1. Ali Z, Zulfiqar S, Klar J, Wikstrom J, Ullah F, Khan A, Abdullah U, Baig S, Dahl N. {{Homozygous GRID2 missense mutation predicts a shift in the D-serine binding domain of GluD2 in a case with generalized brain atrophy and unusual clinical features}}. {BMC Med Genet};2017 (Dec 6);18(1):144.
BACKGROUND: Spinocerebellar ataxias comprise a large and heterogeneous group of disorders that may present with isolated ataxia, or ataxia in combination with other neurologic or non-neurologic symptoms. Monoallelic or biallelic GRID2 mutations were recently reported in rare cases with cerebellar syndrome and variable degree of ataxia, ocular symptoms, hypotonia and developmental delay. CASE PRESENTATION: We report on a consanguineous family with autosomal recessive childhood onset of slowly progressive cerebellar ataxia and delayed psychomotor development in three siblings. MRI of an adult and affected family member revealed slightly widened cerebral and cerebellar sulci, suggesting generalized brain atrophy, and mild cerebellar atrophy. Using whole exome sequencing we identified a novel homozygous missense variant [c.2128C > T, p.(Arg710Trp)] in GRID2 that segregates with the disease. The missense variant is located in a conserved region encoding the extracellular serine-binding domain of the GluD2 protein and predicts a change in conformation of the protein. CONCLUSION: The widespread supratentorial brain abnormalities, absence of oculomotor symptoms, increased peripheral muscle tone and the novel missense mutation add to the clinical and genetic variability in GRID2 associated cerebellar syndrome. The neuroradiological findings in our family indicate a generalized neurodegenerative process to be taken into account in other families segregating complex clinical features and GRID2 mutations.
Lien vers le texte intégral (Open Access ou abonnement)
2. Boivin M, Willemsen R, Hukema RK, Sellier C. {{Potential pathogenic mechanisms underlying Fragile X Tremor Ataxia Syndrome: RAN translation and/or RNA gain-of-function?}}. {Eur J Med Genet};2017 (Dec 6)
Fragile X-associated tremor/ataxia syndrome (FXTAS) is an inherited neurodegenerative disease caused by an expansion of 55-200 CGG repeats located in the FMR1 gene. The main clinical and neuropathological features of FXTAS are progressive intention tremor and gait ataxia associated with brain atrophy, neuronal cell loss and presence of ubiquitin-positive intranuclear inclusions in both neurons and astrocytes. At the molecular level, FXTAS is characterized by increased expression of FMR1 sense and antisense RNA containing expanded CGG or GGC repeats, respectively. Here, we discuss the putative molecular mechanisms underlying FXTAS and notably recent reports that expanded CGG and GGC repeats may be pathogenic through RAN translation into toxic proteins.
Lien vers le texte intégral (Open Access ou abonnement)
3. Cappe E, Poirier N, Sankey C, Belzil A, Dionne C. {{Quality of life of French Canadian parents raising a child with autism spectrum disorder and effects of psychosocial factors}}. {Qual Life Res};2017 (Dec 4)
PURPOSE: This study aimed to investigate the quality of life of parents of a child with autism spectrum disorder in Quebec. METHODS: Seventy-seven participants completed a questionnaire with socio-biographic information and five self-assessed scales, to measure perceived stress, social support and control, coping strategies, and quality of life. RESULTS: Perception of their child’s autonomy level, of the severity of the disorder, of the family’s income, as well as changes in their professional or familial organization influenced parents’ quality of life. Perceiving their situation as a threat predicted poor quality of life, whereas satisfaction of social support predicted good quality of life. In addition, parents who used problem solving and support-seeking coping strategies had a better relationship with their child, whereas those who used more emotion-centered coping strategies struggled. Lastly, parents who felt they had the power to contribute to their child’s development were more satisfied and less disturbed. CONCLUSIONS: Beyond the parents’ actual situation, our results underscore the importance of paying attention to their own perception of the situation in order to provide them with appropriate support.
