1. Bosl W, Tierney A, Tager-Flusberg H, Nelson C. {{Response: Infant EEG activity as a biomarker for autism: A promising approach or a false promise?}}. {BMC Med};2011 (May 20);9(1):60.
ABSTRACT: Correspondence – no abstract Please see research article: http://www.biomedcentral.com/1741-7015/9/18 and commentary article: http://www.biomedcentral.com/1741-7015/9/61.
2. Campos MJ, Pestana CP, Dos Santos AV, Ponchel F, Churchman S, Abdalla-Carvalho CB, Dos Santos JM, Dos Santos FL, Gikovate CG, Santos-Reboucas CB, Pimentel MM. {{A MECP2 missense mutation within the MBD domain in a Brazilian male with autistic disorder}}. {Brain Dev};2011 (May 18)
Point mutations and genomic rearrangements in the MECP2 gene are the major cause of Rett syndrome (RTT), a pervasive developmental disorder affecting almost exclusively females. MECP2 mutations were also identified in patients with autism without RTT. In this study, we present a mutational and gene dosage analysis of the MECP2 in a cohort of 60 Brazilian males with autistic features but not RTT. No duplication or deletion was identified. Sequencing analysis, however, revealed four MECP2 sequence variations. Three of them were previously discussed as non disease causing mutations and one mutation (p.T160S) was novel. It affects a highly conserved amino acid located within the MBD domain, a region of the protein involved in specific recognition and interaction with methylated CpG dinucleotides. The p.T160S variation was not found in the control sample. This mutation may represent a potential genetic factor for autistic phenotype and should be object of further studies.
3. Duchesnay E, Cachia A, Boddaert N, Chabane N, Mangin JF, Martinot JL, Zilbovicius M. {{Feature selection and classification of imbalanced datasets Application to PET images of children with autistic spectrum disorders}}. {Neuroimage};2011 (May 10)
Learning with discriminative methods is generally based on minimizing the misclassification of training samples, which may be unsuitable for imbalanced datasets where the recognition might be biased in favor of the most numerous class. This problem can be addressed with a generative approach, which typically requires more parameters to be determined leading to reduced performances in high dimension. In such situations, dimension reduction becomes a crucial issue. We propose a feature selection/classification algorithm based on generative methods in order to predict the clinical status of a highly imbalanced dataset made of PET scans of forty-five low-functioning children with autism spectrum disorders (ASD) and thirteen non-ASD low functioning children. ASDs are typically characterized by impaired social interaction, narrow interests, and repetitive behaviors, with a high variability in expression and severity. The numerous findings revealed by brain imaging studies suggest that ASD is associated with a complex and distributed pattern of abnormalities that makes the identification of a shared and common neuroimaging profile a difficult task. In this context, our goal is to identify the rest functional brain imaging abnormalities pattern associated with ASD and to validate its efficiency in individual classification. The proposed feature selection algorithm detected a characteristic pattern in the ASD group that included a hypoperfusion in the right Superior Temporal Sulcus (STS) and a hyperperfusion in the contralateral postcentral area. Our algorithm allowed for a significantly accurate (88%), sensitive (91%) and specific (77%) prediction of clinical category. For this imbalanced dataset, with only 13 control scans, the proposed generative algorithm outperformed other state-of-the-art discriminant methods. The high predictive power of the characteristic pattern, which has been automatically identified on whole brains without any priors, confirms previous findings concerning the role of STS in ASD. This work offers exciting possibilities for early autism detection and/or the evaluation of treatment response in individual patients.
