1. {{International society for autism research news}}. {Autism Res};2011 (Jun);4(3):237.
2. Adams JB, Audhya T, McDonough-Means S, Rubin RA, Quig D, Geis E, Gehn E, Loresto M, Mitchell J, Atwood S, Barnhouse S, Lee W. {{Nutritional and Metabolic Status of Children with Autism vs. Neurotypical Children, and the Association with Autism Severity}}. {Nutr Metab (Lond)};2011 (Jun 8);8(1):34.
ABSTRACT: BACKGROUND: The relationship between relative metabolic disturbances and developmental disorders is an emerging research focus. This study compares the nutritional and metabolic status of children with autism with that of neurotypical children and investigates the possible association of autism severity with biomarkers. METHOD: Participants were children ages 5-16 years in Arizona with Autistic Spectrum Disorder (n=55) compared with non-sibling, neurotypical controls (n=44) of similar age, gender and geographical distribution. Neither group had taken any vitamin/mineral supplements in the two months prior to sample collection. Autism severity was assessed using the Pervasive Development Disorder Behavior Inventory (PDD-BI), Autism Treatment Evaluation Checklist (ATEC), and Severity of Autism Scale (SAS). Study measurements included: vitamins, biomarkers of vitamin status, minerals, plasma amino acids, plasma glutathione, and biomarkers of oxidative stress, methylation, sulfation and energy production. RESULTS: Biomarkers of children with autism compared to those of controls using a t-test or Wilcoxon test found the following statistically significant differences (p<0.001): Low levels of biotin, plasma glutathione, RBC SAM, plasma uridine, plasma ATP, RBC NADH, RBC NADPH, plasma sulfate (free and total), and plasma tryptophan; also high levels of oxidative stress markers and plasma glutamate. Levels of biomarkers for the neurotypical controls were in good agreement with accessed published reference ranges. In the Autism group, mean levels of vitamins, minerals, and most amino acids commonly measured in clinical care were within published reference ranges. A stepwise, multiple linear regression analysis demonstrated significant associations between several groups of biomarkers with all three autism severity scales, including vitamins (adjusted R2 of 0.25-0.57), minerals (adj. R2 of 0.22-0.38), and plasma amino acids (adj. R2 of 0.22-0.39). CONCLUSION: The autism group had many statistically significant differences in their nutritional and metabolic status, including biomarkers indicative of vitamin insufficiency, increased oxidative stress, reduced capacity for energy transport, sulfation and detoxification. Several of the biomarker groups were significantly associated with variations in the severity of autism. These nutritional and metabolic differences are generally in agreement with other published results and are likely amenable to nutritional supplementation. Research investigating treatment and its relationship to the co-morbidities and etiology of autism is warranted.
3. Bartell SM, Lewandowski TA. {{Administrative censoring in ecological analyses of autism and a bayesian solution}}. {J Environ Public Health};2011;2011:202783.
Widely cited ecological analyses of autism have reported associations with mercury emissions, with precipitation, and race at the level of counties or school districts. However, state educational agencies often suppress any low numerical autism counts before releasing data-a phenomenon known as « administrative censoring. » Previous analyses did not describe appropriate methods for censored data analysis; common substitution or exclusion methods are known to introduce bias and produce artificially narrow confidence intervals. We apply a Bayesian censored random effects Poisson model to reanalyze associations between 2001 Toxic Release Inventory reported mercury emissions and 2000-2001 autism counts in Texas. Relative risk estimates for autism decreased from 4.44 (95% CI: 4.16, 4.74) per thousand lbs. of air mercury emissions using a naive zero-substitution approach to 1.42 (95% CI: 1.09, 1.78) using the Bayesian approach. Inadequate attention to censoring poses a serious threat to the validity of ecological analyses of autism and other health outcomes.
