Pubmed du 02/08/19

vendredi 2 août 2019

1. Impact of the HealthMatters Train-the-Trainer Program on the Health and Health Behaviors of Staff Supporting Adults With Intellectual and Developmental Disabilities. Workplace Health Saf ;2019 (Aug) ;67(8):436.

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2. Abu-Libdeh B, Ashhab M, Shahrour M, Daana M, Dudin A, Elpeleg O, Edvardson S, Harel T. Homozygous frameshift variant in NTNG2, encoding a synaptic cell adhesion molecule, in individuals with developmental delay, hypotonia, and autistic features. Neurogenetics ;2019 (Aug 2)

Regulation of neuronal connectivity and synaptic communication are key to proper functioning of the brain. The Netrin-G subfamily and their cognate receptors are vertebrate-specific synaptic cell adhesion molecules with a role in synapse establishment and function, which seem to have co-evolved to contribute to higher brain functions. We identified a homozygous frameshift variant in NTNG2 (NM_032536.3 : c.376dup), encoding Netrin-G2, in eight individuals from four families with global developmental delay, hypotonia, secondary microcephaly, and autistic features. Comparison of haplotypes established this as a founder variant. Previous studies showed that Ntng2-knockout mice have impaired visual, auditory, and motor coordination abilities required for demanding tasks, as well as possible spatial learning and memory deficits. Knockout of Ntng2 in a cellular model resulted in short neurites, and knockout of its trans-synaptic partner Ngl2/Lrrc4 in mice revealed autistic-like behavior and reduced NMDAR synaptic plasticity. The Ngl2/Lrrc4-knockout mouse phenotype was rescued by NMDAR activation, suggesting a mechanistic link to autism spectrum disorder. We thus propose NTNG2 as a candidate disease gene and provide further support for the involvement of Netrin-G2 in neuropsychiatric phenotypes.

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3. Anand V, Jauhari P. Autism, Epilepsy and Intellectual Disability : A Clinical Conundrum. Indian J Pediatr ;2019 (Jul 31)

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4. Chen LW, Wang ST, Wang LW, Kao YC, Chu CL, Wu CC, Hsieh YT, Chiang CH, Huang CC. Behavioral characteristics of autism spectrum disorder in very preterm birth children. Mol Autism ;2019 ;10:32.

Background : Lower gestational age may increase autism spectrum disorder (ASD) vulnerability ; however, the incidence of ASD diagnosis through a direct assessment on every very preterm birth child on the population base remains unclear. Moreover, the behavioral characteristics of preterm birth ASD are unknown. Methods : Every very preterm birth child (gestational age < 32 weeks ; birth weight < 1500 g) who was discharged from neonatal intensive care units in Southern Taiwan and prospectively followed to 5 years of age was evaluated using the Autism Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview-Revised (ADI-R). The term birth (gestational age > 37 weeks) ASD children characterized by ADOS and ADI-R were group matched to the preterm birth ASD by age at examination for comparison. ADOS severity scores were calculated by the Mann-Whitney U test and ADI-R by multivariate analysis of variance and canonical discriminant analysis. Results : Two hundred forty-six (87%) of the 283 very preterm survivors were followed prospectively to 5 years of age. Nineteen (7.7%) of the 246 children fulfilled the diagnostic criteria of ASD. After excluding 1 patient with cerebral palsy and profound mental disability, 18 preterm ASD children were compared with 44 term birth ASD children. The two ASD groups were comparable for age at examination, gender, and intelligence quotient. The two groups showed comparable ADOS severity scores in social affect deficits, restricted repetitive behaviors, and total score, but had differences in qualitative abnormalities in reciprocal social interaction (Wilks lambda F value = 6.2, P < 0.001) of ADI-R. Compared to term birth ASD children, preterm birth ASD children exhibited worse nonverbal behaviors that regulate social interaction (OR 2.59, 95% CI 1.41-4.73, P = 0.002) but more favorable peer relationships (OR 0.58, 95% CI 0.38-0.90, P = 0.01) and socioemotional reciprocity (OR 0.55, 95% CI 0.33-0.92, P = 0.02). In contrast to the heterogeneous severity of social reciprocity in the term ASD group, the behavioral characteristics of the preterm ASD group showed a homogeneous reciprocal social interaction pattern. Conclusions : The 5-year incidence rate of ASD was high in very preterm birth children. Preterm birth ASD exhibited a specific behavioral phenotype of reciprocal social interaction.

