Pubmed du 14/06/22

Pubmed du jour

1. Black MH, McGarry S, Churchill L, D’Arcy E, Dalgleish J, Nash I, Jones A, Tse TY, Gibson J, Bölte S, Girdler S. Considerations of the built environment for autistic individuals: A review of the literature. Autism;2022 (Jun 13):13623613221102753.

Factors related to the interiors of buildings, including the layout of rooms, colours, smells, noises, temperature, ventilation, colour and clutter, among other things, can change the way we interact with our environment and the people around us. Autistic individuals can have differences in processing sensory information and may find aspects of the built environment (BE) over-whelming and difficult to navigate. We reviewed the existing literature exploring the BE and autism. This study found that it is possible to make changes to the BE to create more inclusive and friendly environments for everyone, including autistic individuals. Findings from this study provide clear recommendations that can be used by interior designers, architects, builders, and clinical practitioners to make a positive difference. Key recommendations include using simple spatial layouts, compartmentalising and zoning spaces into specific activity sections and providing retreat spaces. The thoughtful placement of windows and blinds and the installation of dimmable lights, for example, will allow users to manage or reduce sensory over-stimulation caused by lights. Similarly, we recommend creating soundproofing and sound absorbent materials to reduce background noise and sound levels. We also recommend using neutral or simple colour palettes and restrained use of patterns. Finally, and most importantly, the BE needs to be flexible and adaptable to meet the unique needs of each person. This study provides a starting point for design guidelines and recommendations towards making a difference to the everyday experiences of the interiors of buildings.

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2. Connacher R, Williams M, Prem S, Yeung PL, Matteson P, Mehta M, Markov A, Peng C, Zhou X, McDermott CR, Pang ZP, Flax J, Brzustowicz L, Lu CW, Millonig JH, DiCicco-Bloom E. Autism NPCs from both idiopathic and CNV 16p11.2 deletion patients exhibit dysregulation of proliferation and mitogenic responses. Stem Cell Reports;2022 (Jun 14);17(6):1380-1394.

Neural precursor cell (NPC) dysfunction has been consistently implicated in autism. Induced pluripotent stem cell (iPSC)-derived NPCs from two autism groups (three idiopathic [I-ASD] and two 16p11.2 deletion [16pDel]) were used to investigate if proliferation is commonly disrupted. All five individuals display defects, with all three macrocephalic individuals (two 16pDel, one I-ASD) exhibiting hyperproliferation and the other two I-ASD subjects displaying hypoproliferation. NPCs were challenged with bFGF, and all hyperproliferative NPCs displayed blunted responses, while responses were increased in hypoproliferative cells. mRNA expression studies suggest that different pathways can result in similar proliferation phenotypes. Since 16pDel deletes MAPK3, P-ERK was measured. P-ERK is decreased in hyperproliferative but increased in hypoproliferative NPCs. While these P-ERK changes are not responsible for the phenotypes, P-ERK and bFGF response are inversely correlated with the defects. Finally, we analyzed iPSCs and discovered that 16pDel displays hyperproliferation, while idiopathic iPSCs were normal. These data suggest that NPC proliferation defects are common in ASD.

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3. Daniel S, Wimpory D, Delafield-Butt JT, Malloch S, Holck U, Geretsegger M, Tortora S, Osborne N, Schögler B, Koch S, Elias-Masiques J, Howorth MC, Dunbar P, Swan K, Rochat MJ, Schlochtermeier R, Forster K, Amos P. Rhythmic Relating: Bidirectional Support for Social Timing in Autism Therapies. Front Psychol;2022;13:793258.

We propose Rhythmic Relating for autism: a system of supports for friends, therapists, parents, and educators; a system which aims to augment bidirectional communication and complement existing therapeutic approaches. We begin by summarizing the developmental significance of social timing and the social-motor-synchrony challenges observed in early autism. Meta-analyses conclude the early primacy of such challenges, yet cite the lack of focused therapies. We identify core relational parameters in support of social-motor-synchrony and systematize these using the communicative musicality constructs: pulse; quality; and narrative. Rhythmic Relating aims to augment the clarity, contiguity, and pulse-beat of spontaneous behavior by recruiting rhythmic supports (cues, accents, turbulence) and relatable vitality; facilitating the predictive flow and just-ahead-in-time planning needed for good-enough social timing. From here, we describe possibilities for playful therapeutic interaction, small-step co-regulation, and layered sensorimotor integration. Lastly, we include several clinical case examples demonstrating the use of Rhythmic Relating within four different therapeutic approaches (Dance Movement Therapy, Improvisational Music Therapy, Play Therapy, and Musical Interaction Therapy). These clinical case examples are introduced here and several more are included in the Supplementary Material (Examples of Rhythmic Relating in Practice). A suite of pilot intervention studies is proposed to assess the efficacy of combining Rhythmic Relating with different therapeutic approaches in playful work with individuals with autism. Further experimental hypotheses are outlined, designed to clarify the significance of certain key features of the Rhythmic Relating approach.

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4. Gao X, Zhao Y, Wang N, Yang L. Migration modulates the prevalence of ASD and ADHD: a systematic review and meta-analysis. BMC Psychiatry;2022 (Jun 13);22(1):395.

