1. Boccuto L, Lauri M, Sarasua SM, Skinner CD, Buccella D, Dwivedi A, Orteschi D, Collins JS, Zollino M, Visconti P, Dupont B, Tiziano D, Schroer RJ, Neri G, Stevenson RE, Gurrieri F, Schwartz CE. {{Prevalence of SHANK3 variants in patients with different subtypes of autism spectrum disorders}}. {Eur J Hum Genet};2012 (Aug 15)
Autism spectrum disorders (ASDs) include three main conditions: autistic disorder (AD), pervasive developmental disorder, not otherwise specified (PDD-NOS), and Asperger syndrome. It has been shown that many genes associated with ASDs are involved in the neuroligin-neurexin interaction at the glutamate synapse: NLGN3, NLGN4, NRXN1, CNTNAP2, and SHANK3. We screened this last gene in two cohorts of ASD patients (133 patients from US and 88 from Italy). We found 5/221 (2.3%) cases with pathogenic alterations: a 106 kb deletion encompassing the SHANK3 gene, two frameshift mutations leading to premature stop codons, a missense mutation (p.Pro141Ala), and a splicing mutation (c.1820-4 G>A). Additionally, in 17 patients (7.7%) we detected a c.1304+48C>T transition affecting a methylated cytosine in a CpG island. This variant is reported as SNP rs76224556 and was found in both US and Italian controls, but it results significantly more frequent in our cases than in the control cohorts. The variant is also significantly more common among PDD-NOS cases than in AD cases. We also screened this gene in an independent replication cohort of 104 US patients with ASDs, in which we found a missense mutation (p.Ala1468Ser) in 1 patient (0.9%), and in 8 patients (7.7%) we detected the c.1304+48C>T transition. While SHANK3 variants are present in any ASD subtype, the SNP rs76224556 appears to be significantly associated with PDD-NOS cases. This represents the first evidence of a genotype-phenotype correlation in ASDs and highlights the importance of a detailed clinical-neuropsychiatric evaluation for the effective genetic screening of ASD patients.European Journal of Human Genetics advance online publication, 15 August 2012; doi:10.1038/ejhg.2012.175.
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2. Deogracias R, Yazdani M, Dekkers MP, Guy J, Ionescu MC, Vogt KE, Barde YA. {{Fingolimod, a sphingosine-1 phosphate receptor modulator, increases BDNF levels and improves symptoms of a mouse model of Rett syndrome}}. {Proc Natl Acad Sci U S A};2012 (Aug 13)
The functional relevance of brain-derived neurotrophic factor (BDNF) is beginning to be well appreciated not only in mice, but also in humans. Because reduced levels typically correlate with impaired neuronal function, increasing BDNF levels with well-tolerated drugs diffusing into the central nervous system may help in ameliorating functional deficits. With this objective in mind, we used the sphingosine-1 phosphate receptor agonist fingolimod, a drug that crosses the blood-brain barrier. In addition, fingolimod has recently been introduced as the first oral treatment for multiple sclerosis. In cultured neurons, fingolimod increases BDNF levels and counteracts NMDA-induced neuronal death in a BDNF-dependent manner. Ongoing synaptic activity and MAPK signaling is required for fingolimod-induced BDNF increase, a pathway that can also be activated in vivo by systemic fingolimod administration. Mice lacking Mecp2, a gene frequently mutated in Rett syndrome, show decreased levels of BDNF, and fingolimod administration was found to partially rescue these levels as well as the size of the striatum, a volumetric sensor of BDNF signaling in rodents. These changes correlate with increased locomotor activity of the Mecp2-deficient animals, suggesting that fingolimod may improve the functional output of the nervous system, in addition to its well-documented effects on lymphocyte egress from lymph nodes.