4. Bongmba OY, Martinez LA, Elhardt ME, Butler K, Tejada-Simon MV. {{Modulation of dendritic spines and synaptic function by Rac1: A possible link to Fragile X syndrome pathology}}. {Brain Res};2011 (May 17)
Rac1, a protein of the Rho GTPase subfamily, has been implicated in neuronal and spine development as well as the formation of synapses with appropriate partners. Dendrite and spine abnormalities have been implicated in several psychiatric disorders such as Fragile X syndrome, where neurons show a high density of long, thin, and immature dendritic spines. Although abnormalities in dendrites and spines have been correlated with impaired cognitive abilities in mental retardation, the causes of these malformations are not yet well understood. Fragile X syndrome is the most common type of inherited mental retardation caused by the absence of FMRP protein, a RNA-binding protein implicated in the regulation of mRNA translation and transport, leading to protein synthesis. We suggest that FMRP might act as a negative regulator on the synthesis of Rac1. Maintaining an optimal level of Rac1 and facilitating the reorganization of the cytoskeleton likely leads to normal neuronal morphology during activity-dependent plasticity. In our study, we first demonstrated that Rac1 is not only associated but necessary for normal spine development and long-term synaptic plasticity. We further showed that, in Fmr1 knockout mice, lack of FMRP induces an overactivation of Rac1 in the mouse brain and other organs that have been shown to be altered in Fragile X syndrome. In those animals, pharmacological manipulation of Rac1 partially reverses their altered long-term plasticity. Thus, regulation of Rac1 may provide a functional link among deficient neuronal morphology, aberrant synaptic plasticity and cognition impairment in Fragile X syndrome.
5. Curran S, Bolton P, Rozsnyai K, Chiocchetti A, Klauck SM, Duketis E, Poustka F, Schlitt S, Freitag CM, Lee I, Muglia P, Poot M, Staal W, de Jonge MV, Ophoff RA, Lewis C, Skuse D, Mandy W, Vassos E, Fossdal R, Magnusson P, Hreidarsson S, Saemundsen E, Stefansson H, Stefansson K, Collier D. {{No association between a common single nucleotide polymorphism, rs4141463, in the MACROD2 Gene and Autism Spectrum Disorder}}. {Am J Med Genet B Neuropsychiatr Genet};2011 (Jun 8)
The Autism Genome Project (AGP) Consortium recently reported genome-wide significant association between autism and an intronic single nucleotide polymorphism marker, rs4141463, within the MACROD2 gene. In the present study we attempted to replicate this finding using an independent case-control design of 1,170 cases with autism spectrum disorder (ASD) (874 of which fulfilled narrow criteria for Autism (A)) from five centers within Europe (UK, Germany, the Netherlands, Italy, and Iceland), and 35,307 controls. The combined sample size gave us a non-centrality parameter (NCP) of 11.9, with 93% power to detect allelic association of rs4141463 at an alpha of 0.05 with odds ratio of 0.84 (the best odds ratio estimate of the AGP Consortium data), and for the narrow diagnosis of autism, an NCP of 8.9 and power of 85%. Our case-control data were analyzed for association, stratified by each center, and the summary statistics were combined using the meta-analysis program, GWAMA. This resulted in an odds ratio (OR) of 1.03 (95% CI 0.944-1.133), with a P-value of 0.5 for ASD and OR of 0.99 (95% CI 0.88-1.11) with P-value = 0.85 for the Autism (A) sub-group. Therefore, this study does not provide support for the reported association between rs4141463 and autism. (c) 2011 Wiley-Liss, Inc.
6. Delmolino L, Harris SL. {{Matching Children on the Autism Spectrum to Classrooms: A Guide for Parents and Professionals}}. {J Autism Dev Disord};2011 (Jun 7)
Meeting the needs of a learner with an autism spectrum disorder requires specialized expertise. Assessing the extent to which a potential program or classroom meets a child’s needs is a source of serious challenge for parents and professionals alike. Indeed, identifying, prioritizing and agreeing upon the child’s needs are complex questions for which there are no clear and straightforward answers. The process of establishing a match between a student and a placement must explore several primary dimensions: child, setting, and instructor variables, treatment philosophy and strategies, assessment and evaluation, and family needs and involvement. Additionally, there is a great deal of complexity considering how to interpret, integrate and apply empirical research findings and prominent professional opinions to develop sound and practical solutions. Discussion and agreement about the importance of each of these factors and how they apply in a specific situation forms the foundation of an interactive dialogue between service providers and families to create a « best fit » between student and program.
7. Esposito G, Venuti P, Bornstein MH. {{ASSESSMENT OF DISTRESS IN YOUNG CHILDREN: A COMPARISON OF AUTISTIC DISORDER, DEVELOPMENTAL DELAY, AND TYPICAL DEVELOPMENT}}. {Res Autism Spectr Disord};2011;5(4):1510-1516.
