1. Baldan F, Gnan C, Franzoni A, Ferino L, Allegri L, Passon N, Damante G. {{Genomic Deletion Involving the IMMP2L Gene in Two Cases of Autism Spectrum Disorder}}. {Cytogenet Genome Res};2018 (May 23)
Mutations/deletions of the IMMP2L gene have been associated with different cognitive/behavioral disturbances, including autism spectrum disorders (ASD). The penetrance of these defects is not complete since they often are inherited from a healthy parent. Using array-CGH in a cohort of 37 ASD patients, we found 2 subjects harboring a deletion inside the IMMP2L gene. In both cases, the IMMP2L gene deletion was inherited: from a healthy mother in one case and from a dyslectic father in the other. In the latter family, the IMMP2L deletion was also detected in the patient’s brother, who showed delayed language development. In a cohort of 100 normal controls, no deletions including the IMMP2L gene were observed. However, a recent meta-analysis found no association between IMMP2L deletions and ASD. Our data would indicate that deletions involving the IMMP2L gene may contribute to the development of a subgroup of cognitive/behavioral disorders.
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2. Broder-Fingert S, Feinberg E, Silverstein M. {{Improving Screening for Autism Spectrum Disorder: Is It Time for Something New?}}. {Pediatrics};2018 (May 21)
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3. Canali G, Garcia M, Hivert B, Pinatel D, Goullancourt A, Oguievetskaia K, Saint-Martin M, Girault JA, Faivre-Sarrailh C, Goutebroze L. {{Genetic variants in autism-related CNTNAP2 impair axonal growth of cortical neurons}}. {Hum Mol Genet};2018 (Jun 1);27(11):1941-1954.
The CNTNAP2 gene, coding for the cell adhesion glycoprotein Caspr2, is thought to be one of the major susceptibility genes for autism spectrum disorder (ASD). A large number of rare heterozygous missense CNTNAP2 variants have been identified in ASD patients. However, most of them are inherited from an unaffected parent, questioning their clinical significance. In the present study, we evaluate their impact on neurodevelopmental functions of Caspr2 in a heterozygous genetic background. Performing cortical neuron cultures from mouse embryos, we demonstrate that Caspr2 plays a dose-dependent role in axon growth in vitro. Loss of one Cntnap2 allele is sufficient to elicit axonal growth alteration, revealing a situation that may be relevant for CNTNAP2 heterozygosity in ASD patients. Then, we show that the two ASD variants I869T and G731S, which present impaired binding to Contactin2/TAG-1, do not rescue axonal growth deficits. We find that the variant R1119H leading to protein trafficking defects and retention in the endoplasmic reticulum has a dominant-negative effect on heterozygous Cntnap2 cortical neuron axon growth, through oligomerization with wild-type Caspr2. Finally, we identify an additional variant (N407S) with a dominant-negative effect on axon growth although it is well-localized at the membrane and properly binds to Contactin2. Thus, our data identify a new neurodevelopmental function for Caspr2, the dysregulation of which may contribute to clinical manifestations of ASD, and provide evidence that CNTNAP2 heterozygous missense variants may contribute to pathogenicity in ASD, through selective mechanisms.
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4. Honda T, Sofuku K, Matsunaga H, Tachibana M, Mohri I, Taniike M, Tomonaga K. {{Prevalence of antibodies against Borna disease virus proteins in Japanese children with autism spectrum disorder}}. {Microbiol Immunol};2018 (May 22)
Bornavirus infection is observed in both animals, including humans. However, bornavirus epidemiology in humans, especially in children, remains unclear. Here, we evaluated antibodies against bornaviruses in Japanese children with autism spectrum disorder (ASD) using immunofluorescence analysis, western blotting, and radio ligand assay. The prevalence of antibodies against bornavirus-specific speckles, N, and P proteins were 22%, 48%, and 33%, respectively, in the ASD children. According to our criteria, the prevalence of antibodies against bornaviruses was 7.4% in the ASD children. This is the first report of the serological prevalence of bornavirus in Japanese children. Our results provide valuable baseline-data regarding bornavirus epidemiology in children for future studies.