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5. den Houting J, Pellicano E. A Portfolio Analysis of Autism Research Funding in Australia, 2008-2017. J Autism Dev Disord ;2019 (Aug 2)

Autism research funding across the world has disproportionately been invested in biological and genetic research, despite evidence that these topics are not prioritized by community members. We sought to determine whether a similar pattern was evident in Australia’s autism research funding landscape between 2008 and 2017, by analysing the nation’s portfolio of autism research investments. We also examined whether there was any change in this pattern of funding since the establishment in 2013 of the Cooperative Research Centre for Living with Autism (Autism CRC). Overall, Australian autism research funding during 2008-2017 followed a similar pattern to other countries, but shifted in the past 5 years. Further progress is required to bring research funding into line with community priorities.

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6. Du Y, Li Z, Liu Z, Zhang N, Wang R, Li F, Zhang T, Jiang Y, Zhi X, Wang Z, Wu J. Correction : Nonrandom occurrence of multiple de novo coding variants in a proband indicates the existence of an oligogenic model in autism. Genet Med ;2019 (Aug 1)

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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7. Eissa N, Azimullah S, Jayaprakash P, Jayaraj RL, Reiner D, Ojha SK, Beiram R, Stark H, Lazewska D, Kiec-Kononowicz K, Sadek B. The dual-active histamine H3 receptor antagonist and acetylcholine esterase inhibitor E100 ameliorates stereotyped repetitive behavior and neuroinflammation in sodium valproate induced autism in mice. Chem Biol Interact ;2019 (Jul 30):108775.

Postnatal exposure to valproic acid (VPA) in rodents induces autism-like neurobehavioral defects which are comparable to the motor and cognitive deficits observed in humans with autism spectrum disorder (ASD). Histamine H3 receptor (H3R) and acetylcholine esterase (AChE) are involved in several cognitive disorders such as Alzheimer’s disease, schizophrenia, anxiety, and narcolepsy, all of which are comorbid with ASD. Therefore, the present study aimed at evaluating effect of the novel dual-active ligand E100 with high H3R antagonist affinity and balanced AChE inhibition on autistic-like repetitive behavior, anxiety parameters, locomotor activity, and neuroinflammation in a mouse model of VPA-induced ASD in C57BL/6 mice. E100 (5, 10, and 15mg/kg) dose-dependently and significantly ameliorated repetitive and compulsive behaviors by reducing the increased percentages of nestlets shredded (all P<0.05). Moreover, pretreatment with E100 (10 and 15mg/kg) attenuated disturbed anxiety levels (P<0.05) but failed to restore the hyperactivity observed in the elevated open field test. Furthermore, pretreatment with E100 (10mg/kg) mitigated the increase in the levels of proinflammatory cytokines and expression of NF-kappaB, iNOS, and COX-2 in the cerebellum as well as the hippocampus (all P<0.05). These results demonstrate the ameliorative effects of E100 on repetitive compulsive behaviors in a mouse model of ASD. To our knowledge, this is the first in vivo demonstration of the effectiveness of a potent dual-active H3R antagonist and AChE inhibitor against autistic-like repetitive compulsive behaviors and neuroinflammation, and provides evidence for the role of such compounds in treating ASD.

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8. Gadelkarim W, Shahper S, Reid J, Wikramanayake M, Kaur S, Kolli S, Osman S, Fineberg NA. Overlap of obsessive-compulsive personality disorder and autism spectrum disorder traits among OCD outpatients : an exploratory study. Int J Psychiatry Clin Pract ;2019 (Aug 2):1-10.

