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The hypothetical 'AXAS' gene network model that profiles functional patterns of heterogeneous DNA variants overrepresented in autism spectrum disorder (ASD), X-linked intellectual disability, attention deficit and hyperactivity disorder and schizophrenia was used in this current study to analyze whole exome sequencing data from an Australian ASD cohort. An optimized DNA variant filtering pipeline was used to identify loss-of-function DNA variations. Inherited variants from parents with a broader autism phenotype and de novo variants were found to be significantly associated with ASD. Gene ontology analysis revealed that putative rare causal variants cluster in key neurobiological processes and are overrepresented in functions involving neuronal development, signal transduction and synapse development including the neurexin trans-synaptic complex. We also show how a complex gene network model can be used to fine map combinations of inherited and de novo variations in families with ASD that converge in the L1CAM pathway. Our results provide an important step forward in the molecular characterization of ASD with potential for developing a tool to analyze the pathogenesis of individual affected families.

This study investigated the involvement of inner speech limitations in the executive dysfunction associated with autism spectrum disorders (ASDs). Seventeen children with ASD and 18 controls, statistically-matched in age and IQ, performed a computer-based card sorting test (CST) to assess cognitive flexibility under four conditions: baseline, with articulatory suppression, with a concurrent mouthing task, and while verbalizing their strategies aloud. Articulatory suppression adversely affected CST performance for the control group but not the ASD group. The results additionally showed that overtly verbalizing strategies did not benefit the ASD children as it did the typically developing children. The findings thus provide further evidence that ASD children do not use inner speech to the same extent, or with the same effectiveness, as typically developing children when performing executive tasks.

Findings that a subgroup of children with an autism spectrum disorder (ASD) have linguistic capabilities that resemble specific language impairment (SLI) have led some authors to hypothesise that ASD and SLI have a shared aetiology. While considerable research has explored overlap in the language phenotypes of the two conditions, little research has examined possible overlap in cognitive characteristics. In this study, we explored nonword and sentence repetition performance, as well as performance on the Children's Embedded Figures Test (CEFT) for children with ASD or SLI. As expected, 'language impaired' children with ASD (ALI) and children with SLI performed worse than both 'language normal' ASD (ALN) and typically developing (TD) children on the nonword and sentence repetition tests. Further, the SLI children performed worse than all other groups on the CEFT. This finding supports distinct cognitive profiles in ASD and SLI and may provide further evidence for distinct aetiological mechanisms in the two conditions.

Extensive empirical evidence indicates that the lesser variant of Autism Spectrum Disorders (ASD) involves a communication impairment that is similar to, but milder than, the deficit in clinical ASD. This research explored the relationship between the broader autism phenotype (BAP) among parents, an index of genetic liability for ASD, and proband communication difficulties. ASD probands with at least one BAP parent (identified using the Autism Spectrum Quotient) had greater structural and pragmatic language difficulties (assessed using the Children's Communication Checklist-2) than ASD probands with no BAP parent. This finding provides support for the position that genetic liability for ASD is associated with increased communication difficulties across structural and pragmatic domains.

Complementary and alternative medicine is widely used for children with autism spectrum disorder, despite uncertainty regarding efficacy. This review describes complementary and alternative practices commonly used among this population, the rationale for the use of each practice, as well as the side-effect profile and evidence for efficacy. The existing evidence base indicates that melatonin can be recommended as a treatment for sleeping disturbances associated with autism spectrum disorder, while secretin can be rejected as an efficacious treatment for broader autistic symptoms. There is insufficient evidence to draw conclusions on the efficacy of modified diets, hyperbaric oxygen therapy, immune therapy, and vitamin and fatty acid supplementation. There is a clear need for methodologically rigorous studies to provide evidence-based guidance to families and clinicians regarding complementary and alternative practices for individuals with autism spectrum disorders., (© 2013 The Author. Journal of Paediatrics and Child Health © 2013 Paediatrics and Child Health Division (Royal Australasian College of Physicians).)

We tested whether maternal vitamin D insufficiency during pregnancy is related to the autism phenotype. Serum 25(OH)-vitamin D concentrations of 929 women were measured at 18 weeks' pregnancy. The mothers of the three children with a clinical diagnosis of autism spectrum disorder had 25(OH)-vitamin D concentrations above the population mean. The offspring of 406 women completed the Autism-Spectrum Quotient in early adulthood. Maternal 25(OH)-vitamin D concentrations were unrelated to offspring scores on the majority of scales. However, offspring of mothers with low 25(OH)-vitamin D concentrations (<49 nmol/L) were at increased risk for 'high' scores (≥2SD above mean) on the Attention Switching subscale (odds ratio: 5.46, 95% confidence interval: 1.29, 23.05). The involvement of maternal vitamin D during pregnancy in autism requires continued investigation.

