1. Bailey CD, Alves NC, Nashmi R, De Biasi M, Lambe EK. {{Nicotinic alpha5 Subunits Drive Developmental Changes in the Activation and Morphology of Prefrontal Cortex Layer VI Neurons}}. {Biol Psychiatry};2011 (Oct 24)
BACKGROUND: Nicotinic signaling in prefrontal layer VI pyramidal neurons is important to the function of mature attention systems. The normal incorporation of alpha5 subunits into alpha4beta2* nicotinic acetylcholine receptors augments nicotinic signaling in these neurons and is required for normal attention performance in adult mice. However, the role of alpha5 subunits in the development of the prefrontal cortex is not known. METHODS: We sought to answer this question by examining nicotinic currents and neuronal morphology in layer VI neurons of medial prefrontal cortex of wild-type and alpha5 subunit knockout (alpha5(-/-)) mice during postnatal development and in adulthood. RESULTS: In wild-type but not in alpha5(-/-) mice, there is a developmental peak in nicotinic acetylcholine currents in the third postnatal week. At this juvenile time period, the majority of neurons in all mice have long apical dendrites extending into cortical layer I. Yet, by early adulthood, wild-type but not alpha5(-/-) mice show a pronounced shift toward shorter apical dendrites. This cellular difference occurs in the absence of genotype differences in overall cortical morphology. CONCLUSIONS: Normal developmental changes in nicotinic signaling and dendritic morphology in prefrontal cortex depend on alpha5-comprising nicotinic acetylcholine receptors. It appears that these receptors mediate a specific developmental retraction of apical dendrites in layer VI neurons. This finding provides novel insight into the cellular mechanisms underlying the known attention deficits in alpha5(-/-) mice and potentially also into the pathophysiology of developmental neuropsychiatric disorders such as attention-deficit disorder and autism.
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2. Doherty-Sneddon G, Riby DM, Whittle L. {{Gaze aversion as a cognitive load management strategy in autism spectrum disorder and Williams syndrome}}. {J Child Psychol Psychiatry};2011 (Oct 26)
Background: During face-to-face questioning, typically developing children and adults use gaze aversion (GA), away from their questioner, when thinking. GA increases with question difficulty and improves the accuracy of responses. This is the first study to investigate whether individuals with autism spectrum disorder (ASD; associated with reduced sociability and atypical face gaze) and Williams syndrome (WS; associated with hypersociability and atypical face gaze) use GA to manage cognitive load during face-to-face interactions. Methods: Two studies were conducted exploring the typicality of GA during face-to-face questioning in (a) ASD and (b) WS. Results: In Study 1, children with ASD increased their GA as question difficulty increased. In addition, they used most GA when thinking about their responses to questions, mirroring evidence from typically developing children. An important atypicality for participants with ASD was a significantly higher level of GA when listening to interlocutors. In Study 2, participants with WS showed typical patterns of GA in relation to question difficulty and across different points of the interaction. Conclusions: Two different neuro-developmental disorders, both characterized by significant problems with executive control of attention and atypicalities of social interactions, exhibited generally typical patterns of GA. All groups used most GA while thinking about questions, and increased their GA as questions got harder. In addition, children with ASD showed elevated levels of GA while listening to questions, but not while thinking about or making their responses, suggesting that they sometimes fail to see the relevance of attending to visual cues rather than actively avoiding them. Results have important implications for how professionals interpret GA in these populations and for social skills training.
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3. Feliciano P. {{Cntnap2(-/-) autism model}}. {Nat Genet};2011;43(11):1053.
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4. Freitag C, Herpertz-Dahlmann B, Dose M, Luken M. {{[Statement on a letter by <<Pyramid Educational Consultants Germany UG>> of May 2010]}}. {Z Kinder Jugendpsychiatr Psychother};2011 (Nov);39(6):417-419.
In the present statement, a letter by the company <<Pyramid Educational Consultants of Germany UG>> on training and therapeutic aspects of PECS for children with autism is critically reflected.
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5. Liu SQ, Lei P, Lv Y, Wang SP, Yan XP, Ma HJ, Ma J. {{[Systematic review of gastrointestinal injury caused by magnetic foreign body ingestions in children and adolescence]}}. {Zhonghua Wei Chang Wai Ke Za Zhi};2011 (Oct);14(10):756-761.
OBJECTIVE: To study the diagnosis and treatment of gastrointestinal injury caused by magnetic foreign body ingestions in children. METHODS: A literature search was performed to identify all the studies related to gastrointestinal tract injury caused by ingesting magnetic foreign body using databases including Google, Medline, ISI Web of Knowledge, Ovid, Wanfang data, VIP, CNKI, degree dissertation, meeting abstracts, and request for document delivery. Language was limited to English, Chinese, Japanese, and Korean. Parameters studies were age at diagnosis, gender, country, regional distribution, number of magnetic foreign bodies, source of magnetic foreign bodies, clinical features, diagnosis, and method for foreign body removal. RESULTS: A total of 98 cases of magnet ingestion were identified from 17 countries and regions. There were 94 patients under the age of 18, with most children younger than 5 years old(62.2%,61/98). The age at peak incidence was 3 years old (16.3%, 16/98). Magnetic foreign bodies ingested included toys(74.5%), medical apparatus(8.2%), accessories(4.1%), and others(6.2%). The number of bodies ranged from 2 to 100. Eleven (11.2%) patients were complicated with allotriophagia or autism. Delay diagnosis and treatment existed in all the patients to varying extents, of whom one died from severe infection. Exploratory laprotomy showed a wide range of bowel damage from the esophagus to the colon, including perforation and intestinal fistula. Intestinal damage was the most common injury (51.0%), followed by intestine-colon fistula (15.3%). All the patients required bowel resection with anastomosis or fistula repair except for 2 children who were managed by endoscopic removal of the foreign bodies. CONCLUSION: Ingesting more than one magnet will lead to severe gastrointestinal injury. Early diagnosis and surgical intervention are important. More precautious measures should be taken for children aged younger than 5 years old.
