Pubmed du 14/06/19

vendredi 14 juin 2019

1. Aoki S, Kagitani-Shimono K, Matsuzaki J, Hanaie R, Nakanishi M, Tominaga K, Nagai Y, Mohri I, Taniike M. Lesser suppression of response to bright visual stimuli and visual abnormality in children with autism spectrum disorder : a magnetoencephalographic study. J Neurodev Disord. 2019 ; 11(1) : 9.

BACKGROUND : Visual abnormality is a common sensory impairment in autism spectrum disorder (ASD), which may cause behavioral problems. However, only a few studies exist on the neural features corresponding to the visual symptoms in ASD. The purpose of this study was to investigate the relationship between cortical responses to visual stimuli and visual abnormality to examine the neurophysiological mechanisms of the visual abnormality in ASD. METHODS : Twenty-two high-functioning children with ASD (10.95 +/- 2.01 years old) and 23 age-matched typically developing (TD) children (10.13 +/- 2.80 years old) participated in this study. We measured the cortical responses (i.e., activated intensity and attenuation ratio) elicited by the Original visual image and other two types of bright images (the Dot noise or Blind image, which includes overlapped particles onto the Original image or the enhanced-brightness version of the Original image, respectively) using magnetoencephalography. RESULTS : The severity of visual abnormalities was significantly associated with behavioral problems in children with ASD. In addition, we found the increased cortical activation in response to the Original image in the left supramarginal gyrus (SMG) and middle temporal gyrus in children with ASD. However, there were no inter-group differences in the primary visual and medial orbitofrontal cortices. Furthermore, when we compared cortical responses according to the type of images, children with ASD showed lesser attenuation of the activated intensities than children with TD in response to the bright images compared with the Original image in the right SMG. These attenuation ratios (Dot noise/Original and Blind/Original) were also associated with the severity of visual abnormalities. CONCLUSIONS : Our results show that dysfunction of stimulus-driven neural suppression plays a crucial role in the neural mechanism of visual abnormality in children with ASD. To the best of our knowledge, this is the first magnetoencephalography study to demonstrate the association between the severity of visual abnormality and lower attenuation ratios in children with ASD. Our results contribute to the knowledge of the mechanisms underlying visual abnormality in children with ASD, and may therefore lead to more effective diagnosis and earlier intervention.

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2. Avraam R, Binur N, Hadad BS. Typical perceptual organization in autism : Perceptual grouping and spatial distortion. Autism Res. 2019.

The extensive literature on global-local processing in people with autism spectrum disorder (ASD) has recently shifted from arguing for a processing impairment among those with ASD to positing an attenuated preference for global processing. One suggestion is that the fast extraction of the global gist is less efficient in ASD, in contrast to the superior attention-driven processing of local elements. To examine this claim of attenuated global processing, the present study tested how perceptual grouping affected the global organization of visual scenes, specifically testing the claim of less mandatory, more optional global processing in ASD. Participants judged the distance between grouped and ungrouped elements in displays in which illusory distortions were inherent in configurations exemplifying the Gestalt principles of organization. Results from six experiments manipulating different Gestalt cues showed a consistent pattern, indicating that for individuals with ASD, as for typically developed (TD) individuals, grouping processes are organizational in nature, incorporating the grouping of related elements while parsing these from other unrelated elements. This parsing is accompanied by distortions in the spatial relationships perceived in the visual scene. ASD participants exhibited an overall larger tendency to overestimate the distances, but they also demonstrated typical perceptual organization processes that were robust and mandatory and, as in neurotypicals, affected the perception of the whole scene. Autism Res 2019. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY : It is known that individuals with autism spectrum disorder (ASD) perceive the world in a different way than their typically developed (TD) peers. While TD individuals exhibit strong bias toward processing the global structure of visual scenes, individuals with ASD exhibit enhanced perception of the local elements. We showed that when the local and global levels are not competing, individuals with autism demonstrate robust global organization that operates even when not directly instructed.

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3. Baker JK, Fenning RM, Moffitt J. A Cross-Sectional Examination of the Internalization of Emotion Co-regulatory Support in Children with ASD. J Autism Dev Disord. 2019.

