1. Falck-Ytter T. {{Young children with autism spectrum disorder use predictive eye movements in action observation}}. {Biol Lett}. 2009 Dec 23.
Does a dysfunction in the mirror neuron system (MNS) underlie the social symptoms defining autism spectrum disorder (ASD)? Research suggests that the MNS matches observed actions to motor plans for similar actions, and that these motor plans include directions for predictive eye movements when observing goal-directed actions. Thus, one important question is whether children with ASD use predictive eye movements in action observation. Young children with ASD as well as typically developing children and adults were shown videos in which an actor performed object-directed actions (human agent condition). Children with ASD were also shown control videos showing objects moving by themselves (self-propelled condition). Gaze was measured using a corneal reflection technique. Children with ASD and typically developing individuals used strikingly similar goal-directed eye movements when observing others’ actions in the human agent condition. Gaze was reactive in the self-propelled condition, suggesting that prediction is linked to seeing a hand-object interaction. This study does not support the view that ASD is characterized by a global dysfunction in the MNS.
2. Good P. {{Did acetaminophen provoke the autism epidemic?}}. {Altern Med Rev}. 2009 Dec;14(4):364-72.
Schultz et al (2008) raised the question whether regression into autism is triggered, not by the measles-mumps-rubella (MMR) vaccine, but by acetaminophen (Tylenol) given for its fever and pain. Considerable evidence supports this contention, most notably the exponential rise in the incidence of autism since 1980, when acetaminophen began to replace aspirin for infants and young children. The impetus for this shift – a Centers for Disease Control and Prevention warning that aspirin was associated with Reye’s syndrome – has since been compellingly debunked. If aspirin is not to be feared as a cause of Reyes syndrome, and acetaminophen is to be feared as a cause of autism, can the autism epidemic be reversed by replacing acetaminophen with aspirin or other remedies?
3. Haldeman-Englert CR, Chapman KA, Kruger H, Geiger EA, McDonald-McGinn DM, Rappaport E, Zackai EH, Spinner NB, Shaikh TH. {{A de novo 8.8-Mb deletion of 21q21.1-q21.3 in an autistic male with a complex rearrangement involving chromosomes 6, 10, and 21}}. {Am J Med Genet A}. Jan;152A(1):196-202.
We report here on a normal-appearing male with pervasive developmental disorder who was found to have a de novo, apparently balanced complex rearrangement involving chromosomes 6, 10, and 21: 46,XY,ins(21;10)(q11.2;p11.2p13)t(6;21)(p23;q11.2). Further analysis by high-density oligonucleotide microarray was performed, showing an 8.8-Mb heterozygous deletion at 21q21.1-q21.3. Interestingly, the deletion is distal to the translocation breakpoint on chromosome 21. The deletion involves 19 genes, including NCAM2 and GRIK1, both of which are associated with normal brain development and function, and have been considered as possible candidate genes in autism and other neurobehavioral disorders. This case underscores the utility of genomewide microarray analysis for the detection of copy number alterations in patients with apparently balanced complex rearrangements and abnormal phenotypes.
4. Kenworthy L, Case L, Harms MB, Martin A, Wallace GL. {{Erratum to: Adaptive Behavior Ratings Correlate With Symptomatology and IQ Among Individuals With High-Functioning Autism Spectrum Disorders}}. {J Autism Dev Disord}. 2009 Dec 22.
5. Knaus TA, Silver AM, Kennedy M, Lindgren KA, Dominick KC, Siegel J, Tager-Flusberg H. {{Language laterality in autism spectrum disorder and typical controls: A functional, volumetric, and diffusion tensor MRI study}}. {Brain Lang}. 2009 Dec 21.
