1. Assaf M, Jagannathan K, Calhoun VD, Miller L, Stevens MC, Sahl R, O’Boyle JG, Schultz RT, Pearlson GD. {{Abnormal functional connectivity of default mode sub-networks in autism spectrum disorder patients}}. {Neuroimage} (Jun 2)
Autism spectrum disorders (ASDs) are characterized by deficits in social and communication processes. Recent data suggest that altered functional connectivity (FC), i.e. synchronous brain activity, might contribute to these deficits. Of specific interest is the FC integrity of the default mode network (DMN), a network active during passive resting states and cognitive processes related to social deficits seen in ASD, e.g. Theory of Mind. We investigated the role of altered FC of default mode sub-networks (DM-SNs) in 16 patients with high-functioning ASD compared to 16 matched healthy controls of short resting fMRI scans using independent component analysis (ICA). ICA is a multivariate data-driven approach that identifies temporally coherent networks, providing a natural measure of FC. Results show that compared to controls, patients showed decreased FC between the precuneus and medial prefrontal cortex/anterior cingulate cortex, DMN core areas, and other DM-SNs areas. FC magnitude in these regions inversely correlated with the severity of patients’ social and communication deficits as measured by the Autism Diagnostic Observational Schedule and the Social Responsiveness Scale. Importantly, supplemental analyses suggest that these results were independent of treatment status. These results support the hypothesis that DM-SNs under-connectivity contributes to the core deficits seen in ASD. Moreover, these data provide further support for the use of data-driven analysis with resting-state data for illuminating neural systems that differ between groups. This approach seems especially well suited for populations where compliance with and performance of active tasks might be a challenge, as it requires minimal cooperation.
2. Bloemen OJ, Deeley Q, Sundram F, Daly EM, Barker GJ, Jones DK, van Amelsvoort TA, Schmitz N, Robertson D, Murphy KC, Murphy DG. {{White matter integrity in Asperger syndrome: a preliminary diffusion tensor magnetic resonance imaging study in adults}}. {Autism Res} (Jul 12)
Background: Autistic Spectrum Disorder (ASD), including Asperger syndrome and autism, is a highly genetic neurodevelopmental disorder. There is a consensus that ASD has a biological basis, and it has been proposed that it is a « connectivity » disorder. Diffusion Tensor Magnetic Resonance Imaging (DT-MRI) allows measurement of the microstructural integrity of white matter (a proxy measure of « connectivity »). However, nobody has investigated the microstructural integrity of whole brain white matter in people with Asperger syndrome. Methods: We measured the fractional anisotropy (FA), mean diffusivity (MD) and radial diffusivity (RD) of white matter, using DT-MRI, in 13 adults with Asperger syndrome and 13 controls. The groups did not differ significantly in overall intelligence and age. FA, MD and RD were assessed using whole brain voxel-based techniques. Results: Adults with Asperger syndrome had a significantly lower FA than controls in 13 clusters. These were largely bilateral and included white matter in the internal capsule, frontal, temporal, parietal and occipital lobes, cingulum and corpus callosum. Conclusions: Adults with Asperger syndrome have widespread significant differences from controls in white matter microstructural integrity.
3. Briegel W, Schimek M, Kamp-Becker I. {{Moebius sequence and autism spectrum disorders-Less frequently associated than formerly thought}}. {Res Dev Disabil} (Jul 9)
Moebius sequence is a rare congenital disorder usually defined as a combination of facial weakness with impairment of ocular abduction. It is questionable, whether there is a strong association of the sequence with autism spectrum disorders (ASDs) as suggested in some earlier case reports and studies. Twenty-two participants with Mobius sequence aged 6-16 years followed a request of the German Moebius foundation to participate in a nationwide study. All patients had a physical examination and intelligence testing. Primary caregivers were asked to complete two screening measures of ASD (Behaviour and Communication Questionnaire, VSK; Marburger Asperger’s Syndrome Rating Scale, MBAS). For those who reached the cut-off for ASD and/or showed behavioural aspects indicative of ASDs during IQ testing and/or physical examination, well standardized diagnostic instruments (Autism Diagnostic Interview-Revised, Autism Diagnostic Observation Schedule, and Kinder-DIPS) were administered. Minimal diagnostic criteria for Mobius sequence were congenital facial weakness (uni- or bilateral) and impairment of ocular abduction (uni- or bilateral). Three boys (one of them mentally retarded) out of 22 participants (12 males and 10 females) were found suspicious of ASD by screening, but none of them fulfilled diagnostic criteria of ASD on a clinical consensus conference. Therefore, ASDs seem to be not as frequent as reported in previous studies on patients with Mobius sequence.