Cross-sectional data from Fenning et al. (J Autism Dev Disord, 48:3858-3870, 2018) were used to examine age differences in processes related to the development of emotion regulation in children with autism spectrum disorder (ASD). Forty-six children with ASD between the ages of 4 and 11 years and their primary caregivers participated in structured laboratory tasks from which parental scaffolding and child dysregulation were coded. Moderation analyses suggested increased internalization of parental co-regulatory support with age, as evidenced by more coherence in dysregulation across dyadic and independent contexts and a stronger inverse relation between parental scaffolding and independent dysregulation. Children’s estimated mental age did not account for these effects. Implications for understanding and promoting the development of emotion regulation in children with ASD are discussed.

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4. Bodaleo F, Tapia-Monsalves C, Cea-Del Rio C, Gonzalez-Billault C, Nunez-Parra A. Structural and Functional Abnormalities in the Olfactory System of Fragile X Syndrome Models. Front Mol Neurosci. 2019 ; 12 : 135.

Fragile X Syndrome (FXS) is the most common inherited form of intellectual disability. It is produced by mutation of the Fmr1 gene that encodes for the Fragile Mental Retardation Protein (FMRP), an important RNA-binding protein that regulates the expression of multiple proteins located in neuronal synapses. Individuals with FXS exhibit abnormal sensory information processing frequently leading to hypersensitivity across sensory modalities and consequently a wide array of behavioral symptoms. Insects and mammals engage primarily their sense of smell to create proper representations of the external world and guide adequate decision-making processes. This feature in combination with the exquisitely organized neuronal circuits found throughout the olfactory system (OS) and the wide expression of FMRP in brain regions that process olfactory information makes it an ideal model to study sensory alterations in FXS models. In the last decade several groups have taken advantage of these features and have used the OS of fruit fly and rodents to understand neuronal alteration giving rise to sensory perception issues. In this review article, we will discuss molecular, morphological and physiological aspects of the olfactory information processing in FXS models. We will highlight the decreased inhibitory/excitatory synaptic balance and the diminished synaptic plasticity found in this system resulting in behavioral alteration of individuals in the presence of odorant stimuli.

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5. Catala-Lopez F, Ridao M, Hurtado I, Nunez-Beltran A, Genova-Maleras R, Alonso-Arroyo A, Tobias A, Aleixandre-Benavent R, Catala MA, Tabares-Seisdedos R. Prevalence and comorbidity of autism spectrum disorder in Spain : study protocol for a systematic review and meta-analysis of observational studies. Systematic reviews. 2019 ; 8(1) : 141.

BACKGROUND : Autism spectrum disorder (ASD) is a complex developmental disorder characterised by impaired social interaction and communication, and restrictive and repetitive behaviour. Previous systematic reviews have traditionally assessed the prevalence of ASD on global or regional context, with very few meta-analyses at the country level. The objective of this study will be to systematically evaluate published and unpublished observational studies that present prevalence and comorbidity of ASD among children, adolescent and adult population in Spain. METHODS/DESIGN : We designed and registered a study protocol for a systematic review and meta-analysis of descriptive epidemiology data. Observational studies (cohort, cross-sectional) reporting the prevalence of ASD and conducted in a wide range of people (e.g. general population, outpatient and/or school settings) will be included. The primary outcome will be the prevalence of ASD. Secondary outcomes will be the prevalence of any physical or mental comorbidity in association with ASD. No limitations will be imposed on publication status, study conduct period, and language of dissemination. Comprehensive literature searches will be conducted in seven electronic databases (from January 1980 onwards), including PubMed/MEDLINE, EMBASE, Scopus, Web of Science, PsycINFO, IME-Spanish Medical Index and IBECS-Spanish Bibliographic Index of Health Sciences. Grey literature will be identified through searching dissertation databases, Google Scholar and conference abstracts. Two team members will independently screen all citations, full-text articles, and abstract data. Potential conflicts will be resolved through discussion. The study methodological quality (or bias) will be appraised using an appropriate tool. If feasible, we will conduct random effects meta-analysis of observational data. Prevalence estimates will be stratified according to gender, age and geographical location. Additional analyses will be conducted to explore the potential sources of heterogeneity (e.g. methodological quality, sample size, diagnostic criteria). DISCUSSION : This systematic review and meta-analysis of observational data will identify, evaluate and integrate the epidemiological knowledge underlying the prevalence of ASD in Spain. The results of this study will be of interest to multiple audiences including patients, their families, caregivers, healthcare professional, scientists and policy makers. Results will be published in a peer-reviewed journal. Implications for future epidemiological research will be discussed. SYSTEMATIC REVIEW REGISTRATION : PROSPERO CRD42018090372.

