1. Akcakaya NH, Tekturk P, Cagatay A, Tur EK, Yapici Z. {{Atypical enterovirus encephalitis causing behavioral changes and autism-like clinical manifestations: case report}}. {Acta Neurol Belg};2016 (Feb 19)
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2. Brownstein CA, Kleiman RJ, Engle EC, Towne MC, D’Angelo EJ, Yu TW, Beggs AH, Picker J, Fogler JM, Carroll D, Schmitt RC, Wolff RR, Shen Y, Lip V, Bilguvar K, Kim A, Tembulkar S, O’Donnell K, Gonzalez-Heydrich J. {{Overlapping 16p13.11 deletion and gain of copies variations associated with childhood onset psychosis include genes with mechanistic implications for autism associated pathways: Two case reports}}. {Am J Med Genet A};2016 (Feb 16)
Copy number variability at 16p13.11 has been associated with intellectual disability, autism, schizophrenia, epilepsy, and attention-deficit hyperactivity disorder. Adolescent/adult- onset psychosis has been reported in a subset of these cases. Here, we report on two children with CNVs in 16p13.11 that developed psychosis before the age of 7. The genotype and neuropsychiatric abnormalities of these patients highlight several overlapping genes that have possible mechanistic relevance to pathways previously implicated in Autism Spectrum Disorders, including the mTOR signaling and the ubiquitin-proteasome cascades. A careful screening of the 16p13.11 region is warranted in patients with childhood onset psychosis. (c) 2016 Wiley Periodicals, Inc.
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3. Faja S, Dawson G, Sullivan K, Meltzoff AN, Estes A, Bernier R. {{Executive function predicts the development of play skills for verbal preschoolers with autism spectrum disorders}}. {Autism Res};2016 (Feb 18)
Executive function and play skills develop in early childhood and are linked to cognitive and language ability. The present study examined these abilities longitudinally in two groups with autism spectrum disorder-a group with higher initial language (n = 30) and a group with lower initial language ability (n = 36). Among the lower language group, concurrent nonverbal cognitive ability contributed most to individual differences in executive function and play skills. For the higher language group, executive function during preschool significantly predicted play ability at age 6 over and above intelligence, but early play did not predict later executive function. These results suggested that factors related to the development of play and executive function differ for subgroups of children with different language abilities and that early executive function skills may be critical in order for verbal children with autism to develop play. Autism Res 2016. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc.
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4. Gul H, Erol N, Pamir Akin D, Ustun Gullu B, Akcakin M, Alpas B, Oner O. {{EMOTIONAL AVAILABILITY IN EARLY MOTHER-CHILD INTERACTIONS FOR CHILDREN WITH AUTISM SPECTRUM DISORDERS, OTHER PSYCHIATRIC DISORDERS, AND DEVELOPMENTAL DELAY}}. {Infant Ment Health J};2016 (Feb 19)
Emotional availability (EA) is a method to assess early parent-child dyadic interactions for emotional awareness, perception, experience, and expression between child and parent that describe global relational quality (Z. Biringen & M. Easterbrooks, ). The current study aimed to examine the effects of an infant’s diagnosis of autism spectrum disorders (ASDs), other psychiatric disorders (OPD), and developmental delay (DD) on the maternal EA Scale (EAS; Z. Biringen & M. Easterbrooks, ; Z. Biringen, J.L. Robinson, & R.N. Emde, ) scores and the relative contributions of infant’s age, gender, diagnosis, developmental level, and maternal education on EAS scores in a clinical Turkish sample. Three hundred forty-five infant-mother dyads participated in this study. Results of the research indicated that EAS adult scores were associated with maternal education and infant’s diagnosis whereas child scores were associated with infant’s age, diagnosis, and developmental level. Infants’ involvement and responsiveness to the mother were lower in the group with ASD. Children with OPD, particularly when their mothers have lower education, might be at increased risk of having problems in parent-child interactions. Young ASD subjects with developmental delay are in greatest need of support to increase reactions toward their mother. These findings underscore the importance of using all of the EA dimensions rather than only one measure on children in high-risk populations.
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5. Guo W, Molinaro G, Collins KA, Hays SA, Paylor R, Worley PF, Szumlinski KK, Huber KM. {{Selective Disruption of Metabotropic Glutamate Receptor 5-Homer Interactions Mimics Phenotypes of Fragile X Syndrome in Mice}}. {J Neurosci};2016 (Feb 17);36(7):2131-2147.