4. Durand CM, Perroy J, Loll F, Perrais D, Fagni L, Bourgeron T, Montcouquiol M, Sans N. {{SHANK3 mutations identified in autism lead to modification of dendritic spine morphology via an actin-dependent mechanism}}. {Mol Psychiatry};2011 (May 24)
Genetic mutations of SHANK3 have been reported in patients with intellectual disability, autism spectrum disorder (ASD) and schizophrenia. At the synapse, Shank3/ProSAP2 is a scaffolding protein that connects glutamate receptors to the actin cytoskeleton via a chain of intermediary elements. Although genetic studies have repeatedly confirmed the association of SHANK3 mutations with susceptibility to psychiatric disorders, very little is known about the neuronal consequences of these mutations. Here, we report the functional effects of two de novo mutations (STOP and Q321R) and two inherited variations (R12C and R300C) identified in patients with ASD. We show that Shank3 is located at the tip of actin filaments and enhances its polymerization. Shank3 also participates in growth cone motility in developing neurons. The truncating mutation (STOP) strongly affects the development and morphology of dendritic spines, reduces synaptic transmission in mature neurons and also inhibits the effect of Shank3 on growth cone motility. The de novo mutation in the ankyrin domain (Q321R) modifies the roles of Shank3 in spine induction and morphology, and actin accumulation in spines and affects growth cone motility. Finally, the two inherited mutations (R12C and R300C) have intermediate effects on spine density and synaptic transmission. Therefore, although inherited by healthy parents, the functional effects of these mutations strongly suggest that they could represent risk factors for ASD. Altogether, these data provide new insights into the synaptic alterations caused by SHANK3 mutations in humans and provide a robust cellular readout for the development of knowledge-based therapies.Molecular Psychiatry advance online publication, 24 May 2011; doi:10.1038/mp.2011.57.
5. Griffin R, Westbury C. {{Infant EEG activity as a biomarker for autism: A promising approach or a false promise?}}. {BMC Med};2011 (May 20);9(1):61.
ABSTRACT: The ability to determine an infant’s likelihood of developing autism via a relatively simple neurological measure would constitute an important scientific breakthrough. In their recent publication in this journal, Bosl and colleagues claim that a measure of EEG complexity can be used to detect, with very high accuracy, infants at high risk for autism (HRA). On the surface, this appears to be that very scientific breakthrough and as such the paper has received widespread media attention. But a close look at how these high accuracy rates were derived tells a very different story. This stems from a conflation between « high risk » as a population-level property and « high risk » as a property of an individual. We describe the approach of Bosl et al and examine their results with respect to baseline prevalence rates, the inclusion of which is necessary to distinguish infants with a biological risk of autism from typically developing infants with a sibling with autism. This is an important distinction that should not be overlooked. Please see research article: http://www.biomedcentral.com/1741-7015/9/18 and correspondence article: http://www.biomedcentral.com/1741-7015/9/60.
6. Marquenie K, Rodger S, Mangohig K, Cronin A. {{Dinnertime and bedtime routines and rituals in families with a young child with an autism spectrum disorder}}. {Aust Occup Ther J};2011 (Jun);58(3):145-154.
Background/aim: Routines are thought to be critical in laying the foundation for ritual development, and in turn rituals are considered important for forming a strong and healthy family unit. This article provides a description of the experiences of dinnertime and bedtime routines and rituals in Australian families with a young child with an Autism Spectrum Disorder (ASD), as well as common challenges experienced. Methods: Fourteen Australian mothers with a young child with an ASD between the ages of two and five years were interviewed about their performance of dinnertime and bedtime routines and rituals and their perceptions of both occupations. Descriptive qualitative interviews were audio taped and transcribed. Transcripts were analysed using thematic content analysis. Results: Two overarching themes emerged, including ‘centred on ASD’ and ‘ASD alters meaning’. Mothers’ descriptions revealed that families with a young child with an ASD experienced unstructured and chaotic routines at dinnertime. In contrast, bedtime involved the performance of more structured, and at times, non-functional routines. Moreover, dinnertime was bereft of meaningful interactions and rituals, whereas bedtime contained some positive meaningful interactions and rituals. Conclusions: Occupational therapists need to consider supporting mothers and the child with an ASD in enhancing their participation within all aspects of family life, by encouraging them to develop structured and more predictable dinnertime and bedtime routines inclusive of all family members. In doing so, this action will support mothers to develop a strong and cohesive family unit.
