1. Bachmann SO, Sledziowska M, Cross E, Kalbassi S, Waldron S, Chen F, Ranson A, Baudouin SJ. {{Behavioral training rescues motor deficits in Cyfip1 haploinsufficiency mouse model of autism spectrum disorders}}. {Translational psychiatry}. 2019; 9(1): 29.
Deletions in the 15q11.2 region of the human genome are associated with neurobehavioral deficits, and motor development delay, as well as in some cases, symptoms of autism or schizophrenia. The cytoplasmic FMRP-interacting protein 1 (CYFIP1) is one of the four genes contained within this locus and has been associated with other genetic forms of autism spectrum disorders (ASD). In mice, Cyfip1 haploinsufficiency leads to alteration of dendritic spine morphology and defects in synaptic plasticity, two pathophysiological hallmarks of mouse models of ASD. At the behavioral level, however, Cyfip1 haploinsufficiency leads to minor phenotypes, not directly relevant for 15q11.2 deletion syndrome or ASD. A fundamental question is whether neuronal phenotypes caused by the mutation of Cyfip1 are relevant for the human condition. Here, we describe a synaptic cluster of ASD-associated proteins centered on CYFIP1 and the adhesion protein Neuroligin-3. Cyfip1 haploinsufficiency in mice led to decreased dendritic spine density and stability associated with social behavior and motor learning phenotypes. Behavioral training early in development resulted in alleviating the motor learning deficits caused by Cyfip1 haploinsufficiency. Altogether, these data provide new insight into the neuronal and behavioral phenotypes caused by Cyfip1 mutation and proof-of-concept for the development of a behavioral therapy to treat phenotypes associated with 15q11.2 syndromes and ASD.
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2. Begara Iglesias O, Gomez Sanchez LE, Alcedo Rodriguez MA. {{Do young people with Asperger syndrome or intellectual disability use social media and are they cyberbullied or cyberbullies in the same way as their peers?}}. {Psicothema}. 2019; 31(1): 30-7.
BACKGROUND: The aim of the present study is to explore how youth with intellectual disability or Asperger syndrome use new technologies and social media in comparison with their peers without disability. METHOD: Participants were 181 adolescents with a mean age of 16 years old (SD=3.7) who completed the « Cyber-aggression Questionnaire for Adolescents », the « Cyber-victimization Questionnaire for Adolescents » and a questionnaire on social media and new technologies. RESULTS: Percentages of use of new technologies (61% tablets, 93% computers, 97% mobiles) are similar among groups but adolescents with Asperger syndrome or intellectual disability have been using them since more recent times and their uses are more limited. They also use social media less; the group with Asperger syndrome uses them the least. There are no significant differences in the frequency of cyberbullying. CONCLUSION: Despite using social media less, the frequency of cyberbullying is similar to their peers. Besides, the observed prevalence of cyberbullying is higher than that mentioned in previous studies in which informants were not the youths themselves.
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3. Burd E, Doyle EA. {{Challenges in the Treatment of Iron Deficiency Anemia in a Child With Autism Spectrum Disorder: A Case Study}}. {J Pediatr Health Care}. 2019.
Children with autism spectrum disorder (ASD) face many challenges, including feeding problems due to behavioral issues and food aversions. Therefore, pediatric nurse practitioners need to assess for different mineral deficiencies, including iron deficiency anemia (IDA). The following case study describes a 4-year-old with ASD with persistent IDA despite typical recommendation of oral iron supplementation. Other potential etiologies of IDA are reviewed. Finally, different management approaches for managing IDA in children with ASD are described.
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4. Candini M, Giuberti V, Santelli E, di Pellegrino G, Frassinetti F. {{When social and action spaces diverge: A study in children with typical development and autism}}. {Autism}. 2019: 1362361318822504.
The space around the body has been defined as action space ( peripersonal space) and a social space ( interpersonal space). Within the current debate about the characteristics of these spaces, here we investigated the functional properties and plasticity of action and social space in developmental age. To these aims, children with typical development and autism spectrum disorders were submitted to Reaching- and Comfort-distance tasks, to assess peripersonal and interpersonal space, respectively. Participants approached a person (confederate) or an object and stopped when they thought they could reach the stimulus (Reaching-distance task), or they felt comfortable with stimulus’ proximity (Comfort-distance task). Both tasks were performed before and after a cooperative tool-use training, in which participant and confederate actively cooperated to reach tokens by using either a long (Experiment 1) or a short (Experiment 2) tool. Results showed that in both groups, peripersonal space extended following long-tool-use but not short-tool-use training. Conversely, in typical development, but not in autism spectrum disorders children, interpersonal space toward confederate reduced following the cooperative tool-use training. These findings reveal that action and social spaces are functionally dissociable both in typical and atypical development, and that action but not social space regulation is intact in children with autism.
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5. Chu CH, Tsai CL, Chen FC, Sit CHP, Chen PL, Pan CY. {{The role of physical activity and body-related perceptions in motor skill competence of adolescents with autism spectrum disorder}}. {Disabil Rehabil}. 2019: 1-9.