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5. Hou YM, Stewart L, Iao LS, Wu CC. {{Parenting stress and depressive symptoms in Taiwanese mothers of young children with autism spectrum disorder: Association with children’s behavioural problems}}. {J Appl Res Intellect Disabil};2018 (May 23)
BACKGROUND: This study examined the severity of parenting stress and depressive symptoms in Taiwanese mothers of young children with autism spectrum disorder (ASD) compared to mothers of young children with developmental delay (DD). The associations between parenting stress, depressive symptoms, and children’s behavioural problems were also tested. METHODS: The study sample included 51 young children with ASD (mean age = 31 months), 51 young children with DD (mean age = 30 months) and their mothers. RESULTS: The results confirmed that mothers of young children with ASD experienced higher levels of parenting stress and depressive symptoms than mothers of young children with DD. In addition, children’s behavioural problems were robust predictors of parenting stress and depressive symptoms in mothers of young children with ASD, but not in mothers of young children with DD. CONCLUSION: The findings indicated that one of the critical goals in early intervention for young children with ASD and their families is to reduce children’s behavioural problems.
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6. Kirsten TB, Casarin RC, Bernardi MM, Felicio LF. {{Pioglitazone abolishes autistic-like behaviors via the IL-6 pathway}}. {PLoS One};2018;13(5):e0197060.
Autism is characterized by social deficits, communication abnormalities, and repetitive behaviors. The risk factors appear to include genetic and environmental conditions, such as prenatal infections and maternal dietary factors. Previous investigations by our group have demonstrated that prenatal exposure to lipopolysaccharide (LPS), which mimics infections by gram-negative bacteria, induces autistic-like behaviors. No effective treatment yet exists for autism. Therefore, we used our rat model to test a possible treatment for autism. We selected pioglitazone to block or ease the impairments induced by LPS because although this drug was designed as an anti-diabetic drug (it has an insulin effect), it also exerts anti-inflammatory effects. Juvenile offspring were treated daily with pioglitazone, and the main behaviors related to autism, namely, socialization (play behavior) and communication (50-kHz ultrasonic vocalizations), were studied. Biomarkers linked to autism and/or pioglitazone were also studied to attempt to understand the mechanisms involved, namely, IL-6, TNF-alpha, MCP-1, insulin, and leptin. Prenatal LPS exposure induced social deficits and communicational abnormalities in juvenile rat offspring as well as elevated plasma IL-6 levels. Daily postnatal pioglitazone treatment blocked the impairments found in terms of the time spent on social interaction, the number of vocalizations (i.e., autistic-like behaviors) and the elevated plasma IL-6 levels. Thus, pioglitazone appears to be a relevant candidate for the treatment of autism. The present findings may contribute to a better understanding and treatment of autism and associated diseases.
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7. Laure T, Dimitry G, Oren Z, Marcela K, Timothee T, Rasha M, Nir W, Hila BA, Meital NO, Omry K, Evan E. {{Dysbiosis of microbiome and probiotic treatment in a genetic model of autism spectrum disorders}}. {Brain Behav Immun};2018 (May 19)
Recent studies have determined that the microbiome has direct effects on behavior, and may be dysregulated in neurodevelopmental conditions. Considering that neurodevelopmental conditions, such as autism, have a strong genetic etiology, it is necessary to understand if genes associated with neurodevelopmental disorders, such as Shank3, can influence the gut microbiome, and if probiotics can be a therapeutic tool. In this study, we have identified dysregulation of several genera and species of bacteria in the gut and colon of both male and female Shank3 KO mice. L. reuteri, a species with decreased relative abundance in the Shank3 KO mice, positively correlated with the expression of gamma-Aminobutyric acid (GABA) receptor subunits in the brain. Treatment of Shank3 KO mice with L. reuteri induced an attenuation of unsocial behavior specifically in male Shank3 mice, and a decrease in repetitive behaviors in both male and female Shank3 KO mice. In addition, L. reuteri treatment affected GABA receptor gene expression and protein levels in multiple brain regions. This study identifies bacterial species that are sensitive to an autism-related mutation, and further suggests a therapeutic potential for probiotic treatment.