4. Chamak B. {{[Autism: overestimation of the genetic origins.]}}. {Med Sci (Paris)} (Jul-Aug);26(6-7):659-662.
Since the 1990s the genetic causes of autism have been brought to the fore. Despite scientific efforts and huge fundings, less than 20% of cases of autism have been linked to genetic abnormalities. These results do not slow the spread of discourse on the genetic origin of autism, and the concomitant neglect of risks linked to perinatal factors. A detailed analysis of results and assertions in favour of a strong genetic origin of autism reveals methodological biases, misinterpretations and erroneous approximations, as well as an exaggerated media coverage. Studies on twins are illustrative of these biases. The recent demonstration of an excess of twins among sibling pairs with autism, and especially a 10-fold increase for monozygotic twins compared with the general population frequencies, has questioned the relevance of conclusions from earlier twin studies. Indeed, if being a twin is a risk factor for autism, then there may be an upwards bias in estimates of the genetic contribution to autism, and the intrauterine environment, including competition for nutrients, has been neglected.
5. Eagleson KL, Gravielle MC, Schlueter McFadyen-Ketchum LJ, Russek SJ, Farb DH, Levitt P. {{Genetic disruption of the autism spectrum disorder risk gene PLAUR induces GABAA receptor subunit changes}}. {Neuroscience} (Jul 14);168(3):797-810.
Disruption of the GABAergic system has been implicated in multiple developmental disorders, including epilepsy, autism spectrum disorder and schizophrenia. The human gene encoding uPAR (PLAUR) has been shown recently to be associated with the risk of autism. The uPAR(-/-) mouse exhibits a regionally-selective reduction in GABAergic interneurons in frontal and parietal regions of the cerebral cortex as well as in the CA1 and dentate gyrus subfields of the hippocampus. Behaviorally, these mice exhibit increased sensitivity to pharmacologically-induced seizures, heightened anxiety, and atypical social behavior. Here, we explore potential alterations in GABAergic circuitry that may occur in the context of altered interneuron development. Analysis of gene expression for 13 GABA(A) receptor subunits using quantitative real-time polymerase chain reaction (PCR) indicates seven subunit mRNAs (alpha(1), alpha(2), alpha(3), beta(2), beta(3), gamma(2S) and gamma(2L)) of interest. Semi-quantitative in situ hybridization analysis focusing on these subunit mRNAs reveals a complex pattern of potential gene regulatory adaptations. The levels of alpha(2) subunit mRNAs increase in frontal cortex, CA1 and CA3, while those of alpha3 decrease in frontal cortex and CA1. In contrast, alpha(1) subunit mRNAs are unaltered in any region examined. beta(2) subunit mRNAs are increased in frontal cortex whereas beta(3) subunit mRNAs are decreased in parietal cortex. Finally, gamma(2S) subunit mRNAs are increased in parietal cortex while gamma(2L) subunit mRNAs are increased in the dentate gyrus, potentially altering the gamma(2S):gamma(2L) ratio in these two regions. For all subunits, no changes were observed in forebrain regions where GABAergic interneuron numbers are normal. We propose that disrupted differentiation of GABAergic neurons specifically in frontal and parietal cortices leads to regionally-selective alterations in local circuitry and subsequent adaptive changes in receptor subunit composition. Future electrophysiological studies will be useful in determining how alterations in network activity in the cortex and hippocampus relate to the observed behavioral phenotype.
6. Endo T, Kitamura H, Tamura R, Egawa J, Sugai T, Fukui N, Suzuki Y, Someya T. {{5-HTTLPR polymorphism influences prefrontal neurochemical metabolites in autism spectrum disorder}}. {Psychiatry Res} (Jul 7)
We investigated whether the promoter region of the serotonin transporter gene (5-HTTLPR) polymorphism influenced neurochemical metabolism in 26 individuals with autism spectrum disorder. Individuals with the S/S genotype of the 5-HTTLPR polymorphism showed significantly lower levels of N-acetylaspartate/creatine in the right medial prefrontal cortex compared with those with the S/L genotype.
7. Faras H, Al Ateeqi N, Tidmarsh L. {{Autism spectrum disorders}}. {Ann Saudi Med} (Jul-Aug);30(4):295-300.
Pervasive developmental disorders are a group of neurodevelopmental disorders characterized by impairments in communication, reciprocal social interaction and restricted repetitive behaviors or interests. The term autism spectrum disorders (ASD) has been used to describe their variable presentation. Although the cause of these disorders is not yet known, studies strongly suggest a genetic basis with a complex mode of inheritance. More research is needed to explore environmental factors that could be contributing to the cause of these disorders. The occurrence of ASD has been increasing worldwide, with the most recent prevalence studies indicating that they are present in 6 per 1000 children. The objectives of this article are to provide physicians with relevant information needed to identify and refer children presenting with symptoms suggestive of ASDs to specialized centers early, and to make them feel comfortable in dealing with public concerns regarding controversial issues about the etiology and management of these disorders.