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3. Egelhoff K, Lane AE. {{Brief Report: Preliminary Reliability, Construct Validity and Standardization of the Auditory Behavior Questionnaire (ABQ) for Children with Autism Spectrum Disorders}}. {J Autism Dev Disord};2012 (Aug 14)
The Auditory Behavior Questionnaire (ABQ) evaluates abnormal behavioral responses to auditory stimulation in children with Autism Spectrum Disorder (ASD). This study reports preliminary reliability, construct validity and standardization of the ABQ. Parents of children with ASD aged 7-21 years (n = 165) completed the ABQ on-line. Cronbach’s alpha was 0.94 indicating strong internal consistency. Factor analysis revealed a four-factor structure supporting previous theoretical discussion of global sensory processing difficulties and the construct validity of the ABQ. The 4-factors, (1) Difficulty in Background Noise, (2) Aversive Reactions, (3) Unresponsiveness, and (4) Stereotypic/Repetitive Behaviors, are very similar to Dunning’s (Development of a questionnaire to assess auditory behaviors in children diagnosed with autism spectrum disorders, The Ohio State University, Columbus, 2003) hypothesized factor domains. Standard factor scores for children with ASD are reported.
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4. Erdodi L, Lajiness-O’Neill R, Schmitt TA. {{Learning Curve Analyses in Neurodevelopmental Disorders: Are Children with Autism Spectrum Disorder Truly Visual Learners?}}. {J Autism Dev Disord};2012 (Aug 14)
Visual and auditory verbal learning using a selective reminding format was studied in a mixed clinical sample of children with autism spectrum disorder (ASD) (n = 42), attention-deficit hyperactivity disorder (n = 83), velocardiofacial syndrome (n = 17) and neurotypicals (n = 38) using the Test of Memory and Learning to (1) more thoroughly characterize and examine the integrity of learning and memory processes, (2) to better understand the mechanisms of learning impairment, and (3) to inform instructional practices in ASD. Contrary to expectations, children with ASD demonstrated a relative weakness in the rate of acquisition of visual in contrast to verbal learning compared to neurotypicals. They also showed a complex pattern of consolidation. Overall, between-group differences were more likely to emerge during the visual learning task, suggesting that it may be more sensitive for detecting neurodevelopmental differences. The heuristic value of assessing memory and learning across multiple trials and comparing performance during immediate and delayed recall is discussed.
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5. Forgeot d’Arc B, Dawson M, Soulieres I, Mottron L. {{Self-Injury in Autism is Largely Unexplained: Now What?}}. {J Autism Dev Disord};2012 (Aug 14)
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6. Kosaka H, Munesue T, Ishitobi M, Asano M, Omori M, Sato M, Tomoda A, Wada Y. {{Long-term oxytocin administration improves social behaviors in a girl with autistic disorder}}. {BMC Psychiatry};2012 (Aug 13);12(1):110.
ABSTRACT: BACKGROUND: Patients with autism spectrum disorders (ASDs) exhibit core autistic symptoms including social impairments from early childhood and mostly show secondary disabilities such as irritability and aggressive behavior based on core symptoms. However, there are still no radical treatments of social impairments in these patients. Oxytocin has been reported to play important roles in multiple social behaviors dependent on social recognition, and has been expected as one of the effective treatments of social impairments of patients with ASDs. CASE PRESENTATION: We present a case of a 16-year-old girl with autistic disorder who treated by long-term administration of oxytocin nasal spray. Her autistic symptoms were successfully treated by two month administration; the girl’s social interactions and social communication began to improve without adverse effects. Her irritability and aggressive behavior also improved dramatically with marked decreases in aberrant behavior checklist scores from 69 to 7. CONCLUSION: This case is the first to illustrate long-term administration of oxytocin nasal spray in the targeted treatment of social impairments in a female with autistic disorder. This case suggests that long-term nasal oxytocin spray is promising and well-tolerated for treatment of social impairments of patients with ASDs.
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7. Sato W, Toichi M, Uono S, Kochiyama T. {{Impaired social brain network for processing dynamic facial expressions in autism spectrum disorders}}. {BMC Neurosci};2012 (Aug 13);13(1):99.
