1. Boyd BA, McDonough SG, Bodfish JW. {{Evidence-Based Behavioral Interventions for Repetitive Behaviors in Autism}}. {J Autism Dev Disord};2011 (May 17)
Restricted and repetitive behaviors (RRBs) are a core symptom of autism spectrum disorders (ASD). There has been an increased research emphasis on repetitive behaviors; however, this research primarily has focused on phenomenology and mechanisms. Thus, the knowledge base on interventions is lagging behind other areas of research. The literature suggests there are evidence-based practices to treat « lower order » RRBs in ASD (e.g., stereotypies); yet, there is a lack of a focused program of intervention research for « higher order » behaviors (e.g., insistence on sameness). This paper will (a) discuss barriers to intervention development for RRBs; (b) review evidence-based interventions to treat RRBs in ASD, with a focus on higher order behaviors; and (c) conclude with recommendations for practice and research.
2. Brock J. {{Commentary: Complementary approaches to the developmental cognitive neuroscience of autism – reflections on Pelphrey et al. (2011)}}. {J Child Psychol Psychiatry};2011 (Jun);52(6):645-646.
3. Chan AS, Sze SL, Cheung MC, Han YM, Leung WW, Shi D. {{Dejian mind-body intervention improves the cognitive functions of a child with autism}}. {Evid Based Complement Alternat Med};2011;2011:549254.
There has been increasing empirical evidence for the enhancing effects of Dejian Mind-Body Intervention (DMBI), a traditional Chinese Shaolin healing approach, on human frontal brain activity/functions, including patients with autism who are well documented to have frontal lobe problems. This study aims to compare the effects of DMBI with a conventional behavioural/cognitive intervention (CI) on enhancing the executive functions and memory of a nine-year-old boy with low-functioning autism (KY) and to explore possible underlying neural mechanism using EEG theta cordance. At post-one-month DMBI, KY’s inhibitory control, cognitive flexibility, and memory functioning have significantly improved from « severely-to-moderately impaired » to « within-normal » range. This improvement was not observed from previous 12-month CI. Furthermore, KY showed increased cordance gradually extending from the anterior to the posterior brain region, suggesting possible neural mechanism underlying his cognitive improvement. These findings have implicated potential applicability of DMBI as a rehabilitation program for patients with severe frontal lobe and/or memory disorders.
4. Chien YL, Wu YY, Chiu YN, Liu SK, Tsai WC, Lin PI, Chen CH, Gau SS, Chien WH. {{Association study of the CNS patterning genes and autism in Han Chinese in Taiwan}}. {Prog Neuropsychopharmacol Biol Psychiatry};2011 (May 5)
Autism is a complex neurodevelopmental disorder with high heritability. Despite different approaches worldwide to identify susceptibility loci or genes for autism spectrum disorders (ASDs), no consistent result has been reported. CNS patterning genes have been recognized as candidate genes for autism based on neuroimage and neuropathology evidence. This study investigated four candidate genes (WNT2, EN2, SHANK3, and FOXP2) by a tag SNP approach in a family-based association study. The trio samples include 1164 subjects from 393 families, including 393 probands (aged 9.1+/-4.0years; male, 88.6%) diagnosed with autistic disorder (n=373) or Asperger’s disorder (n=20) according to the DSM-IV diagnostic criteria and confirmed by the Chinese ADI-R interview. Three tag SNPs of EN2 (7q36), 6 SNPs of WNT2 (7q31-33), 5 SNPs of SHANK3 (22q13.3), 3 SNPs of FOXP2 (7q31) were genotyped. TDT analysis was done to test the association of each tag SNP and haplotype. There was no association with autism for 17 tag SNPs of WNT2, EN2, SHANK3, and FOXP2 based on SNP analyses. Haplotype analyses did not reveal significant association except for the 6 tag SNPs of WNT2 gene showing a significant association on one haplotype composed of rs2896218 and rs6950765 (G-G) (p=0.0095). Other haplotypes composed of rs2896218 and rs6950765 (G-G) were also significantly associated with autism. The present study indicates that SHANK3 may not be a critical gene for the etiology of ASDs in Han Chinese population. Inconsistent findings in EN2, FOXP2 in the Han Chinese population need further clarification. A haplotype of WNT2 (rs2896218-rs6950765: G-G) is significantly associated with ASDs in our trios samples, this finding warrants further validation by different sample and confirmation by functional study.
