Pubmed du 27/06/19

jeudi 27 juin 2019

1. Prenatal and infant exposure to ambient pesticides and autism spectrum disorder in children : population based case-control study. Bmj ;2019 (Jun 25) ;365:l4032.

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2. Class QA. Maternal infection associated with autism and depression in their offspring. J Pediatr ;2019 (Jul) ;210:239-242.

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3. Como DH, Florindez LI, Tran CF, Cermak SA, Stein Duker LI. Examining unconscious bias embedded in provider language regarding children with autism. Nurs Health Sci ;2019 (Jun 25)

In healthcare settings, language used by healthcare providers can influence provider-patient encounters with individuals with autism spectrum disorder, impacting feelings of stigma and marginalization. This study highlights the unconscious biases healthcare providers might have regarding their patients with autism spectrum disorder and how those beliefs are articulated. Seven pediatric dentists participated in two focus groups to describe strategies to improve oral care for children with autism spectrum disorder. While completing the primary analyses, additional codes emerged related to healthcare provider biases ; these data are the focus of this study. Three themes were identified : (i) "healthcare microaggressions" describe how healthcare providers portray their patients in subtly negative ways ; (ii) "marginalization" denotes the use of exclusionary language identifying children with autism spectrum disorder as different ; and (iii) "preconceptions" include comments that highlight biases about patients. The findings provide insight into the implicit biases that might be held by healthcare providers and how they manifest in language. Despite increased emphasis on cultural competency, healthcare providers might unconsciously use language that could negatively impact patient-provider rapport and increase stigma in already marginalized populations. Further research is necessary to explore how these biases could relate to quality of care.

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4. Day TC, McNaughton KA, Naples AJ, McPartland JC. Self-reported social impairments predict depressive disorder in adults with autism spectrum disorder. Autism ;2019 (Jun 25):1362361319857375.

In adults with autism spectrum disorder, co-occurring psychiatric conditions are prevalent, and depression is one of the most common co-occurring disorders. This study examined the relationship between depression and cognitive ability, autism symptom severity, and self-reported social impairments in autism spectrum disorder. A total of 33 adults with autism spectrum disorder and 28 adults with typical development completed a standardized psychiatric interview, cognitive test, measure of clinician-rated autism symptom severity, and self-report of social impairments. Nine participants with autism spectrum disorder (27%) met the criteria for a depressive disorder (autism spectrum disorder + depressive disorder). Relatively more females with autism spectrum disorder had a co-occurring depressive disorder. The typical development group had a higher intelligence quotient than the autism spectrum disorder group, but the autism spectrum disorder + depressive disorder group did not differ from the typical development or autism spectrum disorder group. While the autism spectrum disorder + depressive disorder group had lower clinician-rated autism symptom severity than the autism spectrum disorder group, the autism spectrum disorder + depressive disorder group reported more social impairments than the autism spectrum disorder group. Self-reported social impairments predicted depression in adults with autism spectrum disorder when accounting for symptom severity and cognitive ability. These findings suggest that more self-perceived social impairments are related to depressive disorders in autism spectrum disorder, and may help clinicians identify individuals who are vulnerable in developing a co-occurring depressive disorder. Future directions include follow-up studies with larger cohorts and longitudinal designs to support inferences regarding directionality of these relationships.

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5. Ghanizadeh A, Molla M, Olango GJ. The effect of stimulants on irritability in autism comorbid with ADHD : a systematic review. Neuropsychiatr Dis Treat ;2019 ;15:1547-1555.

Introduction : While there is a very high rate of comorbidity of autism and ADHD, there are controversies about prescribing stimulants in children with autism. This is a systematic review about the effect of stimulants on irritability in children with both autism and ADHD. Methods : A systematic review was conducted to study the possible effect of stimulants on irritability in autism and ADHD using the databases of PubMed, Scopus, EMBASE, and ScienceDirect in September 2018. Eligible clinical trials of stimulants in the treatment of Autism and ADHD without restriction of language were included. The primary outcome was irritability score. The full texts of relevant articles were studied, and their references were scanned for any possible related article. Results : Out of 1,315 citations, there were 26 relevant articles. Of the relevant articles, 16 were not interventional studies and were excluded. There were 10 interventional studies. None of them considered irritability as a main outcome. Also, none of them studied the effect of stimulants on irritability in autism plus ADHD. Current uncontrolled evidence about the association of stimulants with irritability is controversial. Conclusion : The current evidence is not enough to support or discourage the effect of stimulants on irritability in children and adolescents with both autism and ADHD. Well-designed controlled clinical trials need to be conducted for this ignored research area.