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6. Gata-Garcia A, Diamond B. Maternal Antibody and ASD : Clinical Data and Animal Models. Frontiers in immunology. 2019 ; 10 : 1129.

Over the past several decades there has been an increasing interest in the role of environmental factors in the etiology of neuropsychiatric and neurodevelopmental disorders. Epidemiologic studies have shifted from an exclusive focus on the identification of genetic risk alleles for such disorders to recognizing and understanding the contribution of xenobiotic exposures, infections, and the maternal immune system during the prenatal and early post-natal periods. In this review we discuss the growing literature regarding the effects of maternal brain-reactive antibodies on fetal brain development and their contribution to the development of neuropsychiatric and neurodevelopmental disorders. Autoimmune diseases primarily affect women and are more prevalent in mothers of children with neurodevelopmental disorders. For example, mothers of children with Autism Spectrum Disorder (ASD) are significantly more likely to have an autoimmune disease than women of neurotypically developing children. Moreover, they are four to five times more likely to harbor brain-reactive antibodies than unselected women of childbearing age. Many of these women exhibit no apparent clinical consequence of harboring these antibodies, presumably because the antibodies never access brain tissue. Nevertheless, these maternal brain-reactive antibodies can access the fetal brain, and some may be capable of altering brain development when present during pregnancy. Several animal models have provided evidence that in utero exposure to maternal brain-reactive antibodies can permanently alter brain anatomy and cause persistent behavioral or cognitive phenotypes. Although this evidence supports a contribution of maternal brain-reactive antibodies to neurodevelopmental disorders, an interplay between antibodies, genetics, and other environmental factors is likely to determine the specific neurodevelopmental phenotypes and their severity. Additional modulating factors likely also include the microbiome, sex chromosomes, and gonadal hormones. These interactions may help to explain the sex-bias observed in neurodevelopmental disorders. Studies on this topic provide a unique opportunity to learn how to identify and protect at risk pregnancies while also deciphering critical pathways in neurodevelopment.

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7. Huang G, Zhu H, Wu S, Cui M, Xu T. Long Noncoding RNA Can Be a Probable Mechanism and a Novel Target for Diagnosis and Therapy in Fragile X Syndrome. Front Genet. 2019 ; 10 : 446.

Fragile X syndrome (FXS) is the most common congenital hereditary disease of low intelligence after Down syndrome. Its main pathogenic gene is fragile X mental retardation 1 (FMR1) gene associated with intellectual disability, autism, and fragile X-related primary ovarian insufficiency (FXPOI) and fragile X-associated tremor/ataxia syndrome (FXTAS). FMR1 gene transcription leads to the absence of fragile X mental retardation protein (FMRP). How to relieve or cure disorders associated with FXS has also become a clinically disturbing problem. Previous studies have recently shown that long noncoding RNAs (lncRNAs) contribute to the pathogenesis. And it has been identified that several lncRNAs including FMR4, FMR5, and FMR6 contribute to developing FXPOI/FXTAS, originating from the FMR1 gene locus. FMR4 is a product of RNA polymerase II and can regulate the expression of relevant genes during differentiation of human neural precursor cells. FMR5 is a sense-oriented transcript while FMR6 is an antisense lncRNA produced by the 3’ UTR of FMR1. FMR6 is likely to contribute to developing FXPOI, and it overlaps exons 15-17 of FMR1 as well as two microRNA binding sites. Additionally, BC1 can bind FMRP to form an inhibitory complex and lncRNA TUG1 also can control axonal development by directly interacting with FMRP through modulating SnoN-Ccd1 pathway. Therefore, these lncRNAs provide pharmaceutical targets and novel biomarkers. This review will : (1) describe the clinical manifestations and traditional pathogenesis of FXS and FXTAS/FXPOI ; (2) summarize what is known about the role of lncRNAs in the pathogenesis of FXS and FXTAS/FXPOI ; and (3) provide an outlook of potential effects and future directions of lncRNAs in FXS and FXTAS/FXPOI researches.

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8. Jacobs D, Steyaert J, Dierickx K, Hens K. Physician View and Experience of the Diagnosis of Autism Spectrum Disorder in Young Children. Frontiers in psychiatry. 2019 ; 10 : 372.

