Managing complexity: impact of organization and processing style on nonverbal memory in autism spectrum disorders.

The contributions of cognitive style and organization to processing and recalling a complex novel stimulus were examined by comparing the Rey Osterrieth Complex Figure (ROCF) test performance of children, adolescents, and adults with ASD to clinical controls (CC) and non-impaired controls (NC) using the Developmental Scoring System. The ROCF task involves a complex structure with strong organizational or integrative processing demands. The individuals with ASD relied on a predominantly part-oriented strategy to cope with the complexity of the task and did not make the typical developmental shift to a configurational approach. Both processing style and organization (whether pieces of information were perceived as connected to one another in a meaningful way) contributed to structural recall in the ASD group.

Disruption of neurexin 1 associated with autism spectrum disorder.

Autism is a neurodevelopmental disorder of complex etiology in which genetic factors play a major role. We have implicated the neurexin 1 (NRXN1) gene in two independent subjects who display an autism spectrum disorder (ASD) in association with a balanced chromosomal abnormality involving 2p16.3. In the first, with karyotype 46,XX,ins(16;2)(q22.1;p16.1p16.3)pat, NRXN1 is directly disrupted within intron 5. Importantly, the father possesses the same chromosomal abnormality in the absence of ASD, indicating that the interruption of alpha-NRXN1 is not fully penetrant and must interact with other factors to produce ASD. The breakpoint in the second subject, with 46,XY,t(1;2)(q31.3;p16.3)dn, occurs approximately 750 kb 5' to NRXN1 within a 2.6 Mb genomic segment that harbors no currently annotated genes. A scan of the NRXN1 coding sequence in a cohort of ASD subjects, relative to non-ASD controls, revealed that amino acid alterations in neurexin 1 are not present at high frequency in ASD. However, a number of rare sequence variants in the coding region, including two missense changes in conserved residues of the alpha-neurexin 1 leader sequence and of an epidermal growth factor (EGF)-like domain, respectively, suggest that even subtle changes in NRXN1 might contribute to susceptibility to ASD.

What is known about autism: genes, brain, and behavior.

Autism is a neurodevelopmental disorder of genetic origins, with a heritability of about 90%. Autistic disorder is classed within the broad domain of pervasive developmental disorders (PDD) that also includes Rett syndrome, childhood disintegrative disorder, Asperger syndrome, and PDD not otherwise specified (PDD-NOS). Prevalence estimates suggest a rate of 0.1-0.2% for autism and 0.6% for the range of PDD disorders. There is considerable phenotypic heterogeneity within this class of disorders as well as continued debate regarding their clinical boundaries. Autism is the prototypical PDD, and is characterized by impairments in three core domains: social interaction, language development, and patterns of behavior (restricted and stereotyped). Clinical pattern and severity of impairment vary along these dimensions, and the level of cognitive functioning of individuals with autism spans the entire range, from profound mental retardation to superior intellect. There is no single biological or clinical marker for autism, nor is it expected that a single gene is responsible for its expression; as many as 15+ genes may be involved. However, environmental influences are also important, as concordance in monozygotic twins is less than 100% and the phenotypic expression of the disorder varies widely, even within monozygotic twins. Multiple susceptibility factors are being explored using varied methodologies, including genome-wide linkage studies, and family- and case-control candidate gene association studies. This paper reviews what is currently known about the genetic and environmental risk factors, neuropathology, and psychopharmacology of autism. Discussion of genetic factors focuses on the findings from linkage and association studies, the results of which have implicated the involvement of nearly every chromosome in the human genome. However, the most consistently replicated linkage findings have been on chromosome 7q, 2q, and 15q. The positive associations from candidate gene studies are largely unreplicated, with the possible exceptions of the GABRB3 and serotonin transporter genes. No single region of the brain or pathophysiological mechanism has yet been identified as being associated with autism. Postmortem findings, animal models, and neuroimaging studies have focused on the cerebellum, frontal cortex, hippocampus, and especially the amygdala. The cerebello-thalamo-cortical circuit may also be influential in autism. There is evidence that overall brain size is increased in some individuals with autism. Presently there are no drugs that produce major improvements in the core social or pragmatic language deficits in autism, although several have limited effects on associated behavioral features. The application of new techniques in autism research is being proposed, including the investigation of abnormal regulation of gene expression, proteomics, and the use of MRI and postmortem analysis of the brain.

Concurrent validity and classification accuracy of the Leiter and Leiter-R in low-functioning children with autism.

The concurrent validity of the Leiter International Performance Scale (Leiter) and Leiter International Performance Scale-Revised (Leiter-R) was examined in a sample of children with autism who could not be assessed with more traditional measures of intelligence (e.g., the Wechsler scales). The sample consisted of 26 children ranging in age from 4 to 16 years. The correlation between the Leiter scales was high (r = .87), and there was a difference of 3.7 points between the two mean scores, nonsignificant at both statistical and clinical levels. However, significant intraindividual discrepancies were present in 10 cases, 2 of which were both large (24 and 36 points) and clinically meaningful. The mean profile of performance on Leiter-R subtests is also presented for this sample of children with autism, to allow for comparison with other groups. Based on the results of this initial evaluation, together with the current normative data, good psychometric properties, and availability of global and subtest scores with the Leiter-R, the instrument is generally recommended for use with children with autism. However, because of changes in the design of the Leiter-R, there may be greater clinical success with the original Leiter for those children who are very low functioning and severely affected, particularly younger children.

Reduced thalamic volume in high-functioning individuals with autism.

BACKGROUND: In this study, specific consideration is given to a role for the thalamus in autism. METHODS: A volumetric analysis of the thalamus was conducted using magnetic resonance imaging, based on segmentation of continuous 1.2 mm(3) coronal images. The sample consisted of 12 high-functioning individuals with autism, mean age of 21.0 years (SD = 10.4) and mean IQ of 106.4 (SD = 18.3). Normal control subjects were selected to match this group; the mean age was 18.1 years (SD = 6.3); mean IQ was 108.8 (SD = 15.6). RESULTS: Unadjusted mean thalamic volume was not significantly different; however, there were significant differences in the relationship between thalamic volume and total brain volume (TBV). The correlation was strong and positive in the control group but statistically nonsignificant in the autism group. Group differences were found when adjustments were made for TBV, achieved by grouping subjects' measurements on this variable using a split median procedure. Mean thalamic volume was significantly reduced in the autism group relative to normal control subjects, specifically within the high TBV group. CONCLUSION: The increase in thalamic volume with increase in TBV was not seen in autism, suggesting underdeveloped connections between cortical and subcortical regions and indicating a need to examine this structure further.

Outcome research in Asperger syndrome and autism.

This article presents findings from the outcome literature on autism, Asperger syndrome (AS), and related disorders. The discussion of outcome principally focuses on life adaptation, but also considers outcome in AS in relationship to other diagnostic groups and across time. The current research in this area is neither substantial nor systematic. Thus, in this examination of the literature, the goal is to highlight salient findings, but also to put forward questions that might direct meaningful research in this area for the future and to consider implications for treatment.