Background : Whereas the phenomenology of obsessive-compulsive personality disorder (OCPD) shows similarities to that of obsessive compulsive and related disorders (OCRDs) as well as with autism spectrum disorder (ASD), the relationship between these disorders is poorly understood. Aims : Within a clinical sample, we aimed to investigate the distribution of OCD, OCPD and ASD symptoms and traits and their interrelationship, as well as to evaluate insight and treatment refractoriness. Methods : Consecutive adult OCD outpatients were assessed for OCPD traits (Compulsive Personality Assessment Scale (CPAS)), OCD symptoms (Yale-Brown Obsessive Compulsive Scale (Y-BOCS)), ASD traits (Autism Spectrum Quotient (AQ)), insight (Brown Assessment of Beliefs Scale (BABS)) and treatment resistance (clinical records). Those scoring highly on the AQ underwent a diagnostic interview for ASD. Results : Sixty-seven consenting individuals completed the CPAS, BABS and AQ, and 65 completed the Y-BOCS. Twenty-four patients (35.8%) were diagnosed with OCPD. Patients with OCPD were less likely to be employed (p=.04). They demonstrated elevated AQ scores (p=.004) and rates of ASD diagnosis (54.2%) (p <.001). OCPD traits (CPAS) showed a highly significant correlation with ASD traits (AQ) (p<.001), and no association with Y-BOCS, BABS or treatment resistance. Conclusions : In an OCD cohort limited by small size, OCPD associated strongly with unemployment and ASD, with implications for diagnosis, treatment and outcome. KEY POINTS Clinicians should exercise a high level of vigilance for OCPD and ASD in patients presenting with obsessive compulsive symptoms. The presence of OCPD may indicate a likelihood of disabling ASD traits, including cognitive inflexibility, poor central coherence and poor social communication. These neuropsychological factors may require separate clinical intervention strategies.

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9. Gomes T, Khuu W, Tadrous M, Vigod S, Cobigo V, Lunsky Y. Antipsychotic initiation among adults with intellectual and developmental disabilities in Ontario : a population-based cohort study. BMJ Open ;2019 (Jul 30) ;9(7):e028125.

OBJECTIVES : To describe factors associated with initiating antipsychotics and patterns of persistence to antipsychotic therapy in a large cohort of adults with intellectual and developmental disabilities. DESIGN : Population-based cohort study. SETTING : Ontario, Canada. PARTICIPANTS : Adults with intellectual and developmental disabilities (IDD) in Ontario. OUTCOME MEASURES : We used multivariable logistic regression to investigate patient characteristics associated with antipsychotic initiation. Patient characteristics studied included sociodemographic characteristics, measures of clinical comorbidity and health service use. RESULTS : Among 39 244 individuals eligible for this study, 6924 (17.6%) initiated an antipsychotic over the accrual window, of whom 1863 (26.9%) had no psychiatric diagnosis in the prior 2 years. A number of factors were significantly associated with antipsychotic initiation, including male gender, residence in a group home, prior use of benzodiazepines, antidepressants or cognitive enhancers, a recent emergency department visit or mental health hospitalisation and a visit to a psychiatrist or family physician in the prior 90 days. In a secondary analysis, the association between antipsychotic initiation and age, prior diagnosis of diabetes or myocardial infarction and polypharmacy differed slightly on the basis of whether an individual had a previously diagnosed psychiatric disorder. CONCLUSIONS : Factors associated with the initiation of an antipsychotic differ according to the presence of a psychiatric diagnosis. Given the long duration of antipsychotic use in this population, future research is needed to understand the appropriateness of antipsychotic initiation among adults with IDD and the safety implications of long-term use of these products.

