A replication of the Autism Diagnostic Observation Schedule (ADOS) revised algorithms.

Objective: To replicate the factor structure and predictive validity of revised Autism Diagnostic Observation Schedule algorithms in an independent dataset (N = 1,282).

Method: Algorithm revisions were replicated using data from children ages 18 months to 16 years collected at 11 North American sites participating in the Collaborative Programs for Excellence in Autism and the Studies to Advance Autism Research and Treatment.

Results: Sensitivities and specificities approximated or exceeded those of the old algorithms except for young children with phrase speech and a clinical diagnosis of pervasive developmental disorders not otherwise specified.

Heterogeneous association between engrailed-2 and autism in the CPEA network.

Autism is a neurodevelopmental disorder characterized by an early onset of abnormal social, communicative, and repetitive behavior. Engrailed-2 (EN2) was identified as an autism candidate gene because its influence on cerebellar development in mice parallels neurodevelopmental abnormalities seen in individuals with autism. Studies investigating association between markers at EN2 (chr7q36), a location associated with language disorders, and autism reveal mixed findings.

Mapping autism risk loci using genetic linkage and chromosomal rearrangements.

Autism spectrum disorders (ASDs) are common, heritable neurodevelopmental conditions. The genetic architecture of ASDs is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASDs by using Affymetrix 10K SNP arrays and 1,181 [corrected] families with at least two affected individuals, performing the largest linkage scan to date while also analyzing copy number variation in these families.

Discrimination learning and reversal of the conditioned eyeblink reflex in a rodent model of autism.

Offspring of rats exposed to valproic acid (VPA) on gestational day (GD) 12 have been advocated as a rodent model of autism because they show neuron loss in brainstem nuclei and the cerebellum resembling that seen in human autistic cases . Studies of autistic children have reported alterations in acquisition of classical eyeblink conditioning and in reversal of instrumental discrimination learning . Acquisition of discriminative eyeblink conditioning depends on known brainstem-cerebellar circuitry whereas reversal depends on interactions of this circuitry with the hippocampus and prefrontal cortex.

Head circumference and height in autism: a study by the Collaborative Program of Excellence in Autism.

Data from 10 sites of the NICHD/NIDCD Collaborative Programs of Excellence in Autism were combined to study the distribution of head circumference and relationship to demographic and clinical variables. Three hundred thirty-eight probands with autism-spectrum disorder (ASD) including 208 probands with autism were studied along with 147 parents, 149 siblings, and typically developing controls. ASDs were diagnosed, and head circumference and clinical variables measured in a standardized manner across all sites.

Induction of the homeotic gene Hoxa1 through valproic acid's teratogenic mechanism of action.

Background: Valproic acid (VPA) exposure in utero has been associated with an increased risk of both neural tube defects and autism spectrum disorders (ASDs). The terata induced by VPA suggest interference with pattern formation. Retinoic acid produces similar terata and is known to act in part by increasing the expression of Hoxa1.

The teratology of autism.

Autism spectrum disorders affect behaviors that emerge at ages when typically developing children become increasingly social and communicative, but many lines of evidence suggest that the underlying alterations in the brain occur long before the period when symptoms become obvious. Studies of the behavior of children in the first year of life demonstrate that symptoms are often detectable in the first 6 months. The environmental factors known to increase the risk of autism have critical periods of action during embryogenesis.

Environmental causes of central nervous system maldevelopment.

The central nervous system is the most vulnerable of all body systems to developmental injury. This review focuses on developmental processes by which the nervous system is formed and how those processes are known or suspected to be injured by toxic agents. The processes discussed are establishment of neuron numbers; migration of neurons; establishment of connections, neurotransmitter activity, and receptor numbers; deposition of myelin; and 2 processes that are prominent in postnatal development, trimming back of connections and postnatal neurogenesis.

Alleles of a reelin CGG repeat do not convey liability to autism in a sample from the CPEA network.

A recent study by Persico et al. [2001: Mol Psychiatry 6:150-159] suggests alleles of a CGG polymorphism, just 5' of the reelin gene (RELN) initiator codon, confer liability for autism, especially alleles bearing 11 or more CGG repeats (long alleles). The association is consistent across both a case-control and family-based sample.

Association between the HOXA1 A218G polymorphism and increased head circumference in patients with autism.

Background: The HOXA1 gene plays a major role in brainstem and cranial morphogenesis. The G allele of the HOXA1 A218G polymorphism has been previously found associated with autism.

Methods: We performed case-control and family-based association analyses, contrasting 127 autistic patients with 174 ethnically matched controls, and assessing for allelic transmission disequilibrium in 189 complete trios.

Converging evidence for brain stem injury in autism.

The hypothesis that brain stem injury plays a role in the autism spectrum disorders was suggested by evidence that exposure to thalidomide during the earliest stages of brain development increases the risk of autism spectrum disorders. The implications for the embryological origin of autism first led to studies of neuroanatomy in a human case and an animal model and then to examinations of minor craniofacial features in autism. But the general hypothesis had much broader implications.