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8. Oien RA, Schjolberg S, Volkmar FR, Shic F, Cicchetti DV, Nordahl-Hansen A, Stenberg N, Hornig M, Havdahl A, Oyen AS, Ventola P, Susser ES, Eisemann MR, Chawarska K. {{Clinical Features of Children With Autism Who Passed 18-Month Screening}}. {Pediatrics};2018 (May 21)
OBJECTIVES: We compared sex-stratified developmental and temperamental profiles at 18 months in children screening negative for autism spectrum disorder (ASD) on the Modified Checklist for Autism in Toddlers (M-CHAT) but later receiving diagnoses of ASD (false-negative group) versus those without later ASD diagnoses (true-negative group). METHODS: We included 68 197 screen-negative cases from the Norwegian Mother and Child Cohort Study (49.1% girls). Children were screened by using the 6 critical items of the M-CHAT at 18 months. Groups were compared on domains of the Ages and Stages Questionnaire and the Emotionality Activity Sociability Temperament Survey. RESULTS: Despite passing M-CHAT screening at 18 months, children in the false-negative group exhibited delays in social, communication, and motor skills compared with the true-negative group. Differences were more pronounced in girls. However, with regard to shyness, boys in the false-negative group were rated as more shy than their true-negative counterparts, but girls in the false-negative group were rated as less shy than their counterparts in the true-negative group. CONCLUSIONS: This is the first study to reveal that children who pass M-CHAT screening at 18 months and are later diagnosed with ASD exhibit delays in core social and communication areas as well as fine motor skills at 18 months. Differences appeared to be more pronounced in girls. With these findings, we underscore the need to enhance the understanding of early markers of ASD in boys and girls, as well as factors affecting parental report on early delays and abnormalities, to improve the sensitivity of screening instruments.
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9. Patrick KE, Hurewitz F, McCurdy MD, Agate FT, Daly BP, Tarazi RA, Chute DL, Schultheis MT. {{Driving Comparisons Between Young Adults with Autism Spectrum Disorder and Typical Development}}. {J Dev Behav Pediatr};2018 (May 18)
OBJECTIVE: Many individuals with autism spectrum disorder (ASD) are reluctant to pursue driving because of concerns about their ability to drive safely. This study aimed to assess differences in simulated driving performance in young adults with ASD and typical development, examining relationships between driving performance and the level of experience (none, driver’s permit, licensed) across increasingly difficult driving environments. METHOD: Participants included 50 English-speaking young adults (16-26 years old) with ASD matched for sex, age, and licensure with 50 typically-developing (TD) peers. Participants completed a structured driving assessment using a virtual-reality simulator that included increasingly complex environmental demands. Differences in mean speed and speed and lane variability by diagnostic group and driving experience were analyzed using multilevel linear modeling. RESULTS: Young adults with ASD demonstrated increased variability in speed and lane positioning compared with controls, even during low demand tasks. When driving demands became more complex, group differences were moderated by driving experience such that licensed drivers with ASD drove similarly to TD licensed drivers for most tasks, whereas unlicensed drivers with ASD had more difficulty with speed and lane management than TD drivers. CONCLUSION: Findings suggest that young adults with ASD may have more difficulty with basic driving skills than peers, particularly in the early stages of driver training. Increased difficulty compared with peers increases as driving demands become more complex, suggesting that individuals with ASD may benefit from a slow and gradual approach to driver training. Future studies should evaluate predictors of driving performance, on-road driving, and ASD-specific driving interventions.
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10. Rayan A, Ahmad M. {{The psychometric properties of the mindful attention awareness scale among Arab parents of children with autism spectrum disorder}}. {Arch Psychiatr Nurs};2018 (Jun);32(3):444-448.
AIM: The purpose of this study was to examine the psychometric properties and the theoretical structure of the mindful attention awareness scale (MAAS) with parents of children with autism spectrum disorder (ASD) in Jordan. METHOD: A sample of 104 parents of children with ASD in Jordan completed the study. Exploratory and confirmatory factor analyses were conducted to assess the factor structure of MAAS. Internal consistency was assessed using Cronbach’s alpha. The convergent validity was assessed using Pearson’s product-moment correlations between the MAAS and measures of psychological distress and Quality of life. RESULTS: A confirmatory factor analysis showed that the modified 13-item MAAS fits the data significantly better than the original 15-item model. However, both the 13-item and the 15-item models showed a single factor structure, with excellent internal consistency and convergent validity. CONCLUSION: This preliminary study supports using the MAAS in Arab parents of children with ASD.
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11. Salgado TM, Fedrigon A, Riccio Omichinski D, Meade MA, Farris KB. {{Identifying Medication Management Smartphone App Features Suitable for Young Adults With Developmental Disabilities: Delphi Consensus Study}}. {JMIR Mhealth Uhealth};2018 (May 23);6(5):e129.