Lien vers le texte intégral (Open Access ou abonnement)
4. Chang JM, Zeng H, Han R, Chang YM, Shah R, Salafia CM, Newschaffer C, Miller RK, Katzman P, Moye J, Fallin M, Walker CK, Croen L. {{Autism risk classification using placental chorionic surface vascular network features}}. {BMC Med Inform Decis Mak};2017 (Dec 6);17(1):162.
BACKGROUND: Autism Spectrum Disorder (ASD) is one of the fastest-growing developmental disorders in the United States. It was hypothesized that variations in the placental chorionic surface vascular network (PCSVN) structure may reflect both the overall effects of genetic and environmentally regulated variations in branching morphogenesis within the conceptus and the fetus’ vital organs. This paper provides sound evidences to support the study of ASD risks with PCSVN through a combination of feature-selection and classification algorithms. METHODS: Twenty eight arterial and 8 shape-based PCSVN attributes from a high-risk ASD cohort of 89 placentas and a population-based cohort of 201 placentas were examined for ranked relevance using a modified version of the random forest algorithm, called the Boruta method. Principal component analysis (PCA) was applied to isolate principal effects of arterial growth on the fetal surface of the placenta. Linear discriminant analysis (LDA) with a 10-fold cross validation was performed to establish error statistics. RESULTS: The Boruta method selected 15 arterial attributes as relevant, implying the difference in high and low ASD risk can be explained by the arterial features alone. The five principal features obtained through PCA, which accounted for about 88% of the data variability, indicated that PCSVNs associated with placentas of high-risk ASD pregnancies generally had fewer branch points, thicker and less tortuous arteries, better extension to the surface boundary, and smaller branch angles than their population-based counterparts. CONCLUSION: We developed a set of methods to explain major PCSVN differences between placentas associated with high risk ASD pregnancies and those selected from the general population. The research paradigm presented can be generalized to study connections between PCSVN features and other maternal and fetal outcomes such as gestational diabetes and hypertension.
Lien vers le texte intégral (Open Access ou abonnement)
5. Cole EJ, Slocombe KE, Barraclough NE. {{Abilities to Explicitly and Implicitly Infer Intentions from Actions in Adults with Autism Spectrum Disorder}}. {J Autism Dev Disord};2017 (Dec 6)
Previous research suggests that Autism Spectrum Disorder (ASD) might be associated with impairments on implicit but not explicit mentalizing tasks. However, such comparisons are made difficult by the heterogeneity of stimuli and the techniques used to measure mentalizing capabilities. We tested the abilities of 34 individuals (17 with ASD) to derive intentions from others’ actions during both explicit and implicit tasks and tracked their eye-movements. Adults with ASD displayed explicit but not implicit mentalizing deficits. Adults with ASD displayed typical fixation patterns during both implicit and explicit tasks. These results illustrate an explicit mentalizing deficit in adults with ASD, which cannot be attributed to differences in fixation patterns.
Lien vers le texte intégral (Open Access ou abonnement)
6. do Egito JHT, Ferreira GMR, Goncalves MI, Osorio AAC. {{Brief Report: Factor Analysis of the Brazilian Version of the Adult Autism Spectrum Quotient}}. {J Autism Dev Disord};2017 (Dec 4)
This study examined the factor structure of the Brazilian version of the Autism-Spectrum Quotient. This is a self-report questionnaire for continuous and quantitative assessment of autistic spectrum traits in adults. Confirmatory factor analysis was performed on the five-factor model (social skill, attention switching, attention to detail, communication and imagination) proposed by the original authors, support not being found for this model in our sample. An exploratory factor analysis was then performed that resulted in an alternative three-factor model (social skills, details/patterns and imagination). Confirmatory factor analysis of the latter model revealed adequate psychometric indexes. The Brazilian version of the AQ was shown to be an adequate instrument for the evaluation of signs compatible with the autism spectrum in adults.