Distress emotions in very young children are manifest in vocal, facial, and bodily cues. Moreover, children with different developmental conditions (i.e. Autistic Disorder- AD, Developmental Delay- DD, Typically Developing- TD) appear to manifest their distress emotions via different channels. To decompose channel of emotional distress display by group, we conducted a study in which video clips of crying of 18 children 18 months of age belonging to three groups (AD, DD, TD) were modified to isolate vocal, facial, or bodily cues, and 42 female adults were asked to judge the distress and typicality (expected normality) of the different stimuli. We find variation in adult judgements of distress and typicality by child group (AD, DD, TD) and by isolated cues (vocal, facial, or body). Although there is some overlap between responses to episodes of crying of children with AD and those with DD, the different cues of crying of children with AD tend to be considered more atypical and distressed than those of the other two groups (DD and TD). Early assessment of different cues of the expression of distress, and more generally of emotional expressivity in a child, may provide useful information for pediatricians and practitioners who are in contact with young children and must make clinical screening decisions. The findings also alert parents of children with AD to important aspects of their cries.
8. Geurts HM, Vissers ME. {{Elderly with Autism: Executive Functions and Memory}}. {J Autism Dev Disord};2011 (Jun 8)
Cognitive autism research is mainly focusing on children and young adults even though we know that autism is a life-long disorder and that healthy aging already has a strong impact on cognitive functioning. We compared the neuropsychological profile of 23 individuals with autism and 23 healthy controls (age range 51-83 years). Deficits were observed in attention, working memory, and fluency. Aging had a smaller impact on fluency in the high functioning autism (HFA) group than in the control group, while aging had a more profound effect on visual memory performance in the HFA group. Hence, we provide novel evidence that elderly with HFA have subtle neuropsychological deficits and that the developmental trajectories differ between elderly with and without HFA in particular cognitive domains.
9. Jackson P, Skirrow P, Hare DJ. {{Asperger Through the Looking Glass: An Exploratory Study of Self-Understanding in People with Asperger’s Syndrome}}. {J Autism Dev Disord};2011 (Jun 7)
Hobson (Autism and the development of mind. Lawrence Erlbaum, Hove, UK 1993) has proposed that the cognitive and linguistic disabilities that characterise autism result from abnormalities in inter-subjective engagement during infancy, which in turn results in impaired reflective self-awareness. The aim of the present study was to test Hobson’s hypothesis by examining self-understanding in Asperger’s syndrome (AS) using Damon and Hart’s (Self-understanding in childhood and adolescence. Cambridge University Press, Cambridge, 1988) model of self-concept. Ten participants with Asperger’s syndrome were compared with ten non AS controls using the Self-understanding Interview (Damon and Hart in Self-understanding in Childhood and Adolescence. Cambridge University Press, Cambridge, 1988). The study found that the Asperger’s group demonstrated impairment in the « self-as-object » and « self-as-subject » domains of the Self-understanding Interview, which supported Hobson’s concept of an impaired capacity for self-awareness and self-reflection in people with ASD. The results are discussed with reference to previous research regarding the development of self-understanding in people with ASD.
10. Kagohara DM, Sigafoos J, Achmadi D, van der Meer L, O’Reilly MF, Lancioni GE. {{Teaching students with developmental disabilities to operate an iPod Touch((R)) to listen to music}}. {Res Dev Disabil};2011 (Jun 4)
We evaluated an intervention procedure for teaching three students with developmental disabilities to independently operate a portable multimedia device (i.e., an iPod Touch((R))) to listen to music. The intervention procedure included the use of video modeling, which was presented on the same iPod Touch((R)) that the students were taught to operate to listen to music. Four phases (i.e., baseline, intervention, fading, and follow-up) were arranged in accordance with a delayed multiple-probe across participants design. During baseline, the students performed from 25 to 62.5% of the task analyzed steps correctly. With intervention, all three students correctly performed 80-100% of the steps and maintained this level of performance when video modeling was removed and during follow-up. The findings suggest that the video modeling procedure was effective for teaching the students to independently operate a portable multimedia device to access age-appropriate leisure content.
11. Kao B, Romero-Bosch L, Plante W, Lobato D. {{The experiences of Latino siblings of children with developmental disabilities}}. {Child Care Health Dev};2011 (Jun 8)
Objective This qualitative study explored the experiences of Latino siblings of children with developmental disabilities. Methods Parents and typically developing siblings from 15 Latino families with a child with a developmental disability participated in separate interviews. Results Using consensual qualitative research methodology, domains reflecting siblings’ relationships, emotional experiences and communication about the disability were identified. The child’s need for caregiving was a prominent topic in the sibling and parent narratives. Parents reported concerns about siblings’ experience of differential treatment, whereas siblings reported concerns about restricted social activities because of their brother/sister. Conclusions Including multiple informants revealed commonalities and differences in parents’ and siblings’ perspectives on the impact of a child’s disability. The importance of considering sibling adaptation in sociocultural context is discussed.