ABSTRACT: BACKGROUND: Impairment of social interaction via facial expressions represents a core clinical feature of autism spectrum disorders (ASD). However, the neural correlates of this dysfunction remain unidentified. Because this dysfunction is manifested in real-life situations, we hypothesized that the observation of dynamic, compared with static, facial expressions would reveal abnormal brain functioning in individuals with ASD. We presented dynamic and static facial expressions of fear and happiness to individuals with high-functioning ASD and to age- and sex-matched typically developing controls and recorded their brain activities using functional magnetic resonance imaging (fMRI). Result Regional analysis revealed reduced activation of several brain regions in the ASD group compared with controls in response to dynamic versus static facial expressions, including the middle temporal gyrus (MTG), fusiform gyrus, amygdala, medial prefrontal cortex, and inferior frontal gyrus (IFG). Dynamic causal modeling analyses revealed that bi-directional effective connectivity involving the primary visual cortex-MTG-IFG circuit was enhanced in response to dynamic as compared with static facial expressions in the control group. Group comparisons revealed that all these modulatory effects were weaker in the ASD group than in the control group. CONCLUSIONS: These results suggest that weak activity and connectivity of the social brain network underlie the impairment in social interaction involving dynamic facial expressions in individuals with ASD.
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8. Scassellati B, Henny A, Mataric M. {{Robots for use in autism research}}. {Annu Rev Biomed Eng};2012 (Aug 15);14:275-294.
Autism spectrum disorders are a group of lifelong disabilities that affect people’s ability to communicate and to understand social cues. Research into applying robots as therapy tools has shown that robots seem to improve engagement and elicit novel social behaviors from people (particularly children and teenagers) with autism. Robot therapy for autism has been explored as one of the first application domains in the field of socially assistive robotics (SAR), which aims to develop robots that assist people with special needs through social interactions. In this review, we discuss the past decade’s work in SAR systems designed for autism therapy by analyzing robot design decisions, human-robot interactions, and system evaluations. We conclude by discussing challenges and future trends for this young but rapidly developing research area.
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9. Sheinkopf SJ, Iverson JM, Rinaldi ML, Lester BM. {{Atypical Cry Acoustics in 6-Month-Old Infants at Risk for Autism Spectrum Disorder}}. {Autism Res};2012 (Aug 13)
This study examined differences in acoustic characteristics of infant cries in a sample of babies at risk for autism and a low-risk comparison group. Cry samples derived from vocal recordings of 6-month-old infants at risk for autism spectrum disorder (ASD; n = 21) and low-risk infants (n = 18) were subjected to acoustic analyses using analysis software designed for this purpose. Cries were categorized as either pain-related or non-pain-related based on videotape coding. At-risk infants produced pain-related cries with higher and more variable fundamental frequency (F (0) ) than low-risk infants. At-risk infants later classified with ASD at 36 months had among the highest F (0) values for both types of cries and produced cries that were more poorly phonated than those of nonautistic infants, reflecting cries that were less likely to be produced in a voiced mode. These results provide preliminary evidence that disruptions in cry acoustics may be part of an atypical vocal signature of autism in early life. Autism Res 2012, **: **-**. (c) 2012 International Society for Autism Research, Wiley Periodicals, Inc.
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10. Sullivan A, Winograd G, Verkuilen J, Fish MC. {{Children on the autism spectrum: grandmother involvement and family functioning}}. {J Appl Res Intellect Disabil};2012 (Sep);25(5):484-494.
Background This study investigated associations between the presence of a child with autism or Asperger’s disorder in the family, family functioning and grandmother experiences with the goal of better understanding grandparent involvement in the lives of grandchildren on the autism spectrum and their families. Methods Mothers and grandmothers of children who were either typically developing or on the autism spectrum completed parallel forms of a grandparent involvement measure. Mothers reported on the functioning of the immediate family. Data were analysed via multilevel modelling with mother-grandmother dyads as the unit of observation. Results Autism spectrum disorders in children were associated with more flexible family functioning, lower levels of family satisfaction, greater grandmother difficulties and more grandmother information needs. Conclusions Participation of grandparents in diagnostic and treatment meetings and increased communication among family members may facilitate grandparent support and involvement in families with a child on the autism spectrum.