Lien vers le texte intégral (Open Access ou abonnement)
7. Ehrhart F, Bahram Sangani N, Curfs LMG. {{Current developments in the genetics of Rett and Rett-like syndrome}}. {Curr Opin Psychiatry};2017 (Dec 4)
PURPOSE OF REVIEW: This article reviews the current molecular genetic studies, which investigate the genetic causes of Rett syndrome or Rett-like phenotypes without a classical MECP2 mutation. RECENT FINDINGS: As next generation sequencing becomes broadly available, especially whole exome sequencing is used in clinical diagnosis of the genetic causes of a wide spectrum of intellectual disability, autism, and encephalopathies. Patients who were diagnosed with Rett syndrome or Rett-like syndrome because of their phenotype but were negative for mutations in the MECP2, CDKL5 or FOXG1 genes were subjected to whole exome sequencing and the results of the last few years revealed yet 69 different genes. Many of these genes are involved in epigenetic gene regulation, chromatin shaping, neurotransmitter action or RNA transcription/translation. Genetic data also allow to investigate the individual genetic background of an individual patient, which can modify the sereneness of a genetic disorder. SUMMARY: We conclude that the Rett syndrome phenotype has a much broader underlying genetic cause and the typical phenotype overlap with other genetic disorders. For proper genetic counselling, patient perspective and treatment it is important to include both phenotype and genetic information.
Lien vers le texte intégral (Open Access ou abonnement)
8. Esnafoglu E, Cirrik S. {{Increased serum midkine levels in autism spectrum disorder patients}}. {Int J Neurosci};2017 (Dec 6):1-5.
BACKGROUND: Midkine (MK) is a heparin binding growth factor and is involved in neurogenesis, neural development and neuroprotection. Additionally, MK may contribute to cancer development and pathogenesis of neurodegenerative disorders and schizophrenia. Considering these effects of MK, this study researched whether MK is involved in autism spectrum disorders (ASD) pathogenesis. METHODS: We evaluated serum MK levels of 38 patients with ASD and 32 healthy control group. MK levels were measured with ELISA, while ASD severity was assessed with Childhood Autism Rating Scale. RESULTS: Our data showed that the serum MK concentration in ASD patients (mean +/- SD, 11.51 +/- 8.53 pg/ml) is significantly higher than healthy controls (mean +/- SD, 6.19 +/- 3.94 pg/ml) (p = 0.007). CONCLUSIONS: According to these results, MK may play a role in ASD pathogenesis.
Lien vers le texte intégral (Open Access ou abonnement)
9. Hoover DW, Kaufman J. {{Adverse childhood experiences in children with autism spectrum disorder}}. {Curr Opin Psychiatry};2017 (Dec 4)
PURPOSE OF REVIEW: Recent years have shown an uptick in studies assessing bullying and other adverse childhood experiences (ACEs) in children with autism spectrum disorder (ASD). This article reviews extant findings, and points to gaps in the literature. RECENT FINDINGS: Children with ASD are bullied by peers at a rate three to four times that of nondisabled peers with negative impacts on academic functioning and mental health symptoms, including increased risk for suicidality. Children with ASD are also at enhanced risk for other ACES, particularly parental divorce and income insufficiency, and as observed in the general population, children with ASD who experience an increased number of ACES are at elevated risk for comorbid psychiatric and medical health problems. Children with ASD with an elevated number of ACES also experience a delay in ASD diagnosis and treatment initiation. There is no evidence of increased risk of child maltreatment within the ASD population. SUMMARY: As bullying and other adverse experiences are common and associated with deleterious outcomes in children with ASD, there is a need for additional research on intervention strategies to prevent and mitigate the impact of these experiences. Ongoing work on the assessment of trauma experiences and PTSD symptoms in children on the spectrum is also needed.
Lien vers le texte intégral (Open Access ou abonnement)
10. Huang DN, Jin YT. {{[Advances on the research of the environmental risk factors of children autism]}}. {Zhonghua Yu Fang Yi Xue Za Zhi};2017 (Dec 6);51(12):1128-1131.