6. Mikhail FM, Lose EJ, Robin NH, Descartes MD, Rutledge KD, Rutledge SL, Korf BR, Carroll AJ. {{Clinically relevant single gene or intragenic deletions encompassing critical neurodevelopmental genes in patients with developmental delay, mental retardation, and/or autism spectrum disorders}}. {Am J Med Genet A};2011 (Oct);155A(10):2386-2396.
Recent studies suggest that copy number variations (CNVs) encompassing several genes involved in neurodevelopmental pathways are associated with a variety of neuropsychiatric phenotypes, including developmental delay (DD), mental retardation (MR), and autism spectrum disorders (ASDs). Here we present eight patients in a cohort of approximately 1,200 patients referred for clinical array CGH testing for various neurodevelopmental phenotypes,whowere identified to carry small (<1.0Mb with the majority <500 kb) either total gene or intragenic deletions encompassing critical synaptic and other neurodevelopmental genes. The presentations of these patients included variable degrees of DD, speech problems, learning disabilities, MR, autistic-like features, and mild non-specific dysmorphic features. These genes belong to four functional categories, including neuronal transcription factor genes (NFIA at 1p31.3, MEF2C at 5q14.3, andCAMAT1at 1p36.23p36.31), neuron-specific splicing factor genes (RBFOX1 at 16p13.2p13.3), genes involved in synapse formation and maintenance (CNTNAP2 at 7q35 and LRFN5 at 14q21.2), and genes involved in neurotransmission (CHRNA7 at 15q13.3 and IL1RAPL1 at Xp21.2p21.3). Our report expands the list of neurodevelopmental genes deleted in various neurobehavioral phenotypes, expands the phenotypes caused by haploinsufficiency of previously reported critical neurodevelopmental genes, and elucidates the clinical relevance and need for careful clinical interpretation of some small CNVs<500 kb. This report also suggests that small clinically relevant deletions encompassing critical synaptic and other neurodevelopmental genes can present clinically with various neurobehavioral phenotypes, which implies the existence of overlapping neuronal pathways in the pathogenesis of these phenotypes.
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7. Peca J, Ting J, Feng G. {{SnapShot: Autism and the Synapse}}. {Cell};2011 (Oct 28);147(3):706-706 e701.
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8. Thanseem I, Anitha A, Nakamura K, Suda S, Iwata K, Matsuzaki H, Ohtsubo M, Ueki T, Katayama T, Iwata Y, Suzuki K, Minoshima S, Mori N. {{Elevated Transcription Factor Specificity Protein 1 in Autistic Brains Alters the Expression of Autism Candidate Genes}}. {Biol Psychiatry};2011 (Oct 24)
BACKGROUND: Profound changes in gene expression can result from abnormalities in the concentrations of sequence-specific transcription factors like specificity protein 1 (Sp1). Specificity protein 1 binding sites have been reported in the promoter regions of several genes implicated in autism. We hypothesize that dysfunction of Sp1 could affect the expression of multiple autism candidate genes, contributing to the heterogeneity of autism. METHODS: We assessed any alterations in the expression of Sp1 and that of autism candidate genes in the postmortem brain (anterior cingulate gyrus [ACG], motor cortex, and thalamus) of autism patients (n = 8) compared with healthy control subjects (n = 13). Alterations in the expression of candidate genes upon Sp1/DNA binding inhibition with mithramycin and Sp1 silencing by RNAi were studied in SK-N-SH neuronal cells. RESULTS: We observed elevated expression of Sp1 in ACG of autism patients (p = .010). We also observed altered expression of several autism candidate genes. GABRB3, RELN, and HTR2A showed reduced expression, whereas CD38, ITGB3, MAOA, MECP2, OXTR, and PTEN showed elevated expression in autism. In SK-N-SH cells, OXTR, PTEN, and RELN showed reduced expression upon Sp1/DNA binding inhibition and Sp1 silencing. The RNA integrity number was not available for any of the samples. CONCLUSIONS: Transcription factor Sp1 is dysfunctional in the ACG of autistic brain. Consequently, the expression of potential autism candidate genes regulated by Sp1, especially OXTR and PTEN, could be affected. The diverse downstream pathways mediated by the Sp1-regulated genes, along with the environmental and intracellular signal-related regulation of Sp1, could explain the complex phenotypes associated with autism.