Introduction : Clinicians working with children with autism spectrum disorder (ASD) occupy an important position between parents and the wide-ranging research findings. However, it is not widely known how clinicians view and experience ASD in children, even though their perspective has been shown to significantly influence their work. Material and methods : Sixteen physicians working with preschool children without a diagnosis of (intellectual or other) disability with a (presumed) diagnosis of ASD participated in a semistructured interview. They described their professional views on ASD, and how they experienced its use in their clinical practice. The data were analyzed by applying the qualitative research method of interpretative phenomenological analysis of the data through Nvivo 11. Results : The main topic of the interviewed physicians’ views and experiences of ASD in a young child comprised three inductively established themes : 1) physicians’ views on ASD are multifaceted but fit within their personal clinical styles ; 2) the ASD diagnosis is a "descriptive" part of a clinical trajectory ; and 3) ASD treatment is a mix of "standard" approaches and a personalized search. These physicians’ perspectives on ASD are composed of multiple and sometimes ambiguous facets. However, their views are embedded in their personal clinical styles in general (i.e., beyond ASD) and are experienced as clinically "workable." With the aim of finding an adequate approach to the problems parents bring to their office, many interviewed physicians say that-complementary to or rather than a classificatory diagnosis-they prefer using a personalized "profile" of a child in a therapeutic "process." Conclusions : The interviewed physicians consider doubts and concerns to be an inherent part of their clinical work with ASD in young children, but do not experience this ambiguity as an obstacle to clinical care. These physicians deal with the multiplicity of their views on ASD by basing their eclectic views on their generally adopted clinical styles, and by selecting what works for them, and for the parents and child, from what they regard as the ’textbook knowledge’ on ASD. We discuss the implications of these findings for translating research results to the clinic.

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9. Keehn B, Kadlaskar G, McNally Keehn R, Francis AL. Auditory Attentional Disengagement in Children with Autism Spectrum Disorder. J Autism Dev Disord. 2019.

Despite early differences in orienting to sounds, no study to date has investigated whether children with ASD demonstrate impairments in attentional disengagement in the auditory modality. Twenty-one 9-15-year-old children with ASD and 20 age- and IQ-matched TD children were presented with an auditory gap-overlap paradigm. Evidence of impaired disengagement in ASD was mixed. Differences in saccadic reaction time for overlap and gap conditions did not differ between groups. However, children with ASD did show increased no-shift trials in the overlap condition, as well as reduced disengagement efficiency compared to their TD peers. These results provide further support for disengagement impairments in ASD, and suggest that these deficits include disengaging from and shifting to unimodal auditory information.

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10. Kerns CM, Berkowitz SJ, Moskowitz LJ, Drahota A, Lerner MD, Newschaffer CJ. Screening and treatment of trauma-related symptoms in youth with autism spectrum disorder among community providers in the United States. Autism. 2019 : 1362361319847908.

Using a cross-sectional survey of 673 multidisciplinary autism spectrum disorder providers recruited from five different sites in the United States, we examined the frequency with which community-based providers inquire about, screen, and treat trauma-related symptoms in their patients/students and assessed their perceptions regarding the need for and barriers to providing these services. Univariate and bivariate frequencies of self-reported trauma service provision, training needs, and barriers were estimated. Multivariable logistic regressions identified provider and patient-related factors associated with trauma-related symptoms screening and treatment. Over 50% of providers reported some screening and treatment of trauma-related symptoms in youth with autism spectrum disorder. Over 70% informally inquired about trauma-related symptoms ; only 10% universally screened. Screening and treatment varied by provider discipline, setting, amount of interaction, and years of experience with autism spectrum disorder, as well as by patient/student sex, ethnicity, and socioeconomic status. Most providers agreed that trauma screening is a needed service impeded by inadequate provider training in trauma identification and treatment. The findings indicate that community providers in the United States of varied disciplines are assessing and treating trauma-related symptoms in youth with autism spectrum disorder, and that evidence-based approaches are needed to inform and maximize these efforts.

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11. Koller J, Shalev R, Schallamach C, Gumpel TP, Begin M. The Role of Demographics in the Age of Autism Diagnosis in Jerusalem. J Autism Dev Disord. 2019.

