic evaluations in children with IDs.

Using Standardized Psychometric Tests to Identify Learning Disabilities in Students with Sensorineural Hearing Impairments

The purpose of this study was to evaluate the use of standardized psychoeducational diagnostic instruments to identify learning disabilities in students with sensorineural hearing impairments. Nineteen students were evaluated: 14 males and 5 females between the ages of 7 and 13. Results indicated that 12 were functioning at grade level, 2 had cognitive delays, and 2 had learning disabilities. Of the 3 remaining students, 2 had unilateral hearing loss and 1 had a precipitous high-frequency hearing loss; these students were used as controls. Students with hearing impairment were found to demonstrate learning disabilities with a frequency similar to that found in students with normal hearing. These results suggest that standardized instruments can be used effectively to identify learning disabilities in students with sensorineural hearing loss.