Altered function of the Gq-coupled, Group 1 metabotropic glutamate receptors, specifically mGlu5, is implicated in multiple mouse models of autism and intellectual disability. mGlu5 dysfunction has been most well characterized in the fragile X syndrome mouse model, the Fmr1 knock-out (KO) mouse, where pharmacological and genetic reduction of mGlu5 reverses many phenotypes. mGlu5 is less associated with its scaffolding protein Homer in Fmr1 KO mice, and restoration of mGlu5-Homer interactions by genetic deletion of a short, dominant negative of Homer, H1a, rescues many phenotypes of Fmr1 KO mice. These results suggested that disruption of mGlu5-Homer leads to phenotypes of FXS. To test this idea, we examined mice with a knockin mutation of mGlu5 (F1128R; mGlu5(R/R)) that abrogates binding to Homer. Although FMRP levels were normal, mGlu5(R/R) mice mimicked multiple phenotypes of Fmr1 KO mice, including reduced mGlu5 association with the postsynaptic density, enhanced constitutive mGlu5 signaling to protein synthesis, deficits in agonist-induced translational control, protein synthesis-independent LTD, neocortical hyperexcitability, audiogenic seizures, and altered behaviors, including anxiety and sensorimotor gating. These results reveal new roles for the Homer scaffolds in regulation of mGlu5 function and implicate a specific molecular mechanism in a complex brain disease. SIGNIFICANCE STATEMENT: Abnormal function of the metabotropic, or Gq-coupled, glutamate receptor 5 (mGlu5) has been implicated in neurodevelopmental disorders, including a genetic cause of intellectual disability and autism called fragile X syndrome. In brains of a mouse model of fragile X, mGlu5 is less associated with its binding partner Homer, a scaffolding protein that regulates mGlu5 localization to synapses and its ability to activate biochemical signaling pathways. Here we show that a mouse expressing a mutant mGlu5 that cannot bind to Homer is sufficient to mimic many of the biochemical, neurophysiological, and behavioral symptoms observed in the fragile X mouse. This work provides strong evidence that Homer-mGlu5 binding contributes to symptoms associated with neurodevelopmental disorders.
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6. Hall SS, Wright HF, Mills DS. {{What Factors Are Associated with Positive Effects of Dog Ownership in Families with Children with Autism Spectrum Disorder? The Development of the Lincoln Autism Pet Dog Impact Scale}}. {PLoS One};2016;11(2):e0149736.
Scientific literature exploring the value of assistance dogs to children with autism spectrum disorder (ASD) is rapidly emerging. However, there is comparably less literature reporting the effects of pet (as opposed to assistance) dogs to these children. In particular, there are no known validated scales which assess how children may alter their behaviours in the presence of the dog, to evaluate the efficacy of pet dogs to these families. Additionally, given the highly individualised nature of ASD it is likely that some children and families gain more benefits from dog ownership than others, yet no research has reported the effect of individual differences. This pilot study reports the development of a 28-item scale based on the perceived impact of a pet dog on a child with autism by parents (Lincoln Autism Pet Dog Impact Scale-LAPDIS). The scale is comprised of three mathematically derived factors: Adaptability, Social Skills and Conflict Management. We assessed how individual differences (aspects) may be associated with scores on these three factors. Family Aspects and Dog Aspects were not significantly associated with ratings on the three factors, but Child Aspects (including: contact with horses, child age, disability level and language abilities) were related to impact of the dog on all factors. Training Aspects were related to scores on Social Skills (formal training with children with ASD and dogs and attendance at PAWS workshops run by Dogs for Good). These results suggest that individual differences associated with the child and the training approach may be important considerations for a positive impact from dog ownership on families with children with ASD. Differences in family features and the dog may not be so important, but may be worthy of further investigations given the early stage of development in this field.
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7. Moulton E, Barton M, Robins DL, Abrams DN, Fein D. {{Early Characteristics of Children with ASD Who Demonstrate Optimal Progress Between Age Two and Four}}. {J Autism Dev Disord};2016 (Feb 19)
Although for many children, Autism Spectrum Disorder (ASD) is a lifelong disability, a subset of children with ASD lose their diagnosis and show typical cognitive and adaptive abilities. The ages at which this transition can occur is not known, but it sometimes occurs quite early. Participants in the current study were 207 children with an ASD at age two who were reevaluated at age four. Eighty-three percent retained an ASD diagnosis at reevaluation and 9 % showed « optimal progress »: clear ASD at age two but not at age four, and average cognition, language, communication and social skills at age four. Early child-level factors predicted optimal progress: diagnosis of PDD-NOS, fewer repetitive behaviors, less severe symptomatology and stronger adaptive skills.
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8. Rodgers J, Wigham S, McConachie H, Freeston M, Honey E, Parr JR. {{Development of the anxiety scale for children with autism spectrum disorder (ASC-ASD)}}. {Autism Res};2016 (Feb 17)
Many children with autism spectrum disorder (ASD) experience high levels of anxiety. A widely used measure for typically developing children is the Revised Child Anxiety and Depression Scale (RCADS). However, such anxiety measures may require adaptation to accommodate characteristics of those with ASD. An adapted version of the RCADS was created based on empirical evidence of anxiety phenomenology in ASD, which included additional items related to sensory anxiety, intolerance of uncertainty, and phobias. Content validity was refined during focus groups with parents. Polychoric factor analysis was undertaken on data from 170 children with ASD, aged 8-16, and their parents. This process resulted in the creation of a new 24 item scale (self and parent report) each with four subscales: Performance Anxiety, Uncertainty, Anxious Arousal, and Separation Anxiety, with evidence of good reliability and validity. The freely available Anxiety Scale for Children – ASD, Parent and Child versions (ASC-ASD) has promising psychometric properties including good internal consistency, validity, and 1 month test-retest reliability. Autism Res 2016. & 2016 International Society for Autism Research, Wiley Periodicals, Inc.