5. Fendri-Kriaa N, Hsairi I, Kifagi C, Ellouze E, Mkaouar-Rebai E, Triki C, Fakhfakh F. {{A case of a Tunisian Rett patient with a novel double-mutation of the MECP2 gene}}. {Biochem Biophys Res Commun};2011 (May 7)
Rett syndrome is an X-linked dominant disorder caused frequently by mutations in the methyl-CpG-binding protein 2 gene (MECP2). Rett patients present an apparently normal psychomotor development during the first 6-18months of life. Thereafter, they show a short period of developmental stagnation followed by a rapid regression in language and motor development. The aim of this study was to perform a mutational analysis of the MECP2 gene in a classical Rett patient by sequencing the corresponding gene and modeling the found variants. The results showed the presence of a double-mutation: a new and de novo mutation c.535C>T (p.P179S) and the common c.763C>T (p.R255X) transition of the MECP2 gene. The p.P179S mutation was located in a conserved amino acid in CRIR domain (corepressor interacting region). Modeling results showed that the P179S transition could change local electrostatic properties by adding a negative charge due to serine hydroxyl group of this region of MeCP2 which may affect the function and stability of the protein. The p.R255X mutation is located in TRD-NLS domain (transcription repression domain-nuclear localization signal) of MeCP2 protein.
6. Freedman BH, Kalb LG, Zablotsky B, Stuart EA. {{Relationship Status Among Parents of Children with Autism Spectrum Disorders: A Population-Based Study}}. {J Autism Dev Disord};2011 (May 18)
Despite speculation about an 80% divorce rate among parents of children with an Autism Spectrum Disorder (ASD), very little empirical and no epidemiological research has addressed the issue of separation and divorce among this population. Data for this study was taken from the 2007 National Survey of Children’s Health, a population-based, cross-sectional survey. A total of 77,911 parent interviews were completed on children aged 3-17 years, of which 913 reported an ASD diagnosis. After controlling for relevant covariates, results from multivariate analyses revealed no evidence to suggest that children with ASD are at an increased risk for living in a household not comprised of their two biological or adoptive parents compared to children without ASD in the United States.
7. Frye RE, Sreenivasula S, Adams JB. {{Traditional and non-traditional treatments for autism spectrum disorder with seizures: an on-line survey}}. {BMC Pediatr};2011 (May 18);11(1):37.
ABSTRACT: BACKGROUND: Despite the high prevalence of seizure, epilepsy and abnormal electroencephalograms in individuals with autism spectrum disorder (ASD), there is little information regarding the relative effectiveness of treatments for seizures in the ASD population. In order to determine the effectiveness of traditional and non-traditional treatments for improving seizures and influencing other clinical factor relevant to ASD, we developed a comprehensive on-line seizure survey. METHODS: Announcements (by email and websites) by ASD support groups asked parents of children with ASD to complete the on-line surveys. Survey responders choose one of two surveys to complete: a survey about treatments for individuals with ASD and clinical or subclinical seizures or abnormal electroencephalograms, or a control survey for individuals with ASD without clinical or subclinical seizures or abnormal electroencephalograms. Survey responders rated the perceived effect of traditional antiepileptic drug (AED), non-AED seizure treatments and non-traditional ASD treatments on seizures and other clinical factors (sleep, communication, behavior, attention and mood), and listed up to three treatment side effects. RESULTS: Responses were obtained concerning 733 children with seizures and 290 controls. In general, AEDs were perceived to improve seizures but worsened other clinical factors for children with clinical seizure. Valproic acid, lamotrigine, levetiracetam and ethosuximide were perceived to improve seizures the most and worsen other clinical factors the least out of all AEDs in children with clinical seizures. Traditional non-AED seizure and non-traditional treatments, as a group, were perceived to improve other clinical factors and seizures but the perceived improvement in seizures was significantly less than that reported for AEDs. Certain traditional non-AED treatments, particularly the ketogenic diet, were perceived to improve both seizures and other clinical factors. For ASD individuals with reported subclinical seizures, other clinical factors were reported to be worsened by AEDs and improved by non-AED traditional seizure and non-traditional treatments. The rate of side effects was reportedly higher for AEDs compared to traditional non-AED treatments. CONCLUSION: Although this survey-based method only provides information regarding parental perceptions of effectiveness, this information may be helpful for selecting seizure treatments in individuals with ASD.
