1. Khemir S, Halayem S, Azzouz H, Siala H, Ferchichi M, Guedria A, Bedoui A, Abdelhak S, Messaoud T, Tebib N, Belhaj A, Kaabachi N. {{Autism in Phenylketonuria Patients: From Clinical Presentation to Molecular Defects}}. {J Child Neurol}. 2016.
Autism has been reported in untreated patients with phenylketonuria. The authors aimed to explore autism in 14 Tunisian and 4 Algerian phenylketonuria patients, and report their clinical, biochemical and molecular peculiarities. The Childhood Autism Rating Scale and the Autism Diagnostic Interview-Revised were used for the diagnosis of autism. Five exons of phenylalanine hydroxylase gene (7, 6, 10, 11, and 5) were amplified by polymerase chain reaction and directly sequenced. Among these patients, 15 were suffering from autism at the time of evaluation. Six mutations were identified: p.E280K, p.G352Vfs, IVS10nt11, p.I224T, p.R261Q, and p.R252W. There was no correlation between autism and mutations affecting the phenylalanine hydroxylase gene, but the age of diet onset was the determining factor in autistic symptoms’ evolution.
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2. Lorenz T, Frischling C, Cuadros R, Heinitz K. {{Autism and Overcoming Job Barriers: Comparing Job-Related Barriers and Possible Solutions in and outside of Autism-Specific Employment}}. {PLoS One}. 2016; 11(1): e0147040.
The aim of this study was to discover how individuals with autism succeed in entering the job market. We therefore sought to identify expected and occurred barriers, keeping them from taking up and staying in employment as well as to identify the solutions used to overcome these barriers. Sixty-six employed individuals with autism-17 of them with autism-specific employment-participated in an online survey. Results showed a variety of possible barriers. Individuals in autism-specific employment named formality problems-problems with organizational and practical process-related aspects of the job entry-most frequently while individuals in non-autism-specific employment mentioned social problems-obstacles concerning communication and human interaction-most. In terms of solutions, both groups used their own resources as much as external help, but differed in their specific strategies. In addition, correlations of an autism-specific employment with general and occupational self-efficacy as well as life and job satisfaction were examined. Possible implications of the results are discussed with regard to problem solving behavior and the use of strengths.
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3. Minshawi NF, Wink LK, Shaffer R, Plawecki MH, Posey DJ, Liu H, Hurwitz S, McDougle CJ, Swiezy NB, Erickson CA. {{A randomized, placebo-controlled trial of d-cycloserine for the enhancement of social skills training in autism spectrum disorders}}. {Mol Autism}. 2016; 7: 2.
BACKGROUND: Researchers have demonstrated that d-cycloserine (DCS) can enhance the effects of behavioral interventions in adults with anxiety and enhances prosocial behavior in animal models of autism spectrum disorders (ASD). This study extended upon this background by combining DCS with behavioral social skills therapy in youth with ASD to assess its impact on the core social deficits of ASD. We hypothesized that DCS used in combination with social skills training would enhance the acquisition of social skills in children with ASD. METHODS: A 10-week, double-blind, placebo-controlled trial of DCS (50 mg) given 30 min prior to weekly group social skills training was conducted at two sites. Children with ASD were randomized to receive 10 weeks (10 doses) of DCS or placebo in a 1:1 ratio. RESULTS: No statistically significant difference attributable to drug treatment was observed in the change scores for the primary outcome measure, the Social Responsiveness Scale (SRS), total score (p = 0.45), or on secondary outcome measures. CONCLUSIONS: The results of this trial demonstrated no drug-related short-term improvement on the primary outcome measure, or any of the secondary outcome measures. However, an overall significant improvement in SRS total raw score was observed from baseline to end of treatment for the entire group of children with ASD. This suggests a need to further study the efficacy of the social skills training protocol. Limitations to the current study and areas for future research are discussed. TRIAL REGISTRATION: ClinicalTrials.govNCT01086475.
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4. Poopal AC, Schroeder LM, Horn PS, Bassell GJ, Gross C. {{Increased expression of the PI3K catalytic subunit p110delta underlies elevated S6 phosphorylation and protein synthesis in an individual with autism from a multiplex family}}. {Mol Autism}. 2016; 7: 3.
