1. Fujita E, Tanabe Y, Imhof BA, Momoi MY, Momoi T. {{A complex of synaptic adhesion molecule CADM1, a molecule related to Autism Spectrum Disorder, with MUPP1 in the cerebellum}}. {Journal of neurochemistry}. 2012 Sep 20.
Mutations in the synaptic adhesion protein CADM1 (RA175/SynCAM1) are associated with Autism spectrum disorder (ASD), a neurodevelopmental disorder of uncertain molecular origin. Cadm1 knock out (KO) mice exhibit smaller cerebella with decreased number of synapse of Purkinje cells and some ASD-like symptoms, including impaired ultrasonic vocalization. In the present study, we examined the alteration of the Cadm1 synaptic complex in the mouse cerebellum at postnatal stages. The C-terminal peptide of Cadm1 associated with Mupp1 at PDZ(1-5), a scaffold protein containing 13 PDZ domains, which interacted with GABBR2 at PDZ13, but not with PSD-95. The GABBR2 was detected in a set of proteins interacting with Cadm1 C-terminal. Cadm1 co-localized with Mupp1 and GABBR2 on the dendrites of Purkinje cells in the molecular layers of the developing cerebellum and on the dendrites of hippocampal neurons cultured in vitro. These observations suggest that the Cadm1 synaptic receptor complex, including Mupp1-GABBR2, is located on the dendrites of Purkinje cells. The amount of GABBR2 protein but not mRNA was increased in the cerebella of Cadm1 KO mice, suggesting that lack of Cadm1 does not affect transcription of GABBR2 but may stabilize the Mupp1-GABBR2 complex; the Mupp1-GABBR2 interaction may be stabilized by conformational change in Mupp1 or association with other adhesion molecules and by anchorage to the postsynaptic membrane. Up-regulation of GABBR2 in the cerebellum in the absence of CADM1 may be associated with ASD pathogenesis. (c) 2012 The Authors Journal of Neurochemistry (c) 2012 International Society forNeurochemistry.
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2. Gondalia SV, Palombo EA, Knowles SR, Cox SB, Meyer D, Austin DW. {{Molecular Characterisation of Gastrointestinal Microbiota of Children With Autism (With and Without Gastrointestinal Dysfunction) and Their Neurotypical Siblings}}. {Autism Res}. 2012 Sep 20.
Many children with autism spectrum disorders (ASDs) suffer from gastrointestinal problems such as diarrhoea, constipation and abdominal pain. This has stimulated investigations into possible abnormalities of intestinal microbiota in autistic patients. Therefore, we designed this study to identify differences (and/or similarities) in the microbiota of children with autism (without gastrointestinal dysfunction: n = 23; with gastrointestinal dysfunction: n = 28) and their neurotypical siblings (n = 53) who share a similar environment using bacterial tag-encoded FLX amplicon pyrosequencing. Regardless of the diagnosis and sociodemographic characteristics, overall, Firmicutes (70%), Bacteroidetes (20%) and Proteobacteria (4%) were the most dominant phyla in samples. Results did not indicate clinically meaningful differences between groups. The data do not support the hypothesis that the gastrointestinal microbiota of children with ASD plays a role in the symptomatology of ASD. Other explanations for the gastrointestinal dysfunction in this population should be considered including elevated anxiety and self-restricted diets. Autism Res 2012, **: **-**. (c) 2012 International Society for Autism Research, Wiley Periodicals, Inc.
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3. Han S, Tai C, Westenbroek RE, Yu FH, Cheah CS, Potter GB, Rubenstein JL, Scheuer T, de la Iglesia HO, Catterall WA. {{Autistic-like behaviour in Scn1a+/- mice and rescue by enhanced GABA-mediated neurotransmission}}. {Nature}. 2012 Sep 20;489(7416):385-90.