PURPOSE: This study assessed the associations of motor skill competence with physical activity and physical self-perception of adolescents with autism spectrum disorder (ASD). STUDY DESIGN: Cross-sectional study. METHODS: A total of 63 male adolescents, aged 12-18 years, with ASD participated in the study. The Bruininks-Oseretsky Test of Motor Proficiency-Second Edition and the Chinese version of the Physical Self-Perception Profile were administered. Physical activity was assessed using a uniaxial accelerometer. RESULTS: The main findings were that (a) both moderate-to-vigorous physical activity and self-perceived physical condition were positively related to manual coordination (MC) and strength and agility (SA); (b) moderate-to-vigorous physical activity was the only predictor of MC and accounted for 14% of the variance; and (c) perceived physical condition explained 16% of the variance in SA, and moderate-to-vigorous physical activity and perceived physical condition together accounted for 26% of the SA. CONCLUSION: Future interventions aimed at improving motor skill competence in adolescents with ASD should focus on improving the time spent on moderate-to-vigorous physical activity and developing a positive perceived physical condition. Implications for rehabilitation Less than half of the participants with ASD accumulated at least 60 min of daily moderate-to-vigorous physical activity. Of the participants with ASD, only 19% had clinical levels of total motor impairments. Activities that promote successful moderate-to-vigorous physical activity and support positive physical self-perception (i.e., physical condition) are most likely to develop motor skill competency in adolescents with ASD.
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6. Croteau C, Ben Amor L, Ilies D, Mottron L, Tarride JE, Dorais M, Perreault S. {{Impact of Psychoactive Drug Use on Developing Obesity among Children and Adolescents with Autism Spectrum Diagnosis: A Nested Case-Control Study}}. {Childhood obesity (Print)}. 2019.
BACKGROUND: Obesity in children on the autism spectrum (AS) is becoming a significant health concern. The purpose of this study was to identify the predictors of obesity in a cohort of AS youth and to assess the impact of psychoactive medication use while exploring the second-generation antipsychotics (SGAs) dose-response curve. STUDY DESIGN: A nested case-control study was conducted using Quebec public administrative databases. Subjects with AS <18 years [>/=2 diagnoses International Classification of Diseases: 9th revision (ICD-9): 299.X] were identified (January 1993 to May 2011). Cases were defined as subjects with an obesity diagnosis (ICD-9: 278.X) during the coverage period and matched to 10 controls for age, gender, and follow-up duration. Potential risk factors for obesity (sociodemographic characteristics, other neuropsychiatric conditions, and psychoactive drug use) were evaluated and analyzed using conditional logistic regression. RESULTS: From a cohort of 5369 AS subjects, we identified 135 obesity cases. Among the different risk factors, only SGAs [rate ratio (RR): 1.04, 95% confidence interval (CI): 1.01-1.07] increased the probability of obesity in multivariate analysis. Exposure for >/=12 months increased significantly the likelihood of obesity (RR: 2.01, 95% CI: 1.18-3.42). Higher risk was observed with chlorpromazine-equivalent daily doses >/=100 mg (RR: 2.20, 95% CI: 1.00-4.84). Among SGA users, concomitant antidepressants (per 30-day exposure) slightly increased the probability (RR: 1.08, 95% CI: 1.01-1.15). CONCLUSIONS: Longer and higher SGA exposure increased the risk of obesity, which has to be considered in relation to the paucity of evidence supporting long-term psychoactive medication use in AS children. Results highlight the need to promote optimal use and interventions to mitigate metabolic side effects of SGAs in this population.
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7. Dissanayake C, Searles J, Barbaro J, Sadka N, Lawson LP. {{Cognitive and behavioral differences in toddlers with autism spectrum disorder from multiplex and simplex families}}. {Autism Res}. 2019.
Prospective, longitudinal designs utilizing « high-risk » infant siblings of children diagnosed with Autism Spectrum Disorder (ASD-sibs) have provided unique and valuable insights regarding the early ASD phenotype. However, it remains unclear whether these cases are representative of all children with ASD. The objective in the present study was to investigate whether the early development of toddlers with ASD from multiplex (MPX) families, who have an affected older sibling, is similar or different to toddlers with ASD from simplex (SPX) families, where there is no affected sibling. A further aim was to examine patterns of association between autism symptom severity and cognitive functioning within each group to inform possible mechanisms for group similarities/differences. Behavioral and cognitive assessment data from a sample of toddlers with ASD was utilized, comprising 45 MPX, 127 first-born SPX, and 72 later-born SPX toddlers. Participants in the MPX group had significantly higher developmental quotients on the Mullen Scales of Early Learning compared to those in the SPX groups, who did not differ from each other. However, all three groups were similar on their autism severity scores (measured using the Autism Diagnostic Observation Schedule and the Autism Diagnostic Interview), and the pattern of relationships between cognitive ability and autism symptom severity. The results suggest that caution be exercised in generalizing findings from ASD-sib samples to other samples of children with ASD. The higher cognitive abilities in the MPX group, in addition to biological differences, may also be an outcome of family environmental factors, which deserves further investigation. Autism Research 2019. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: We sought to establish whether toddlers with autism from families where there is more than one affected child, called multiplex families, are different to children from simplex families, where there is only one affected child, and no other members within the immediate family with an autism diagnosis. We found that while toddlers from multiplex families were similar to those from simplex families in their autism symptoms, they were more developmentally advanced than children in the latter group.
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8. Fontes-Dutra M, Della-Flora Nunes G, Terra JS, Souza-Nunes W, Bauer-Negrini G, Hirsch MM, Green L, Riesgo R, Gottfried C, Bambini-Junior V. {{Abnormal empathy-like pro-social behaviour in the valproic acid model of autism spectrum disorder}}. {Behav Brain Res}. 2019.
