1. 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.
2. Antshel KM, Polacek C, McMahon M, Dygert K, Spenceley L, Dygert L, Miller L, Faisal F. {{Comorbid ADHD and Anxiety Affect Social Skills Group Intervention Treatment Efficacy in Children With Autism Spectrum Disorders}}. {J Dev Behav Pediatr};2011 (Jun 7)
OBJECTIVE:: To assess the influence of psychiatric comorbidity on social skill treatment outcomes for children with autism spectrum disorders (ASDs). METHODS:: A community sample of 83 children (74 males, 9 females) with an ASD (mean age = 9.5 yr; SD = 1.2) and common comorbid disorders participated in 10-week social skills training groups. The first 5 weeks of the group focused on conversation skills and the second 5 weeks focused on social problem solving skills. A concurrent parent group was also included in the treatment. Social skills were assessed using the Social Skills Rating System. Ratings were completed by parents at pre- and posttreatment time periods. RESULTS:: Children with ASD and children with an ASD and comorbid anxiety disorder improved in their parent reported social skills. Children with ASD and comorbid attention deficit/hyperactivity disorder failed to improve. CONCLUSION:: Psychiatric comorbidity affects social skill treatment gains in the ASD population.
3. Bolte S, Schlitt S, Gapp V, Hainz D, Schirman S, Poustka F, Weber B, Freitag C, Ciaramidaro A, Walter H. {{A Close Eye on the Eagle-Eyed Visual Acuity Hypothesis of Autism}}. {J Autism Dev Disord};2011 (Jun 10)
Autism spectrum disorders (ASD) have been associated with sensory hypersensitivity. A recent study reported visual acuity (VA) in ASD in the region reported for birds of prey. The validity of the results was subsequently doubted. This study examined VA in 34 individuals with ASD, 16 with schizophrenia (SCH), and 26 typically developing (TYP). Participants with ASD did not show higher VA than those with SCH and TYP. There were no substantial correlations of VA with clinical severity in ASD or SCH. This study could not confirm the eagle-eyed acuity hypothesis of ASD, or find evidence for a connection of VA and clinical phenotypes. Research needs to further address the origins and circumstances associated with altered sensory or perceptual processing in ASD.
4. 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.
5. Elder JH, Donaldson SO, Kairalla J, Valcante G, Bendixen R, Ferdig R, Self E, Walker J, Palau C, Serrano M. {{In-Home Training for Fathers of Children with Autism: A Follow up Study and Evaluation of Four Individual Training Components}}. {J Child Fam Stud};2011 (Jun);20(3):263-271.
Literature regarding fathers of children with autism remains sparse, and because mothers are the more common intervening parent, few training methods have focused on fathers. Thus, we sought to evaluate effects of in-home training directed at fathers and their ability to train mothers in the same manner in which they were trained. Fathers were taught four skills commonly associated with in-home training interventions for parents of children with autism: following the child’s lead, imitation with animation, commenting on the child, and expectant waiting. Father skills were evaluated twice a week for 12 weeks during videotaped in-home father-child play sessions. Analyses included visual inspection of graphed data and statistical analyses of father skill acquisition, mother skill acquisition, and child behaviors with both parents. A multivariate repeated measures analysis of 18 dyads revealed significant increases in frequencies of fathers’ imitation with animation, expectant waiting, and commenting on the child. Child initiating rates increased significantly as did frequencies of child non-speech vocalizations. Analysis of mothers revealed significant increases in frequencies of imitation with animation, expectant waiting, and following the child’s lead. Child behaviors had similar results for father and mother sessions. Findings are consistent with those from our first study indicating that fathers can effectively implement skills that promote father-child social interactions and that children respond positively to this approach.
6. Freilinger M, Dunkler D, Lanator I, Item CB, Muhl A, Fowler B, Bodamer OA. {{Effects of Creatine Supplementation in Rett Syndrome: A Randomized, Placebo-Controlled Trial}}. {J Dev Behav Pediatr};2011 (Jun 7)
OBJECTIVE:: To evaluate the effects of creatine monohydrate (CMH) supplementation on global DNA methylation and disease-specific clinical symptoms in female patients with Rett syndrome (RTT). METHODS:: Double-blind, randomized, placebo-controlled crossover trial of female patients with RTT. Participants received 200 mg/kg of either CMH or placebo daily for 6 months and switched following a 4-week washout period. Primary endpoints were change in global DNA methylation and in a RTT-specific symptom score as defined by medical history and clinical evaluation with Rett Syndrome Motor and Behavioral Assessment. Secondary endpoints were changes in biochemical markers of methionine metabolism. RESULTS:: Eighteen female patients aged 3 to 25 years with clinically diagnosed typical RTT and MECP2 mutation at clinical Stages III or IV were studied. CMH supplementation resulted in a statistically significant increase of global methylation by 0.11 (95% confidence interval 0.03-0.19, p = .009) compared with placebo. Total and subscores of Rett Syndrome Motor and Behavioral Assessment tended to improve but without statistical significance. CONCLUSION:: CMH supplementation increases global DNA methylation statistically significantly. Scores were lower for creatine than for placebo reflecting clinical improvement but not reaching statistical significance. Biochemical variables of methionine-homocysteine remethylation are unaffected. Multicenter studies are urgently warranted to evaluate the long-term effects of CMH supplementation in an optimally homogenous RTT population over a prolonged period.