8. Hess CR, Landa RJ. {{Predictive and Concurrent Validity of Parent Concern About Young Children at Risk for Autism}}. {J Autism Dev Disord};2011 (May 17)
Parents’ concerns about their children’s development were examined prospectively at 14, 24, and 36 months for 89 younger siblings of a child with autism. Parent reported concern was high at all ages (40-75%) and was higher at 24 and 36 months in children with ASD than non-ASD outcomes (p < .05). Communication concerns were reported most frequently. Parent concern compared to impairment classification based on concurrent standardized tests provided better specificity than sensitivity, and was better for communication than social functioning. Parent communication concern (but not social concern) at 24 months and 36 months predicted ASD versus non-ASD outcome; however, children’s impairment on standardized tests yielded greater predictive value at all ages (p < .001). Close monitoring of this at risk group is warranted.
9. Leekam SR, Prior MR, Uljarevic M. {{Restricted and repetitive behaviors in autism spectrum disorders: A review of research in the last decade}}. {Psychol Bull};2011 (May 16)
Restricted and repetitive behaviors (RRBs) are a core feature of autism spectrum disorders. They constitute a major barrier to learning and social adaptation, but research on their definition, cause, and capacity for change has been relatively neglected. The last decade of research has brought new measurement techniques that have improved the description of RRBs. Research has also identified distinctive subtypes of RRBs in autism spectrum disorders. Research on potential causal origins and immediate triggers for RRBs is still at an early stage. However, promising new ideas and evidence are emerging from neurobiology and developmental psychology that identify neural adaptation, lack of environmental stimulation, arousal, and adaptive functions as key factors for the onset and maintenance of RRBs. Further research is needed to understand how these factors interact with each other to create and sustain atypical levels of RRB. The literature indicates that RRBs have the potential to spontaneously reduce across time, and this is enhanced for those with increased age and cognitive and language ability. Research on interventions is sparse. Pharmacological treatments can be helpful in some children but have adverse side effects. Behavioral intervention methods provide the better intervention option with positive effects, but a more systematic and targeted approach is urgently needed. Evidence suggests that we will learn best from the last decade of research by taking a developmental perspective, by directing future research toward subtypes of RRBs, and by implementing early intervention targeted to improve RRBs before these behaviors become entrenched. (PsycINFO Database Record (c) 2011 APA, all rights reserved).