Autism spectrum disorder is a lifelong neurodevelopmental disorder, characterized by social interaction and communication impairments, accompanied by repetitive behaviors. Little is known about the causes and contributing factors for autism. It is difficult to prevent and cure, and has become a globe public health problem. With the development in the prevalence of autism, the idea how the environmental factors cause the autism, gains all attentions. Summarizing latest epidemiological studies and experimental evidence, this review is focused on the effect of environmental factors, including air pollutant, heavy metal and pesticides, and discussed the relation between environmental risk factors and autism. The results showed that risks of autism in children may increase following in prenatal exposure to air pollutants, heavy metal and pesticides. It is needed to do the research on the mechanism of environmental risk factor and autism for more prevention, treatment and control suggestions.
Lien vers le texte intégral (Open Access ou abonnement)
11. Jia F, Shan L, Wang B, Li H, Miao C, Xu Z, Lin CP, Saad K. {{Bench to bedside review: Possible role of vitamin D in autism spectrum disorder}}. {Psychiatry Res};2017 (Dec 6);260:360-365.
Autism spectrum disorder (ASD) is a group of dysfunctions in social interaction, communication, and behaviors. Studies have demonstrated that vitamin D deficiency during pregnancy and in individuals increased the risk of ASD. A genetic polymorphism study has pinpointed that genotype AA/A-allele of GC rs4588 in children is associated with ASD, which encodes the vitamin D binding protein. Translating the mentioned points into clinical practice, several clinical trials have demonstrated that vitamin D supplementation can improve the core symptoms in children with ASD. One paper also showed that possible prophylactic effect for the reoccurrence of ASD by vitamin D supplement during pregnancy and early childhood. Herein, this review aims to address the recent advances in this field and to clarify the possible role of vitamin D in ASD.
Lien vers le texte intégral (Open Access ou abonnement)
12. Keen D, Adams D, Simpson K, den Houting J, Roberts J. {{Anxiety-related symptomatology in young children on the autism spectrum}}. {Autism};2017 (Dec 1):1362361317734692.
Anxiety symptomatology is frequently reported in autistic children, and the prevalence of anxiety disorder is estimated at around 40%. However, most studies have focused upon children of age 8 years or above, so little is known about early signs of anxiety in younger children with autism. This study sought to describe anxiety-related symptomatology in 95 5- to 6-year-old autistic children using the Anxiety Scale for Children with Autism Spectrum Disorder. Wide variability was found in levels of symptomatology with the most frequently reported items within the ‘uncertainty’ subscale and the least frequently reported items in the ‘anxious arousal’ subscale. Comparisons of those with scores less than or greater than 70 on adaptive behaviour suggests some influence of ability on presentation of anxiety-related symptomatology.
Lien vers le texte intégral (Open Access ou abonnement)
13. Marshall B, Kollia B, Wagner V, Yablonsky D. {{Identifying Depression in Parents of Children With Autism Spectrum Disorder: Recommendations for Professional Practice}}. {J Psychosoc Nurs Ment Health Serv};2017 (Dec 6):1-5.
Parents of children with autism spectrum disorder (ASD) face many challenges, not the least of which can be dealing with their own depression. Depression decreases an individual’s capacity for self-care and is often overlooked in this population striving to manage the demands of parenting their child with ASD. This article examines current literature related to prevalence, diagnosis, and interventions for depression in parents of children with ASD. The review indicates that depression is more common in parents of children with ASD than in the general public. However, most literature addresses parenting skills rather than depression and associated self-care deficits identified in these parents. Suggestions for best practice models and proactive interventions to caregivers are provided. [Journal of Psychosocial Nursing and Mental Health Services, xx(x), xx-xx.].
Lien vers le texte intégral (Open Access ou abonnement)
14. Mesuret G, Dannenberg J, Arnoldt M, Grutzner AA, Niebert M, Hulsmann S. {{Breathing disturbances in a model of Rett syndrome: A potential involvement of the glycine receptor alpha3 subunit?}}. {Respir Physiol Neurobiol};2017 (Dec 5);248:43-47.
