1. Alisch RS, Wang T, Chopra P, Visootsak J, Conneely KN, Warren ST. {{Genome-wide analysis validates aberrant methylation in fragile X syndrome is specific to the FMR1 locus}}. {BMC Med Genet};2013 (Jan 29);14(1):18.
ABSTRACT: BACKGROUND: Fragile X syndrome (FXS) is a common form of inherited intellectual disability caused by an expansion of CGG repeats located in the 5[prime] untranslated region (UTR) of the FMR1 gene, which leads to hypermethylation and silencing of this locus. Although a dramatic increase in DNA methylation of the FMR1 full mutation allele is well documented, the extent to which these changes affect DNA methylation throughout the rest of the genome has gone unexplored. METHODS: Here we examined genome-wide methylation in both peripheral blood (N = 62) and induced pluripotent stem cells (iPSCs; N = 10) from FXS individuals and controls. RESULTS: We not only found the expected significant DNA methylation differences in the FMR1 promoter and 5[prime] UTR, we also saw that these changes inverse in the FMR1 gene body. Importantly, we found no other differentially methylated loci throughout the remainder of the genome, indicating the aberrant methylation of FMR1 in FXS is locus-specific. CONCLUSIONS: This study provides a comprehensive methylation profile of FXS and helps refine our understanding of the mechanisms behind FMR1 silencing.
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2. Feliciano P. {{Hotspots in autism}}. {Nat Genet};2013 (Feb);45(2):123.
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3. Haebig E, McDuffie A, Ellis Weismer S. {{Brief Report: Parent Verbal Responsiveness and Language Development in Toddlers on the Autism Spectrum}}. {J Autism Dev Disord};2013 (Jan 30)
This study examined the longitudinal associations between parent verbal responsiveness and language 3 years later in 34 toddlers with a diagnosis of an autism spectrum disorder. Parent-child play samples were coded for child engagement and communication acts and for parent verbal responsiveness. Measures of responsive verbal behaviors were used to predict language gain scores 3 years later. Parent directives for language that followed into the child’s focus of attention were predictive of child receptive language gains. Parent comments that followed into the child’s focus of attention yielded differential effects depending on initial levels of child language. Children who were minimally verbal at age 2(1/2) benefited from parent comments that followed into the their focus of attention, whereas children who were verbally fluent did not demonstrate such a benefit.
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4. Omori M, Yamamoto JI. {{Stimulus pairing training for Kanji reading skills in students with developmental disabilities}}. {Res Dev Disabil};2013 (Jan 25);34(4):1109-1118.
Japanese students with developmental disabilities often exhibit difficulties in reading, particularly in Kanji (ideogram) reading, and in acquiring the equivalence relations between pictures, written words, and sounds. Previous research suggested that one student with autism could acquire Kanji reading along with equivalence relations through stimulus pairing training. However, maintenance rates tended to be very low, possibly due to the lack of picture stimuli. In this study, we examined the acquisition and maintenance of Kanji reading skills through stimulus pairing training using corresponding pictures for six students with developmental disabilities. We prepared stimulus pairs consisting of picture stimuli that the students could name along with a corresponding Kanji character that they could not read. All students successfully acquired and maintained the Kanji reading skills through this procedure. These findings suggest that the nameability of picture stimuli in stimulus pairing training may facilitate the acquisition and maintenance of equivalence relations for reading.
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5. Pettem KL, Yokomaku D, Takahashi H, Ge Y, Craig AM. {{Interaction between autism-linked MDGAs and neuroligins suppresses inhibitory synapse development}}. {J Cell Biol};2013 (Jan 28)
Rare variants in MDGAs (MAM domain-containing glycosylphosphatidylinositol anchors), including multiple protein-truncating deletions, are linked to autism and schizophrenia, but the function of these genes is poorly understood. Here, we show that MDGA1 and MDGA2 bound to neuroligin-2 inhibitory synapse-organizing protein, also implicated in neurodevelopmental disorders. MDGA1 inhibited the synapse-promoting activity of neuroligin-2, without altering neuroligin-2 surface trafficking, by inhibiting interaction of neuroligin-2 with neurexin. MDGA binding and suppression of synaptogenic activity was selective for neuroligin-2 and not neuroligin-1 excitatory synapse organizer. Overexpression of MDGA1 in cultured rat hippocampal neurons reduced inhibitory synapse density without altering excitatory synapse density. Furthermore, RNAi-mediated knockdown of MDGA1 selectively increased inhibitory but not excitatory synapse density. These results identify MDGA1 as one of few identified negative regulators of synapse development with a unique selectivity for inhibitory synapses. These results also place MDGAs in the neurexin-neuroligin synaptic pathway implicated in neurodevelopmental disorders and support the idea that an imbalance between inhibitory and excitatory synapses may contribute to these disorders.
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6. Rosenthal M, Wallace GL, Lawson R, Wills MC, Dixon E, Yerys BE, Kenworthy L. {{Impairments in real-world executive function increase from childhood to adolescence in autism spectrum disorders}}. {Neuropsychology};2013 (Jan);27(1):13-18.