Language and communication deficits are among the core features of autism spectrum disorder (ASD). Reduced or reversed asymmetry of language has been found in a number of disorders, including ASD. Studies of healthy adults have found an association between language laterality and anatomical measures but this has not been systematically investigated in ASD. The goal of this study was to examine differences in gray matter volume of perisylvian language regions, connections between language regions, and language abilities in individuals with typical left lateralized language compared to those with atypical (bilateral or right) asymmetry of language functions. Fourteen adolescent boys with ASD and 20 typically developing adolescent boys participated, including equal numbers of left- and right-handed individuals in each group. Participants with typical left lateralized language activation had smaller frontal language region volume and higher fractional anisotropy of the arcuate fasciculus compared to the group with atypical language laterality, across both ASD and control participants. The group with typical language asymmetry included the most right-handed controls and fewest left-handers with ASD. Atypical language laterality was more prevalent in the ASD than control group. These findings support an association between laterality of language function and language region anatomy. They also suggest anatomical differences may be more associated with variation in language laterality than specifically with ASD. Language laterality therefore may provide a novel way of subdividing samples, resulting in more homogenous groups for research into genetic and neurocognitive foundations of developmental disorders.
6. Kuhlthau K, Orlich F, Hall TA, Sikora D, Kovacs EA, Delahaye J, Clemons TE. {{Health-Related Quality of Life in Children with Autism Spectrum Disorders: Results from the Autism Treatment Network}}. {J Autism Dev Disord}. 2009 Dec 24.
We examined data collected as a part of the Autism Treatment Network, a group of 15 autism centers across the United States and Canada. Mean Health-Related Quality of Life (HRQoL) scores of the 286 children assessed were significantly lower than those of healthy populations (according to published norms). When compared to normative data from children with chronic conditions, children with ASD demonstrated worse HRQoL for total, psychosocial, emotional and social functioning, but did not demonstrate differing scores for physical and school functioning. HRQoL was not consistently related to ASD diagnosis or intellectual ability. However, it was consistently related to internalizing and externalizing problems as well as repetitive behaviors, social responsiveness, and adaptive behaviors. Associations among HRQoL and behavioral characteristics suggest that treatments aimed at improvements in these behaviors may improve HRQoL.
7. Monnerat LS, Moreira AD, Alves MC, Bonvicino CR, Vargas FR. {{Identification and characterization of novel sequence variations in MECP2 gene in Rett syndrome patients}}. {Brain Dev}. 2009 Dec 21.
Rett syndrome (RS) is a neurodevelopmental disorder caused by mutations in MECP2 gene. Exons 2, 3, and 4, in addition to intronic and 3’UTR adjacent regions, were sequenced in 80 patients with RS. Twenty-nine sequence variations were detected in 49 patients, 34 (69.4%) patients with the classic form of RS, and 15 (30.6%) patients with atypical forms of RS. Thirteen of the 29 detected mutations represent novel sequence variations. Missense mutation T158M was the most commonly observed mutation, detected in nine patients (11.2%). Six hotspot pathogenic mutations (R133C, T158M, R168X, R255X, R270X, and R294X) were responsible for the phenotype in 26/80 patients (32.5%).
8. Muskett T, Perkins M, Clegg J, Body R. {{Inflexibility as an interactional phenomenon: Using conversation analysis to re-examine a symptom of autism}}. {Clin Linguist Phon}. Jan;24(1):1-16.
Many accounts of autism spectrum disorder (ASD) imply that the condition’s behavioural ‘symptoms’ are direct reflexes of underlying deficits. In doing so, however, they invariably overlook the social contexts in which symptomatic behaviours occur and are identified as pathological. This study addresses this issue, using conversation analysis (CA) to examine the emergence of inflexibility, a behavioural trait symptomatic of ASD, during play involving an adult and diagnosed child. We argue that ‘inflexibility’ is the product of the child’s strategic attempts to retain control over the unfolding interaction, within a context where such attempts breach normative expectations about adult-child play. Furthermore, it demonstrates that the adult does not resist these attempts, on occasion even explicitly providing opportunity for subsequent inflexibility. This challenges the assumption that ASD’s behavioural profile solely represents the endpoint of underlying deficit, and demonstrates how ‘non-impaired’ speakers can be implicated in the manifestation of symptomatic behaviours.