The glycine receptor alpha3 subunit is known to be a target for cAMP/PKA-mediated phosphorylation and regulation. Mice that lack this subunit are apparently normal but the 5-HT1A-receptor mediated modulation of respiratory network activity is disturbed. Since the intracellular cAMP-concentration is reduced in mice that lack the transcriptional modulator methyl-CpG-binding protein 2 (MeCP2) gene, we aimed to test if the alpha3 subunit of the glycine receptor is involved in the development of the breathing phenotype of MeCP2-deficient mice (Mecp2(-/y)). Therefore, we generated a double knock-out mouse line that lacks both the Mecp2 gene as well as the gene (Glra3) for the alpha3 subunit of the ionotropic glycine receptor. As compared to WT and Glra3(-/-) mice, both Mecp2(-/y) mice and Mecp2(-/y); Glra3(-/-) mice (DKO) showed a slower respiratory rate and a tendency towards higher numbers of apneas. Interestingly, the irregularity of the breathing was significantly reduced in DKO as compared to Mecp2(-/y) littermates. In the light of the unaltered survival of DKO mice, however, the contribution of the glycine receptor alpha3 subunit for development and progression of the breathing disturbances in the mouse model of Rett syndrome appears to be only of minor relevance.
Lien vers le texte intégral (Open Access ou abonnement)
15. Posar A, Visconti P. {{Tribute to Grunya Efimovna Sukhareva, the Woman who First Described Infantile Autism}}. {J Pediatr Neurosci};2017 (Jul-Sep);12(3):300-301.
Lien vers le texte intégral (Open Access ou abonnement)
16. Ratto AB, Kenworthy L, Yerys BE, Bascom J, Wieckowski AT, White SW, Wallace GL, Pugliese C, Schultz RT, Ollendick TH, Scarpa A, Seese S, Register-Brown K, Martin A, Anthony LG. {{What About the Girls? Sex-Based Differences in Autistic Traits and Adaptive Skills}}. {J Autism Dev Disord};2017 (Dec 4)
There is growing evidence of a camouflaging effect among females with autism spectrum disorder (ASD), particularly among those without intellectual disability, which may affect performance on gold-standard diagnostic measures. This study utilized an age- and IQ-matched sample of school-aged youth (n = 228) diagnosed with ASD to assess sex differences on the ADOS and ADI-R, parent-reported autistic traits, and adaptive skills. Although females and males were rated similarly on gold-standard diagnostic measures overall, females with higher IQs were less likely to meet criteria on the ADI-R. Females were also found to be significantly more impaired on parent reported autistic traits and adaptive skills. Overall, the findings suggest that some autistic females may be missed by current diagnostic procedures.
Lien vers le texte intégral (Open Access ou abonnement)
17. Raveau M, Shimohata A, Amano K, Miyamoto H, Yamakawa K. {{DYRK1A-haploinsufficiency in mice causes autistic-like features and febrile seizures}}. {Neurobiol Dis};2017 (Dec 6);110:180-191.
Mutations and copy number variants affecting DYRK1A gene encoding the dual-specificity tyrosine phosphorylation-regulated kinase 1A are among the most frequent genetic causes of neurodevelopmental disorders including autism spectrum disorder (ASD) associated with microcephaly, febrile seizures and severe speech acquisition delay. Here we developed a mouse model harboring a frame-shift mutation in Dyrk1a resulting in a protein truncation and elimination of its kinase activity site. Dyrk1a(+/-) mice showed significant impairments in cognition and cognitive flexibility, communicative ultrasonic vocalizations, and social contacts. Susceptibility to hyperthermia-induced seizures was also significantly increased in these mice. The truncation leading to haploinsufficiency of DYRK1A in mice thus recapitulates the syndromic phenotypes observed in human patients and constitutes a useful model for further investigations of the mechanisms leading to ASD, speech delay and febrile seizures.
