The Autistic Place

Previous research has found that in typically developing individuals, behavioral performance declines and electrophysiological brain responses are altered when the face is inverted. Such effects are generally attributed to disruption of configural information. Individuals with autism spectrum disorder (ASD) have been found to show less pronounced inversion effects, a result in line with the view that featural processing of faces is enhanced in ASD. No study has determined if, or how, such local bias is reflected in the eye movements used in face observation. In this eye tracking study, looking time and pupil dilation were investigated during the presentation of upright and inverted faces in preschool children with ASD and typically developing preschoolers. On average, both children with ASD and typically developing children looked less at the face and the eye areas during inverted presentations than during upright presentations. Nevertheless, individuals with ASD had a stronger tendency than typically developing children to look at the same face features during upright and inverted presentations, which is suggestive of a local bias. Pupil dilation, reflecting increased processing load, was larger for inverted than upright faces in the ASD group only, and pupillary inversion effects were stronger in ASD than in typically developing children.

Autism and specific language impairment (SLI) are developmental disorders that, although distinct by definition, have in common some features of both language and social behavior. The goal of this study was to further explore the extent to which specific clinical features of autism are seen in SLI. The children with the two disorders, matched for non-verbal IQ, were compared on the Autism Diagnostic Interview - Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS). In the SLI group, 41% met autism or autism spectrum cut-offs for social or communication domains either on the ADI or ADOS or both. No relationship was found between the language deficits exhibited by the children with SLI and their scores on the ADI and ADOS. These findings contribute to evidence that there is some overlap in social and communicative deficits between autism and SLI, supporting the view that autism and SLI share etiologic factors. This continuum of pathology between SLI and autism appears to range from structural language abnormalities as seen in individuals with SLI to individuals with SLI with both structural and social abnormalities to individuals with autism with pragmatic impairment and language abnormalities.

Objectives: To assay if plasma antibody levels in children with autism or developmental delays (DD) differ from those with typical development as an indicator of immune function and to correlate antibody levels with severity of behavioral symptoms.Methods: Plasma was collected from children with autistic disorder (AU; n=116), DD but not autism (n=32), autism spectrum disorder but not full autism (n=27), and age-matched typically developing (TD) controls (n=96). Samples were assayed for systemic levels of immunoglobulin (IgG, IgM, IgA, and IgE) by enzyme-linked immunosorbent assay. Subjects with autism were evaluated using the Autism Diagnostic Observation Schedule and the Autism Diagnostic Interview - Revised, and all subjects were scored on the Aberrant Behavior Checklist (ABC) by the parents. Numerical scores for each of the ABC subscales as well as the total scores were then correlated with Ig levels.Results: Children with AU have a significantly reduced level of plasma IgG (5.39±0.29 mg/mL) compared to the TD (7.72±0.28 mg/mL; P<0.001) and DD children (8.23±0.49 mg/mL; P<0.001). Children with autism also had a reduced level of plasma IgM (0.670.06mg/mL) compared to TD (0.79±0.05 mg/mL; P<0.05). Ig levels were negatively correlated with ABC scores for all children (IgG: r=-0.334, P<0.0001; IgM: r=-0.167, P=0.0285).Conclusion: Children with AU have significantly reduced levels of plasma IgG and IgM compared to both DD and TD controls, suggesting an underlying defect in immune function. This reduction in specific Ig levels correlates with behavioral severity, where those patients with the highest scores in the behavioral battery have the most reduced levels of IgG and IgM.

Since the 1970s, the prevalence of multiple births (MBs) in the United States has increased significantly. This has been attributed, in large part, to iatrogenic MBs resulting from infertility treatments that include ovulation stimulation. A past study has indicated that children from MBs have an increased prevalence of cerebral palsy (CP). Other studies also have suggested an association between MBs and intellectual disabilities (ID) and autism spectrum disorders (ASDs); however, results have been inconsistent. From the Autism and Developmental Disabilities Monitoring (ADDM) Network, a surveillance project among several US populations, we obtained MB estimates among children born in 1994 and classified by 8 years of age as having: an ASD (n=1,626 total children from 11 sites; 50 born as part of an MB); CP (n=302 total children from 3 sites; 25 born as part of an MB); or ID (n=1,195 total children from 3 sites; 45 born as part of an MB). All three MB estimates were notably higher than age-adjusted expected estimates of naturally conceived MBs derived from 1971 US natality data. However, when MB estimates from the ADDM Network were compared with expected MB estimates derived from 1994 natality data for the states corresponding to the relevant ADDM Network sites, we observed no association with ASDs (observed/expected=1.08 [0.78-1.38]), a moderate, but not statistically significant association with ID (observed/expected=1.34 [0.95-1.73]), and a strong association with CP (observed/expected=2.96 [1.80-4.12]). Further investigation of specific types of MBs (natural vs. iatrogenic) is warranted.

