1. Chen FS, Yoon JM. {{Brief Report: Broader Autism Phenotype Predicts Spontaneous Reciprocity of Direct Gaze}}. {J Autism Dev Disord};2010 (Nov 16)
We report evidence for a relationship in the general population between self-reported autism-associated traits and the spontaneous reciprocation of direct gaze, a behavior that we propose may reflect a tendency to synchronize with social partners. Adults viewed videos of actors whose gaze was either directed towards or averted from them. Individuals with lower scores on four subscales of the Autism-Spectrum Quotient (AQ) scale showed a greater tendency to look at directed relative to averted eyes; individuals with higher scores on the AQ did not. This relationship was specific to autism-associated traits and to gaze towards the eyes; it did not generalize to a social anxiety measure or to gaze towards the mouth. We discuss implications for our understanding of the broader autism phenotype.
2. Coolican J, Smith IM, Bryson SE. {{Brief parent training in pivotal response treatment for preschoolers with autism}}. {J Child Psychol Psychiatry};2010 (Dec);51(12):1321-1330.
Background: Evidence of improved outcomes with early behavioural intervention has placed the early treatment of autism as a health priority. However, long waiting lists for treatment often preclude timely access, raising the question of whether parents could be trained in the interim. Parent training in pivotal response treatment (PRT) has been shown to enhance the communication skills of children with autism. This is typically provided within a 25-hour programme, although less intensive parent training may also be effective. The main objective of the present study was to evaluate the efficacy of brief training in PRT for parents of preschoolers with autism, who were awaiting, or unable to access, more comprehensive treatment. Method: Eight preschoolers with autism and their parents participated in the study. A non-concurrent multiple (across-participants) baseline design was used, in which parents were seen individually for three 2-hour training sessions on PRT. Child and parent outcomes were assessed before, immediately after, and 2 to 4 months following training using standardised tests, questionnaires and behaviour coded directly from video recordings. Results: Overall, children’s communication skills, namely functional utterances, increased following training. Parents’ fidelity in implementing PRT techniques also improved after training, and generally these changes were maintained at follow-up. A moderate to strong relationship was found between parents’ increased ability to implement PRT techniques and improvement in the children’s communication skills. Conclusion: Our findings suggest that brief parent training in PRT promises to provide an immediate, cost-effective intervention that could be adopted widely.
3. Fuentes CT, Mostofsky SH, Bastian AJ. {{Perceptual reasoning predicts handwriting impairments in adolescents with autism}}. {Neurology};2010 (Nov 16);75(20):1825-1829.
BACKGROUND: We have previously shown that children with autism spectrum disorder (ASD) have specific handwriting deficits consisting of poor form, and that these deficits are predicted by their motor abilities. It is not known whether the same handwriting impairments persist into adolescence and whether they remain linked to motor deficits. METHODS: A case-control study of handwriting samples from adolescents with and without ASD was performed using the Minnesota Handwriting Assessment. Samples were scored on an individual letter basis in 5 categories: legibility, form, alignment, size, and spacing. Subjects were also administered an intelligence test and the Physical and Neurological Examination for Subtle (Motor) Signs (PANESS). RESULTS: We found that adolescents with ASD, like children, show overall worse performance on a handwriting task than do age- and intelligence-matched controls. Also comparable to children, adolescents with ASD showed motor impairments relative to controls. However, adolescents with ASD differ from children in that Perceptual Reasoning Indices were significantly predictive of handwriting performance whereas measures of motor skills were not. CONCLUSIONS: Like children with ASD, adolescents with ASD have poor handwriting quality relative to controls. Despite still demonstrating motor impairments, in adolescents perceptual reasoning is the main predictor of handwriting performance, perhaps reflecting subjects’ varied abilities to learn strategies to compensate for their motor impairments.
4. Ghanizadeh A. {{Oxidative stress may mediate association of stereotypy and immunity in autism, a novel explanation with clinical and research implications}}. {J Neuroimmunol};2010 (Nov 12)
5. Marchetto MC, Carromeu C, Acab A, Yu D, Yeo GW, Mu Y, Chen G, Gage FH, Muotri AR. {{A model for neural development and treatment of rett syndrome using human induced pluripotent stem cells}}. {Cell};2010 (Nov 12);143(4):527-539.
Autism spectrum disorders (ASD) are complex neurodevelopmental diseases in which different combinations of genetic mutations may contribute to the phenotype. Using Rett syndrome (RTT) as an ASD genetic model, we developed a culture system using induced pluripotent stem cells (iPSCs) from RTT patients’ fibroblasts. RTT patients’ iPSCs are able to undergo X-inactivation and generate functional neurons. Neurons derived from RTT-iPSCs had fewer synapses, reduced spine density, smaller soma size, altered calcium signaling and electrophysiological defects when compared to controls. Our data uncovered early alterations in developing human RTT neurons. Finally, we used RTT neurons to test the effects of drugs in rescuing synaptic defects. Our data provide evidence of an unexplored developmental window, before disease onset, in RTT syndrome where potential therapies could be successfully employed. Our model recapitulates early stages of a human neurodevelopmental disease and represents a promising cellular tool for drug screening, diagnosis and personalized treatment.