7. Mercier F, Cho Kwon Y, Kodama R. {{Meningeal/vascular alterations and loss of extracellular matrix in the neurogenic zone of adult BTBR T+ tf/J mice, animal model for autism}}. {Neurosci Lett};2011 (May 11)
Autism spectrum disorders are characterized by impaired social and communication skills and seem to result from altered neural development. We sought to determine whether the anatomy of the meninges and extracellular matrix (ECM) is altered in an animal model of autism, the BTBR T+ tf/J mouse. This mouse displays white matter tract anatomical defects and exhibits several symptoms of autism. Immunofluorescence cytochemistry for laminin, a major ECM marker, was performed on series of coronal sections of the adult BTBR T+ tf/J brain and the anatomy was analyzed in comparison to B6 wild type mice. Laminin immunoreactivity visualized meninges, blood vessels and the subventricular zone (SVZ) stem cell-associated ECM structures, which I have named fractones. All BTBR T+ tf/J mice observed showed the same forebrain defects. The lateral ventricle volume was severely reduced, the falx cerebri elongated, the arteries enlarged and the choroid plexus atrophied. Compared to B6 mice, fractone numbers in BTBR T+ tf/J mice were reduced by a factor three in the SVZ of the anterior portion of the lateral ventricle. This represents the primary neurogenic zone during adulthood. Fractones were reduced by a factor 1.5 in posterior portions of the lateral ventricle. Moreover, fractone size was reduced throughout the lateral ventricle SVZ. These results show hitherto unsuspected alterations in connective tissue/vasculature and associated ECM in the adult BTBR T+ tf/J mouse. The drastic changes of the connective tissue and ECM in the neurogenic zone of the lateral ventricle may contribute to incorrect neurogenesis during developmental and adult stages.
8. Mohrmann I, Gillessen-Kaesbach G, Siebert R, Caliebe A, Hellenbroich Y. {{A de novo 0.57 Mb microdeletion in chromosome 11q13.1 in a patient with speech problems, autistic traits, dysmorphic features and multiple endocrine neoplasia type 1}}. {Eur J Med Genet};2011 (Apr 29)
We report a 21-year-old patient with speech problems, autistic traits, dysmorphic facial features, broad thumbs with short distal phalanges and a pancreatic gastrinoma. Array-CGH demonstrated a 0.57 Mb de novo deletion in chromosome 11q13.1. The deleted region contains several genes which likely contribute to the patient’s complex phenotype, including the MEN1 gene. The deletion of the MEN1 gene is causing multiple endocrine neoplasia type 1 (MEN1). The neurodevelopmental phenotype of the patient might be associated with the deletion of the genes NRXN2 and PPP2R5B which have been described to be involved in synaptogenesis and dendritic branching. According to our knowledge, we report for the first time a patient with the combination of a neurodevelopmental phenotype and MEN1 caused by a microdeletion on chromosome 11.
9. Reynolds AM, Malow BA. {{Sleep and autism spectrum disorders}}. {Pediatr Clin North Am};2011 (Jun);58(3):685-698.
Sleep disorders are common in children with autism spectrum disorders and have a significant effect on daytime function and parental stress. The cornerstone of treatment is to establish the cause of the sleep concern, which is often multifactorial. Identifying and treating sleep disorders may result not only in more consolidated sleep, more rapid time to fall asleep, and avoidance of night waking but also favorably affect daytime behavior and parental stress. Targeting effective treatment strategies is dependent on understanding the underlying causes of sleep problems in children with Autism spectrum disorders, therefore further research is paramount.
10. Shih P, Keehn B, Oram JK, Leyden KM, Keown CL, Muller RA. {{Functional Differentiation of Posterior Superior Temporal Sulcus in Autism: A Functional Connectivity Magnetic Resonance Imaging Study}}. {Biol Psychiatry};2011 (May 20)
BACKGROUND: Socio-communicative impairments are salient features of autism spectrum disorder (ASD). Abnormal development of posterior superior temporal sulcus (pSTS)-a key processing area for language, biological motion, and social context-could play a role in these deficits. METHODS: Functional connectivity magnetic resonance imaging was used to examine the synchronization of low-frequency blood oxygen level-dependent fluctuations during continuous performance on a visual search task. Twenty-one children and adolescents with ASD and 26 typically developing individuals-matched on age and IQ-participated in the study. Three subregions of pSTS were delineated with a data-driven approach, and differentiation of pSTS was examined by comparing the connectivity of each subregion. RESULTS: In typically developing individuals, differentiation of networks was positively associated with age and anatomical maturation (cortical thinning in pSTS, greater white matter volume). In the ASD group, differentiation of pSTS connectivity was significantly reduced, and correlations with anatomical measures were weak or absent. Moreover, pSTS differentiation was inversely correlated with autism symptom severity. CONCLUSIONS: Atypical maturation of pSTS suggests altered trajectories for functional segregation and integration of networks in ASD, potentially related to impaired cognitive and sensorimotor development. Furthermore, our findings provide a novel explanation for atypically increased connectivity in ASD that has been observed in some functional connectivity magnetic resonance imaging studies.