12. Karimov CB, Moragianni VA, Cronister A, Srouji S, Petrozza J, Racowsky C, Ginsburg E, Thornton KL, Welt CK. {{Increased frequency of occult fragile X-associated primary ovarian insufficiency in infertile women with evidence of impaired ovarian function}}. {Hum Reprod};2011 (Jun 6)
BACKGROUND The FMR1 premutation is associated with overt primary ovarian insufficiency (POI). However, its prevalence in women with occult POI (i.e. menstrual cycles, but impaired ovarian response) has not been examined. We hypothesized that both the FMR1 premutation and intermediate allele is more frequent in infertile women with occult POI than in controls, and that a repeat length cutoff might predict occult POI. METHODS All subjects were menstruating women <42 years old and with no family history of unexplained mental retardation, autism or fragile X syndrome. Cases had occult POI defined by elevated FSH or poor response to gonadotrophin therapy (n= 535). Control subjects (n= 521) had infertility from other causes or were oocyte donors. Prevalence of the FMR1 premutation and intermediate alleles was examined and allele length was compared between controls and women with occult POI. RESULTS The frequency of the premutation (7/535 versus 1/521; P< 0.05) and intermediate alleles (17/535 versus 7/521; P< 0.05) was higher in women with occult POI than in controls. The allele with the greatest number of CGG repeats was longer in women with occult POI compared with controls (32.7 +/- 7.1 versus 31.6 +/- 4.3; P< 0.01). A receiver operating characteristic curve examining repeat length as a test for occult POI had an area of 0.56 +/- 0.02 (P< 0.01). A repeat cutoff of 45 had a specificity of 98%, but a sensitivity of only 5% to identify occult POI. The positive predictive value was only 21% for a fertility population that has approximately 22% of its patients with occult POI. CONCLUSIONS The data suggest that FMR1 premutations and intermediate alleles are increased in women with occult POI. Thus, FMR1 testing should be performed in these women as some will have fragileX-associated POI. Although the FMR1 repeat lengths were longer in women with occult POI, the data do not support the use of a repeat length cutoff to predict occult POI.
13. Konopka G, Wexler E, Rosen E, Mukamel Z, Osborn GE, Chen L, Lu D, Gao F, Gao K, Lowe JK, Geschwind DH. {{Modeling the functional genomics of autism using human neurons}}. {Mol Psychiatry};2011 (Jun 7)
Human neural progenitors from a variety of sources present new opportunities to model aspects of human neuropsychiatric disease in vitro. Such in vitro models provide the advantages of a human genetic background combined with rapid and easy manipulation, making them highly useful adjuncts to animal models. Here, we examined whether a human neuronal culture system could be utilized to assess the transcriptional program involved in human neural differentiation and to model some of the molecular features of a neurodevelopmental disorder, such as autism. Primary normal human neuronal progenitors (NHNPs) were differentiated into a post-mitotic neuronal state through addition of specific growth factors and whole-genome gene expression was examined throughout a time course of neuronal differentiation. After 4 weeks of differentiation, a significant number of genes associated with autism spectrum disorders (ASDs) are either induced or repressed. This includes the ASD susceptibility gene neurexin 1, which showed a distinct pattern from neurexin 3 in vitro, and which we validated in vivo in fetal human brain. Using weighted gene co-expression network analysis, we visualized the network structure of transcriptional regulation, demonstrating via this unbiased analysis that a significant number of ASD candidate genes are coordinately regulated during the differentiation process. As NHNPs are genetically tractable and manipulable, they can be used to study both the effects of mutations in multiple ASD candidate genes on neuronal differentiation and gene expression in combination with the effects of potential therapeutic molecules. These data also provide a step towards better understanding of the signaling pathways disrupted in ASD.Molecular Psychiatry advance online publication, 7 June 2011; doi:10.1038/mp.2011.60.
14. Koyama T, Wang HT. {{Use of activity schedule to promote independent performance of individuals with autism and other intellectual disabilities: A review}}. {Res Dev Disabil};2011 (Jun 5)
A literature review was conducted on the effectiveness of activity schedules. Twenty three studies that a) were peer-reviewed, b) were experimental, c) implemented activity schedule as a primary intervention, d) incorporated multiple activities, and e) aimed to teach learners to self-manage individual schedules were included in the review. The results demonstrated the effectiveness of activity schedules for promoting independence and self-management skills for a broad range of individuals with intellectual disabilities. An increase in engagement and on-task behavior was the most frequently cited outcome, followed by independent task initiation or transition and self-scheduling. Failure to include social validity measures and caregivers as interventionists were discussed. A corpus of the reviewed studies supports applications of activity schedule in school and (group) home settings.