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6. Gulsrud A, Carr T, Williams J, Panganiban J, Jones F, Kimbrough J, Shih W, Kasari C. Developmental screening and early intervention in a childcare setting for young children at risk for autism and other developmental delays : A feasibility trial. Autism Res ;2019 (Jun 26)

Efforts to decrease disparity in diagnosis and treatment for under-resourced children with developmental delays, such as autism spectrum disorder, have led to increased interest in developing programs in community settings. One potential setting that has already demonstrated feasibility in conducting universal screening is the childcare setting. The current study conducted developmental screening in a total of 116 children ages 16-80 months of age in an urban low-income community childcare center. Parents of 20 children who screened positive were enrolled in the intervention phase of the study, where children received a staff-delivered targeted early intervention or a waitlist control condition. Given the small and imbalanced sample sizes, confidence intervals from mixed effect models were used to measure changes across time for each group. Of the children who received treatment, there was an average increase in child initiated joint engagement, symbolic play, and language use. This study provides initial feasibility data for the implementation of a screening and early intervention program to service a predominantly low-resource and ethnically diverse population within the childcare system in a large metropolitan city. Autism Res 2019, (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY : Identifying and delivering treatment services for young children with developmental delays, such as autism spectrum disorder, may be most successful in community settings, especially for those children from under-resourced areas. This study found preliminary evidence that the childcare setting is a good place to conduct screening and deliver early interventions for children at risk for autism and other developmental delays.

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7. Heifetz M, Brown HK, Chacra MA, Tint A, Vigod S, Bluestein D, Lunsky Y. Mental health challenges and resilience among mothers with intellectual and developmental disabilities. Disabil Health J ;2019 (Jun 15)

BACKGROUND : Mothers with intellectual and developmental disabilities (IDD) frequently experience mental health problems. Yet, they are excluded from broader women’s mental health efforts, and few services exist to support their unique mental health needs. OBJECTIVES : Our objective was to identify key risk, protective, and resilience factors that affect mental health among mothers with IDD. METHODS : We interviewed mothers with IDD on : (1) a quantitative measure to assess demographics and depressive symptoms and (2) qualitative focus groups on parenting and mental health (analyzed through thematic analysis). There were three focus groups, for a total sample of 12 mothers with IDD. RESULTS : The 12 women in the sample had a total of 28 children, with a mean age of 11.3 years (SD=9.9). The mean depressive symptom score in the sample was 13.8 (SD=5.5), with 7 women scoring above the cut-off for clinically significant symptoms. Nine thematic categories were identified, organized into risks, protective factors, and resilience factors. Risks were parenting stress, life stressors, feelings of powerlessness with the child welfare system, and feeling judged. Protective factors were formal and informal supports. Resilience factors were motherhood enjoyment, having a good family life, and wishing to be independent. CONCLUSIONS : Efforts to improve mental health among mothers with IDD should minimize risks that undermine adaptive capabilities and promote resilience to restore efficacy of protective systems. Better training of service-providers working with individuals with IDD, using strength-based approaches and developing alternative, autonomy-building sources of support in the form of peer support groups is recommended.

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8. Hirvikoski T, Boman M, Chen Q, D’Onofrio BM, Mittendorfer-Rutz E, Lichtenstein P, Bolte S, Larsson H. Individual risk and familial liability for suicide attempt and suicide in autism : a population-based study. Psychol Med ;2019 (Jun 26):1-12.