Impairments in social behaviour are a defining feature of autism spectrum disorder (ASD). Individuals with ASD also usually present some difficulty to recognise or understand another person’s feelings. Therefore, it is possible that altered empathy processing could hinder typical social interaction in ASD. Recently, robust paradigms confirmed that rodents show primordial forms of empathy-like behaviour. Therefore, in this work, we used one of these new protocols to test pro-social behaviour in the rat model of autism induced by Valproic Acid (VPA). We also evaluated possible beneficial effects of Resveratrol, since it can prevent social deficits in the VPA model. Rats were tested on their ability to open a restrainer to release a trapped conspecific. Exposure to VPA precludes the timely manifestation of this empathy-like behaviour, but does not affect its continuation after its first expression. We also found a significant correlation between average speed during the first day of test and becoming an Opener. Similarly, rats able to open the restrainer on the first day had an increased likelihood of repeating this behaviour in the later days of the testing programme. We did not find any protective effects of Resveratrol. Further investigation of empathy-like behaviour in the VPA model and in other models of autism could help to clarify the behavioural and neural processes underpinning the basic aspects of empathy alterations in autistic individuals.
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9. Frizzell W, Howard L, Norris HC, Chien J. {{Homicidal Ideation and Individuals on the Autism Spectrum}}. {Journal of forensic sciences}. 2019.
Interest in the relationship between autism and violence has increased in recent years; however, no link has clearly been established between them. Researchers remain curious if autistic people with certain traits (e.g., a history of trauma) are at greater risk of violence than those individuals with autism alone. In this article, we detail two individuals with homicidal ideation (HI) admitted to inpatient psychiatric units who were found to have a diagnosis of autism without language impairment. These cases illustrate the need for mental health providers to consider autism in their differential diagnosis when evaluating an individual with HI. Broadly, we consider how an autistic individual could be susceptible to developing HI and explore treatments specific to autistic individuals that may be helpful in such cases.
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10. Granillo L, Sethi S, Keil KP, Lin Y, Ozonoff S, Iosif AM, Puschner B, Schmidt RJ. {{Polychlorinated biphenyls influence on autism spectrum disorder risk in the MARBLES cohort}}. {Environmental research}. 2018; 171: 177-84.
BACKGROUND: Autism spectrum disorder (ASD) is suspected to have environmental and genetic contributions. Polychlorinated biphenyls (PCBs) are environmental risk factors of interest due to their potential as neurodevelopmental toxicants and environmental persistence despite a US production ban in the 1970s. METHODS: Participants were mother-child pairs from MARBLES, a high-risk pregnancy cohort that enrolls families who have one child diagnosed with ASD and are planning to have another child. PCB concentrations were measured in maternal blood at each trimester of pregnancy using gas chromatography coupled with triple quadruple mass spectrometry. Concentrations were summed into total PCB and two categories based on function/mechanisms of action: dioxin-like (DL), and ryanodine receptor (RyR)-activating PCBs. Multinomial logistic regression assessed risk of clinical outcome classification of ASD and non-typical development (Non-TD) compared to typically developing (TD) in the children at 3 years old. RESULTS: A total of 104 mother-child pairs were included. There were no significant associations for total PCB; however, there were borderline significant associations between DL-PCBs and decreased risk for Non-TD outcome classification (adjusted OR: 0.41 (95% CI 0.15-1.14)) and between RyR-activating PCBs and increased risk for ASD outcome classification (adjusted OR: 2.63 (95% CI 0.87-7.97)). CONCLUSION: This study does not provide strong supporting evidence that PCBs are risk factors for ASD or Non-TD. However, these analyses suggest the need to explore more deeply into subsets of PCBs as risk factors based on their function and structure in larger cohort studies where non-monotonic dose-response patterns can be better evaluated.
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11. Kirby AV, Bakian AV, Zhang Y, Bilder DA, Keeshin BR, Coon H. {{A 20-year study of suicide death in a statewide autism population}}. {Autism Res}. 2019.
SCIENTIFIC SUMMARY: Growing concern about suicide risk among individuals with autism spectrum disorder (ASD) necessitates population-based research to determine rates in representative samples and to inform appropriate prevention efforts. This study used existing surveillance data in Utah to determine incidence of suicide among individuals with ASD over a 20-year period, and to characterize those who died. Between 1998 and 2017, 49 individuals with ASD died by suicide. Suicide cumulative incidence rates did not significantly differ between 1998 and 2012 across the ASD and non-ASD populations. Between 2013 and 2017, the cumulative incidence of suicide in the ASD population was 0.17%, which was significantly higher than in the non-ASD population (0.11%; P < 0.05). During this period, this difference was driven by suicide among females with ASD; suicide risk in females with ASD was over three times higher than in females without ASD (relative risk (RR): 3.42; P < 0.01). Among the individuals with ASD who died by suicide, average age at death and manner of death did not differ significantly between males and females. Ages at death by suicide ranged from 14 to 70 years (M[SD] = 32.41[15.98]). Individuals with ASD were significantly less likely to use firearms as a method of suicide (adjusted odds ratio: 0.33; P < 0.001). Study results expand understanding of suicide risk in ASD and point to the need for additional population-based research into suicide attempts and ideation, as well as exploration of additional risk factors. Findings also suggest a need for further study of female suicide risk in ASD. Autism Research 2019. (c) 2019 The Authors. Autism Research published by International Society for Autism Research published by Wiley Periodicals, Inc. LAY SUMMARY: This study examined suicide risk among individuals with autism spectrum disorder (ASD) in Utah over a 20-year period. Risk of suicide death in individuals with ASD was found to have increased over time and to be greater than in individuals without ASD between 2013 and 2017. Females with ASD were over three times as likely to die from suicide as females without ASD. Young people with ASD were at over twice the risk of suicide than young people without ASD. Individuals with ASD were less likely than others to die from firearm-related suicides. Lien vers le texte intégral (Open Access ou abonnement)
12. Lee H, Thacker S, Sarn N, Dutta R, Eng C. {{Constitutional mislocalization of Pten drives precocious maturation in oligodendrocytes and aberrant myelination in model of autism spectrum disorder}}. {Translational psychiatry}. 2019; 9(1): 13.
