Exploring the origins of developmental disorders.
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Preschool children diagnosed with either global developmental delay (GDD) or developmental language impairment (DLI) were reassessed during their early school years with standardized developmental (Battelle Developmental Inventory [BDI]) and functional (Vineland Adaptive Behavior Scale [VABS]) outcome measures. Of an original cohort of 99 children with GDD and 70 children with DLI assessed and diagnosed at a mean age of 3 years 5 months (SD 1.1) and 3 years 7 months (SD 0.7) respectively, 48 children (34 [71%] males) with GDD and 43 children (36 [84%] males) with DLI were reassessed at a mean age of 7 years 4 months (SD 0.9) and 7 years 5 months (SD 0.7) respectively. The overall total mean BDI score for children with GDD was 66.4 (SD 4.3) versus 71.9 (SD 8.2) for children with DLI (p=0.002). On each subdomain of the BDI, except communication, mean scores for the GDD group were significantly lower than for the DLI group (p<0.05). Similarly, the VABS total score for the GDD group was significantly lower than for the DLI group (p<0.001). For each subdomain of the VABS, the GDD group scored significantly lower than the DLI group (p<0.001). The proportion of children falling below meaningful cut-offs on the outcome measures selected was significantly higher for those initially diagnosed with GDD. Preschool diagnosis of either GDD or DLI has later prognostic validity with regard to persisting developmental and functional deficits.
Cerebellar hypoplasia is a rare malformation caused by a variety of etiologies. It usually manifests clinically as non-progressive cerebellar ataxia with or without mental retardation. We further characterize a syndrome of autosomal recessive cerebellar hypoplasia in the Hutterite population, referred to as dysequilibrium syndrome (DES). We reviewed 12 patients (eight females, four males; age range 4 to 33 y) with this syndrome. Patients were examined and underwent a standard set of investigations to characterize better the clinical features, natural history, and neuroimaging of this syndrome. DES is an autosomal recessive disorder with distinct clinical features including global developmental delay, late ambulation (after age 6 y), truncal ataxia, and a static clinical course. Neuroimaging is characterized by hypoplasia of the inferior portion of the cerebellar hemispheres and vermis, and mild simplification of cortical gyri.
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The Children's Social Behavior Questionnaire (CSBQ) contains items referring to behavior problems seen in children with milder variants of PDD. Data of large samples of children diagnosed as having high-functioning autism, PDDNOS, ADHD, and other child-psychiatric disorders were gathered. Besides the CSBQ, parents completed the Autism Behavior Checklist (ABC) and the Child Behavior Checklist (CBCL). The data provided the basis for scale construction of the CSBQ, a comparison of the CSBQ scales with other instruments and a comparison of groups on scores on the CSBQ. The 5 scales obtained referred to Acting-out behaviors, Social Contact problems, Social Insight problems, Anxious/Rigid behaviors and Stereotypical behaviors. Results show that the CSBQ has good psychometric qualities with respect to both reliability and validity. A comparison of the different groups showed that significant group differences were found on all scales. In general, the autism group received the highest scores, followed by the PDDNOS group and the ADHD group. Exceptions were on the Acting-out scale, where the ADHD group scored highest and on the Social Insight scale, where no significant difference was found between the PDDNOS group and the ADHD group. Implications of the results and suggestions for further research are discussed.
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The question of when it is best to screen for autism may only be answered by a series of empirical studies. These will be difficult to plan, fund, and conduct, and will by necessity take many years because of the need to systematically follow up the whole cohort screened. In our study, we identified 19 of the 50 children with autism by their profile at the 18-month screen (though note that some fell out of risk status at the repeat screen 1 month later--thus sacrificing sensitivity for improved positive predictive power). Through the subsequent surveillance methods we employed, we identified the remaining cases as follows: 5 at 42 months, 4 between 42 months and 7 years, and 25 at 7 years. We do not mean to end on a pessimistic note. Our experiences have been positive both in regard to the instrument we developed and the effects that using it have had on the health practitioners involved in the research study. In discussion, practitioners have commented on the usefulness of knowing what prelanguage and prosocial skills can reliably be looked at during the 18-month check. Training using the CHAT and eliciting its behaviors improved the skills and confidence of primary health practitioners. It is our view that this has had the effect of reducing the age at which autism is recognized and cases are referred on for a developmental assessment. The work reported by Robins er al. makes an important contribution to this ongoing research and clinical process as we attempt to accurately identify children with autism at a young age.
The Child Neurology Society and American Academy of Neurology recently proposed to formulate Practice Parameters for the Diagnosis and Evaluation of Autism for their memberships. This endeavor was expanded to include representatives from nine professional organizations and four parent organizations, with liaisons from the National Institutes of Health. This document was written by this multidisciplinary Consensus Panel after systematic analysis of over 2,500 relevant scientific articles in the literature. The Panel concluded that appropriate diagnosis of autism requires a dual-level approach: (a) routine developmental surveillance, and (b) diagnosis and evaluation of autism. Specific detailed recommendations for each level have been established in this document, which are intended to improve the rate of early suspicion and diagnosis of, and therefore early intervention for, autism.