BACKGROUND: Smartphone apps can be a tool to facilitate independent medication management among persons with developmental disabilities. At present, multiple medication management apps exist in the market, but only 1 has been specifically designed for persons with developmental disabilities. Before initiating further app development targeting this population, input from stakeholders including persons with developmental disabilities, caregivers, and professionals regarding the most preferred features should be obtained. OBJECTIVE: The aim of this study was to identify medication management app features that are suitable to promote independence in the medication management process by young adults with developmental disabilities using a Delphi consensus method. METHODS: A compilation of medication management app features was performed by searching the iTunes App Store, United States, in February 2016, using the following terms: adherence, medication, medication management, medication list, and medication reminder. After identifying features within the retrieved apps, a final list of 42 features grouped into 4 modules (medication list, medication reminder, medication administration record, and additional features) was included in a questionnaire for expert consensus rating. A total of 52 experts in developmental disabilities, including persons with developmental disabilities, caregivers, and professionals, were invited to participate in a 3-round Delphi technique. The purpose was to obtain consensus on features that are preferred and suitable to promote independence in the medication management process among persons with developmental disabilities. Consensus for the first, second, and third rounds was defined as >/=90%, >/=80%, and >/=75% agreement, respectively. RESULTS: A total of 75 responses were received over the 3 Delphi rounds-30 in the first round, 24 in the second round, and 21 in the third round. At the end of the third round, cumulative consensus was achieved for 60% (12/20) items in the medication list module, 100% (3/3) in the medication reminder module, 67% (2/3) in the medication administration record module, and 63% (10/16) in the additional features module. In addition to the medication list, medication reminder, and medication administration record features, experts selected the following top 3 most important additional features: automatic refills through pharmacies; ability to share medication information from the app with providers; and ability to share medication information from the app with family, friends, and caregivers. The top 3 least important features included a link to an official drug information source, privacy settings and password protection, and prescription refill reminders. CONCLUSIONS: Although several mobile apps for medication management exist, few are specifically designed to support persons with developmental disabilities in the complex medication management process. Of the 42 different features assessed, 64% (27/42) achieved consensus for inclusion in a future medication management app. This study provides information on the features of a medication management app that are most important to persons with developmental disabilities, caregivers, and professionals.
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12. Sampson WG, Sandra AE. {{Comparative Study on Knowledge About Autism Spectrum Disorder Among Paediatric and Psychiatric Nurses in Public Hospitals in Kumasi, Ghana}}. {Clin Pract Epidemiol Ment Health};2018;14:99-108.
Background: Despite the existence of autism spectrum disorder in Ghana, few studies have provided the necessary information on the phenomenon. These studies have mostly focused on speech and language therapy for children and modification of classroom environment for children with autism spectrum disorder. This approach has resulted in a paucity of knowledge on nurse’s knowledge of autism spectrum disorder in Ghana. Objective: The study sought to assess the knowledge of paediatric and psychiatric on autism spectrum disorder. Method: In this study, 130 paediatric and 93 psychiatric nurses sampled from five public hospitals in the Kumasi Metropolis participated in the survey. The Knowledge about Childhood Autism among Health Workers (KCAHW) questionnaire was employed to assess their knowledge of autism spectrum disorder. Results: It emerged from the study that psychiatric nurses were more knowledgeable on autism spectrum disorder than paediatric nurses in general and specifically on each of the four domains on the KCAHW questionnaire. However, the level of knowledge on autism spectrum disorder among both groups of nurses remains low. Apart from the previous encounter, there were no significant differences between paediatric and psychiatric nurses’ gender, age, marital status, working experience and their knowledge. Conclusion: In view of the findings, it will be appropriate for autism spectrum disorder to be included in the clinical training curriculum as well as the continuous professional education for both paediatric and psychiatric nurses. This will go a long way in helping paediatric and psychiatric nurses to increase their knowledge of autism spectrum disorder.
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13. Todd BP, Bassuk AG. {{A de novo mutation in PRICKLE1 associated with myoclonic epilepsy and autism spectrum disorder}}. {J Neurogenet};2018 (May 23):1-3.
Homozygous recessive mutations in the PRICKLE1 gene were first described in three consanguineous families with myoclonic epilepsy. Subsequent studies have identified neurological abnormalities in humans and animal models with both heterozygous and homozygous mutations in PRICKLE1 orthologs. We describe a 7-year-old with a novel de novo missense mutation in PRICKLE1 associated with epilepsy, autism spectrum disorder and global developmental delay.