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10. Grandgeorge M, Dubois E, Alavi Z, Bourreau Y, Hausberger M. Do Animals Perceive Human Developmental Disabilities ? Guinea Pigs’ Behaviour with Children with Autism Spectrum Disorders and Children with Typical Development. A Pilot Study. Animals (Basel) ;2019 (Aug 2) ;9(8)

Some cues used by humans and animals during human-animal interactions may have significant effects, modulating these interactions (e.g., gaze direction, heart rate). This study aimed to determine whether an animal in human-animal interactions is capable of "perceiving" its human partner’s potential developmental "disabilities". To test this hypothesis, we studied guinea pigs (GP) behaviours in the presence of 44 6-to-12-year-old children with either typical development (TD children) or with autism spectrum disorders (ASD children). Thus, we recorded the GP behaviours during the entire session (to establish their time budget) and focused in particular on the onset and end of physical interactions. The GP behaviours (e.g., feeding, resting, self-grooming, exploring) were not significantly different between the two groups of children during the whole session. GP behaviours in the presence of children differed slightly when encountering ASD children versus TD children : more positive behaviours toward ASD children at the onset, more feeding and resting in the presence of TD children toward the end of an interaction. TD children showed longer-lasting interactions. One could explain this by GP curiosity toward ASD children behaviours (e.g., no marked behaviours such as attempts to touch), whereas GPs seemed calmer at the end with TD children (i.e., interacting with ASD children may be a little stressful). This partly gave support to our study’s hypothesis. GPs seemed to perceive developmental disabilities during a first encounter with children and to adjust their behaviours to that of children. We discuss the issues of animal training, animals’ well-being and acute stress, whether they are pets or used in animal-assisted interventions. Further studies (on pets or animal-assisted interventions) are warranted.

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11. Heussler H, Cohen J, Silove N, Tich N, Bonn-Miller MO, Du W, O’Neill C, Sebree T. A phase 1/2, open-label assessment of the safety, tolerability, and efficacy of transdermal cannabidiol (ZYN002) for the treatment of pediatric fragile X syndrome. J Neurodev Disord ;2019 (Aug 2) ;11(1):16.

BACKGROUND : Fragile X syndrome (FXS) is characterized by a range of developmental, neuropsychiatric, and behavioral symptoms that cause significant impairment in those with the disorder. Cannabidiol (CBD) holds promise as a potential treatment for FXS symptoms due to its safety profile and positive effects on a number of emotional and behavioral symptoms associated with FXS. The aim of the current study was to evaluate the safety, tolerability, and initial efficacy of ZYN002, a transdermal CBD gel, in a pediatric population with FXS. METHODS : Twenty children and adolescents (aged 6-17 years) with a diagnosis of FXS (confirmed through molecular documentation of FMR1 full mutation) were enrolled in an open-label, multi-site, trial of ZYN002. Transdermal CBD gel was administered twice daily for 12 weeks, titrated from 50 mg to a maximum daily dose of 250 mg. The primary efficacy endpoint was change from screening to week 12 on the Anxiety, Depression, and Mood Scale (ADAMS). Secondary endpoint measures included the Aberrant Behavior Checklist-Community for FXS (ABC-CFXS), Pediatric Anxiety Rating Scale (PARS-R), Pediatric Quality of Life Inventory (PedsQL), three Visual Analogue Scales (VAS), and the Clinical Global Impression Scale-Severity (CGI-S) and Improvement (CGI-I). RESULTS : The majority of treatment-emergent AEs (reported by 85% of participants) were mild in severity (70%), and no serious adverse events were reported. There was a statistically significant reduction in ADAMS total score from screening to week 12 and significant reductions on nearly all other secondary endpoints, including all ADAMS subscales (except depressed mood), all ABC-CFXS subscale scores (e.g., social avoidance, irritability), PARS-R total severity score, and PedsQL total score. CONCLUSIONS : ZYN002 was well tolerated and produced clinically meaningful reductions in anxiety and behavioral symptoms in children and adolescents with FXS. These findings support further study of ZYN002 in a randomized, well-controlled trial for the treatment of behavioral symptoms of FXS. TRIAL REGISTRATION : ANZCTR, ACTRN12617000150347 Registered 27 January 2017.