Early diagnosis of autism spectrum disorder (ASD) in children enables earlier access to services and better ability to predict subsequent development. A vast body of literature consistently shows discrepancies in the age of diagnosis between children from varying socio-economic levels, cultural and ethnic backgrounds. The present study examines the effect of sociodemographic factors on age of ASD diagnosis among the three primary ethnic sectors in Jerusalem region : secular and modern religious Jews, ultra-Orthodox Jews and Arabs. Findings indicate minimal differences in age of diagnosis prior to the age of six, although Arab children of this age were largely minimally verbal. After age six, no Arab children were referred for an evaluation.

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12. McGarry E, Vernon T, Baktha A. Brief Report : A Pilot Online Pivotal Response Treatment Training Program for Parents of Toddlers with Autism Spectrum Disorder. J Autism Dev Disord. 2019.

Despite advances in evidence-based treatment for autism spectrum disorder (ASD), disparities in service access remain a serious concern. Current treatment models may not be feasible for families who live in remote geographical regions or have limited resources. To address this, studies have begun to explore parent-implemented interventions via an online format. The current study examined a new online course designed to help parents implement Pivotal Response Treatment (PRT) for their toddler with ASD. Parents submitted videos of parent-child interactions which were coded for fidelity of implementation (FOI) and social communicative behaviors. The data indicate that PRT fidelity and child behaviors significantly improved following course participation. This suggests that an online intervention may be a feasible approach to disseminating PRT strategies.

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13. Meindl JN, Saba S, Gray M, Stuebing L, Jarvis A. Reducing blood draw phobia in an adult with autism spectrum disorder using low-cost virtual reality exposure therapy. J Appl Res Intellect Disabil. 2019.

BACKGROUND : Needle phobias are common in children and adults worldwide. One effective intervention for this phobia is exposure therapy where a participant is gradually exposed to increasing levels of the fear-evoking stimulus while differential reinforcement is applied. This intervention, however, may be difficult to implement with some medical procedures as it may be difficult to obtain unfettered access to medical facilities and equipment for the purposes of exposure. Virtual reality may overcome these obstacles. METHODS : In this investigation, the present authors developed a low-cost virtual reality-based exposure therapy which was used with an adult male with autism spectrum disorder and a history of extreme needle phobia. The effectiveness of this intervention was evaluated using a changing criterions design with generalization probes. RESULTS : The intervention quickly increased the participant’s compliance in the analogue training setting and the effects were generalized across settings and behaviours, and maintained over time. CONCLUSIONS : The findings indicate combining virtual reality with exposure therapy may produce an effective intervention for medical phobias. The intervention package may remove barriers associate with traditional exposure therapy and was low-cost which may increase access to the intervention.

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14. Moore D, Meays BM, Madduri LSV, Shahjin F, Chand S, Niu M, Albahrani A, Guda C, Pendyala G, Fox HS, Yelamanchili SV. Downregulation of an Evolutionary Young miR-1290 in an iPSC-Derived Neural Stem Cell Model of Autism Spectrum Disorder. Stem cells international. 2019 ; 2019 : 8710180.

The identification of several evolutionary young miRNAs, which arose in primates, raised several possibilities for the role of such miRNAs in human-specific disease processes. We previously have identified an evolutionary young miRNA, miR-1290, to be essential in neural stem cell proliferation and neuronal differentiation. Here, we show that miR-1290 is significantly downregulated during neuronal differentiation in reprogrammed induced pluripotent stem cell- (iPSC-) derived neurons obtained from idiopathic autism spectrum disorder (ASD) patients. Further, we identified that miR-1290 is actively released into extracellular vesicles. Supplementing ASD patient-derived neural stem cells (NSCs) with conditioned media from differentiated control-NSCs spiked with "artificial EVs" containing synthetic miR-1290 oligonucleotides significantly rescued differentiation deficits in ASD cell lines. Based on our earlier published study and the observations from the data presented here, we conclude that miR-1290 regulation could play a critical role during neuronal differentiation in early brain development.

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15. Ng R, Heinrich K, Hodges E. Associations Between ADHD Subtype Symptomatology and Social Functioning in Children With ADHD, Autism Spectrum Disorder, and Comorbid Diagnosis : Utility of Diagnostic Tools in Treatment Considerations. Journal of attention disorders. 2019 : 1087054719855680.