8. Gambino F, Khelfaoui M, Poulain B, Bienvenu T, Chelly J, Humeau Y. {{Synaptic maturation at cortical projections to the lateral amygdala in a mouse model of rett syndrome}}. {PLoS One};5(7):e11399.
Rett syndrome (RTT) is a neuro-developmental disorder caused by loss of function of Mecp2 – methyl-CpG-binding protein 2 – an epigenetic factor controlling DNA transcription. In mice, removal of Mecp2 in the forebrain recapitulates most of behavioral deficits found in global Mecp2 deficient mice, including amygdala-related hyper-anxiety and lack of social interaction, pointing a role of Mecp2 in emotional learning. Yet very little is known about the establishment and maintenance of synaptic function in the adult amygdala and the role of Mecp2 in these processes. Here, we performed a longitudinal examination of synaptic properties at excitatory projections to principal cells of the lateral nucleus of the amygdala (LA) in Mecp2 mutant mice and their wild-type littermates. We first show that during animal life, Cortico-LA projections switch from a tonic to a phasic mode, whereas Thalamo-LA synapses are phasic at all ages. In parallel, we observed a specific elimination of Cortico-LA synapses and a decrease in their ability of generating presynaptic long term potentiation. In absence of Mecp2, both synaptic maturation and synaptic elimination were exaggerated albeit still specific to cortical projections. Surprisingly, associative LTP was unaffected at Mecp2 deficient synapses suggesting that synaptic maintenance rather than activity-dependent synaptic learning may be causal in RTT physiopathology. Finally, because the timing of synaptic evolution was preserved, we propose that some of the developmental effects of Mecp2 may be exerted within an endogenous program and restricted to synapses which maturate during animal life.
9. He Q, Duan Y, Karsch K, Miles J. {{Detecting corpus callosum abnormalities in autism based on anatomical landmarks}}. {Psychiatry Res} (Jul 8)
Autism is a severe developmental disorder whose neurological basis is largely unknown. The aim of this study was to identify the shape differences of the corpus callosum between patients with autism and control subjects. Anatomical landmarks were collected from midsagittal magnetic resonance images of 25 patients and 18 controls. Euclidean distance matrix analysis and thin-plate spline analyses were used to examine the landmark forms. Point-by-point shape comparison was performed both globally and locally. A new local shape comparison scheme was proposed which compared each part of the shape in its local coordinate system. Point correspondence was established among individual shapes based on the inherent landmark correspondence. No significant difference was found in the landmark form between patients and controls, but the distance between the interior genu and the posterior-most section was found to be significantly shorter in patients. Thin-plate spline analysis showed significant group differences between the landmark configurations in terms of the deformation from the overall mean configuration. Significant global shape differences were found in the anterior lower body and posterior bottom, and there was a local shape difference in the anterior bottom. This study can serve as both a clinical reference and a detailed procedural guideline for similar studies in the future.
10. Jarocka-Cyrta E, Wasilewska J, Kaczmarski MG. {{Brief Report: Eosinophilic Esophagitis as a Cause of Feeding Problems in Autistic Boy. The First Reported Case}}. {J Autism Dev Disord} (Jul 13)
Unrecognized gastrointestinal disorders may contribute to the behavioral problems in non-verbal patients, but they are often overlooked since the clinical symptoms are nonspecific. Eosinophilic esophagitis (EE) is a chronic inflammatory disorder manifesting itself predominantly in reflux-type symptoms that do not respond to standard anti-reflux pharmacotherapy. Here we report the first case of EE in an autistic patient with feeding difficulties caused by exacerbated EE symptoms.
11. Kostyuk N, Rajnarayanan RV, Isokpehi RD, Cohly HH. {{Autism from a biometric perspective}}. {Int J Environ Res Public Health} (May);7(5):1984-1995.