Lien vers le texte intégral (Open Access ou abonnement)
18. Rosen TE, Lerner MD. {{Error-related brain activity and anxiety symptoms in youth with autism spectrum disorder}}. {Autism Res};2017 (Dec 6)
Individuals with autism spectrum disorder (ASD) often experience symptoms associated with generalized anxiety disorder, obsessive-compulsive disorder, and social anxiety disorder. In other populations, these same symptoms are associated with a larger error-related negativity (ERN), an event-related potential that reflects endogenous threat sensitivity. As such, it is possible that the ERN may relate to the clinical presentation of anxiety in ASD. However, studies examining these associations in youth with ASD have yielded mixed results. The present study aimed to clarify this relationship by examining the ERN in relation to these specific anxiety symptoms in ASD, and by accounting for typical covariates (e.g., age, verbal abilities, depression, ASD symptoms) of the ERN. Fifty-one youth, ages 8-17, with ASD and intact cognitive ability completed a modified Flanker task, from which the ERN component was obtained. Measures of anxiety, verbal abilities, depression, and ASD symptoms were collected from participants and parents. Results revealed that greater self-reported social anxiety symptoms, specifically performance fears but not humiliation/rejection fears, were associated with an increased neural response to errors, as measured by the ERN. This relationship remained after controlling for other anxiety symptoms, as well as age, verbal IQ, depression symptoms, and ASD symptoms. Findings suggest that heightened threat sensitivity may be characteristic of individuals with ASD who exhibit social fearfulness. Autism Res 2017. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: The error-related negativity (ERN) is a physiological measure of the brain’s response to errors which is thought to reflect threat sensitivity and has been implicated in anxiety disorders in individuals without autism spectrum disorder (ASD). The present study revealed that the ERN is related to social anxiety symptoms, specifically performance fears, in a sample of youth with ASD. Findings suggest that heightened threat sensitivity may be characteristic of individuals with ASD who exhibit social fearfulness.
Lien vers le texte intégral (Open Access ou abonnement)
19. Russell A, Cooper K, Barton S, Ensum I, Gaunt D, Horwood J, Ingham B, Kessler D, Metcalfe C, Parr J, Rai D, Wiles N. {{Protocol for a feasibility study and randomised pilot trial of a low-intensity psychological intervention for depression in adults with autism: the Autism Depression Trial (ADEPT)}}. {BMJ Open};2017 (Dec 3);7(12):e019545.
INTRODUCTION: High rates of co-occurring depression are reported in autism spectrum disorder (ASD), a neurodevelopmental condition characterised by social communication impairments and repetitive behaviours. Cognitive-behavioural interventions adapted for ASD have been effective for anxiety problems. There have been evaluation studies of group cognitive-behavioural therapy for co-occurring depression, but no randomised trials investigating low-intensity psychological interventions as recommended in clinical guidelines for mild-moderate depression. METHODS AND ANALYSIS: A feasibility study comprising a randomised controlled trial (RCT) and nested qualitative evaluation is under way as preparation for a definitive RCT. Participants (n=70) will be randomised to Guided Self-Help: a low-intensity psychological intervention based on behavioural activation adapted for ASD or treatment as usual. Outcomes including depression symptoms, anxiety, social function and service use will be measured at 10, 16 and 24 weeks postrandomisation and will be blind to group allocation for measures that are not self-administered. The analysis will aim to establish the rates of recruitment and retention for a larger-scale RCT as well as the most appropriate measure of depression to serve as primary outcome. The qualitative study will purposively sample up to 24 participants from each treatment group to consider the acceptability and feasibility of the intervention and the trial design. ETHICS AND DISSEMINATION: Ethical approval has been received from WALES REC 3 (IRAS project ID: 191558) and the Health Research Authority with R&D approval from Avon and Wiltshire Mental Health Partnership and Northumberland, Tyne and Wear Foundation NHS Trusts. To our knowledge, this is the first study of a low-intensity intervention for depression in adults with autism. The results will inform the design of a definitive RCT. Dissemination will include peer-reviewed journal publications reporting the quantitative and qualitative research findings of the study and presentations at national and international conferences. TRIAL REGISTRATION NUMBER: ISRCTN54650760; Pre-results.