Many children with autism spectrum disorders (ASD) acquire a sizeable lexicon. However, these children also seem to understand and/or store the meanings of words differently from typically developing children. One of the mechanisms that helps typically developing children learn novel words is the shape bias, in which the referent of a noun is mapped onto the shape of an object, rather than onto its color, texture, or size. We hypothesized that children with autistic disorder would show reduced or absent shape bias. Using the intermodal preferential looking paradigm , we compared the performance of young children with ASD and typically developing children (TYP), across four time points, in their use of shape bias. Neither group showed a shape bias at Visit 1, when half of the children in both groups produced fewer than 50 count nouns. Only the TYP group showed a shape bias at Visits 2, 3, and 4. According to the growth curve analyses, the rate of increase in the shape bias scores over time was significant for the TYP children. The fact that the TYP group showed a shape bias at 24 months of age, whereas children with ASD did not demonstrate a shape bias despite a sizeable vocabulary, supports a dissociation between vocabulary size and principles governing acquisition in ASD children from early in language development.

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To assess the feasibility and relevance of using lymphoblastoid cell lines to study the role of noncoding RNAs in the etiology of autism, we evaluated global expression profiling of 470 mature human microRNAs from six subjects with autism compared with six matched controls. Differential expression (either higher or lower) for 9 of the 470 microRNAs was observed in our autism samples compared with controls. Potential target genes for these microRNAs were identified using computer tools, which included several autism susceptibility genes. Our preliminary results indicate microRNAs should be considered and evaluated in the etiology of autism. In addition, analysis of this class of noncoding RNAs in lymphoblastoid cells has the potential to reveal at least a subset of brain-related microRNAs implicated in autism. Subsequently, this model system should allow for detection of complex subtle changes in susceptibility genes/pathways contributing to autism.

Adults with autism exhibit inhibitory deficits that are often manifested in behavioral modifications, such as repetitive behaviors, and/or sensory hyper-responsiveness. If such behaviors are the result of a generalized deficiency in inhibitory neurotransmission, then it stands to reason that deficits involving localized cortical-cortical interactions - such as in sensory discrimination tasks - could be detected and quantified. This study exemplifies a newly developed method for quantifying sensory testing metrics. Our novel sensory discrimination tests may provide (a) an effective means for biobehavioral assessment of deficits specific to autism and (b) an efficient and sensitive measure of change following treatment. The sensory discriminative capacity of ten subjects with autism and ten controls was compared both before and after short duration adapting stimuli. Specifically, vibrotactile amplitude discriminative capacity was obtained both in the presence and absence of 1 sec adapting stimuli that were delivered 1 sec prior to the comparison stimuli. Although adaptation had a pronounced effect on the amplitude discriminative capacity of the control subjects, little or no impact was observed on the sensory discriminative capacity of the subjects with autism. This lack of impact of the adapting stimuli on the responses of the subjects with autism was interpreted to be consistent with the reduced GABAergic-mediated inhibition described in previous reports. One significant aspect of this study is that the methods could prove to be a useful and efficient way to detect specific neural deficits and monitor the efficacy of pharmacological or behavioral treatments in autism.

In the current study we explored the hypothesis that rare variants in SLC6A4 contribute to autism susceptibility and to rigid-compulsive behaviors in autism. We made use of a large number of unrelated cases with autism spectrum disorders ([sim]350) and controls ([sim]420) and screened for rare exonic variants in SLC6A4 by a high-throughput method followed by sequencing. We observed no difference in the frequency of such variants in the two groups, irrespective of how we defined the rare variants. Furthermore, we did not observe an association of rare coding variants in SLC6A4 with rigid-compulsive traits scores in the cases. These results do not support a significant role for rare coding variants in SLC6A4 in autism spectrum disorders, nor do they support a significant role for SLC6A4 in rigid-compulsive traits in these disorders.

Fragile X syndrome (FXS) is the most commonly known genetic disorder associated with autism spectrum disorder (ASD). Overlapping features in these populations include gaze aversion, communication deficits, and social withdrawal. Although the association between FXS and ASD has been well documented at the behavioral level, the underlying neural mechanisms associated with the social/emotional deficits in these groups remain unclear. We collected functional brain images and eye-gaze fixations from 9 individuals with FXS and 14 individuals with idiopathic ASD, as well as 15 typically developing (TD) individuals, while they performed a facial-emotion discrimination task. The FXS group showed a similar yet less aberrant pattern of gaze fixations compared with the ASD group. The FXS group also showed fusiform gyrus (FG) hypoactivation compared with the TD control group. Activation in FG was strongly and positively associated with average eye fixation and negatively associated with ASD characteristics in the FXS group. The FXS group displayed significantly greater activation than both the TD control and ASD groups in the left hippocampus (HIPP), left superior temporal gyrus (STG), right insula (INS), and left postcentral gyrus (PCG). These group differences in brain activation are important as they suggest unique underlying face-processing neural circuitry in FXS versus idiopathic ASD, largely supporting the hypothesis that ASD characteristics in FXS and idiopathic ASD reflect partially divergent impairments at the neural level, at least in FXS individuals without a co-morbid diagnosis of ASD.