PURPOSE: The aim of this pilot study was to test autistic children, siblings and their parents using a biometric device based on the gas discharge visualization (GDV) technique in order to assess their psycho-emotional and physiological functional state based on the activity of the autonomic nervous system. HYPOTHESIS: WE HYPOTHESIZE THAT THE BIOMETRIC ASSESSMENT BASED ON GDV WILL ENABLE US: (1) to evaluate some specific features associated with autism spectrum disorder (ASD) as well as to compare autistic children to their siblings and to controls; (2) to analyze the differences in individual values of parents of autistic children versus parents of normal children. RESULTS: Out of total of 48 acupuncture points present on ten fingertips of both hands and associated to organs/organ systems, autistic children differed significantly from controls (p < 0.05) in 36 (images without filter) and 12 (images with filter), siblings differed significantly from controls (p < 0.05) in 12 (images without filter) and seven (images with filter), autistic children differed significantly (p < 0.05) from siblings in eight (images without filter) and one (images with filter), fathers of autistic children differed significantly (p < 0.05) from controls in 14 (images without filter) and three (images with filter) and mothers of autistic children differed significantly (p < 0.05) from controls in five (images without filter) and nine (images with filter) acupuncture points. CONCLUSIONS: All compared groups have shown significant difference on both psycho-emotional (images without filter) and physiological (images with filter) levels. However, the differences between autistic children and controls expressed on psycho-emotional level were the most significant as compared to the other groups. Therefore, the activity of the sympathetic autonomic nervous system is significantly altered in children with autism. The biometric method based on GDV is a promising step in autism research that may lead towards creating a disease profile and identify unique signature/biomarker for autism. Further work should involve more participants in order to augment our findings.
12. Lakshmi Priya MD, Geetha A. {{Level of Trace Elements (Copper, Zinc, Magnesium and Selenium) and Toxic Elements (Lead and Mercury) in the Hair and Nail of Children with Autism}}. {Biol Trace Elem Res} (Jul 13)
Autism is a multi-factorial pathology observed in children with altered levels of essential and elevated levels of toxic elements. There are also studies reporting a decrease in nutritional trace elements in the hair and nail of autistic children with healthy controls; moreover, bioelements have been shown to play an important role in the central nervous system. Therefore, the purpose of the present study was to assess the levels of trace elements like copper (Cu), zinc (Zn), magnesium (Mg), and selenium (Se) and toxic elements like mercury (Hg), and lead (Pb) in the hair and nail samples of autistic children and to evaluate whether the level of these elements could be correlated with the severity of autism. The subjects of the study were 45 autistic children with different grades of severity (low (LFA), medium (MFA), and high (HFA) functioning autism) according to Childhood Autism Rating Scale, n = 15 children in each group and 50 healthy children (age and sex matched). The boys and girls ratio involved in this study was 4:1, and they were 4-12 years of age. The study observed a valid indication of Cu body burden in the autistic children. The children with different grades of autism showed high significance (p < 0.001) in the level of copper in their hair and nail samples when compared to healthy controls. The level of Cu in the autistic children could be correlated with their degree of severity (more the Cu burden severe is autism). The study showed a significant elevation (p < 0.001) in the levels of toxic metals Pb and Hg in both hair and nail samples of autistic children when compared to healthy control group. The elevation was much pronounced in LFA group subjects when compared among autistic groups MFA and HFA. The levels of trace elements Mg and Se were significantly decreased (p < 0.001) in autistic children when compared to control. The trace element Zn showed significant variation in both hair and nails of LFA group children when compared to control group and other study groups. The significant elevation in the concentration of Cu, Pb, and Hg and significant decrease in the concentration of Mg and Se observed in the hair and nail samples of autistic subjects could be well correlated with their degrees of severity.
13. Manning MM, Wainwright L, Bennett J. {{The Double ABCX Model of Adaptation in Racially Diverse Families with a School-Age Child with Autism}}. {J Autism Dev Disord} (Jul 10)
In this study, the Double ABCX model of family adaptation was used to explore the impact of severity of autism symptoms, behavior problems, social support, religious coping, and reframing, on outcomes related to family functioning and parental distress. The sample included self-report measures collected from 195 families raising school-age children with autism from racially diverse backgrounds throughout the United States. Hierarchical regression results revealed that the Double ABCX model of family adaptation accounted for a substantial amount of the variance in family functioning (28%) and parental distress (46%). Findings suggest that child behavior problems and reframing are most strongly associated with family outcomes. Clinical implications for working with these families, including the use of strength-based approaches, are discussed.
14. Miller AR. {{Lifetime care for patients with autism}}. {Cmaj} (Jul 13);182(10):1079-1080.
15. Popescu AC, Sidorova E, Zhang G, Eubanks JH. {{Aminoglycoside-mediated partial suppression of MECP2 nonsense mutations responsible for Rett syndrome in vitro}}. {J Neurosci Res} (Aug 15);88(11):2316-2324.
