1. Eigsti IM, Bennetto L. {{Grammaticality judgments in autism: Deviance or delay}}. {J Child Lang}. 2009 Feb 19:1-23.

ABSTRACTLanguage in autism has been the subject of intense interest, because communication deficits are central to the disorder, and because autism serves as an arena for testing theories of language acquisition. High-functioning older children with autism are often considered to have intact grammatical abilities, despite pragmatic impairments. Given the heterogeneity in language skills at younger ages, this assumption merits further investigation. Participants with autism (n=21, aged nine to seventeen years), matched on chronological age, receptive vocabulary and IQ, to 22 typically developing individuals, completed a grammaticality judgment task. Participants with autism were significantly less sensitive than controls, specifically for third person singular and present progressive marking. Performance interacted with sentence length, with lower sensitivity to errors occurring at the end of the longest stimulus sentences. Performance sensitivity was associated with onset of single word and phrase speech, and with severity of autistic symptomatology. Implications of findings are discussed.

2. Glaze DG, Percy AK, Motil KJ, Lane JB, Isaacs JS, Schultz RJ, et al. {{A Study of the Treatment of Rett Syndrome With Folate and Betaine}}. J {Child Neurol}. 2009 Feb 18.

We tested the hypothesis that increasing methyl-group pools might promote transcriptional repression by other methyl-binding proteins or by mutant methyl-CpG-binding protein 2 with altered affinity, ameliorating the clinical features of Rett syndrome. A 12-month, double-blind, placebo-controlled folate-betaine trial enrolled 73 methyl-CpG-binding protein 2 mutation positive female participants meeting consensus criteria for Rett syndrome. Participants were randomized as young (< age 5 years) or old (>/= age 5 years). Structured clinical assessments occurred at baseline, 3, 6, and 12 months. Primary outcome measures included quantitative evaluation of breathing and hand movements during wakefulness, growth, anthropometry, motor/behavioral function, and qualitative evaluations from electroencephalograms and parent questionnaires. In all, 68 participants completed the study. Objective evidence of improvement was not found. Subjective improvement from parent questionnaires was noted for the <5 years group. This study should inform future treatment trials regarding balancing participants with specific mutations and comparable severity to minimize selection bias.

3. Judson MC, Bergman MY, Campbell DB, Eagleson KL, Levitt P. {{Dynamic gene and protein expression patterns of the autism-associated met receptor tyrosine kinase in the developing mouse forebrain}}. {J Comp Neurol}. 2009 Feb 18;513(5):511-31.

The establishment of appropriate neural circuitry depends on the coordination of multiple developmental events across space and time. These events include proliferation, migration, differentiation, and survival-all of which can be mediated by hepatocyte growth factor (HGF) signaling through the Met receptor tyrosine kinase. We previously found a functional promoter variant of the MET gene to be associated with autism spectrum disorder, suggesting that forebrain circuits governing social and emotional function may be especially vulnerable to developmental disruptions in HGF/Met signaling. However, little is known about the spatiotemporal distribution of Met expression in the forebrain during the development of such circuits. To advance our understanding of the neurodevelopmental influences of Met activation, we employed complementary Western blotting, in situ hybridization, and immunohistochemistry to comprehensively map Met transcript and protein expression throughout perinatal and postnatal development of the mouse forebrain. Our studies reveal complex and dynamic spatiotemporal patterns of expression during this period. Spatially, Met transcript is localized primarily to specific populations of projection neurons within the neocortex and in structures of the limbic system, including the amygdala, hippocampus, and septum. Met protein appears to be principally located in axon tracts. Temporally, peak expression of transcript and protein occurs during the second postnatal week. This period is characterized by extensive neurite outgrowth and synaptogenesis, supporting a role for the receptor in these processes. Collectively, these data suggest that Met signaling may be necessary for the appropriate wiring of forebrain circuits, with particular relevance to the social and emotional dimensions of behavior. J. Comp. Neurol. 513:511-531, 2009. (c) 2009 Wiley-Liss, Inc.

4. Zhang A, Shen CH, Ma SY, Ke Y, El Idrissi A. {{Altered expression of Autism-associated genes in the brain of Fragile X mouse model}}. {Biochem Biophys Res Commun}. 2009 Feb 20;379(4):920-3.

Autism is a severe neurodevelopmental disorder, which typically emerges in early childhood. Most cases of autism have not been linked to mutations in a specific gene, and the etioloty of the disorder remains to be established [S.S. Moy, J.J. Nadler, T.R. Magnuson, J.N. Crawley, Mouse models of autism spectrum disorders: the challenge for behavioral genetics, Am. J. Med. Genet. 142 (2006) 40-51]. Fragile X syndrome is caused by mutation in the FMR1 gene and is characterized by mental retardation, physical abnormalities, and, in most case, autistic-like behavior [R.J. Hagerman, A.W. Jackson, A. Levitas, B. Rimland, M. Braden, An analysis of autism in fifty males with the Fragile X syndrome, Am. J. Med. Genet. 23 (1986) 359-374, C.E. Bakker, C. Verheij, R. Willemsen, R. van der Helm, F. Oerlemans, M. Vermeij, A. Bygrave, A.T. Hoogeveen, B.A. Oostra, E. Reyniers, K. De Boulle, R. D’Hooge, P. Cras, D. van Velzen, G. Nagels, J.J. Marti, P. De Deyn, J.K. Darby, P.J. Willems, Fmr1 knockout mice: a model to study Fragile X mental retardation, Cell 78 (1994) 23-33]. The FMR1 knockout (KO) mouse is one of the best characterized animal models for human disorders associated with autism [S.S. Moy, J.J. Nadler, T.R. Magnuson, J.N. Crawley, Mouse models of autism spectrum disorders: the challenge for behavioral genetics, Am. J. Med. Genet. 142 (2006) 40-51]. We have used real-time PCR to investigate changes in expression levels of three genes: WNT2, MECP2, and FMR1 in different brain regions of Fagile X mice and litter mate controls. We found major changes in the expression pattern for the three genes examined. FMR1, MECP2, and WNT2 expression were drastically down regulated in the Fragile X mouse brain.