9. Percy AK, Lee HS, Neul JL, Lane JB, Skinner SA, Geerts SP, Annese F, Graham J, McNair L, Motil KJ, Barrish JO, Glaze DG. {{Profiling Scoliosis in Rett Syndrome}}. {Pediatr Res}. 2009 Dec 21.
To understand scoliosis, related co-morbidities, and phenotype-genotype correlations in individuals with Rett syndrome (RTT), the Rare Disease Clinical Research Network database for RTT was probed. Clinical evaluations included a detailed history and physical examination, comprehensive anthropometric measurements, and two quantitative measures of clinical status, Clinical Severity Scale (CSS) and Motor-Behavioral Analysis (MBA). All data were exported to the Data Technology Coordinating Center (DTCC) at the University of South Florida. Scoliosis assessment was based on direct examination and curvature measurements by radiography (Cobb angle). Statistical analyses included univariate and multiple logistic regression models, adjusting for age at enrollment or mutation type. Scoliosis data were available from 554 classic RTT participants, mean age = 10 years (0-57 yr). Scoliosis was noted in 292 (53%); mean age = 15 yr with scoliosis and 6 yr without. Using multiple regression analysis, MBA severity score, later acquisition, loss, or absent walking, and constipation were associated with scoliosis. Two common methyl-CpG-binding protein 2 (MECP2) mutations, R294X and R306C, had reduced risk for scoliosis. These findings corroborated previous reports on scoliosis and extended understanding of co-morbidities, clinical severity, and relative risk reduction for specific mutations. Clinical trial design should account for scoliosis and related factors judiciously.
10. Puzzo I, Cooper NR, Vetter P, Russo R, Fitzgerald PB. {{Reduced cortico-motor facilitation in a normal sample with high traits of autism}}. {Neurosci Lett}. 2009 Dec 25;467(2):173-7.
Recent research in social neuroscience proposes a link between mirror neuron system (MNS) and social cognition. The MNS has been proposed to be the neural mechanism underlying action recognition and intention understanding and more broadly social cognition. Pre-motor MNS has been suggested to modulate the motor cortex during action observation. This modulation results in an enhanced cortico-motor excitability reflected in increased motor evoked potentials (MEPs) at the muscle of interest during action observation. Anomalous MNS activity has been reported in the autistic population whose social skills are notably impaired. It is still an open question whether traits of autism in the normal population are linked to the MNS functioning. We measured TMS-induced MEPs in normal individuals with high and low traits of autism as measured by the autistic quotient (AQ), while observing videos of hand or mouth actions, static images of a hand or mouth or a blank screen. No differences were observed between the two while they observed a blank screen. However participants with low traits of autism showed significantly greater MEP amplitudes during observation of hand/mouth actions relative to static hand/mouth stimuli. In contrast, participants with high traits of autism did not show such a MEP amplitude difference between observation of actions and static stimuli. These results are discussed with reference to MNS functioning.
11. Rissone A, Sangiorgio L, Monopoli M, Beltrame M, Zucchi I, Bussolino F, Arese M, Cotelli F. {{Characterization of the neuroligin gene family expression and evolution in zebrafish}}. {Dev Dyn}. 2009 Dec 23.
Neuroligins constitute a family of transmembrane proteins localized at the postsynaptic side of both excitatory and inhibitory synapses of the central nervous system. They are involved in synaptic function and maturation and recent studies have linked mutations in specific human Neuroligins to mental retardation and autism. We isolated the human Neuroligin homologs in Danio rerio. Next, we studied their gene structures and we reconstructed the evolution of the Neuroligin genes across vertebrate phyla. Using reverse-transcriptase polymerase chain reaction, we analyzed the expression and alternative splicing pattern of each gene during zebrafish embryonic development and in different adult organs. By in situ hybridization, we analyzed the temporal and spatial expression pattern during embryonic development and larval stages and we found that zebrafish Neuroligins are expressed throughout the nervous system. Globally, our results indicate that, during evolution, specific subfunctionalization events occurred within paralogous members of this gene family in zebrafish. Developmental Dynamics, 2010. (c) 2009 Wiley-Liss, Inc.