15. Lit L, Sharp FR, Bertoglio K, Stamova B, Ander BP, Sossong AD, Hendren RL. {{Gene expression in blood is associated with risperidone response in children with autism spectrum disorders}}. {Pharmacogenomics J};2011 (Jun 7)
Children with autism spectrum disorders (ASDs) often have severe behavioral problems. Not all children with these problems respond to atypical antipsychotic medications; therefore, we investigated whether peripheral blood gene expression before treatment with risperidone, an atypical antipsychotic, was associated with improvements in severe behavioral disturbances 8 weeks following risperidone treatment in 42 ASD subjects (age 112.7+/-51.2 months). Exon expression levels in blood before risperidone treatment were compared with pre-post risperidone change in Aberrant Behavior Checklist-Irritability (ABC-I) scores. Expression of exons within five genes was correlated with change in ABC-I scores across all risperidone-treated subjects: GBP6, RABL5, RNF213, NFKBID and RNF40 (alpha<0.001). RNF40 is located at 16p11.2, a region implicated in autism and schizophrenia. Thus, these genes expressed before treatment were associated with subsequent clinical response. Future studies will be needed to confirm these results and determine whether this expression profile is associated with risperidone response in other disorders, or alternative antipsychotic response within ASD.The Pharmacogenomics Journal advance online publication, 7 June 2011; doi:10.1038/tpj.2011.23.
16. Lord C. {{Epidemiology: How common is autism?}}. {Nature};2011;474(7350):166-168.
17. Sakai Y, Shaw CA, Dawson BC, Dugas DV, Al-Mohtaseb Z, Hill DE, Zoghbi HY. {{Protein interactome reveals converging molecular pathways among autism disorders}}. {Sci Transl Med};2011 (Jun 8);3(86):86ra49.
To uncover shared pathogenic mechanisms among the highly heterogeneous autism spectrum disorders (ASDs), we developed a protein interaction network that identified hundreds of new interactions among proteins encoded by ASD-associated genes. We discovered unexpectedly high connectivity between SHANK and TSC1, previously implicated in syndromic autism, suggesting that common molecular pathways underlie autistic phenotypes in distinct syndromes. ASD patients were more likely to harbor copy number variations that encompass network genes than were control subjects. We also identified, in patients with idiopathic ASD, three de novo lesions (deletions in 16q23.3 and 15q22 and one duplication in Xq28) that involve three network genes (NECAB2, PKM2, and FLNA). The protein interaction network thus provides a framework for identifying causes of idiopathic autism and for understanding molecular pathways that underpin both syndromic and idiopathic ASDs.
18. Suzuki K, Matsuzaki H, Iwata K, Kameno Y, Shimmura C, Kawai S, Yoshihara Y, Wakuda T, Takebayashi K, Takagai S, Matsumoto K, Tsuchiya KJ, Iwata Y, Nakamura K, Tsujii M, Sugiyama T, Mori N. {{Plasma cytokine profiles in subjects with high-functioning autism spectrum disorders}}. {PLoS One};2011;6(5):e20470.
BACKGROUND: Accumulating evidence suggests that dysregulation of the immune system is involved in the pathophysiology of autism spectrum disorders (ASD). The aim of the study was to explore immunological markers in peripheral plasma samples from non-medicated subjects with high-functioning ASD. METHODOLOGY/PRINCIPAL FINDINGS: A multiplex assay for cytokines and chemokines was applied to plasma samples from male subjects with high-functioning ASD (n = 28) and matched controls (n = 28). Among a total of 48 analytes examined, the plasma concentrations of IL-1beta, IL-1RA, IL-5, IL-8, IL-12(p70), IL-13, IL-17 and GRO-alpha were significantly higher in subjects with ASD compared with the corresponding values of matched controls after correction for multiple comparisons. CONCLUSION/SIGNIFICANCE: The results suggest that abnormal immune responses as assessed by multiplex analysis of cytokines may serve as one of the biological trait markers for ASD.
19. Whalley K. {{Autism: Converging pathways}}. {Nat Rev Neurosci};2011 (Jun 8)