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9. Roth BM, Kralovic S, Roizen NJ, Spannagel SC, Minich N, Knapp J. {{Impact of Autism Navigator on Access to Services}}. {J Dev Behav Pediatr};2016 (Feb 17)
OBJECTIVE: To determine whether access to an Autism Patient Navigator (APN) for children diagnosed with autism spectrum disorder (ASD) at <48 months of age would be useful and lead to more appointments with needed services. METHOD: Participants included parents of 39 children diagnosed with ASD in a multidisciplinary clinic. After diagnosis, the patients were randomized to 4 groups: Medicaid early (n = 9) or late support (n = 9) and non-Medicaid early (n = 11) or late support (n = 10). Early access to the APN was at the family meeting and later at 3 months after diagnosis. Data included demographic information and completion by phone interview at 3 months postdiagnosis of a questionnaire on the usefulness of the assessment and parent's desire or ability to obtain recommended services. RESULTS: Demographically, the groups were not different. Children were most frequently male, white, non-Hispanic, and non-Medicaid with a mean age of 35 months. In comparison with the non-Medicaid groups, the Medicaid groups more often endorsed the 9 questions on the usefulness of the assessment as being "A Great Deal" useful (p = .022). Groups with early support were more successful in scheduling or completing appointments for recommended services overall including medical, educational, therapeutic, and parent resource appointments (p = .031). Barriers to services or resources were reported by 35.9%. CONCLUSION: Parents of young children with Medicaid with a recent diagnosis of ASD found the assessment "very useful" compared with non-Medicaid group. The groups with immediate access to an APN were more successful with scheduling and completing appointments.
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10. Schuch JB, Paixao-Cortes VR, Friedrich DC, Tovo-Rodrigues L. {{The contribution of protein intrinsic disorder to understand the role of genetic variants uncovered by autism spectrum disorders exome studies}}. {Am J Med Genet B Neuropsychiatr Genet};2016 (Feb 19)
Several autism spectrum disorders (ASD) exome studies suggest that coding single nucleotide variants (SNVs) play an important role on ASD etiology. Usually, the pathogenic effect of missense mutations is estimated through predictors that lose accuracy for those SNVs placed in intrinsically disordered regions of protein. Here, we used bioinformatics tools to investigate the effect of mutations described in ASD published exome studies (549 mutations) in protein disorder, considering post-translational modification, PEST and Molecular Recognition Features (MoRFs) motifs. Schizophrenia and type 2 diabetes (T2D) datasets were created for comparison purposes. The frequency of mutations predicted as disordered was comparable among the three datasets (38.1% in ASD, 35.7% in schizophrenia, 46.4% in T2D). However, the frequency of SNVs predicted to lead a gain or loss of functional sites or change intrinsic disorder tendencies was higher in ASD and schizophrenia than T2D (46.9%, 36.4%, and 23.1%, respectively). The results obtained by SIFT and PolyPhen-2 indicated that 38.9% and 34.4% of the mutations predicted, respectively, as tolerated and benign showed functional alterations in disorder properties. Given the frequency of mutations placed in IDRs and their functional impact, this study suggests that alterations in intrinsic disorder properties might play a role in ASD and schizophrenia etiologies. They should be taken into consideration when researching the pathogenicity of mutations in neurodevelopmental and psychiatric diseases. Finally, mutations with functional alterations in disorder properties must be potential targets for in vitro and in vivo functional studies. (c) 2016 Wiley Periodicals, Inc.
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11. Werling DM, Parikshak NN, Geschwind DH. {{Gene expression in human brain implicates sexually dimorphic pathways in autism spectrum disorders}}. {Nat Commun};2016;7:10717.
Autism spectrum disorder (ASD) is more prevalent in males, and the mechanisms behind this sex-differential risk are not fully understood. Two competing, but not mutually exclusive, hypotheses are that ASD risk genes are sex-differentially regulated, or alternatively, that they interact with characteristic sexually dimorphic pathways. Here we characterized sexually dimorphic gene expression in multiple data sets from neurotypical adult and prenatal human neocortical tissue, and evaluated ASD risk genes for evidence of sex-biased expression. We find no evidence for systematic sex-differential expression of ASD risk genes. Instead, we observe that genes expressed at higher levels in males are significantly enriched for genes upregulated in post-mortem autistic brain, including astrocyte and microglia markers. This suggests that it is not sex-differential regulation of ASD risk genes, but rather naturally occurring sexually dimorphic processes, potentially including neuron-glial interactions, that modulate the impact of risk variants and contribute to the sex-skewed prevalence of ASD.