There is a strong genetic association between germline PTEN mutation and autism spectrum disorder (ASD), making Pten-mutant models exemplary for the study of ASD pathophysiology. We developed the Pten(m3m4) mouse, where Pten is largely restricted from the nucleus, which recapitulates patient-like, autism-related phenotypes: behavioral changes, macrocephaly, and white matter abnormalities. This study aimed to investigate the contribution of oligodendrocyte (OL) lineage differentiation and functional changes in myelination to the white matter phenotype. OL lineage differentiation and myelination in Pten(m3m4) mice was studied using immunohistochemical and electron microscopic analyses. We also used primary oligodendrocyte progenitor cells (OPCs) to determine the effect of the Pten(m3m4) mutation on OPC proliferation, migration and maturation. Finally, we assessed the myelinating competency of mutant OLs via co-culture with wildtype dorsal root ganglia (DRG) neurons. The in vivo analyses of Pten(m3m4/m3m4) murine brains showed deficits in proteolipid protein (Plp) trafficking in myelinating OLs. Despite the increased expression of myelin proteins in the brain, myelin deposition was observed to be abnormal, often occurring adjacent to, rather than around axons. Mutant primary OPCs showed enhanced proliferation and migration. Furthermore, mutant OPCs matured precociously, exhibiting aberrant myelination in vitro. Mutant OPCs, when co-cultured with wildtype DRG neurons, showed an inability to properly ensheath axons. Our findings provide evidence that the Pten(m3m4) mutation disrupts the differentiation and myelination programs of developing OLs. OL dysfunction in the Pten(m3m4) model explains the leukodystrophy phenotype, a feature commonly associated with autism, and highlights the growing importance of glial dysfunction in autism pathogenesis.
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13. Liu S, Li E, Sun Z, Fu D, Duan G, Jiang M, Yu Y, Mei L, Yang P, Tang Y, Zheng P. {{Altered gut microbiota and short chain fatty acids in Chinese children with autism spectrum disorder}}. {Sci Rep}. 2019; 9(1): 287.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder that is characterized by impairments in social interactions and communication, restricted interests and repetitive behaviors. Several studies report a high prevalence of gastrointestinal (GI) symptoms in autistic individuals. Cumulative evidence reveals that the gut microbiota and its metabolites (especially short-chain fatty acids, SCFAs) play an important role in GI disorders and the pathogenesis of ASD. However, the composition of the gut microbiota and its association with fecal SCFAs and GI symptoms of autistic children remain largely unknown. In the present study, we sequenced the bacterial 16S rRNA gene, detected fecal SCFAs, assessed GI symptoms and analyzed the relationship between the gut microbiome and fecal SCFAs in autistic and neurotypical individuals. The results showed that the compositions of the gut microbiota and SCFAs were altered in ASD individuals. We found lower levels of fecal acetic acid and butyrate and a higher level of fecal valeric acid in ASD subjects. We identified decreased abundances of key butyrate-producing taxa (Ruminococcaceae, Eubacterium, Lachnospiraceae and Erysipelotrichaceae) and an increased abundance of valeric acid associated bacteria (Acidobacteria) among autistic individuals. Constipation was the only GI disorder in ASD children in the present study. We also found enriched Fusobacterium, Barnesiella, Coprobacter and valeric acid-associated bacteria (Actinomycetaceae) and reduced butyrate-producing taxa in constipated autistic subjects. It is suggested that the gut microbiota contributes to fecal SCFAs and constipation in autism. Modulating the gut microbiota, especially butyrate-producing bacteria, could be a promising strategy in the search for alternatives for the treatment of autism spectrum disorder.
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14. McIntosh CE, Kandiah J, Boucher NR. {{Practical Considerations for School Nurses in Improving the Nutrition of Children With Autism Spectrum Disorder}}. {NASN school nurse (Print)}. 2019: 1942602×18822775.
Children with autism spectrum disorder may exhibit issues with food selectivity and/or picky eating habits. Symptoms of autism such as sensory sensitivity contribute to why these children refuse to eat food, but medications, food intolerance, and even financial status can cause this issue to become concerning to a student’s overall health. School nurses are imperative in the health care of children with autism spectrum disorder and must understand why food selectivity occurs in order to maintain or improve the nutrition status of their students. This article provides an overview of food selectivity and where it stems from as well as 10 tips in working with food selective children.
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15. Motil KJ, Lane JB, Barrish JO, Annese F, Geerts S, McNair L, Skinner SA, Neul JL, Glaze DG, Percy AK. {{Biliary Tract Disease in Girls and Young Women with Rett Syndrome}}. {Journal of pediatric gastroenterology and nutrition}. 2019.