Objective: Although several studies have investigated developmental trajectories of executive functioning (EF) in individuals with autism spectrum disorders (ASD) using lab-based tasks, no study to date has directly measured how EF skills in everyday settings vary at different ages. The current study seeks to extend prior work by evaluating age-related differences in parent-reported EF problems during childhood and adolescence in a large cross-sectional cohort of children with ASD. Method: Children (N = 185) with an ASD without intellectual disability participated in the study. Participants were divided into four groups based on age (5-7, 8-10, 11-13, and 14-18-year-olds). The four age groups did not differ in IQ, sex ratio, or autism symptoms. Results: There were significant age effects (i.e., worsening scores with increasing age) in three of G. A. Gioia, P. K. Isquith, S. Guy, and L. Kenworthy’s (2000) BRIEF: Behavior Rating Inventory of Executive Function, Odessa, FL, Psychological Assessment Resources scale scores: Initiate (p = .007), working memory (p = .003), and organization of materials (p = .023). In addition, analysis of the BRIEF scale profile revealed that, although multiple scales were elevated, the shift scale showed the greatest problems in both the youngest and oldest age cohorts. Conclusions: Older children with ASD show greater EF problems compared with the normative sample than younger children with ASD. Specifically, there is a widening divergence from the normative sample in metacognitive executive abilities in children with ASD as they age. This, in combination with significant, albeit more stable, impairments in flexibility, has implications for the challenges faced by high-functioning individuals with ASD as they attempt to enter mainstream work and social environments. (PsycINFO Database Record (c) 2013 APA, all rights reserved).
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7. Rutter M. {{Changing Concepts and Findings on Autism}}. {J Autism Dev Disord};2012 (Nov 29)
New research findings provide major challenges regarding our understanding of the concept of autism. These are critically discussed in relation to research relevant to classification, genetics, environmental risk factors, gene-environment interplay, animal models, biomarkers, clinical features, neuropathology, pharmacotherapy, behavioral treatments, and functioning in adult life. It is concluded that, although there have been major research advances; there is a need for a reconceptualization and an avoidance of claims that go beyond the evidence.
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8. Storch EA, Arnold EB, Lewin AB, Nadeau JM, Jones AM, De Nadai AS, Jane Mutch P, Selles RR, Ung D, Murphy TK. {{The effect of cognitive-behavioral therapy versus treatment as usual for anxiety in children with autism spectrum disorders: a randomized, controlled trial}}. {J Am Acad Child Adolesc Psychiatry};2013 (Feb);52(2):132-142 e132.
OBJECTIVE: To examine the efficacy of a modular cognitive-behavioral therapy (CBT) protocol relative to treatment as usual (TAU) among children with high-functioning autism spectrum disorders (ASD) and clinically significant anxiety. METHOD: A total of 45 children (7-11 years of age) with high-functioning ASD and clinically significant anxiety were randomized to receive 16 sessions of weekly CBT or TAU for an equivalent duration. After screening, assessments were conducted at baseline, post-treatment, and 3-month follow-up. Raters were blind to treatment condition. RESULTS: Youth receiving CBT showed substantial improvement relative to TAU on primary anxiety outcomes. Of 24 children randomized to the CBT arm, 18 (75%) were treatment responders, versus only 3 of 21 children (14%) in the TAU arm. Gains were generally maintained at 3-month follow-up for CBT responders. CONCLUSIONS: Relative to usual care, CBT adapted for anxious youth with high-functioning ASD demonstrates large effects in reducing anxiety symptoms. This study contributes to the growing literature supporting adapted CBT approaches for treating anxiety in youth with ASD. Clinical trial registration information-Cognitive-Behavioral Treatment for Anxiety Disorders in Children With Autism Spectrum Disorders; http://clinicaltrials.gov; NCT01178385.
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9. Valicenti-McDermott M, Burrows B, Bernstein L, Hottinger K, Lawson K, Seijo R, Schechtman M, Shulman L, Shinnar S. {{Use of Complementary and Alternative Medicine in Children With Autism and Other Developmental Disabilities: Associations With Ethnicity, Child Comorbid Symptoms, and Parental Stress}}. {J Child Neurol};2013 (Jan 30)
The use of complementary and alternative medicine by children with autism and the association of its use with child comorbid symptoms and parental stress was studied in an ethnically diverse population, in a cross-sectional study with structured interviews. The sample included 50 families of children with autism and 50 families of children with other developmental disabilities, matched by age/gender. Interview included the Complementary and Alternative Medicine Questionnaire, Gastrointestinal Questionnaire, Children’s Sleep Habits Questionnaire, Aberrant Behavior Checklist, and Parenting Stress Index. In this ethnically diverse sample, the use of complementary and alternative medicine was significantly higher for the autism group. In the autism group, use was significantly related to child’s irritability, hyperactivity, food allergies, and parental stress; in the developmental disabilities group, there was no association with child comorbid symptoms or parental stress. The results contribute information to health care providers about families of children with autism who are more likely to use complementary and alternative medicine.