Haploinsufficiency of the SCN1A gene encoding voltage-gated sodium channel Na(V)1.1 causes Dravet’s syndrome, a childhood neuropsychiatric disorder including recurrent intractable seizures, cognitive deficit and autism-spectrum behaviours. The neural mechanisms responsible for cognitive deficit and autism-spectrum behaviours in Dravet’s syndrome are poorly understood. Here we report that mice with Scn1a haploinsufficiency exhibit hyperactivity, stereotyped behaviours, social interaction deficits and impaired context-dependent spatial memory. Olfactory sensitivity is retained, but novel food odours and social odours are aversive to Scn1a(+/-) mice. GABAergic neurotransmission is specifically impaired by this mutation, and selective deletion of Na(V)1.1 channels in forebrain interneurons is sufficient to cause these behavioural and cognitive impairments. Remarkably, treatment with low-dose clonazepam, a positive allosteric modulator of GABA(A) receptors, completely rescued the abnormal social behaviours and deficits in fear memory in the mouse model of Dravet’s syndrome, demonstrating that they are caused by impaired GABAergic neurotransmission and not by neuronal damage from recurrent seizures. These results demonstrate a critical role for Na(V)1.1 channels in neuropsychiatric functions and provide a potential therapeutic strategy for cognitive deficit and autism-spectrum behaviours in Dravet’s syndrome.
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4. Hwang YS, Kearney P. {{A systematic review of mindfulness intervention for individuals with developmental disabilities: Long-term practice and long lasting effects}}. {Research in developmental disabilities}. 2012 Sep 15;34(1):314-26.
Can individuals with developmental disabilities learn mindfulness? If so, with what result? A systematic literature review identified 12 studies that taught mindfulness practice to individuals with mild to severe developmental disabilities, demonstrating that mindfulness intervention could significantly reduce the behavioural and/or psychological problems of this population. The majority of these mindfulness intervention studies were longitudinal, featuring long intervention periods and long lasting intervention effects. This paper analyses the characteristics and objectives of mindfulness interventions, along with their effects, focusing on the adjustments made to intervention content and instruction strategies to meet the specific requirements of individuals with developmental disabilities. The potential for improving mindfulness interventions for people with developmental disabilities is also discussed.
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5. Lim F, Downs J, Li J, Bao XH, Leonard H. {{Caring for a child with severe intellectual disability in China: The example of Rett syndrome}}. {Disability and rehabilitation}. 2012 Sep 20.
Purpose: Rett syndrome is one of several genetic disorders known to cause severe intellectual and physical disability, mostly in girls. Girls affected by Rett syndrome appear to develop normally in the first 6 months of life, after which the usual clinical presentation comprises regression of communication and hand skills, the appearance of hand stereotypies and impaired gait. Intellectual disability affects more than 1.5% of the population of children in developing countries yet we know little about the daily lives and support services available for them and their caregivers. Method: This qualitative study explored the daily experiences of 14 mothers and one grandmother caring for a child with Rett syndrome in China via telephone interviews. Results: Participants reported a lack of education, rehabilitation and support services available to them. Limited access to information reduced families’ capacity to adequately meet the needs of their child. These gaps were further exacerbated by discrimination and perceived stigma from some members of the community. Conclusions: Additional support services and educational programs at the governmental level can improve the quality of life of persons with an intellectual disability and their families and programs involving community participation in the care of people with disabilities may help to address discrimination. [Box: see text].
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6. Mahjouri S, Lord CE. {{What the DSM-5 Portends for Research, Diagnosis, and Treatment of Autism Spectrum Disorders}}. {Current psychiatry reports}. 2012 Sep 19.
In May 2013 the APA will release DSM-5, which will restructure the diagnostic classification for autism spectrum disorders (ASDs) into a single category. The proposed changes in DSM-5 aim to better reflect the current state of research by consistently identifying the core features in social/communication and restrictive and repetitive behaviors that are specific to ASDs. This review describes the empirical and theoretical bases of research in the nosology of ASDs, given the impending shift in DSM-5 diagnostic criteria. General issues in diagnosis and prevalence are described, with differences between DSM-IV and DSM-5 highlighted. To address concerns about the application of the proposed DSM-5 criteria, the current literature assessing the sensitivity and specificity of the proposed DSM-5 criteria is reviewed. Last, we discuss the implications of the changes in DSM-5 for the treatment of ASDs and recommend areas for future research.