BACKGROUND : Studies on the individual gender-specific risk and familial co-aggregation of suicidal behaviour in autism spectrum disorder (ASD) are lacking. METHODS : We conducted a matched case-cohort study applying conditional logistic regression models on 54 168 individuals recorded in 1987-2013 with ASD in Swedish national registers : ASD without ID n = 43 570 (out of which n = 19035, 43.69% with ADHD) ; ASD + ID n = 10 598 (out of which n = 2894 individuals, 27.31% with ADHD), and 270 840 controls, as well as 347 155 relatives of individuals with ASD and 1 735 775 control relatives. RESULTS : The risk for suicidal behaviours [reported as odds ratio OR (95% confidence interval CI)] was most increased in the ASD without ID group with comorbid ADHD [suicide attempt 7.25 (6.79-7.73) ; most severe attempts i.e. requiring inpatient stay 12.37 (11.33-13.52) ; suicide 13.09 (8.54-20.08)]. The risk was also increased in ASD + ID group [all suicide attempts 2.60 (2.31-2.92) ; inpatient only 3.45 (2.96-4.02) ; suicide 2.31 (1.16-4.57)]. Females with ASD without ID had generally higher risk for suicidal behaviours than males, while both genders had highest risk in the case of comorbid ADHD [females, suicide attempts 10.27 (9.27-11.37) ; inpatient only 13.42 (11.87-15.18) ; suicide 14.26 (6.03-33.72) ; males, suicide attempts 5.55 (5.10-6.05) ; inpatient only 11.33 (9.98-12.86) ; suicide 12.72 (7.77-20.82)]. Adjustment for psychiatric comorbidity attenuated the risk estimates. In comparison to controls, relatives of individuals with ASD also had an increased risk of suicidal behaviour. CONCLUSIONS : Clinicians treating patients with ASD should be vigilant for suicidal behaviour and consider treatment of psychiatric comorbidity.

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9. Hooker JL, Dow D, Morgan L, Schatschneider C, Wetherby AM. Psychometric analysis of the repetitive behavior scale-revised using confirmatory factor analysis in children with autism. Autism Res ;2019 (Jun 27)

Research examining restricted and repetitive patterns of behavior or interests (RRB) in autism spectrum disorder (ASD) has increased our understanding of its contribution to diagnosis and its role in development. Advances in our knowledge of RRB are hindered by the inconsistencies in how RRB is measured. The present study examined the factor structure of the Repetitive Behavior Scale-Revised (RBS-R) in a sample of 350 children with ASD ages 2-9. Confirmatory factor analysis designed for items with categorical response types was implemented to examine six proposed structural models. The five-factor model demonstrated the most parsimonious fit based on common overall fit indices that was further supported by examination of local model fit indicators, though, the four- and six-factor models evidenced adequate-to-good fit as well. Examination of RRB factor score approaches indicated only minor differences between summed item subscale scores and extracted factor scores with regard to associations with diagnostic measures. All RRB subtypes demonstrated significant associations with cognitive functioning and adaptive behavior. Implications for future research validating the RBS-R as a more extensive clinical measure of RRB in ASD are discussed. Autism Res 2019. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY : Repetitive behaviors are one of the two main symptoms of autism spectrum disorder (ASD). To better understand the role of repetitive behaviors, we must establish effective ways of measuring them. This study assessed the measurement qualities of the Repetitive Behavior Scale-Revised (RBS-R) in a sample of 350 children with ASD ages 2-9. We found that the RBS-R measures multiple types of repetitive behaviors and that these behaviors are related to thinking ability and independence.

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10. Levy NS, Umanah GKE, Rogers EJ, Jada R, Lache O, Levy AP. IQSEC2-Associated Intellectual Disability and Autism. Int J Mol Sci ;2019 (Jun 21) ;20(12)

Mutations in IQSEC2 cause intellectual disability (ID), which is often accompanied by seizures and autism. A number of studies have shown that IQSEC2 is an abundant protein in excitatory synapses and plays an important role in neuronal development as well as synaptic plasticity. Here, we review neuronal IQSEC2 signaling with emphasis on those aspects likely to be involved in autism. IQSEC2 is normally bound to N-methyl-D-aspartate (NMDA)-type glutamate receptors via post synaptic density protein 95 (PSD-95). Activation of NMDA receptors results in calcium ion influx and binding to calmodulin present on the IQSEC2 IQ domain. Calcium/calmodulin induces a conformational change in IQSEC2 leading to activation of the SEC7 catalytic domain. GTP is exchanged for GDP on ADP ribosylation factor 6 (ARF6). Activated ARF6 promotes downregulation of surface alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors through a c-jun N terminal kinase (JNK)-mediated pathway. NMDA receptors, AMPA receptors, and PSD-95 are all known to be adversely affected in autism. An IQSEC2 transgenic mouse carrying a constitutively active mutation (A350V) shows autistic features and reduced levels of surface AMPA receptor subunit GluA2. Sec7 activity and AMPA receptor recycling are presented as two targets, which may respond to drug treatment in IQSEC2-associated ID and autism.