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12. Kou J, Le J, Fu M, Lan C, Chen Z, Li Q, Zhao W, Xu L, Becker B, Kendrick KM. Comparison of three different eye-tracking tasks for distinguishing autistic from typically developing children and autistic symptom severity. Autism Res ;2019 (Aug 1)

Altered patterns of visual social attention preference detected using eye-tracking and a variety of different paradigms are increasingly proposed as sensitive biomarkers for autism spectrum disorder. However, few eye-tracking studies have compared the relative efficacy of different paradigms to discriminate between autistic compared with typically developing children and their sensitivity to specific symptoms. To target this issue, the current study used three common eye-tracking protocols contrasting social versus nonsocial stimuli in young (2-7 years old) Chinese autistic (n = 35) and typically developing (n = 34) children matched for age and gender. Protocols included dancing people versus dynamic geometrical images, biological motion (dynamic light point walking human or cat) versus nonbiological motion (scrambled controls), and child playing with toy versus toy alone. Although all three paradigms differentiated autistic and typically developing children, the dancing people versus dynamic geometry pattern paradigm was the most effective, with autistic children showing marked reductions in visual preference for dancing people and correspondingly increased one for geometric patterns. Furthermore, this altered visual preference in autistic children was correlated with the Autism Diagnostic Observation Schedule social affect score and had the highest discrimination accuracy. Our results therefore indicate that decreased visual preference for dynamic social stimuli may be the most effective visual attention-based paradigm for use as a biomarker for autism in Chinese children. Clinical trial ID : NCT03286621 (clinicaltrials.gov) ; Clinical trial name : Development of Eye-tracking Based Markers for Autism in Young Children. Autism Res 2019, 00 : 1-12. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY : Eye-tracking measures may be useful in aiding diagnosis and treatment of autism, although it is unclear which specific tasks are optimal. Here we compare the ability of three different social eye-gaze tasks to discriminate between autistic and typically developing young Chinese children and their sensitivity to specific autistic symptoms. Our results show that a dynamic task comparing visual preference for social (individuals dancing) versus geometric patterns is the most effective both for diagnosing autism and sensitivity to its social affect symptoms.

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13. Luz-Escamilla L, Antonio Morales-Gonzalez J. Association between Interictal Epileptiform Discharges and Autistic Spectrum Disorder. Brain Sci ;2019 (Jul 30) ;9(8)

It has been reported that bioelectric alterations in an electroencephalogram (EEG) may play an etiological role in neurodevelopmental disorders. The clinical impact of interictal epileptiform discharges (IEDs) in association with autistic spectrum disorder (ASD) is unknown. The Autism Diagnostic Interview-Revised (ADI-R) is one of the gold standards for the diagnosis of autistic spectrum disorder. Some studies have indicated high comorbidity of IED and ASD, while other studies have not supported an association between the central symptoms of autism and IED. This review examines the high comorbidity and clinical impact of IED ; patients with epilepsy are excluded from the scope of this review. ASD can be disabling and is diagnosed at an average age of 5 years old, at which point the greatest neurological development has occurred. If an association between IED and ASD is identified, a clinical tool that entails an innocuous procedure could enable diagnosis in the first years of life. However, in the absence of reports that prove an association between IED and ASD, patients should not be subjected to expensive treatments, such as the administration of anticonvulsant therapies.

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14. Reid M, Fesalbon M, Mendoza E, Alvord MK, Rich BA. Examining the Relationship Between Parental Symptomatology and Treatment Outcomes in Children with Autism Spectrum Disorder. J Autism Dev Disord ;2019 (Aug 2)

This report examines the relationship between treatment response in children with ASD and parents’ affective symptomatology. This study examined 29 children with ASD in a manualized group psychotherapy program, Resilience Builder Program((R)) (RBP), where emotional and social functioning of parent and child were measured through pre- and post-treatment questionnaires. Greater parental symptomatology was associated with children’s reduced response to RBP in resilience-based emotion regulation skills. Greater parental interpersonal sensitivity (beta = - .27, p = .024) predicted worse post-treatment scores in child communication skills, greater parental anxious symptoms (beta = - .45, p = .005) predicted worse post-treatment scores in child emotional control, and greater parental depressive (beta = .27, p = .041) and anxious symptoms (beta = .36, p = .004) predicted worse post-treatment scores in child internalizing problems.