BACKGROUND: Dysfunctions in the PI3K/mTOR pathway have gained a lot of attention in autism research. This was initially based on the discovery of several monogenic autism spectrum disorders with mutations or defects in PI3K/mTOR signaling components. Recent genetic studies corroborate that defective PI3K/mTOR signaling might be a shared pathomechanism in autism disorders of so far unknown etiology, but functional molecular analyses in human cells are rare. The goals of this study were to perform a functional screen of cell lines from patients with idiopathic autism for defects in PI3K/mTOR signaling, to test if further functional analyses are suitable to detect underlying molecular mechanisms, and to evaluate this approach as a biomarker tool to identify therapeutic targets. METHODS: We performed phospho-S6- and S6-specific ELISA experiments on 21 lymphoblastoid cell lines from the AGRE collection and on 37 lymphoblastoid cell lines from the Simons Simplex Collection and their healthy siblings. Cell lines from one individual with increased S6 phosphorylation and his multiplex family were analyzed in further detail to identify upstream defects in PI3K signaling associated with autism diagnosis. RESULTS: We detected significantly increased S6 phosphorylation in 3 of the 21 lymphoblastoid cell lines from AGRE compared to a healthy control and in 1 of the 37 lymphoblastoid cell lines from the Simons Simplex Collection compared to the healthy sibling. Further analysis of cells from one individual with elevated S6 phosphorylation showed increased expression of the PI3K catalytic subunit p110delta, which was also observed in lymphoblastoid cells from other autistic siblings but not unaffected members in his multiplex family. The p110delta-selective inhibitor IC87114 reduced elevated S6 phosphorylation and protein synthesis in this cell line. CONCLUSIONS: Our results suggest that functional analysis of PI3K/mTOR signaling is a biomarker tool to identify disease-associated molecular defects that could serve as therapeutic targets in autism. Using this approach, we discovered impaired signaling and protein synthesis through the PI3K catalytic subunit p110delta as an underlying molecular defect and potential treatment target in select autism spectrum disorders. Increased p110delta activity was recently associated with schizophrenia, and our results suggest that p110delta may also be implicated in autism.
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5. Skonieczna-Zydecka K, Gorzkowska I, Pierzak-Sominka J, Adler G. {{The Prevalence of Autism Spectrum Disorders in West Pomeranian and Pomeranian Regions of Poland}}. {J Appl Res Intellect Disabil}. 2016.
BACKGROUND: The prevalence of autism spectrum disorders (ASD) varies worldwide from 1.4/10 000 children in the Arabian Peninsula to 185/10 000 children of Asian population. In Europe, the highest prevalence has been observed in Sweden, while the lowest in Croatia (115/10 000 and 2-3/10 000, respectively). There have been no epidemiological studies on the prevalence of ASD in Polish population. The aim of our study was to assess the prevalence of ASD in children aged 0-16 years, inhabitants of West Pomeranian and Pomeranian regions. MATERIAL AND METHODS: In total, 2514 children (2038 males, 81.1%) were included. The estimates were based on the government registries, whereas data were obtained from Provincial Disability Services Commissions. RESULTS: The prevalence of ASD in children aged 0-16 years varies between two regions of Poland – 32/10 000 in West Pomeranian and 38/10 000 in Pomeranian region. CONCLUSIONS: The average prevalence of ASD was 35/10 000 children and was about 4-fold higher in males (P < 0.05). More studies are necessary. Lien vers le texte intégral (Open Access ou abonnement)
6. Yang X, Si T, Gong Q, Qiu L, Jia Z, Zhou M, Zhao Y, Hu X, Wu M, Zhu H. {{Brain gray matter alterations and associated demographic profiles in adults with autism spectrum disorder: A meta-analysis of voxel-based morphometry studies}}. {Aust N Z J Psychiatry}. 2016.
BACKGROUND: There is increasing evidence that children with autism spectrum disorder are accompanied by specific anatomical alterations. However, the anatomical abnormalities in adults with autism spectrum disorder are poorly understood. This study was aimed to identify the neuroanatomical substrates underlying the pathophysiology of adults with autism spectrum disorder. We also investigated the relationship between neuroanatomical alterations and clinical and demographic characteristics. METHODS: A total of 13 datasets were enrolled, of which 12 studies compared whole-brain differences of 382 adult patients with autism and 393 healthy control subjects. We conducted a meta-analysis to quantitatively estimate regional gray matter volume abnormalities in individuals with autism using the effect-size signed differential mapping. RESULTS: The voxel-wise meta-analysis revealed that relative to controls, adults with autism spectrum disorder had significantly increased gray matter volume in the middle temporal gyrus, superior temporal gyrus, postcentral gyrus and parahippocampal gyrus, and reduced gray matter volume in the anterior cingulate cortex and cerebellum. Variations in gray matter volume were significantly associated with the mean age and mean total IQ score of the patients, as well as with the percentage of male patients with autism. CONCLUSION: These findings confirmed that the neuroanatomical alterations in the fronto-temporal cortices, limbic system and cerebellum in adult individuals with autism were different from the children and young adolescent’s autism. The effects of demographic characteristics on the brain morphological changes allow us to further clarify the neurobiological mechanisms and developmental trajectory in adult population with autism spectrum disorder.