Objective : To assess associations between objective-/caregiver-report measures of attention functioning and social impairment among children with ADHD, autism spectrum disorder (ASD), and co-occurring ASD + ADHD. Method : Patients with ADHD (N = 27), ASD (N = 23), and ASD + ADHD (N = 44) completed measures of intellectual functioning (Wechsler tests) and attention functioning (Continuous Performance Test-Second Edition [CPT-II]) as part of a neurocognitive assessment. Caregivers completed the Conners Third Edition to assess day-to-day inattentiveness, hyperactivity/impulsivity, and the Social Responsiveness Scale (SRS) to assess social functioning. Results : Among patients with ADHD, attention measures contributed to 48% of the variance in total SRS scores, with caregiver-reported hyperactivity/impulsivity as the strongest factor. In contrast, among those with ASD + ADHD, attention measures accounted for 40% of the variance, largely due to inattention problems. No associations between domains were observed among patients with ASD. Conclusion : Differential ADHD symptoms are associated with social impairment among children with ADHD versus ASD + ADHD ; whereas, no associations were observed among those with ASD.

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16. Nojiri J, Yanagawa T. [Effects of the Stepping Stones Triple P for mothers of pre-school children with suspected Autistic Spectrum Disorder]. [Nihon koshu eisei zasshi] Japanese journal of public health. 2019 ; 66(5) : 237-45.

ObjectiveThis study aimed to clarify the effectiveness of the Stepping Stones Triple P (SSTP) for mothers of developmentally delayed children.MethodsThe participants were 36 mothers of children using a development support classroom after a medical examination in A city. The children, aged 2 to 6 years old, were suspected to have autism spectrum disorder (ASD) based on Pervasive Developmental Disorders Autism Society Japan Rating Scale (PARS) scores of 9 points or more. The investigation randomly assigned them to two groups-"the intervention group" and "the control group"-and carried out SSTP. The intervention group answered the questionnaire before and after intervention, three months later. The control group also answered the questionnaire 2 months before the intervention, before and after intervention. Thus, each group answered three times. The questionnaire used the Strengths and Difficulties Questionnaire (SDQ), a Parenting Style scale (PS), the Relationship Quality Index (RQI), and the Japanese version of a Maltreatment scale (JM). For effectiveness of the intervention before and after, an analysis of covariance was carried out on the scores from the first and second questionnaires in the intervention and control groups. For effectiveness 3 months after the intervention, a repeated-measures analysis of variance was performed on the scale scores from the first to the third questionnaire in the intervention group.ResultsThe average age of the children was 3.7+/-1.4 years old, and the average PARS score was 20+/-6.8. They were suspected to have ASD. The average SDQ score was 76.1+/-18.8, and their intelligence was borderline. A significant difference was seen before and after the intervention in SDQ (the issue of action, the total of the difficulty), PS (overreaction, gab, general score), and JM scores ; no significant difference was seen in RQI scores. Three months after the intervention, a lasting effect was seen in SDQ (the issue of action, the total of the difficulty, hyperkinetic) and PS (all items) scores in the intervention group.ConclusionsReceiving SSTP caused a positive change in the mothers’ parenting and improved the problem behavior of the children. It was suggested that SSTP was connected to the prevention of child abuse because it helped stop parents from hitting their children.

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17. Ramos-Cabo S, Vulchanov V, Vulchanova M. Gesture and Language Trajectories in Early Development : An Overview From the Autism Spectrum Disorder Perspective. Front Psychol. 2019 ; 10 : 1211.

The well-documented gesture-language relation in typical communicative development (TD) remains understudied in autism spectrum disorder (ASD). Research on early communication skills shows that gesture production is a strong predictor of language in TD, but little is known about the association between gestures and language in ASD. This review focuses on exploring this relation by addressing two topics : the reliability of gestures as predictor of language competences in ASD and the types of potential differences (quantitative, qualitative, or both) in the gesture-language trajectory in children on the autism spectrum compared to typically developing children. We find evidence that gesture production is indeed a reliable predictor of early communicative skills and that both quantitative and qualitative differences have been established in research in the development of verbal and non-verbal communication skills in ASD, with lower gesture rates at the quantitative level, and a trajectory that starts deviating from the TD trajectory only at some point after the first year of life.

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18. Sonuga-Barke E, Kennedy M, Golm D, Knights N, Kovshoff H, Kreppner J, Kumsta R, Maughan B, O’Connor TG, Schlotz W. Adoptees’ responses to separation from, and reunion with, their adoptive parent at age 4 years is associated with long-term persistence of autism symptoms following early severe institutional deprivation. Development and psychopathology. 2019 : 1-10.