OBJECTIVE: We reviewed medical records and conducted a nationwide survey to characterize the clinical features and determine the prevalence of biliary tract disease in girls and women with Rett syndrome (RTT). METHODS: Sixty-two individuals with RTT and biliary tract disease were identified from the membership of Rett Syndrome Organization (RS.O) and patient files of the principal investigator. Medical records of 46 individuals were reviewed for presenting features, diagnostic tests, and treatment outcomes of biliary tract disease. We designed a questionnaire that probed the frequency of risk factors and treatment outcomes of biliary tract disease in RTT. The questionnaire was completed by 271 parents whose daughters met the clinical criteria for RTT and/or had MECP2 mutations and participated in the Natural History of Rett Syndrome Study. RESULTS: Presenting symptoms identified by record review included abdominal pain (94%), irritability (88%), weight loss (64%), and vomiting (52%). Biliary dyskinesia, cholecystitis, and cholelithiasis, were identified in 90%, 77%, and 70%, respectively, by cholescintigraphy, surgical pathology, and abdominal ultrasound. The prevalence of biliary tract disease was 4.4% (n = 12) in the RTT cohort. Risk factors included older age (p < 0.001) and a positive family history (p < 0.01). Diagnoses included cholecystitis (n = 5), biliary dyskinesia (n = 6), and cholelithiasis (n = 7). Ten individuals underwent surgery; seven had resolution of symptoms after surgical intervention. CONCLUSION: Biliary tract disease is not unique to RTT, but may be under-recognized because of the cognitive impairment of affected individuals. Early diagnostic evaluation and intervention may improve the health and quality of life of individuals affected with RTT and biliary tract disease. Lien vers le texte intégral (Open Access ou abonnement)
16. O’Neill SJ, Smyth S, Smeaton A, O’Connor NE. {{Assistive technology: Understanding the needs and experiences of individuals with autism spectrum disorder and/or intellectual disability in Ireland and the UK}}. {Assistive technology : the official journal of RESNA}. 2019: 1-9.
Assistive technologies (ATs) aimed at improving the life quality of persons with Autism Spectrum Disorder and/or Intellectual Disability (ASD/ID) is an important research area. Few have examined how this population use and experience AT or their vision for future uses of AT. The present study aimed to update and extend previous research and provides insight from caregivers, and other stakeholders (n = 96), living in Ireland and the United Kingdom, on their experiences of assistive technology (AT) for ASD/ID. Caregiver and professional responses to an anonymous online survey showed that focus individuals were rated low in terms of independent and self-management skills, with scheduling and planning and communication identified as desirable future AT functions. Overall, positive experiences of AT were reported, with AT use more than doubling in recent years.
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17. Panerai S, Suraniti GS, Catania V, Zingale M, Ferri R, Raggi A, Trubia G, Elia M. {{Early results from a combined low-intensive psychoeducational intervention for preschoolers with autism spectrum disorder}}. {Disabil Rehabil}. 2019: 1-9.
PURPOSE: Early and Intensive Behavioral Treatments are considered to be evidence-based interventions for children with Autism Spectrum Disorder (ASD). Nevertheless, children with ASD might not always have the opportunity to benefit from intensive treatment; new, more accessible and alternative treatment options need to be tested. The aim of this study was to evaluate the effectiveness of the Combined Low-intensive Psychoeducational Intervention (CLI-PEI) delivered to preschoolers with ASD at the end of the pre-primary school day. METHODS: A quasi-experimental design study, namely a pretest-posttest alternative-treatment comparison groups design, was used. Treatment sessions were carried out over a period of 12 months. Forty-three individuals with autism were included in the study: 24 received the CLI-PEI and 19 were administered the Treatment As Usual. A pre- and posttreatment assessment was carried out using the Psychoeducational Profile-Third edition and the Vineland Adaptive Behavior Scale. RESULTS: The children who received the CLI-PEI showed better gains in both developmental and maladaptive behaviors; furthermore, increased skills were found in all adaptive domains. CONCLUSIONS: The CLI-PEI might seems to be a viable treatment option for children with ASD, when intensive behavioral treatments are not accessible. Implication for rehabilitation Children with ASD might not always have the opportunity to benefit from intensive treatment. The identification of more accessible, less intensive and less expensive evidence-based psychoeducational interventions might represent an appealing challenge for rehabilitation therapists. Less intensive and less expensive evidence-based interventions might also represent a viable option for children and their families, especially in communities with limited resources for autism. A pragmatic approach including components from evidence-based treatments might guarantee flexibility and the possibility to implement an intervention well-tailored to the specific child needs. CLI-PEI for preschoolers with ASD seems to be a promising pragmatic approach, promoting improvements in developmental, adaptive and maladaptive domains.
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18. Patowary A, Won SY, Oh SJ, Nesbitt RR, Archer M, Nickerson D, Raskind WH, Bernier R, Lee JE, Brkanac Z. {{Family-based exome sequencing and case-control analysis implicate CEP41 as an ASD gene}}. {Translational psychiatry}. 2019; 9(1): 4.
Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder with a strong genetic component. Although next-generation sequencing (NGS) technologies have been successfully applied to gene identification in de novo ASD, the genetic architecture of familial ASD remains largely unexplored. Our approach, which leverages the high specificity and sensitivity of NGS technology, has focused on rare variants in familial autism. We used NGS exome sequencing in 26 families with distantly related affected individuals to identify genes with private gene disrupting and missense variants of interest (VOI). We found that the genes carrying VOIs were enriched for biological processes related to cell projection organization and neuron development, which is consistent with the neurodevelopmental hypothesis of ASD. For a subset of genes carrying VOIs, we then used targeted NGS sequencing and gene-based variant burden case-control analysis to test for association with ASD. Missense variants in one gene, CEP41, associated significantly with ASD (p = 6.185(e-05)). Homozygous gene-disrupting variants in CEP41 were initially found to be responsible for recessive Joubert syndrome. Using a zebrafish model, we evaluated the mechanism by which the CEP41 variants might contribute to ASD. We found that CEP41 missense variants affect development of the axonal tract, cranial neural crest migration and social behavior phenotype. Our work demonstrates the involvement of CEP41 heterozygous missense variants in ASD and that biological processes involved in cell projection organization and neuron development are enriched in ASD families we have studied.
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19. Payabvash S, Palacios E, Owen JP, Wang MB, Tavassoli T, Gerdes MR, Brandes Aitken A, Cuneo D, Marco E, Mukherjee P. {{White Matter Connectome Edge Density in Children with Autism Spectrum Disorders: Potential Imaging Biomarkers Using Machine Learning Models}}. {Brain Connect}. 2019.