6. Oliver C, Berg K, Moss J, Arron K, Burbidge C. {{Delineation of Behavioral Phenotypes in Genetic Syndromes: Characteristics of Autism Spectrum Disorder, Affect and Hyperactivity}}. {J Autism Dev Disord};2010 (Nov 16)
We investigated autism spectrum disorder (ASD) symptomatology, hyperactivity and affect in seven genetic syndromes; Angelman (AS; n = 104), Cri du Chat (CdCS; 58), Cornelia de Lange (CdLS; 101), Fragile X (FXS; 191), Prader-Willi (PWS; 189), Smith-Magenis (SMS; 42) and Lowe (LS; 56) syndromes (age range 4-51). ASD symptomatology was heightened in CdLS and FXS. High levels of impulsivity were seen in SMS, AS, CdCS, FXS and adults with CdLS. Negative affect was prominent in adults with CdLS, while positive affect was prominent in adults with AS and FXS. Heightened levels of overactivity and impulsivity were identified in FXS, AS and SMS while low levels were identified in PWS. These findings confirm and extend previously reported behavioral phenotypes.
7. Radua J, Via E, Catani M, Mataix-Cols D. {{Voxel-based meta-analysis of regional white-matter volume differences in autism spectrum disorder versus healthy controls}}. {Psychol Med};2010 (Nov 16):1-12.
BACKGROUND: We conducted a meta-analysis of voxel-based morphometry (VBM) studies in autism spectrum disorder (ASD) to clarify the changes in regional white-matter volume underpinning this condition, and generated an online database to facilitate replication and further analyses by other researchers.MethodPubMed, ScienceDirect, Web of Knowledge and Scopus databases were searched between 2002 (the date of the first white-matter VBM study in ASD) and 2010. Manual searches were also conducted. Authors were contacted to obtain additional data. Coordinates were extracted from clusters of significant white-matter difference between patients and controls. A new template for white matter was created for the signed differential mapping (SDM) meta-analytic method. A diffusion tensor imaging (DTI)-derived atlas was used to optimally localize the changes in white-matter volume. RESULTS: Thirteen datasets comprising 246 patients with ASD and 237 healthy controls met inclusion criteria. No between-group differences were found in global white-matter volumes. ASD patients showed increases of white-matter volume in the right arcuate fasciculus and also in the left inferior fronto-occipital and uncinate fasciculi. These findings remained unchanged in quartile and jackknife sensitivity analyses and also in subgroup analyses (pediatric versus adult samples). CONCLUSIONS: Patients with ASD display increases of white-matter volume in tracts known to be important for language and social cognition. Whether the results apply to individuals with lower IQ or younger age and whether there are meaningful neurobiological differences between the subtypes of ASD remain to be investigated.
8. Shukla DK, Keehn B, Muller RA. {{Tract-specific analyses of diffusion tensor imaging show widespread white matter compromise in autism spectrum disorder}}. {J Child Psychol Psychiatry};2010 (Nov 12)
Background: Previous diffusion tensor imaging (DTI) studies have shown white matter compromise in children and adults with autism spectrum disorder (ASD), which may relate to reduced connectivity and impaired function of distributed networks. However, tract-specific evidence remains limited in ASD. We applied tract-based spatial statistics (TBSS) for an unbiased whole-brain quantitative estimation of the fractional anisotropy (FA), mean diffusion (MD) and axial and radial diffusion of the white matter tracts in children and adolescents with ASD. Methods: DTI was performed in 26 ASD and 24 typically developing (TD) participants, aged 9-20 years. Groups were matched for age and IQ. Each participant’s aligned FA, MD and axial and radial diffusion data were projected onto the mean FA skeleton representing the centers of all tracts and the resulting data fed into voxelwise group statistics. Results: TBSS revealed decreased FA and increased MD and radial diffusion in the ASD group compared to the TD group in the corpus callosum, anterior and posterior limbs of the internal capsule, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, superior longitudinal fasciculus, cingulum, anterior thalamic radiation, and corticospinal tract. No single site with inverse effects (increased FA, reduced MD or radial diffusion in the ASD group) was detected. In clusters of significant group difference, age was positively correlated with FA and negatively correlated with MD and radial diffusion in the TD, but not the ASD group. Conclusions: Our findings reveal white matter compromise affecting numerous tracts in children and adolescents with ASD. Slightly varying patterns of diffusion abnormalities detected for some tracts may suggest tract-specific patterns of white matter abnormalities associated with ASD. Age-dependent effects further show that maturational changes (increasing FA, decreasing MD and radial diffusion with age) are diminished in ASD from school-age childhood into young adulthood.
9. Walsh RM, Hochedlinger K. {{Modeling rett syndrome with stem cells}}. {Cell};2010 (Nov 12);143(4):499-500.
The discovery that somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) raised the exciting possibility of modeling diseases with patient-specific cells. Marchetto et al. (2010) now use iPSC technology to generate, characterize, and treat an in vitro model for the autism spectrum disorder Rett syndrome.