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15. Simmonds C, Sukhareva GE. The first account of the syndrome Asperger described ? Part 2 : the girls. Eur Child Adolesc Psychiatry ;2019 (Jul 31)

Translation of G. E. Sukhareva’s "Die Besonderheiten der schizoiden Psychopathien bei den Madchen", which appeared in 1927 in Monatsschrift fur Psychiatrie und Neurologie as a continuation of "Die schizoiden Psychopathien", previously translated by Sula Wolff. This second paper comprises five case studies of girls and a discussion of the sex differences in the presentation of schizoid psychopathy, potentially what we would now consider part of the autism spectrum.

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16. Studenka BE, Myers K. Preliminary Evidence That Motor Planning Is Slower and More Difficult for Children With Autism Spectrum Disorder During Motor Cooperation. Motor Control ;2019 (Aug 1):1-23.

Children with autism spectrum disorder (ASD) exhibit impairment in helping someone else with a motor action, which may arise from impairment in selecting and preparing motor responses. Five children with ASD and five typically developing children performed a cooperative motor planning task that required them to reach for, lift, and hand an object (hammer or stick) to a researcher. The response, movement, and grasp time were measured. Children with ASD grasped the object longer on trials where they helped, indicating that the action was planned in sequence versus as a whole (i.e., prior to the onset of movement). The hammer object elicited a quicker response than the stick, suggesting the facilitation of planning by tools with inherent action properties. Finally, the increased helping of children with ASD was not mirrored by changes in the response, movement, or grasp time.

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17. Tang X, Drotar J, Li K, Clairmont CD, Brumm AS, Sullins AJ, Wu H, Liu XS, Wang J, Gray NS, Sur M, Jaenisch R. Pharmacological enhancement of KCC2 gene expression exerts therapeutic effects on human Rett syndrome neurons and Mecp2 mutant mice. Sci Transl Med ;2019 (Jul 31) ;11(503)

Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the methyl CpG binding protein 2 (MECP2) gene. There are currently no approved treatments for RTT. The expression of K(+)/Cl(-) cotransporter 2 (KCC2), a neuron-specific protein, has been found to be reduced in human RTT neurons and in RTT mouse models, suggesting that KCC2 might play a role in the pathophysiology of RTT. To develop neuron-based high-throughput screening (HTS) assays to identify chemical compounds that enhance the expression of the KCC2 gene, we report the generation of a robust high-throughput drug screening platform that allows for the rapid assessment of KCC2 gene expression in genome-edited human reporter neurons. From an unbiased screen of more than 900 small-molecule chemicals, we have identified a group of compounds that enhance KCC2 expression termed KCC2 expression-enhancing compounds (KEECs). The identified KEECs include U.S. Food and Drug Administration-approved drugs that are inhibitors of the fms-like tyrosine kinase 3 (FLT3) or glycogen synthase kinase 3beta (GSK3beta) pathways and activators of the sirtuin 1 (SIRT1) and transient receptor potential cation channel subfamily V member 1 (TRPV1) pathways. Treatment with hit compounds increased KCC2 expression in human wild-type (WT) and isogenic MECP2 mutant RTT neurons, and rescued electrophysiological and morphological abnormalities of RTT neurons. Injection of KEEC KW-2449 or piperine in Mecp2 mutant mice ameliorated disease-associated respiratory and locomotion phenotypes. The small-molecule compounds described in our study may have therapeutic effects not only in RTT but also in other neurological disorders involving dysregulation of KCC2.

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18. van den Dries MA, Guxens M, Pronk A, Spaan S, El Marroun H, Jusko TA, Longnecker MP, Ferguson KK, Tiemeier H. Organophosphate pesticide metabolite concentrations in urine during pregnancy and offspring attention-deficit hyperactivity disorder and autistic traits. Environ Int ;2019 (Jul 29) ;131:105002.