Prior neuroimaging studies have reported white matter network underconnectivity as a potential mechanism for Autism Spectrum Disorder (ASD). In this study, we examined the structural connectome of children with ASD using Edge Density Imaging (EDI); and then applied machine leaning algorithms to identify children with ASD based on tract-based connectivity metrics. Boys aged 8 to 12 years were included: 14 with ASD and 33 typically developing children (TDC). The Edge Density (ED) maps were computed from probabilistic streamline tractography applied to high angular resolution diffusion imaging (HARDI). Tract-Based Spatial Statistics (TBSS) was used for voxel-wise comparison and coregistration of ED maps in addition to conventional DTI metrics of Fractional Anisotropy (FA), Mean Diffusivity (MD), and Radial Diffusivity (RD). Tract-based average DTI/connectome metrics were calculated and used as input for different machine learning models: naive Bayes, random forest, support vector machines (SVM), neural networks. For these models, cross-validation was performed with stratified random sampling (x1000 permutations). The average accuracy among validation samples was calculated. In voxel-wise analysis, the body and splenium of corpus callosum, bilateral superior and posterior corona radiata, and left superior longitudinal fasciculus showed significantly lower ED in children with ASD; whereas, we could not find significant difference in FA, MD, and RD maps between the two study groups. Overall, machine-learning models using tract-based ED metrics had better performance in identification of children with ASD compared to those using FA, MD, and RD. The EDI-based random forest models had greater average accuracy (75.3%), specificity (97.0%), and positive predictive value (81.5%), whereas EDI-based polynomial SVM had greater sensitivity (51.4%), and negative predictive values (77.7%). In conclusion, we found reduced density of connectome edges in the posterior white matter tracts of children with ASD; and demonstrated the feasibility of connectome-based machine-learning algorithms in identification of children with ASD.
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20. Schob C, Morellini F, Ohana O, Bakota L, Hrynchak MV, Brandt R, Brockmann MD, Cichon N, Hartung H, Hanganu-Opatz IL, Kraus V, Scharf S, Herrmans-Borgmeyer I, Schweizer M, Kuhl D, Wohr M, Vorckel KJ, Calzada-Wack J, Fuchs H, Gailus-Durner V, Hrabe de Angelis M, Garner CC, Kreienkamp HJ, Kindler S. {{Cognitive impairment and autistic-like behaviour in SAPAP4-deficient mice}}. {Translational psychiatry}. 2019; 9(1): 7.
In humans, genetic variants of DLGAP1-4 have been linked with neuropsychiatric conditions, including autism spectrum disorder (ASD). While these findings implicate the encoded postsynaptic proteins, SAPAP1-4, in the etiology of neuropsychiatric conditions, underlying neurobiological mechanisms are unknown. To assess the contribution of SAPAP4 to these disorders, we characterized SAPAP4-deficient mice. Our study reveals that the loss of SAPAP4 triggers profound behavioural abnormalities, including cognitive deficits combined with impaired vocal communication and social interaction, phenotypes reminiscent of ASD in humans. These behavioural alterations of SAPAP4-deficient mice are associated with dramatic changes in synapse morphology, function and plasticity, indicating that SAPAP4 is critical for the development of functional neuronal networks and that mutations in the corresponding human gene, DLGAP4, may cause deficits in social and cognitive functioning relevant to ASD-like neurodevelopmental disorders.
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21. Sernheim AS, Hemmingsson H, Lidstrom H, Witt Engerstrom I, Liedberg GM. {{Rett syndrome: Teenagers’ and young adults’ activities, usage of time and responses during an ordinary week – a diary study}}. {Scandinavian journal of occupational therapy}. 2019: 1-13.
BACKGROUND: Little is known about the everyday life of individuals with Rett syndrome. AIM/OBJECTIVE: To describe ten participants’ (teenagers/young adults) activities during a period of seven days, the time-use, where and with whom the activities were performed and the participants’ responses in the form of visible/audible reactions during activities. MATERIAL AND METHOD: A time-geographic self-administered diary was filled in by 63 informants (parents/support staff) and analysed using the software, DAILY LIFE 2011. RESULTS/FINDINGS: The most frequently reported activities were hygiene/toilet, moving around indoors, eating and getting dressed. Most time was spent in sleeping, daily care, medical health care and travel/transportation. Little time remained for receptive activities, daytime rest, physical, social/creative, communication, school/daily work and domestic chore activities, especially for the young adults. Most time was spent with staff, thereafter with families and the least time was spent with friends. The most reported response was « interested », and « opposed » was the least reported. CONCLUSIONS: Daily and medical health care activities were time consuming. Improved communication between all parties may increase participation and well-being and provide solutions for handling unpleasant activities and sedentary time. SIGNIFICANCE: A more varied range of activities may improve the everyday life for individuals with Rett syndrome.
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22. Sragovich S, Malishkevich A, Piontkewitz Y, Giladi E, Touloumi O, Lagoudaki R, Grigoriadis N, Gozes I. {{The autism/neuroprotection-linked ADNP/NAP regulate the excitatory glutamatergic synapse}}. {Translational psychiatry}. 2019; 9(1): 2.