10. Manning SE, Davin CA, Barfield WD, Kotelchuck M, Clements K, Diop H, Osbahr T, Smith LA. {{Early Diagnoses of Autism Spectrum Disorders in Massachusetts Birth Cohorts, 2001-2005}}. {Pediatrics};2011 (May 16)
Objective: We examined trends in autism spectrum disorder diagnoses by age 36 months (early diagnoses) and identified characteristics associated with early diagnoses. Methods: Massachusetts birth certificate and early-intervention program data were linked to identify infants born between 2001 and 2005 who were enrolled in early intervention and receiving autism-related services before age 36 months (through December 31, 2008). Trends in early autism spectrum disorders were examined using Cochran-Armitage trend tests. chi(2) Statistics were used to compare distributions of selected characteristics for children with and without autism spectrum disorders. Multivariate logistic regression analyses were conducted to identify independent predictors of early diagnoses. Results: A total of 3013 children (77.5 per 10 000 study population births) were enrolled in early intervention for autism spectrum disorder by age 36 months. Autism spectrum disorder incidence increased from 56 per 10 000 infants among the 2001 birth cohort to 93 per 10 000 infants in 2005. Infants of mothers younger than 24 years of age, whose primary language was not English or who were foreign-born had lower odds of an early autism spectrum disorder diagnosis. Maternal age older than 30 years was associated with increased odds of an early autism spectrum disorder diagnosis. Odds of early autism spectrum disorders were 4.5 (95% confidence interval: 4.1-5.0) times higher for boys than girls. Conclusions: Early autism spectrum disorder diagnoses are increasing in Massachusetts, reflecting the national trend observed among older children. Linkage of early-intervention program data with population-based vital statistics is valuable for monitoring autism spectrum disorder trends and planning developmental and educational service needs.
11. Mouridsen SE, Rich B, Isager T. {{Fractures in Individuals With and Without a History of Infantile Autism. A Danish Register Study Based on Hospital Discharge Diagnoses}}. {J Autism Dev Disord};2011 (May 17)
We compared the prevalence and types of fractures in a clinical sample of 118 individuals diagnosed as children with infantile autism (IA) with 336 matched controls from the general population. All participants were screened through the nationwide Danish National Hospital Register. The average observation time was 30.3 years (range 27.3-30.4 years), and mean age at follow-up was 42.7 years (range 27.3-57.3 years). Of the 118 individuals with IA, 14 (11.9%) were registered with at least one fracture diagnosis against 83 (24.7%) in the comparison group (p = 0.004; OR = 0.41; 95%CI 0.22-0.76), but the nature of their fractures seems somewhat different. Epilepsy was a risk factor, but only in the comparison group. Our results lend no support to the notion that fracture is a common comorbid condition in a population of people diagnosed with IA as children.
12. Neves MD, Tremeau F, Nicolato R, Lauar H, Romano-Silva MA, Correa H. {{[Facial emotion recognition deficits in relatives of children with autism are not associated with 5HTTLPR.]}}. {Rev Bras Psiquiatr};2011 (May 13)
OBJECTIVE: A large body of evidence suggests that several aspects of face processing are impaired in autism and that this impairment might be hereditary. This study was aimed at assessing facial emotion recognition in parents of children with autism and its associations with a functional polymorphism of the serotonin transporter (5HTTLPR). METHOD: We evaluated 40 parents of children with autism and 41 healthy controls. All participants were administered the Penn Emotion Recognition Test (ER-40) and were genotyped for 5HTTLPR. RESULTS: Our study showed that parents of children with autism performed worse in the facial emotion recognition test than controls. Analyses of error patterns showed that parents of children with autism over-attributed neutral to emotional faces. We found evidence that 5HTTLPR polymorphism did not influence the performance in the Penn Emotion Recognition Test, but that it may determine different error patterns. CONCLUSION: Facial emotion recognition deficits are more common in first-degree relatives of autistic patients than in the general population, suggesting that facial emotion recognition is a candidate endophenotype for autism.
13. Stephenson DT, O’Neill SM, Narayan S, Tiwari A, Arnold E, Samaroo H, Du F, Ring R, Campbell B, Pletcher M, Vaidya VA, Morton D. {{Histopathologic characterization of the BTBR mouse model of autistic-like behavior reveals selective changes in neurodevelopmental proteins and adult hippocampal neurogenesis}}. {Mol Autism};2011 (May 16);2(1):7.