Institutionally deprived young children often display distinctive patterns of attachment, classified as insecure/other (INS/OTH), with their adoptive parents. The associations between INS/OTH and developmental trajectories of mental health and neurodevelopmental symptoms were examined. Age 4 attachment status was determined for 97 Romanian adoptees exposed to up to 24 months of deprivation in Romanian orphanages and 49 nondeprived UK adoptees. Autism, inattention/overactivity and disinhibited-social-engagement symptoms, emotional problems, and IQ were measured at 4, 6, 11, and 15 years and in young adulthood. Romanian adoptees with over 6 months deprivation (Rom>6) were more often classified as INS/OTH than UK and Romanian adoptees with less than 6 months deprivation combined. INS/OTH was associated with cognitive impairment at age 4 years. The interaction between deprivation, attachment status, and age for autism spectrum disorder assessment was significant, with greater symptom persistence in Rom>6 INS/OTH(+) than other groups. This effect was reduced when IQ at age 4 was controlled for. Age 4 INS/OTH in Rom>6 was associated with worse autism spectrum disorder outcomes up to two decades later. Its association with cognitive impairment at age 4 is consistent with INS/OTH being an early marker of this negative developmental trajectory, rather than its cause.

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19. Tang S, Terzic B, Wang IJ, Sarmiento N, Sizov K, Cui Y, Takano H, Marsh ED, Zhou Z, Coulter DA. Altered NMDAR signaling underlies autistic-like features in mouse models of CDKL5 deficiency disorder. Nat Commun. 2019 ; 10(1) : 2655.

CDKL5 deficiency disorder (CDD) is characterized by epilepsy, intellectual disability, and autistic features, and CDKL5-deficient mice exhibit a constellation of behavioral phenotypes reminiscent of the human disorder. We previously found that CDKL5 dysfunction in forebrain glutamatergic neurons results in deficits in learning and memory. However, the pathogenic origin of the autistic features of CDD remains unknown. Here, we find that selective loss of CDKL5 in GABAergic neurons leads to autistic-like phenotypes in mice accompanied by excessive glutamatergic transmission, hyperexcitability, and increased levels of postsynaptic NMDA receptors. Acute, low-dose inhibition of NMDAR signaling ameliorates autistic-like behaviors in GABAergic knockout mice, as well as a novel mouse model bearing a CDD-associated nonsense mutation, CDKL5 R59X, implicating the translational potential of this mechanism. Together, our findings suggest that enhanced NMDAR signaling and circuit hyperexcitability underlie autistic-like features in mouse models of CDD and provide a new therapeutic avenue to treat CDD-related symptoms.

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20. Uljarevic M, Hedley D, Rose-Foley K, Magiati I, Cai RY, Dissanayake C, Richdale A, Trollor J. Anxiety and Depression from Adolescence to Old Age in Autism Spectrum Disorder. J Autism Dev Disord. 2019.

This study examined age trends in anxious and depressive symptoms, from older adolescence to old age, and explored the association between anxious and depressive symptoms with gender, ASD severity, and socio-economic factors. Two hundred and fifty-five individuals with ASD (151 males, Mage = 33.52 years, SDage = 14.98) took part. More than one-third of participants reported clinically significant anxiety (38.4%) or depression (38%). A slight trend for an increase in the severity of both anxiety and depression from adolescence to middle adulthood, and then a slight decline in older adulthood was found. Female gender and higher ASD severity predicted more anxiety and depression symptoms. Our findings emphasise the need to provide timely assessment and treatment of anxiety and depression in ASD.

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21. Valeri G, Casula L, Napoli E, Stievano P, Trimarco B, Vicari S, Scalisi TG. Executive Functions and Symptom Severity in an Italian Sample of Intellectually Able Preschoolers with Autism Spectrum Disorder. J Autism Dev Disord. 2019.

A novel battery (BAFE ; Valeri et al. 2015) was used in order to assess three executive function (EF) abilities (working memory, inhibition and shifting) in a sample of 27 intellectually able preschoolers with autism spectrum disorder (ASD) compared with 27 typically developing children matched on age and nonverbal IQ. Differences in EF skills were analyzed in participants with distinct ASD symptom severity. Children with ASD performed worse than typical controls on both set-shifting and inhibition, but not on visuo-spatial working memory. Additionally, children with more severe ASD symptoms showed a worse performance on inhibition than children with milder symptoms. These results confirm the presence of EF deficits and highlight a link between ASD symptoms and EF impairments in preschool age.

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