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7. Zaman S, Yazdani U, Deng Y, Li W, Gadad BS, Hynan L, Karp D, Roatch N, Schutte C, Nathan Marti C, Hewitson L, German DC. {{A Search for Blood Biomarkers for Autism: Peptoids}}. {Sci Rep}. 2016; 6: 19164.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interaction and communication, and restricted, repetitive patterns of behavior. In order to identify individuals with ASD and initiate interventions at the earliest possible age, biomarkers for the disorder are desirable. Research findings have identified widespread changes in the immune system in children with autism, at both systemic and cellular levels. In an attempt to find candidate antibody biomarkers for ASD, highly complex libraries of peptoids (oligo-N-substituted glycines) were screened for compounds that preferentially bind IgG from boys with ASD over typically developing (TD) boys. Unexpectedly, many peptoids were identified that preferentially bound IgG from TD boys. One of these peptoids was studied further and found to bind significantly higher levels (>2-fold) of the IgG1 subtype in serum from TD boys (n = 60) compared to ASD boys (n = 74), as well as compared to older adult males (n = 53). Together these data suggest that ASD boys have reduced levels (>50%) of an IgG1 antibody, which resembles the level found normally with advanced age. In this discovery study, the ASD1 peptoid was 66% accurate in predicting ASD.
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8. Zamzow RM, Ferguson BJ, Stichter JP, Porges EC, Ragsdale AS, Lewis ML, Beversdorf DQ. {{Effects of propranolol on conversational reciprocity in autism spectrum disorder: a pilot, double-blind, single-dose psychopharmacological challenge study}}. {Psychopharmacology (Berl)}. 2016.
RATIONALE: Pharmacological intervention for autism spectrum disorder (ASD) is an important addition to treatment, yet currently available agents target co-morbid psychiatric concerns, such as aggression and irritability. Propranolol, a beta-adrenergic antagonist with anxiolytic effects, has been shown to improve verbal fluency and working memory in adults and adolescents with ASD in single-dose challenges. OBJECTIVES: The present pilot study explores the acute effects of propranolol on a measure of conversational reciprocity in this population. We also examined whether autonomic activity and anxiety moderate or mediate response to the drug, given relationships between these variables and ASD, as well as the drug’s effects. METHODS: In a within-subject crossover design, 20 individuals with ASD received a single dose of propranolol or placebo during two sessions in a double-blinded, counterbalanced manner. After drug administration, participants performed a conversational reciprocity task by engaging in a short conversation with the researcher. Measurements of autonomic activity and anxiety were obtained before and after drug administration. RESULTS: Propranolol significantly improved performance on the conversational reciprocity task total [d = 0.40] and nonverbal communication domain scores when compared to the placebo condition. However, neither autonomic activity nor anxiety was significantly associated with drug response. CONCLUSIONS: Acute propranolol administration improved conversational reciprocity in ASD. Further exploration of these preliminary findings, as well as other potential treatment response predictors, with serial doses is warranted.
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9. Zhao X, Zhang P, Fu L, Maes JH. {{Attentional biases to faces expressing disgust in children with autism spectrum disorders: an exploratory study}}. {Sci Rep}. 2016; 6: 19381.
Previous studies on attentional bias towards emotional faces in individuals with autism spectrum disorders (ASD) provided mixed results. This might be due to differences in the examined attentional bias components and emotional expressions. This study assessed three bias components, hypervigilance, disengagement, and avoidance, using faces with a disgust, happy, or neutral expression in a dot-probe and external cuing task in 18 children with ASD and 21 typically developing (TD) children. The children with ASD initially displayed hypervigilance towards the disgust faces, followed by a general tendency to avoid looking back at the spatial location at which any face, irrespective of its emotional expression, had been presented. These results highlight the importance of differentiating between attentional bias components in research on ASD.