Lien vers le texte intégral (Open Access ou abonnement)
20. Shepherd D, Csako R, Landon J, Goedeke S, Ty K. {{Documenting and Understanding Parent’s Intervention Choices for Their Child with Autism Spectrum Disorder}}. {J Autism Dev Disord};2017 (Dec 6)
Understanding why parents choose some interventions but not others for their child with autism is important for a number of reasons. Estimating the proportion of evidence-based interventions engaged, identifying the agencies influencing parental decisions, and elucidating the barriers or reasons leading to intervention rejection or discontinuation can result in better service provision. New Zealand parents (n = 570) of a child with autism reported what interventions were being engaged, and why some interventions were engaged but not others. Funding was a major determinant of intervention engagement, while medical professionals exerted the most influence. Sources of support were not related to intervention engagement, but parental perceptions of their child’s symptom severity were. Finally, non-engagement does not necessarily reflect parental opposition to an intervention, but rather the existence of barriers.
Lien vers le texte intégral (Open Access ou abonnement)
21. Tachibana Y, Miyazaki C, Ota E, Mori R, Hwang Y, Kobayashi E, Terasaka A, Tang J, Kamio Y. {{A systematic review and meta-analysis of comprehensive interventions for pre-school children with autism spectrum disorder (ASD)}}. {PLoS One};2017;12(12):e0186502.
BACKGROUND: There has an increasing number of published trials on psychosocial intervention programmes for pre-school children with autism spectrum disorder (ASD). To achieve better quality of unbiased evidence for the effectiveness of ASD interventions, it is necessary to conduct a comprehensive review that covers studies with adequate quality standards, such as randomised controlled trials (RCTs), and different types of intervention In this study, we categorize interventions for ASD as behavioural, social-communication focused, and multimodal developmental based on Howlin’s classification of early interventions for children with ASD. The aim of this study was to compare these three models and investigate the strengths and weaknesses of each type of intervention and to identify the approaches that contribute to a successful outcome for children with autism. METHODS: We performed a systematic review and meta-analysis. We included RCTs targeting children with ASD 6 years old or younger. A random effects model was used to present the effect estimate for the outcomes. This study also performed combined meta-analyses of all the three models to investigate the overall effectiveness of the intervention programmes. RESULTS: 32 randomized controlled studies were found to be eligible for inclusion. The synthesized data included 594 children from 14 RCTs. There was no statistically significant difference in the effects on autism general symptoms between the social-communication-focused model and the multimodal developmental model (p = 0.83). The results suggest that there is evidence of an effect on ‘reciprocity of social interaction towards others’ (standard mean difference [95% confidential interval] = 0.53[0.29,0.78], p<0.01) and 'parental synchrony' (SMD = 0.99[0.70,1.29], p<0.01). CONCLUSION: The small number of studies included in the present study limited the ability to make inferences when comparing the three models and investigating the strengths and weaknesses of each type of intervention with respect to important outcomes. Since the outcome of 'reciprocity of social interaction towards others' could be a dependent variable that might be context-bound to interactions with the child's parent, we cannot conclude the interventions for pre-school children with ASD have significant effects on a generalized skill to engage in reciprocal interactions with others. However, the outcomes of 'reciprocity of social interaction towards others' and 'parental synchrony' may be promising targets for interventions involving pre-school children with ASD. TRIAL REGISTRATION: Prospero CRD42011001349. Lien vers le texte intégral (Open Access ou abonnement)
22. Tora D, Gomez AM, Michaud JF, Yam PT, Charron F, Scheiffele P. {{Cellular Functions of the Autism Risk Factor PTCHD1 in Mice}}. {J Neurosci};2017 (Dec 6);37(49):11993-12005.