12. Silverman JL, Tolu SS, Barkan CL, Crawley JN. {{Repetitive Self-Grooming Behavior in the BTBR Mouse Model of Autism is Blocked by the mGluR5 Antagonist MPEP}}. {Neuropsychopharmacology}. 2009 Dec 23.
Autism is a neurodevelopmental disorder characterized by abnormal reciprocal social interactions, communication deficits, and repetitive behaviors with restricted interests. BTBR T+tf/J (BTBR) is an inbred mouse strain that shows robust behavioral phenotypes with analogies to all three of the diagnostic symptoms of autism, including well-replicated deficits in reciprocal social interactions and social approach, unusual patterns of ultrasonic vocalization, and high levels of repetitive self-grooming. These phenotypes offer straightforward behavioral assays for translational investigations of pharmacological compounds. Two suggested treatments for autism were evaluated in the BTBR mouse model. Methyl-6-phenylethynyl-pyridine (MPEP), an antagonist of the mGluR5 metabotropic glutamate receptor, blocks aberrant phenotypes in the Fmr1 mouse model of Fragile X, a comorbid neurodevelopmental disorder with autistic features. Risperidone has been approved by the United States Food and Drug Administration for the treatment of irritability, tantrums, and self-injurious behavior in autistic individuals. We evaluated the actions of MPEP and risperidone on two BTBR phenotypes, low sociability and high repetitive self-grooming. Open field activity served as an independent control for non-social exploratory activity and motor functions. C57BL/6J (B6), an inbred strain with high sociability and low self-grooming, served as the strain control. MPEP significantly reduced repetitive self-grooming in BTBR, at doses that had no sedating effects on open field activity. Risperidone reduced repetitive self-grooming in BTBR, but only at doses that induced sedation in both strains. No overall improvements in sociability were detected in BTBR after treatment with either MPEP or risperidone. Our findings suggest that antagonists of mGluR5 receptors may have selective therapeutic efficacy in treating repetitive behaviors in autism.Neuropsychopharmacology advance online publication, 23 December 2009; doi:10.1038/npp.2009.201.
13. Steinman KJ, Mostofsky SH, Denckla MB. {{Toward a narrower, more pragmatic view of developmental dyspraxia}}. {J Child Neurol}. Jan;25(1):71-81.
Apraxia traditionally refers to impaired ability to carry out skilled movements in the absence of fundamental sensorimotor, language, or general cognitive impairment sufficient to preclude them. The child neurology literature includes a much broader and varied usage of the term developmental dyspraxia. It has been used to describe a wide range of motor symptoms, including clumsiness and general coordination difficulties, in various developmental disorders (including autistic spectrum disorders, developmental language disorders, and perinatal stroke). We argue for the need to restrict use of the term developmental dyspraxia to describe impaired performance of skilled gestures, recognizing that, unlike acquired adult-onset apraxia, coexisting sensory and motor problems can also be present.
14. Verhoeven JS, De Cock P, Lagae L, Sunaert S. {{Neuroimaging of autism}}. {Neuroradiology}. Jan;52(1):3-14.
Neuroimaging studies done by means of magnetic resonance imaging (MRI) have provided important insights into the neurobiological basis for autism. The aim of this article is to review the current state of knowledge regarding brain abnormalities in autism. Results of structural MRI studies dealing with total brain volume, the volume of the cerebellum, caudate nucleus, thalamus, amygdala and the area of the corpus callosum are summarised. In the past 5 years also new MRI applications as functional MRI and diffusion tensor imaging brought considerable new insights in the pathophysiological mechanisms of autism. Dysfunctional activation in key areas of verbal and non-verbal communication, social interaction, and executive functions are revised. Finally, we also discuss white matter alterations in important communication pathways in the brain of autistic patients.