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Studies of the broader autism phenotype, and of subtle changes in autism symptoms over time, have been compromised by a lack of established quantitative assessment tools. The Social Responsiveness Scale (SRS-formerly known as the Social Reciprocity Scale) is a new instrument that can be completed by parents and/or teachers in 15-20 minutes. We compared the SRS with the Autism Diagnostic Interview-Revised (ADI-R) in 61 child psychiatric patients. Correlations between SRS scores and ADI-R algorithm scores for DSM-IV criterion sets were on the order of 0.7. SRS scores were unrelated to I.Q. and exhibited inter-rater reliability on the order of 0.8. The SRS is a valid quantitative measure of autistic traits, feasible for use in clinical settings and for large-scale research studies of autism spectrum conditions.
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Results from ROC curves of items from two scales, the Autism Diagnostic Interview (ADI) and Autism Diagnostic Interview-Revised (ADI-R), operationalizing DSM-IV criteria for autism are presented for 319 autistic and 113 other subjects from 8 international autism centers. Analyses indicate that multiple items were necessary to attain adequate sensitivity and specificity if samples with varying levels of language were considered separately. Although considering only current behavior was generally sufficient when a combination cutoff and additive model was employed, predictive power was highest when history was taken into account. A single set of criteria, as operationalized by individually structured questions in the ADI/ADI-R, was effective in differentiating autism from mental handicap and language impairment in subjects with a range of chronological ages and developmental levels.
Recent research has yielded increasing support for neurobiologic theories of autism. A number of family and twin studies support the role of genetics and have led to wide acceptance of autism as an organically based disorder. Controversy persists, however, over the role of congenital medical conditions in the etiology of autism. Two rather divergent views have emerged. One, advocated by Gillberg and colleagues, proposes that up to 30% of cases of autism are associated with a known medical condition. On the other hand, research by Rutter and colleagues suggests the incidence may be closer to 10%. In this retrospective study records on 211 subjects with autism and other developmental disorders are reviewed to determine the prevalence of associated medical conditions and its variability related to the system used to diagnose autism. Results suggest the prevalence of medical conditions with suspected etiologic relationship with autism varies between 10 and 15%, depending on the diagnostic system employed. Further variability in prevalence rates results from a less strict definition of "medical condition" and yields rates between 25 and 37%. Disparate findings in previous research may stem from variability in both diagnostic system employed and which medical conditions are considered significant in the etiology of autism.
This study evaluated the impact of intensive behavioral treatment on the development of young autistic children. The treatment reported in this study was home based and was implemented by parents of autistic children with the assistance of community-based clinicians. Although treatment was unable to be observed directly, parents reported that therapy was based on methods developed by Lovaas et al. (1981). Treatment differed from that described in previous reports of intensive behavior therapy for this population in that it was implemented outside an academic setting and for a shorter period. In addition, children received fewer hours per week of therapy than in previous reports. Children in the experimental treatment group were pairwise matched to children in a control group (who received conventional school-based and brief one-on-one interventions) on the basis of pretreatment chronological and mental age, diagnosis (autism vs. PDD), and length of treatment. The groups did not differ on pretreatment IQ. Children receiving the experimental treatment had significantly higher posttreatment IQ scores. Smaller, but still statistically significant effects on symptom severity were also found, though experimental subjects still met diagnostic criteria for autism or PDD.
This study investigated social attention impairments in autism (social orienting, joint attention, and attention to another's distress) and their relations to language ability. Three- to four-year-old children with autism spectrum disorder (ASD; n = 72), 3- to 4-year-old developmentally delayed children (n = 34), and 12- to 46-month-old typically developing children (n = 39), matched on mental age, were compared on measures of social orienting, joint attention, and attention to another's distress. Children with autism performed significantly worse than the comparison groups in all of these domains. Combined impairments in joint attention and social orienting were found to best distinguish young children with ASD from those without ASD. Structural equation modeling indicated that joint attention was the best predictor of concurrent language ability. Social orienting and attention to distress were indirectly related to language through their relations with joint attention. These results help to clarify the nature of social attention impairments in autism, offer clues to developmental mechanisms, and suggest targets for early intervention.
Recreation-based family groups were formed as modalities in the treatment of school-age children enrolled at a day treatment center and of preschoolers with potential for enrollment. The groups, which had psychoeducational and self-help components, were successful in involving hitherto unwilling parents in their children's treatment, in helping them acquire parenting skills, and in reducing family conflict.
It is now well established that genetic factors play an important role in the pathogenesis of autism disorder and converging lines of evidence suggest the implication of the X chromosome. Using a sample of subjects diagnosed with autism spectrum disorders, exclusively composed of males from French-Canadian (FC) origin, we tested markers covering the entire X chromosome using a family-based association study. Our initial analysis revealed the presence of association at two loci: DXS6789 (P=0.026) and DXS8043 (P=0.0101). In a second step, we added support to the association at DXS8043 using additional markers, additional subjects and a haplotype-based analysis (best obtained P-value=0.00001). These results provide support for the existence of a locus on the X chromosome that predisposes the FC to autism spectrum disorders.