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14. Vagenas D, Totsika V. {{Modelling correlated data: Multilevel models and generalized estimating equations and their use with data from research in developmental disabilities}}. {Res Dev Disabil};2018 (May 18)
BACKGROUND: The use of Multilevel Models (MLM) and Generalized Estimating Equations (GEE) for analysing clustered data in the field of intellectual and developmental disability (IDD) research is still limited. METHOD: We present some important features of MLMs and GEEs: main function, assumptions, model specification and estimators, sample size and power. We provide an overview of the ways MLMs and GEEs have been used in IDD research. RESULTS: While MLMs and GEEs are both appropriate for longitudinal and/or clustered data, they differ in the assumptions they impose on the data, and the inferences made. Estimators in MLMs require appropriate model specification, while GEEs are more resilient to misspecification at the expense of model complexity. Studies on sample size seem to suggest that Level 1 coefficients are robust to small samples/clusters, with any higher-level coefficients less so. MLMs have been used more frequently than GEEs in IDD research, especially for fitting developmental trajectories. CONCLUSIONS: Clustered data from research in the IDD field can be analysed flexibly using MLMs and GEEs. These models would be more widely used if journals required the inclusion of technical specification detail, simulation studies examined power for IDD study characteristics, and researchers developed core skills during basic studies.
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15. Wilkes-Gillan S, Lincoln M. {{Parent-mediated intervention training delivered remotely for children with autism spectrum disorder (ASD) has preliminary evidence for parent intervention fidelity and improving parent knowledge and children’s social behaviour and communication skills}}. {Aust Occup Ther J};2018 (May 21)
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16. Zeidler S, Pop AS, Jaafar IA, de Boer H, Buijsen RAM, de Esch CEF, Nieuwenhuizen-Bakker I, Hukema RK, Willemsen R. {{Paradoxical effect of baclofen on social behavior in the fragile X syndrome mouse model}}. {Brain Behav};2018 (Apr 26):e00991.
INTRODUCTION: Fragile X syndrome (FXS) is a common monogenetic cause of intellectual disability, autism spectrum features, and a broad range of other psychiatric and medical problems. FXS is caused by the lack of the fragile X mental retardation protein (FMRP), a translational regulator of specific mRNAs at the postsynaptic compartment. The absence of FMRP leads to aberrant synaptic plasticity, which is believed to be caused by an imbalance in excitatory and inhibitory network functioning of the synapse. Evidence from studies in mice demonstrates that GABA, the major inhibitory neurotransmitter in the brain, and its receptors, is involved in the pathogenesis of FXS. Moreover, several FXS phenotypes, including social behavior deficits, could be corrected in Fmr1 KO mice after acute treatment with GABAB agonists. METHODS: As FXS would probably require a lifelong treatment, we investigated the effect of chronic treatment with the GABAB agonist baclofen on social behavior in Fmr1 KO mice on two behavioral paradigms for social behavior: the automated tube test and the three-chamber sociability test. RESULTS: Unexpectedly, chronic baclofen treatment resulted in worsening of the FXS phenotypes in these behavior tests. Strikingly, baclofen treatment also affected wild-type animals in both behavioral tests, inducing a phenotype similar to that of untreated Fmr1 KO mice. CONCLUSION: Altogether, the disappointing results of recent clinical trials with the R-baclofen enantiomer arbaclofen and our current results indicate that baclofen should be reconsidered and further evaluated before its application in targeted treatment for FXS.
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17. Zwaigenbaum L, Penner M. {{Autism spectrum disorder: advances in diagnosis and evaluation}}. {Bmj};2018 (May 21);361:k1674.
Autism spectrum disorder (ASD) has a variety of causes, and its clinical expression is generally associated with substantial disability throughout the lifespan. Recent advances have led to earlier diagnosis, and deep phenotyping efforts focused on high risk infants have helped advance the characterization of early behavioral trajectories. Moreover, biomarkers that measure early structural and functional connectivity, visual orienting, and other biological processes have shown promise in detecting the risk of autism spectrum disorder even before the emergence of overt behavioral symptoms. Despite these advances, the mean age of diagnosis is still 4-5 years. Because of the broad consistency in published guidelines, parameters for high quality comprehensive assessments are available; however, such models are resource intensive and high demand can result in greatly increased waiting times. This review describes advances in detecting early behavioral and biological markers, current options and controversies in screening for the disorder, and best practice in its diagnostic evaluation including emerging data on innovative service models.