Rett syndrome is a pediatric neurological condition that affects primarily girls. Approximately 30% of Rett syndrome cases arise from point mutations that introduce a premature stop codon into the MECP2 gene. Several studies have now shown that certain aminoglycosides can facilitate read-through of some types of nonsense mutations in a context-dependent manner and allow the generation of a full-length protein. It remains mostly unclear whether different nonsense mutations of MECP2 will be responsive to aminoglycoside treatment. In this study, we tested whether the common premature terminating mutations of MECP2 seen in Rett syndrome cases can be partially suppressed by aminoglycoside administration. Our results show that aminoglycosides allow different mutant forms of MECP2 to be overcome in transiently transfected HEK293 cells, but with differing levels of efficiency. In addition, we also show that aminoglycosides increased the prevalence of full-length MeCP2 protein in a dose-dependent manner in a lymphocyte cell line derived from a Rett syndrome girl with the R255X mutation. This study helps to establish the « proof of principle » that some nonsense mutations causing Rett syndrome can be at least partially suppressed by drug treatment. (c) 2010 Wiley-Liss, Inc.
16. Sauvage D. {{[Autism, information, deontology.]}}. {Encephale} (Jun);36(3):187-188.
17. Scarpinato N, Bradley J, Kurbjun K, Bateman X, Holtzer B, Ely B. {{Caring for the child with an autism spectrum disorder in the acute care setting}}. {J Spec Pediatr Nurs} (Jul);15(3):244-254.
PURPOSE: This article explores the challenges that patients with autistic spectrum disorders (ASDs) face when hospitalized and provides assessment strategies and plan-of-care suggestions for nursing caregivers. CONCLUSIONS: With a high prevalence rate of medical comorbidities among this population, such as gastrointestinal complaints and seizures, nurses are likely to care for hospitalized patients with an ASD. PRACTICE IMPLICATIONS: For a child with an ASD, hospitalization can be an overwhelming sensory and cognitive experience. Nurses equipped with an understanding of the unique needs of a child with ASD can tailor the plan of care to reduce patient and family anxiety, optimize treatment goals, and reduce the stress of hospitalization.
18. Soulieres I, Mottron L, Giguere G, Larochelle S. {{Category induction in autism: Slower, perhaps different, but certainly possible}}. {Q J Exp Psychol (Colchester)} (Jul 8):1-17.
Available studies on categorization in autism indicate possibly intact category formation, performed through atypical processes. Category learning was investigated in 16 high-functioning autistic and 16 IQ-matched nonautistic participants, using a category structure that could generate a conflict between the application of a rule and exemplar memory. Same-different and matching-to-sample tasks allowed us to verify discrimination abilities for the stimuli to be used in category learning. Participants were then trained to distinguish between two categories of imaginary animals, using categorization tests early in the training and at the end (160 trials). A recognition test followed, in order to evaluate explicit exemplar memory. Similar discrimination performance was found in control tasks for both groups. For the categorization task, autistic participants did not use any identifiable strategy early in the training, but used strategies similar to those of the nonautistic participants by the end, with the same level of accuracy. Memory for the exemplars was poor in both groups. Our findings confirm that categorization may be successfully performed by autistics, but may necessitate longer exposure to material, as the top-down use of rules may be only secondary to a guessing strategy in autistics.
19. Valentine K. {{A consideration of medicalisation: Choice, engagement and other responsibilities of parents of children with autism spectrum disorder}}. {Soc Sci Med} (Jun 23)
Classic studies of medicalisation point to the ‘rise of the experts’ as disempowering patients and refusing to acknowledge their expertise in their own lives. More recently, medicalisation scholarship has taken a different turn, arguing that patient choice is both a responsibility imposed on patients, and a driver of medicalisation. To what extent does autism, a childhood developmental disorder in which parents are invited to take a close role, instantiate these different manifestations of medicalisation? This paper reports on a qualitative study of parents’ experience of diagnosis and treatment, conducted in four states in Australia in 2008-2009. It draws on 49 interviews with parents of young children with autism, and with early intervention service providers and clinicians. Our study shows that the importance of choice in decisions around treatment cannot be subsumed under the single category of disenfranchisement or engagement. The diverse responses of parents to the diffuse, complex field of autism treatment illustrate an admixture of consumption, advocacy and education driving contemporary medicalisation.
20. van de Lagemaat LN, Grant SG. {{Genome Variation and Complexity in the Autism Spectrum}}. {Neuron} (Jul 15);67(1):8-10.
A large international consortium reports in Nature on the diversity of genomic changes in families with autism spectrum disorders. Inherited and de novo mutations affecting many genes were discovered implicating disruption to postsynaptic and cellular signaling processes.