7. 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.
8. 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.
9. Kott A. {{Autism risk in second children is associated with close birthspacing}}. {Perspect Sex Reprod Health};2011 (Jun);43(2):130-131.
10. Lord C. {{Epidemiology: How common is autism?}}. {Nature};2011;474(7350):166-168.
11. Nayate A, Tonge BJ, Bradshaw JL, McGinley JL, Iansek R, Rinehart NJ. {{Differentiation of High-Functioning Autism and Asperger’s Disorder Based on Neuromotor Behaviour}}. {J Autism Dev Disord};2011 (Jun 10)
Autism and Asperger’s disorder (AD) are characterised by impairments in social interaction, stereotypic behaviours or restricted interests. Although currently listed as distinct clinical disorders, the validity of their distinction remains controversial. This study examined gait in children with autism and AD. Eleven children with high-functioning autism and eleven children with AD completed a series of walking tasks. Results indicated distinct movement disturbance; these findings are discussed in light of seminal papers in this field by Vilensky et al. (Arch Neurol 38:646-649, 1981) and Hallett et al. (Arch Neurol 50:1304-1308, 1993) who interpret the gait of individuals with autism using parkinsonian and cerebellar-ataxia patient models, respectively. Distinctions in gait patterns implicating perhaps unique motor circuit disturbances support the hypothesis that autism and AD may have unique neurodevelopmental trajectories.
12. Qurashi A, Li W, Zhou JY, Peng J, Jin P. {{Nuclear Accumulation of Stress Response mRNAs Contributes to the Neurodegeneration Caused by Fragile X Premutation rCGG Repeats}}. {PLoS Genet};2011 (Jun);7(6):e1002102.
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder seen in Fragile X premutation carriers. Previous studies found that Fragile X rCGG repeats are sufficient to cause neurodegeneration and that the rCGG repeat-binding proteins Pur alpha and hnRNP A2/B1 can modulate rCGG-mediated neuronal toxicity. To explore the role of Pur alpha in rCGG-mediated neurodegeneration further, we took a proteomic approach and identified more than 100 proteins that interact with Pur alpha. Of particular interest is Rm62, the Drosophila ortholog of p68 RNA helicase, which could modulate rCGG-mediated neurodegeneration. Here we show that rCGG repeats decreased the expression of Rm62 posttranscriptionally, leading to the nuclear accumulation of Hsp70 transcript, as well as additional mRNAs involved in stress and immune responses. Together these findings suggest that abnormal nuclear accumulation of these mRNAs, likely as a result of impaired nuclear export, could contribute to FXTAS pathogenesis.
13. Saalasti S, Tiippana K, Katsyri J, Sams M. {{The effect of visual spatial attention on audiovisual speech perception in adults with Asperger syndrome}}. {Exp Brain Res};2011 (Jun 10)
Individuals with Asperger syndrome (AS) have problems in following conversation, especially in the situations where several people are talking. This might result from impairments in audiovisual speech perception, especially from difficulties in focusing attention to speech-relevant visual information and ignoring distracting information. We studied the effect of visual spatial attention on the audiovisual speech perception of adult individuals with AS and matched control participants. Two faces were presented side by side, one uttering /aka/ and the other /ata/, while an auditory stimulus of /apa/ was played. The participants fixated on a central cross and directed their attention to the face that an arrow pointed to, reporting which consonant they heard. We hypothesized that the adults with AS would be more distracted by a competing talking face than the controls. Instead, they were able to covertly attend to the talking face, and they were as distracted by a competing face as the controls. Independently of the attentional effect, there was a qualitative difference in audiovisual speech perception: when the visual articulation was /aka/, the control participants heard /aka/ almost exclusively, while the participants with AS heard frequently /ata/. This finding may relate to difficulties in face-to-face communication in AS.
14. 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.
15. Silva LM, Schalock M, Ayres R. {{A model and treatment for autism at the convergence of Chinese medicine and Western science: First 130 cases}}. {Chin J Integr Med};2011 (Jun);17(6):421-429.
OBJECTIVE: To present a model for autism showing that impairment of sensory and self-regulation is the core deficit that underlies delays in social/language skills and abnormal behavior in autism; and to demonstrate the efficacy of a treatment for autism based on Chinese medicine. METHODS: Children with autism under 6 years of age were assigned to treatment or wait-list conditions. A total of 130 children were treated and the results compared with 45 wait-list controls. Treatment is a tuina methodology directed at sensory impairment-Kai Qiao Tuina. The treatment was a five-month protocol that was implemented daily by trained parents via trained support staff. The effects of treatment on the main symptoms, autistic behavior, social/language delay, sensory and self-regulatory impairment, as well as on parenting stress, were observed and compared. RESULTS: The treatment had a large effect size (P<0.0001) on measures of sensory and self-regulation. The evaluations done by pre-school teachers demonstrated improvement in the measures of autism (P<0.003), and were confirmed by evaluations done by parents (P<0.0001). There was a large decrease (P<0.0001) in parenting stress. CONCLUSIONS: Sensory and self-regulatory impairment is a main factor in the development and severity of autism. Treatment of young children with autism with Kai Qiao Tuina resulted in a decrease in sensory and self-regulatory impairment and a reduction in severity of measures of autism.
