1. Bangash MA, Park JM, Melnikova T, Wang D, Jeon SK, Lee D, et al. {{Enhanced Polyubiquitination of Shank3 and NMDA Receptor in a Mouse Model of Autism}}. {Cell}. 2011 May 11.
We have created a mouse genetic model that mimics a human mutation of Shank3 that deletes the C terminus and is associated with autism. Expressed as a single copy [Shank3(+/DeltaC) mice], Shank3DeltaC protein interacts with the wild-type (WT) gene product and results in >90% reduction of Shank3 at synapses. This « gain-of-function » phenotype is linked to increased polyubiquitination of WT Shank3 and its redistribution into proteasomes. Similarly, the NR1 subunit of the NMDA receptor is reduced at synapses with increased polyubiquitination. Assays of postsynaptic density proteins, spine morphology, and synapse number are unchanged in Shank3(+/DeltaC) mice, but the amplitude of NMDAR responses is reduced together with reduced NMDAR-dependent LTP and LTD. Reciprocally, mGluR-dependent LTD is markedly enhanced. Shank3(+/DeltaC) mice show behavioral deficits suggestive of autism and reduced NMDA receptor function. These studies reveal a mechanism distinct from haploinsufficiency by which mutations of Shank3 can evoke an autism-like disorder.
2. Chiocchetti A, Pakalapati G, Duketis E, Wiemann S, Poustka A, Poustka F, et al. {{Mutation and expression analyses of the ribosomal protein gene RPL10 in an extended German sample of patients with autism spectrum disorder}}. {Am J Med Genet A}. 2011 May 12.
3. Gal G, Abiri L, Reichenberg A, Gabis L, Gross R. {{Time Trends in Reported Autism Spectrum Disorders in Israel, 1986-2005}}. {J Autism Dev Disord}. 2011 May 13.
Reports indicate sharp increase in prevalence of autism spectrum disorders (ASD). We aimed to assess the time trend in prevalence of ASD in Israel and describe demographic characteristics of the registered cases. We reviewed the autism registry of the Israeli Ministry of Social Affairs which includes 4,709 cases and identified 4,138 cases born between the years 1986 and 2005. Registered cases were mainly males (84.4%) and Jewish (96.6%). Prevalence data indicated an increase from 1.2 per 1,000 in those born in 1986 to 3.6 per 1,000 in 2003. Greater increase was seen in males, reaching a peak of 5.7 per 1,000, compared to 1.2 per 1,000 in females. Increased ASD prevalence was observed among Israeli children born in 1986-2005.
4. Pellicano E, Stears M. {{Bridging autism, science and society: moving toward an ethically informed approach to autism research}}. {Autism Res}. 2011 May 12.
Recent developments in the science of autism have provoked widespread unease among autism activists. Drawing on the findings of a major international gathering of researchers, ethicists, and activists, this paper presents the first major analysis of the ethical questions arising from this unease. We outline the scientific developments that have provoked the most discomfort, analyze the response to these developments from within and without the autism community, and trace the current state of the ethical debate. Having done so, we contend that these ethical questions are unlikely to be resolved as they depend on fundamentally conflicting assumptions about the nature and desirability of neurocognitive difference. We conclude by arguing for a new range of democratic mechanisms that could enable the scientific community, autistics, and other concerned parties to respond collectively to such entrenched ethical disputes. Autism Res 2011,4:xxx-xxx. (c) 2011 International Society for Autism Research, Wiley Periodicals, Inc.
5. Raja M, Azzoni A, Frustaci A. {{AUTISM Spectrum Disorders and Suicidality}}. {Clin Pract Epidemiol Ment Health}. 2011;7:97-105.
The paper describes the suicidal ideation and behavior in a series of 26 adult psychiatric patients affected by Autism Spectrum Disorders (ASDs), the clinical features and the psychiatric comorbidity of patients presenting suicidal behavior, and the history of suicide or suicide attempt in their relatives. Two (7,7%) patients committed suicide. One (3.8%) patient attempted suicide twice, and one (3.8%) patient self-harmed by cutting his face and one finger of his hand with a razor. Eight (30.8%) patients presented suicidal ideation. Two (7.7%) patients had one relative who had attempted suicide, and two (7.7%) patients had one or more relatives who had committed suicide. Most patients with suicidal behavior or ideation presented psychotic symptoms. Although it is not clear whether the high suicidal risk is related with ASDs per se or with psychotic symptoms, a high index of suspicion is warranted in evaluating suicidal risk in patients affected by ASDs, whatever is their age, psychiatric comorbidity, and setting of visit.
6. Shinawi M, Sahoo T, Maranda B, Skinner SA, Skinner C, Chinault C, et al. {{11p14.1 microdeletions associated with ADHD, autism, developmental delay, and obesity}}. {Am J Med Genet A}. 2011 May 12.
Genomic copy number imbalances are being increasingly identified as an important cause of intellectual disability and behavioral abnormalities. The typical deletion in WAGR syndrome encompasses the PAX6 and WT1 genes, but larger deletions have been associated with neurobehavioral abnormalities and obesity. We identified four patients with overlapping interstitial deletions on 11p14.1 and extending telomeric to the WAGR critical domain. The minimal overlapping critical chromosomal region was 2.3 Mb at 11p14.1. The deletions encompass the BDNF and LIN7C genes that are implicated in the regulation of development and differentiation of neurons and synaptic transmission. All patients with this deletion exhibit variable degrees of developmental delay, behavioral problems, and obesity. Our data show that ADHD, autism, developmental delay, and obesity are highly associated with deletion involving 11p14.1 and provide additional support for a significant role of BDNF in obesity and neurobehavioral problems. (c) 2011 Wiley-Liss, Inc.
7. Ventola P, Saulnier CA, Steinberg E, Chawarska K, Klin A. {{Early-Emerging Social Adaptive Skills in Toddlers with Autism Spectrum Disorders: An Item Analysis}}. {J Autism Dev Disord}. 2011 May 13.
Individuals with ASD have significant impairments in adaptive skills, particularly adaptive socialization skills. The present study examined the extent to which 20 items from the Vineland Adaptive Behavior Scales-Socialization Domain differentiated between ASD and developmentally delayed (DD) groups. Participants included 108 toddlers with ASD or DD under the age of 3 years. Nine of the 20 items significantly distinguished the groups. The ASD group demonstrated significantly weaker socialization skills, including deficits in basic social behaviors. The results support the notion that (a) socialization deficits in ASD impact foundational social skills typically emerging in the first year of life, (b) examination of specific social adaptive behaviors contribute to differential diagnosis, and (c) foundational social behaviors should be targeted for intervention.