ABSTRACT: BACKGROUND: The inbred mouse strain, BTBR T+ tf/J (BTBR) exhibits behavioral deficits which mimic the core deficits of autism. Neuroanatomically, the BTBR strain is also characterized by a complete absence of the corpus callosum. The goal of this study was to identify novel molecular and cellular changes in the BTBR mouse focusing on, neuronal, synaptic, glial and plasticity markers in the limbic system as a model for identifying putative molecular and cellular substrates associated with autistic behaviors. . METHODS: Forebrains of 8 to 10 week old male BTBR and aged matched C57Bl/6J controls were evaluated by immunohistochemistry using free floating and paraffin embedded sections. Twenty antibodies directed to antigens specific to neurons, synapses and glia were used. Nissl, Timm’s and acetylcholinesterase (AchE) stains were performed to assess cytoarchitecture, mossy fibers and cholinergic fiber density, respectively. In the hippocampus, quantitative stereological estimates for the mitotic marker bromodeoxyuridine were performed to determine hippocampal progenitor proliferation, survival and differentiation and BDNF mRNA was quantified by in situ hybridization. Quantitative image analysis was performed for NG2, doublecortin, NeuroD, GAD67 and PSA-NCAM. RESULTS: In midline structures including the region of the absent corpus callosum of BTBR mice, myelin markers myelin basic protein (MBP) and 2′ , 3′ -cyclic nucleotide 3′ -phosphodiesterase (CNPase) were reduced and oligodendrocyte precursor NG2 was increased. MBP and CNPase were expressed in small ectopic white matter bundles within the cingulate cortex. Microglia and astrocytes showed no evidence of gliosis, yet orientations of glial fibers were altered in specific white matter areas. In the hippocampus, evidence of reduced neurogenesis included significant reductions in the number of doublecortin, PSA-NCAM, and NeuroD immunoreactive cells in the subgranular zone of the dentate gyrus and a marked reduction in the number of BrdU positive progenitors Furthermore, a significant and profound reduction in BDNF mRNA in the BTBR dentate gyrus was observed. No significant differences were observed in the expression of acetylcholinesterase, mossy fiber synapses, and immunoreactivities for MAP2, parvalbumin, GAD65 and GAD67. CONCLUSIONS: We documented modest and selective alterations in glia, neurons and synapses in BTBR forebrain, along with reduced adult hippocampal neurogenesis. Of all markers examined, the most distinctive changes were observed in the neurodevelopmental proteins NG2, PSA-NCAM, NeuroD and doublecortin. Our results are consistent with aberrant development of the nervous system in BTBR mice and may reveal novel substrates to link callosal abnormalities and autistic behaviors. The changes that we observed in the BTBR mice suggest potential novel therapeutic strategies for intervention in autism spectrum disorders.
14. Zwaigenbaum L, Scherer S, Szatmari P, Fombonne E, Bryson SE, Hyde K, Anognostou E, Brian J, Evans A, Hall G, Nicholas D, Roberts W, Smith I, Vaillancourt T, Volden J. {{The NeuroDevNet Autism Spectrum Disorders Demonstration Project}}. {Semin Pediatr Neurol};2011 (Mar);18(1):40-48.
The NeuroDevNet Autism Spectrum Disorder Demonstration Project interfaces at many levels with the network’s research themes and priorities. Our interdisciplinary team aims to improve understanding of genetic factors underlying vulnerability to autism spectrum disorders (ASDs) to develop better diagnostic strategies and, ultimately, to pinpoint molecular pathways relevant to developing biologically based treatments. Linking our existing longitudinal ASD cohorts with both genetics and neuroimaging studies will provide, for the first time, integrated data on how the genetic variation influences brain and behavioral development in ASD. Importantly, as our science progresses and we translate this information to the health care system, we will also educate policy makers, media, and business, so an informed society is prepared to capitalize on new genomic advances and effectively integrate these into health services for the broader community. We believe that this research has the potential to transform assessment and care for individuals with ASD.