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11. Lozovaya N, Nardou R, Tyzio R, Chiesa M, Pons-Bennaceur A, Eftekhari S, Bui TT, Billon-Grand M, Rasero J, Bonifazi P, Guimond D, Gaiarsa JL, Ferrari DC, Ben-Ari Y. Early alterations in a mouse model of Rett syndrome : the GABA developmental shift is abolished at birth. Sci Rep ;2019 (Jun 25) ;9(1):9276.

Genetic mutations of the Methyl-CpG-binding protein-2 (MECP2) gene underlie Rett syndrome (RTT). Developmental processes are often considered to be irrelevant in RTT pathogenesis but neuronal activity at birth has not been recorded. We report that the GABA developmental shift at birth is abolished in CA3 pyramidal neurons of Mecp2(-/y) mice and the glutamatergic/GABAergic postsynaptic currents (PSCs) ratio is increased. Two weeks later, GABA exerts strong excitatory actions, the glutamatergic/GABAergic PSCs ratio is enhanced, hyper-synchronized activity is present and metabotropic long-term depression (LTD) is impacted. One day before delivery, maternal administration of the NKCC1 chloride importer antagonist bumetanide restored these parameters but not respiratory or weight deficits, nor the onset of mortality. Results suggest that birth is a critical period in RTT with important alterations that can be attenuated by bumetanide raising the possibility of early treatment of the disorder.

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12. Phung JN, Goldberg WA. Promoting Executive Functioning in Children with Autism Spectrum Disorder Through Mixed Martial Arts Training. J Autism Dev Disord ;2019 (Jun 25)

The present study evaluated the effectiveness of a mixed martial arts (MMA) intervention in improving executive functions (EFs) in a sample with autism spectrum disorder (ASD). School-aged children with ASD were randomly assigned to a MMA intervention group or a waitlist control (WLC) group. The intervention featured a 26-class program over a 13-week period ; the WLC group did not participate in any martial arts between pre- and post-test. Results indicated that the MMA group had significantly better EFs at post-test compared to the WLC group. The intervention appeared to be efficacious in meeting its goals of improving the executive functioning of children with ASD. The present study extends the current literature on the malleability of EFs among children with ASD.

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13. Pretzsch CM, Voinescu B, Mendez MA, Wichers R, Ajram L, Ivin G, Heasman M, Williams S, Murphy DG, Daly E, McAlonan GM. The effect of cannabidiol (CBD) on low-frequency activity and functional connectivity in the brain of adults with and without autism spectrum disorder (ASD). J Psychopharmacol ;2019 (Jun 25):269881119858306.

BACKGROUND : The potential benefits of cannabis and its major non-intoxicating component cannabidiol (CBD) are attracting attention, including as a potential treatment in neurodevelopmental disorders such as autism spectrum disorder (ASD). However, the neural action of CBD, and its relevance to ASD, remains unclear. We and others have previously shown that response to drug challenge can be measured using functional magnetic resonance imaging (fMRI), but that pharmacological responsivity is atypical in ASD. AIMS : We hypothesized that there would be a (different) fMRI response to CBD in ASD. METHODS : To test this, task-free fMRI was acquired in 34 healthy men (half with ASD) following oral administration of 600 mg CBD or matched placebo (random order ; double-blind administration). The ’fractional amplitude of low-frequency fluctuations’ (fALFF) was measured across the whole brain, and, where CBD significantly altered fALFF, we tested if functional connectivity (FC) of those regions was also affected by CBD. RESULTS : CBD significantly increased fALFF in the cerebellar vermis and the right fusiform gyrus. However, post-hoc within-group analyses revealed that this effect was primarily driven by the ASD group, with no significant change in controls. Within the ASD group only, CBD also significantly altered vermal FC with several of its subcortical (striatal) and cortical targets, but did not affect fusiform FC with other regions in either group. CONCLUSION : Our results suggest that, especially in ASD, CBD alters regional fALFF and FC in/between regions consistently implicated in ASD. Future studies should examine if this affects the complex behaviours these regions modulate.