16. Solomon M, Frank MJ, Smith AC, Ly S, Carter CS. {{Transitive inference in adults with autism spectrum disorders}}. {Cogn Affect Behav Neurosci};2011 (Jun 10)
Individuals with autism spectrum disorders (ASDs) exhibit intact rote learning with impaired generalization. A transitive inference paradigm, involving training on four sequentially presented stimulus pairs containing overlapping items, with subsequent testing on two novel pairs, was used to investigate this pattern of learning in 27 young adults with ASDs and 31 matched neurotypical individuals (TYPs). On the basis of findings about memory and neuropathology, we hypothesized that individuals with ASDs would use a relational flexibility/conjunctive strategy reliant on an intact hippocampus, versus an associative strength/value transfer strategy requiring intact interactions between the prefrontal cortex and the striatum. Hypotheses were largely confirmed. ASDs demonstrated reduced interference from intervening pairs in early training; only TYPs formed a serial position curve by test; and ASDs exhibited impairments on the novel test pair consisting of end items with intact performance on the inner test pair. However, comparable serial position curves formed for both groups by the end of the first block.
17. Sung M, Ooi YP, Goh TJ, Pathy P, Fung DS, Ang RP, Chua A, Lam CM. {{Effects of Cognitive-Behavioral Therapy on Anxiety in Children with Autism Spectrum Disorders: A Randomized Controlled Trial}}. {Child Psychiatry Hum Dev};2011 (Jun 10)
We compared the effects of a 16-week Cognitive-Behavioral Therapy (CBT) program and a Social Recreational (SR) program on anxiety in children with Autism Spectrum Disorders (ASD). Seventy children (9-16 years old) were randomly assigned to either of the programs (n (CBT) = 36; n (SR) = 34). Measures on child’s anxiety using the Spence Child Anxiety Scale-Child (SCAS-C) and the Clinical Global Impression-Severity scale (CGI-S) were administered at pre-, post-treatment, and follow-ups (3- and 6-month). Children in both programs showed significantly lower levels of generalized anxiety and total anxiety symptoms at 6-month follow-up on SCAS-C. Clinician ratings on the CGI-S demonstrated an increase in the percentage of participants rated as « Normal » and « Borderline » for both programs. Findings from the present study suggest factors such as regular sessions in a structured setting, consistent therapists, social exposure and the use of autism-friendly strategies are important components of an effective framework in the management of anxiety in children and adolescents with ASD.
18. Thomas AM, Bui N, Perkins JR, Yuva-Paylor LA, Paylor R. {{Group I metabotropic glutamate receptor antagonists alter select behaviors in a mouse model for fragile X syndrome}}. {Psychopharmacology (Berl)};2011 (Jun 10)
RATIONALE: Studies in the Fmr1 knockout (KO) mouse, a model of fragile X syndrome (FXS), suggest that excessive signaling through group I metabotropic glutamate receptors (mGluRs), comprised of subtypes mGluR1 and mGluR5, may play a role in the pathogenesis of FXS. Currently, no studies have assessed the effect of mGluR1 modulation on Fmr1 KO behavior, and there has not been an extensive behavioral analysis of mGluR5 manipulation in Fmr1 KO mice. OBJECTIVES: The goals for this study were to determine if pharmacologic blockade of mGluR1 may affect Fmr1 KO behavior as well as to expand on the current literature regarding pharmacologic blockade of mGluR5 on Fmr1 KO behavior. METHODS: Reduction of mGluR1 or mGluR5 activity was evaluated on a variety of behavioral assays in wild-type (WT) and Fmr1 KO mice through the use of antagonists: JNJ16259685 (JNJ, mGluR1 antagonist) and MPEP (mGluR5 antagonist). RESULTS: JNJ and MPEP decreased marble burying in both WT and Fmr1 KO mice without reductions in activity. Neither JNJ nor MPEP affected the prepulse inhibition in either WT or Fmr1 KO mice. JNJ did not affect Fmr1 KO motor coordination but did impair WT performance. MPEP improved a measure of motor learning in Fmr1 KO but not WT mice. While both JNJ and MPEP decreased the audiogenic seizures in the Fmr1 KO, MPEP completely abolished the manifestation of seizures. CONCLUSION: These data illustrate that, while the manipulation of either mGluR1 or mGluR5 can affect select behaviors in the Fmr1 KO, we observe greater effects upon mGluR5 reduction.
19. Whalley K. {{Autism: Converging pathways}}. {Nat Rev Neurosci};2011 (Jun 8)