Activity-dependent neuroprotective protein (ADNP), essential for brain formation, was discovered as a leading de novo mutated gene causing the autism-like ADNP syndrome. This syndrome is phenotypically characterized by global developmental delays, intellectual disabilities, speech impediments, and motor dysfunctions. The Adnp haploinsufficient mouse mimics the human ADNP syndrome in terms of synapse density and gene expression patterns, as well as in developmental, motor, and cognitive abilities. Peripheral ADNP was also discovered as a biomarker for Alzheimer’s disease and schizophrenia, with nasal administration of the ADNP snippet peptide NAP (enhancing endogenous ADNP activity) leading to partial cognitive and functional protection at the cellular, animal and clinical settings. Here, a novel formulation for effective delivery of NAP is provided with superior brain penetration capabilities. Also provided are methods for treating pertinent clinical implications such as autism, cognitive impairments, olfactory deficits, and muscle strength using the formulation in the Adnp haploinsufficient mouse. Results showed a dramatically specific increase in brain/body bioavailability with the new formulation, without breaching the blood brain barrier. Additional findings included improvements using daily intranasal treatments with NAP, at the behavioral and brain structural levels, diffusion tensor imaging (DTI), translatable to clinical practice. Significant effects on hippocampal and cerebral cortical expression of the presynaptic Slc17a7 gene encoding vesicular excitatory glutamate transporter 1 (VGLUT1) were observed at the RNA and immunohistochemical levels, explaining the DTI results. These findings tie for the first time a reduction in presynaptic glutamatergic synapses with the autism/Alzheimer’s/schizophrenia-linked ADNP deficiency coupled with amelioration by NAP (CP201).
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23. Tse CYA, Lee HP, Chan KSK, Edgar BV, Wilkinson-Smith A, Lai WHE. {{Examining the impact of physical activity on sleep quality and executive functions in children with autism spectrum disorder: A randomized controlled trial}}. {Autism}. 2019: 1362361318823910.
Sleep disturbance and executive dysfunction have been widely reported in children with autism spectrum disorder. While the positive impacts of physical activity on sleep quality and cognition are documented in children with typical development, similar studies in children with autism spectrum disorder are scarce. The objective of this study was to examine the impact of physical activity on sleep quality and cognition in children with autism spectrum disorder. A total of 40 children diagnosed with autism spectrum disorder (mean age = 9.95 years) were randomly assigned into two groups: physical activity intervention and control. Four sleep parameters (sleep efficiency, sleep onset latency, sleep duration, and wake after sleep onset) and two executive functions (inhibition control and working memory) were assessed. Results revealed a significant improvement in sleep efficiency, sleep onset latency, and sleep duration in the intervention group but not in the control group during weekdays. Moreover, a significant improvement in inhibitory control was shown in the intervention group but not in the control group. No significant improvement in working memory capacity was documented in either group ( ps > 0.05). Our findings highlight the value of physical activity in improving sleep quality and cognition among children with autism spectrum disorder, but specific physical activity may be required to benefit individual executive functions.
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24. Vincent A, Da Fonseca D, Baumstarck K, Charvin I, Alcaraz-Mor R, Lehucher-Michel MP. {{The quality of life and the future of young adults with Asperger syndrome}}. {Disabil Rehabil}. 2019: 1-8.
PURPOSE: This pilot study describes the socio-professional development and quality of life of young adults with Asperger syndrome in France. METHODS: Those young adults, between 18 and 30 years old, receiving care in a child psychiatry department for autistic spectrum disorder, were requested to respond to the Ad Hoc, World Health Organization Quality Of Life – Bref and Copenhagen psychosocial questionnaires regarding their socio-professional background and feelings about their future. RESULTS: Of the 79 eligible subjects, 24 were selected to participate in our study. Their average age at the time of the pilot study was 22.2 years (standard deviation 3.4 years), and their average age when they were diagnosed was 17.5 years (standard deviation 3.7 years.). There were 54% who reported a psychiatric comorbidity anxiety disorder. Half stated they had completed secondary school and benefitted from being professionally employed. During this study, only six were employed, while the others remained financially dependent on their parents. The group’s quality of life self-assessment scores were significantly lower compared to the French general population in overall psychology (43.6 versus 68.7) and social relationships (48.9 versus 76.5). However, the study’s participants perceived work as an important means to their personal development. Hence, in order to cope with their difficulties, they hoped to benefit from customized support adapted to their autistic disorder and for their workplace colleagues to be better informed about Asperger syndrome. CONCLUSIONS: Our results are in line with international data. Additional studies need to be done in order to determine socio-professional integration factors and, in particular, the integration of potential contributions by occupational health departments with those social and medical teams supporting these young adults. Implications for rehabilitation Young adults with Asperger syndrome benefit from the support of their family in determining their professional goals. Support may be required to enhance social and communicative abilities to help integration. Employees would benefit from information on the syndrome and how best to support.
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25. Weiber I, Tengland PA, Berglund JS, Eklund M. {{Everyday life when growing up with a mother with an intellectual or developmental disability: Four retrospective life-stories}}. {Scandinavian journal of occupational therapy}. 2019: 1-13.
BACKGROUND: The voices of those who have grown up in a family with maternal intellectual or developmental disability (IDD) are valuable for gaining an understanding of their situation, which is essential in order to be able to support these families and avoid potentially detrimental situations. AIM: The study aim was to describe the experience of having grown up in a family where the mother has an IDD, with a focus on everyday life and perceived health consequences in adult life. METHOD: A qualitative method with retrospective narrative interviews and narrative content analysis was chosen. In-depth interviews were performed with four women who had experiences of a childhood with maternal IDD. FINDINGS: Four themes emerged: Living under adverse circumstances; Dealing with one’s everyday life situation; Receiving insufficient support and wishing for more; and The echo from childhood into adult life. The findings revealed a distressing childhood, characterized by neglect, abuse, anxiety, and overburdening responsibilities, and also endeavors to keep the family situation a secret, while at the same time wanting the adult world to react. DISCUSSION: The findings can hopefully stimulate occupational therapists and other professionals to more effectively identify the situation of these children and provide support to prevent adverse future health conditions and poor well-being.