The gene patched domain containing 1 (PTCHD1) is mutated in patients with autism spectrum disorders and intellectual disabilities and has been hypothesized to contribute to Sonic hedgehog (Shh) signaling and synapse formation. We identify a panel of Ptchd1-interacting proteins that include postsynaptic density proteins and the retromer complex, revealing a link to critical regulators of dendritic and postsynaptic trafficking. Ptchd1 knock-out (KO) male mice exhibit cognitive alterations, including defects in a novel object recognition task. To test whether Ptchd1 is required for Shh-dependent signaling, we examined two Shh-dependent cell populations that express high levels of Ptchd1 mRNA: cerebellar granule cell precursors and dentate granule cells in the hippocampus. We found that proliferation of these neuronal precursors was not altered significantly in Ptchd1 KO male mice. We used whole-cell electrophysiology and anatomical methods to assess synaptic function in Ptchd1-deficient dentate granule cells. In the absence of Ptchd1, we observed profound disruption in excitatory/inhibitory balance despite normal dendritic spine density on dentate granule cells. These findings support a critical role of the Ptchd1 protein in the dentate gyrus, but indicate that it is not required for structural synapse formation in dentate granule cells or for Shh-dependent neuronal precursor proliferation.SIGNIFICANCE STATEMENT The mechanisms underlying neuronal and cellular alterations resulting from patched domain containing 1 (Ptchd1) gene mutations are unknown. The results from this study support an association with dendritic trafficking complexes of Ptchd1. Loss-of-function experiments do not support a role in sonic hedgehog-dependent signaling, but reveal a disruption of synaptic transmission in the mouse dentate gyrus. The findings will help to guide ongoing efforts to understand the etiology of neurodevelopmental disorders arising from Ptchd1 deficiency.
Lien vers le texte intégral (Open Access ou abonnement)
23. Vivanti G, Kasari C, Green J, Mandell D, Maye M, Hudry K. {{Implementing and evaluating early intervention for children with autism: Where are the gaps and what should we do?}}. {Autism Res};2017 (Dec 5)
Despite recent advances, the evidence base supporting early intervention for young children with autism spectrum disorder (ASD) remains relatively sparse. The International Society for Autism Research (INSAR) recently sponsored a Special Interest Group (SIG) on Implementing and Evaluating Community-Based Early Intervention. Across three meetings, in 2015, 2016, and 2017, conveners of this SIG engaged >200 members to identify knowledge gaps and research priorities for moving the field forward. Here, we summarize the perspectives that emerged from group discussion at the SIG meetings as represented by scholars working actively in the field. Despite encouraging progress, critical gaps and research priorities were identified across all the stages of intervention development and testing from conceptualization to community implementation. Key issues include the need for (a) formal theories to guide early intervention development, evaluation, and implementation; and alignment of intervention goals with scientific knowledge and societal changes that have occurred in the decades since interventions were originally developed; (b) increased focus on feasibility of treatment procedures and alignment with stakeholder values during pilot evaluations; (c) use of research designs that allow for comparisons of different interventions and formats, analyses of active ingredients of treatment, and identification of moderators and mediators of outcome; (d) use of community-partnered participatory research to guide adaptation of intervention models to community settings; (e) inclusion of constructs related to implementation processes and outcomes in treatment trials and; (f) an iterative approach to the progression of knowledge from intervention development to implementation. Autism Res 2017. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: In this article, we summarize the themes discussed at the INSAR Special Interest Group (SIG) on Implementing and Evaluating Community-Based Early Intervention. Priorities for moving the field forward identified in the SIG included the need for (a) formal theories to guide the development and evaluation of interventions, (b) pilot evaluations that investigate feasibility and acceptability of interventions, (c) methodologies that allow us to determine for whom different interventions bring most benefit and why this is so, (d) strategies to include community members and other stakeholders in the process of developing and evaluating interventions, and (e) understanding of factors that make interventions more likely to be adopted and successfully implemented in the real world.