An existing randomised controlled trial was used to investigate whether multiple ultrasound scans may be associated with the autism phenotype. From 2,834 single pregnancies, 1,415 were selected at random to receive ultrasound imaging and continuous wave Doppler flow studies at five points throughout pregnancy (Intensive) and 1,419 to receive a single imaging scan at 18 weeks (Regular), with further scans only as indicated on clinical grounds. There was no significant difference in the rate of Autism Spectrum Disorder between the Regular (9/1,125, 0.8 %) and Intensive (7/1,167, 0.6 %) groups, nor a difference between groups in the level of autistic-like traits in early adulthood. There is no clear link between the frequency and timing of prenatal ultrasound scans and the autism phenotype.

Fetal head circumference (HC) growth was examined prospectively in children with autism spectrum disorder (ASD). ASD participants (N = 14) were each matched with four control participants (N = 56) on a range of parameters known to influence fetal growth. HC was measured using ultrasonography at approximately 18 weeks gestation and again at birth using a paper tape-measure. Overall body size was indexed by fetal femur-length and birth length. There was no between-groups difference in head circumference at either time-point. While a small number of children with ASD had disproportionately large head circumference relative to body size at both time-points, the between-groups difference did not reach statistical significance in this small sample. These preliminary findings suggest that further investigation of fetal growth in ASD is warranted.

Background: Developmental language disorder is a heterogeneous diagnostic category. Little research has compared the long-term outcomes of children with different subtypes of language impairment., Aims: To determine whether the pattern of language impairment in childhood related to language and literacy outcomes in adulthood., Methods & Procedures: Adults who took part in previous studies as children were traced. There were four groups of participants, each with a different childhood diagnosis: specific language impairment (SLI; n = 19, mean age at follow-up = 24;8), pragmatic language impairment (PLI; n = 7, mean age at follow-up = 22;3), autism spectrum disorder (ASD; n = 11; mean age at follow-up = 21;9), and no childhood diagnosis (typical; n = 12; mean age at follow-up = 21;6). Participants were administered a battery of language and literacy tests., Outcomes & Results: Adults with a history of SLI had persisting language impairment as well as considerable literacy difficulties. Pragmatic deficits also appeared to develop over time in these individuals. The PLI group had enduring difficulties with language use, but presented with relatively intact language and literacy skills. Although there were some similarities in the language profile of the PLI and ASD groups, the ASD group was found to have more severe pragmatic deficits and parent-reported linguistic difficulties in conversational speech., Conclusions & Implications: The pattern of deficits observed in different subtypes of developmental language disorder persists into adulthood. The findings highlight the importance of a wide-ranging clinical assessment in childhood, which may provide an indication of outcome in adulthood.

Background: The few studies that have tracked children with developmental language disorder to adulthood have found that these individuals experience considerable difficulties with psychosocial adjustment (for example, academic, vocational and social aptitude). Evidence that some children also develop autistic symptomatology over time has raised suggestions that developmental language disorder may be a high-functioning form of an autism spectrum disorder (ASD). It is not yet clear whether these outcomes vary between individuals with different subtypes of language impairment., Aims: To compare the adult psychosocial outcomes of children with specific language impairment (SLI), pragmatic language impairment (PLI) and ASD., Methods & Procedures: All participants took part in research as children. In total, there were 19 young adults with a childhood history of Specific Language Impairment (M age = 24;8), seven with PLI (M age = 22;3), 11 with high functioning ASD (M age = 21;9) and 12 adults with no history of developmental disorder (Typical; n = 12; M age = 21;6). At follow-up, participants and their parents were interviewed to elicit information about psychosocial outcomes., Outcomes & Results: Participants in the SLI group were most likely to pursue vocational training and work in jobs not requiring a high level of language/literacy ability. The PLI group tended to obtain higher levels of education and work in 'skilled' professions. The ASD participants had lower levels of independence and more difficulty obtaining employment than the PLI and SLI participants. All groups had problems establishing social relationships, but these difficulties were most prominent in the PLI and ASD groups. A small number of participants in each group were found to experience affective disturbances. The PLI and SLI groups showed lower levels of autistic symptomatology than the ASD group., Conclusions & Implications: The between-group differences in autistic symptomatology provide further evidence that SLI, PLI, and ASD are related disorders that vary along qualitative dimensions of language structure, language use and circumscribed interests. Childhood diagnosis showed some relation to adult psychosocial outcome. However, within-group variation highlights the importance of evaluating children on a case-by-case basis.