BACKGROUND : Prenatal exposure to organophosphate (OP) pesticides has been associated with altered neuronal cell development and behavioral changes in animal offspring. However, the few studies investigating the association between prenatal OP pesticide exposure and neurodevelopmental outcomes such as Attention-Deficit Hyperactivity Disorder (ADHD) and autistic traits in children produced mixed findings. OBJECTIVE : The objective of the present study was to examine whether maternal urinary concentrations of OP pesticide metabolites are associated with ADHD and autistic traits in children participating in the Generation R Study, a population-based birth cohort from Rotterdam, the Netherlands. METHOD : Maternal concentrations of 6 dialkylphosphates (DAPs) were measured using gas chromatography coupled with tandem mass spectrometry in urine samples collected at <18weeks, 18-25weeks, and>25weeks of gestation in 784 mother-child pairs. DAP metabolite concentrations were expressed as molar concentrations divided by creatinine levels and log10 transformed. ADHD traits were measured at ages 3, 6, and 10years using the Child Behavior Checklist (CBCL) (n=781) and autistic traits were measured at age 6years using the Social Responsiveness Scale (SRS) (n=622). First, regression models were fit for the averaged prenatal exposure across pregnancy. Second, we investigated associations for each collection phase separately, and applied a mutually adjusted model in which the effect of prenatal DAP concentrations from each time period on ADHD and autistic traits were jointly estimated. All associations were adjusted for relevant confounders. RESULTS : Median DAP metabolite concentration was 309nmol/g creatinine at <18weeks, 316nmol/g creatinine at 18-25weeks, and 308nmol/g creatinine at >25weeks of gestation. Overall, DAP metabolite concentrations were not associated with ADHD traits. For instance, a log10 increase in averaged total DAP concentrations across gestation was not associated with a lower ADHD score (-0.03 per SD 95 CI : -0.28 to 0.23). Similarly, no associations between maternal DAP concentrations and autistic traits were detected. CONCLUSIONS : In this study of maternal urinary DAP metabolite concentrations during pregnancy, we did not observe associations with ADHD and autistic traits in children. These are important null observations because of the relatively high background DAP concentrations across pregnancy, the relatively large sample size, and the 10-year follow-up of the offspring. Given the measurement error inherent in our OP pesticide exposure biomarkers, future studies using more urine samples are needed to accurately measure OP pesticide exposure over pregnancy in relation to ADHD and autistic traits.

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19. Young GS, Constantino JN, Dvorak S, Belding A, Gangi D, Hill A, Hill M, Miller M, Parikh C, Schwichtenberg AJ, Solis E, Ozonoff S. A video-based measure to identify autism risk in infancy. J Child Psychol Psychiatry ;2019 (Aug 1)

BACKGROUND : Signs of autism are present in the first 2 years of life, but the average age of diagnosis lags far behind. Instruments that improve detection of autism risk in infancy are needed. This study developed and tested the psychometric properties of a novel video-based approach to detecting ASD in infancy. METHODS : A prospective longitudinal study of children at elevated or lower risk for autism spectrum disorder was conducted. Participants were 76 infants with an older sibling with ASD and 37 infants with no known family history of autism. The Video-referenced Infant Rating System for Autism (VIRSA) is a web-based application that presents pairs of videos of parents and infants playing together and requires forced-choice judgments of which video is most similar to the child being rated. Parents rated participants on the VIRSA at 6, 9, 12, and 18 months of age. We examined split-half and test-retest reliability ; convergent and discriminant validity ; and sensitivity, specificity, and negative and positive predictive value for concurrent and 36-month ASD diagnoses. RESULTS : The VIRSA demonstrated satisfactory reliability and convergent and discriminant validity. VIRSA ratings were significantly lower for children ultimately diagnosed with ASD than children with typical development by 12 months of age. VIRSA scores at 18 months identified all children diagnosed with ASD at that age, as well as 78% of children diagnosed at 36 months. CONCLUSIONS : This study represents an initial step in the development of a novel video-based approach to detection of ASD in infancy. The VIRSA’s psychometric properties were promising when used by parents with an older affected child, but still must be tested in community samples with no family history of ASD. If results are replicated, then the VIRSA’s low-burden, web-based format has the potential to reduce disparities in communities with limited access to screening.

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