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26. Yasin H, Gibson WT, Langlois S, Stowe RM, Tsang ES, Lee L, Poon J, Tran G, Tyson C, Wong CK, Marra MA, Friedman JM, Zahir FR. {{A distinct neurodevelopmental syndrome with intellectual disability, autism spectrum disorder, characteristic facies, and macrocephaly is caused by defects in CHD8}}. {Journal of human genetics}. 2019.
A decade ago, we described novel de novo submicroscopic deletions of chromosome 14q11.2 in three children with developmental delay, cognitive impairment, and similar dysmorphic features, including widely-spaced eyes, short nose with flat nasal bridge, long philtrum, prominent Cupid’s bow of the upper lip, full lower lip, and auricular anomalies. We suggested that this constituted a new multiple congenital anomaly-intellectual disability syndrome due to defects in CHD8 and/or SUPT16H. The three patients in our original cohort were between 2 years and 3 years of age at the time. Here we present a fourth patient and clinical updates on our previous patients. To document the longitudinal course more fully, we integrate published reports of other patients and describe genotype-phenotype correlations among them. Children with the disorder present with developmental delay, intellectual disability, and/or autism spectrum disorder in addition to characteristic facies. Gastrointestinal and sleep problems are notable. The identification of multiple patients with the same genetic defect and characteristic clinical phenotype, confirms our suggestion that this is a syndromic disorder caused by haploinsufficiency or heterozygous loss of function of CHD8.
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27. Zhang F, Roeyers H. {{Exploring brain functions in autism spectrum disorder: A systematic review on functional near-infrared spectroscopy (fNIRS) studies}}. {International journal of psychophysiology : official journal of the International Organization of Psychophysiology}. 2019; 137: 41-53.
A growing body of research has investigated the functional development of the brain in autism spectrum disorder (ASD). Functional near-infrared spectroscopy (fNIRS) is increasingly being used in this respect. This method has several advantages over other functional neuroimaging techniques in studying brain functions in ASD, including portability, low cost, and availability in naturalistic settings. This article reviews thirty empirical studies, published in the past decade, that used fNIRS in individuals with ASD or in infants with a high risk of developing ASD. These studies investigated either brain activation using multiple tasks (e.g., face processing, joint attention and working memory) or functional organization under a resting-state condition in ASD. The majority of these studies reported atypical brain activation in the prefrontal cortex, inferior frontal gyrus, middle and superior temporal gyrus. Some studies revealed altered functional connectivity, suggesting an inefficient information transfer between brain regions in ASD. Overall, the findings suggest that fNIRS is a promising tool to explore neurodevelopment in ASD from an early age.
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28. Zhang L, Qin Y, Gong X, Peng R, Cai C, Zheng Y, Du Y, Wang H. {{A promoter variant in ZNF804A decreasing its expression increases the risk of autism spectrum disorder in the Han Chinese population}}. {Translational psychiatry}. 2019; 9(1): 31.
Synaptic pathology may be one of the cellular substrates underlying autism spectrum disorder (ASD). ZNF804A is a transcription factor that can affect or regulate the expression of many candidate genes involved in ASD. It also localizes at synapses and regulates neuronal and synaptic morphology. So far, few reports have addressed possible associations between ZNF804A polymorphisms and ASD. This study aimed to investigate whether ZNF804A genetic variants contribute to ASD susceptibility and its possible pathological role in the disorder. We analyzed the relationship of two polymorphisms (rs10497655 and rs34714481) in ZNF804A promoter region with ASD in 854 cases versus 926 controls. The functional analyses of rs10497655 were then performed using real-time quantitative polymerase chain reaction, electrophoretic mobility shift assays, chromatin immunoprecipitation and dual-luciferase assays. The variant rs10497655 was significantly associated with ASD (P = 0.007851), which had a significant effect on ZNF804A expression, with the T risk allele homozygotes related with reduced ZNF804A expression in human fetal brains. HSF2 acted as a suppressor by down-regulating ZNF804A expression and had a stronger binding affinity for the T allele of rs10497655 than for the C allele. This was the first experiment to elucidate the process in which a disease-associated SNP affects the level of ZNF804A expression by binding with the upstream regulation factor HSF2. This result indicates that the rs10497655 allelic expression difference of ZNF804A during the critical period of brain development may have an effect on postnatal phenotypes of ASD. It reveals new roles of ZNF804A polymorphisms in the pathogenesis of psychiatric disorders.
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29. Zhou Y, Yin H, Wang M, Wang J. {{The effect of family-focused psychoeducational therapy for autism spectrum disorder children’s parents on parenting self-efficacy and emotion}}. {Archives of psychiatric nursing}. 2019; 33(1): 17-22.
The purpose of this pilot study was to design, implement, and evaluate the family-focused psychoeducational therapy (FFPT) for autism spectrum disorder (ASD) family. In Phase I, 64 parents of ASD children (ASD-group) and 63 parents of typically development children (TD-group) were invited to investigate parenting self-efficacy and emotion at baseline. In Phase II, the 4-week of FFPT was offered for the ASD-group. Date was collected at baseline, post-intervention and one-month follow-up, using the parental self-efficacy, Self-Rating Anxiety Scale and Self-Rating Depression Scale. The results showed that ASD-group significantly lower levels of parenting self-efficacy and worse emotion than TD-group (p<0.05); And after attending the program, ASD-group had significant improvements for all outcome measures and these changes maintained over a period of time (p<0.05). This preliminary study suggests that the FFPT may effectively improve parenting self-efficacy, reduce anxiety and depression for parents of children with ASD. Lien vers le texte intégral (Open Access ou abonnement)