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14. Protic D, Salcedo-Arellano MJ, Dy JB, Potter LA, Hagerman RJ. New Targeted Treatments in Fragile X Syndrome. Curr Pediatr Rev ;2019 (Jun 25)

Fragile X Syndrome (FXS) is the most common cause of inherited intellectual disability with prevalence rates estimated at 1:5,000 males and 1:8,000 females. The expansion of >200 Cytosine Guanine Guanine (CGG) repeats in the 5’ untranslated region of the Fragile X Mental Retardation 1 (FMR1) gene results in transcriptional silencing on the FMR1 gene with subsequent reduced or absent fragile X mental retardation protein (FMRP), an RNA binding protein involved in the maturation and elimination of synapses. In addition to intellectual disability, common features of FXS are behavioral problems, autism, language deficits and atypical physical features. There are still no currently approved curative therapies for FXS, and clinical management continues to focus on symptomatic treatment of comorbid behaviors and psychiatric problems. Here we discuss several targeted treatments for FXS that are clinically available at present and the data that suggest that these medications can be helpful for those with FXS.

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15. Silva C, Jover C, Da Fonseca D, Esteves F, Deruelle C. Acting on observed social exclusion and pro-social behaviour in autism spectrum disorder. Autism ;2019 (Jun 25):1362361319857578.

Humans are commonly motivated towards cooperation and prosociality. In this study, we examined this motivational predisposition in autistic individuals. Using an adaptation of the Cyberball paradigm, we investigated subsequent pro-social behaviour after witnessing social exclusion. Participants witnessed and played a series of Cyberball games, rated their affective state and valued emotional faces with respect to their approachability. Results showed that participants from both groups were aware of the social exclusion. However, while neurotypically developing participants engaged in pro-social behaviour in reaction to the exclusion, autistic participants showed less alterations, in terms of either behaviour or affective state. The current findings suggest a distinct motivational drive and processing of social reward stimuli in autism, which may result in behavioural responses divergent from typical development when engaging in the social world.

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16. Slomski A. Wearable Device Promotes Socialization in Kids With Autism. Jama ;2019 (Jun 25) ;321(24):2396.

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17. Spisak T, Roman V, Papp E, Kedves R, Saghy K, Csolle CK, Varga A, Gajari D, Nyitrai G, Spisak Z, Kincses ZT, Levay G, Lendvai B, Czurko A. Purkinje cell number-correlated cerebrocerebellar circuit anomaly in the valproate model of autism. Sci Rep ;2019 (Jun 25) ;9(1):9225.

While cerebellar alterations may play a crucial role in the development of core autism spectrum disorder (ASD) symptoms, their pathophysiology on the function of cerebrocerebellar circuit loops is largely unknown. We combined multimodal MRI (9.4 T) brain assessment of the prenatal rat valproate (VPA) model and correlated immunohistological analysis of the cerebellar Purkinje cell number to address this question. We hypothesized that a suitable functional MRI (fMRI) paradigm might show some altered activity related to disrupted cerebrocerebellar information processing. Two doses of maternal VPA (400 and 600 mg/kg, s.c.) were used. The higher VPA dose induced 3% smaller whole brain volume, the lower dose induced 2% smaller whole brain volume and additionally a focal gray matter density decrease in the cerebellum and brainstem. Increased cortical BOLD responses to whisker stimulation were detected in both VPA groups, but it was more pronounced and extended to cerebellar regions in the 400 mg/kg VPA group. Immunohistological analysis revealed a decreased number of Purkinje cells in both VPA groups. In a detailed analysis, we revealed that the Purkinje cell number interacts with the cerebral BOLD response distinctively in the two VPA groups that highlights atypical function of the cerebrocerebellar circuit loops with potential translational value as an ASD biomarker.

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