BACKGROUND: Migration has been implicated as a risk factor for autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), but evidence is still limited and inconsistent. We aim to investigate the relationship between migration status and risk of ASD and ADHD. METHODS: Electronic databases including PubMed, EMBASE, Web of Science, and PsychINFO were searched to identify observational studies on this topic, from inception to February 2021. Random-effects meta-analysis models were used to pool the summary odds ratio (OR) and 95% confidence interval (95% CI), and subgroup analyses were conducted to detect possible discrepancies in associations. Certainty of evidence was assessed as per the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) guidelines. RESULTS: A total of 13 studies (6,532,546 participants) for ASD, five studies (2,875,070 participants) for ADHD, and six studies (31,158 participants) for hyperactivity were included. Overall, the pooled results indicated that migration was associated with increased risk of ASD (pooled OR: 1.32; 95% CI: 1.07-1.63; P for Z test = 0.010), but no association was found between migration and ADHD (pooled OR: 0.84; 95% CI: 0.53-1.32; P for Z test = 0.452) or hyperactivity (pooled standardized mean difference: -0.073; 95% CIs: - 0.383-0.236; P for Z test = 0.642). Subgroup analyses further demonstrated that maternal migration was ASD risk factor (pooled OR: 1.49; 95% CI: 1.19-1.87), and migrant children were more likely to develop ASD with comorbid intellectual disability (ID) (pooled OR: 1.21, P for interaction = 0.006) than ASD without ID. After standardized the origin of migrants, European migrant children from Americas were at higher risk of ASD and ADHD (pooled OR were 4.13 and 1.26), and increased ASD risk was also observed in African children (pooled OR: 2.72). The GRADE of evidence was very low. CONCLUSIONS: Maternal migration is a risk factor for ASD, and migrant ASD children are more likely comorbid ID. The role of migration on ADHD remains controversial, more studies are needed to assess the association between migration status and ADHD. Health care practitioners should consider screening and providing extra resources for migrant children.

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5. Garvey CC, Ferguson JL, Milne C, Cihon JH, Leaf JB, Leaf R, McEachin J, Schulze K. Comparing In-View to Out-of-View Stimulus Arrangements When Teaching Receptive Labels for Children Diagnosed With Autism Spectrum Disorder. Behav Anal Pract;2022 (Jun);15(2):475-484.

One common best practice recommendation for teaching receptive labels to individuals diagnosed with autism spectrum disorder is for the stimulus array to be arranged outside of the view of the learner. Another strategy that may have benefits would be to arrange the stimuli in view of the learner. The purpose of this study was to compare the relative effectiveness and efficiency of arranging the stimulus array in view versus out of view of the learner when teaching receptive labels to three children diagnosed with autism spectrum disorder. The results of an adapted alternating-treatments design demonstrated that both conditions were effective, and all participants reached the mastery criterion on all training sets. However, the in-view condition was more, or equally, efficient with respect to sessions to mastery when compared to the out-of-view condition. The results are discussed with respect to clinical and research implications for best practice recommendations related to teaching receptive language.

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6. Gross C, Banerjee A, Tiwari D, Longo F, White AR, Allen AG, Schroeder-Carter LM, Krzeski JC, Elsayed NA, Puckett R, Klann E, Rivero RA, Gourley SL, Bassell GJ. Correction to: Isoform-selective phosphoinositide 3-kinase inhibition ameliorates a broad range of fragile X syndrome-associated deficits in a mouse model. Neuropsychopharmacology;2022 (Jun 14)

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7. Haigh SM, Brosseau P, Eack SM, Leitman DI, Salisbury DF, Behrmann M. Hyper-Sensitivity to Pitch and Poorer Prosody Processing in Adults With Autism: An ERP Study. Front Psychiatry;2022;13:844830.

Individuals with autism typically experience a range of symptoms, including abnormal sensory sensitivities. However, there are conflicting reports on the sensory profiles that characterize the sensory experience in autism that often depend on the type of stimulus. Here, we examine early auditory processing to simple changes in pitch and later auditory processing of more complex emotional utterances. We measured electroencephalography in 24 adults with autism and 28 controls. First, tones (1046.5Hz/C6, 1108.7Hz/C#6, or 1244.5Hz/D#6) were repeated three times or nine times before the pitch changed. Second, utterances of delight or frustration were repeated three or six times before the emotion changed. In response to the simple pitched tones, the autism group exhibited larger mismatch negativity (MMN) after nine standards compared to controls and produced greater trial-to-trial variability (TTV). In response to the prosodic utterances, the autism group showed smaller P3 responses when delight changed to frustration compared to controls. There was no significant correlation between ERPs to pitch and ERPs to prosody. Together, this suggests that early auditory processing is hyper-sensitive in autism whereas later processing of prosodic information is hypo-sensitive. The impact the different sensory profiles have on perceptual experience in autism may be key to identifying behavioral treatments to reduce symptoms.

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8. Hessl D, Rosselot H, Miller R, Espinal G, Famula J, Sherman SL, Todd PK, Cabal Herrera AM, Lipworth K, Cohen J, Hall DA, Leehey M, Grigsby J, Weber JD, Alusi S, Wheeler A, Raspa M, Hudson T, Sobrian SK. The International Fragile X Premutation Registry: building a resource for research and clinical trial readiness. J Med Genet;2022 (Jun 14)

FMR1 premutation cytosine-guanine-guanine repeat expansion alleles are relatively common mutations in the general population that are associated with a neurodegenerative disease (fragile X-associated tremor/ataxia syndrome), reproductive health problems and potentially a wide range of additional mental and general health conditions that are not yet well-characterised. The International Fragile X Premutation Registry (IFXPR) was developed to facilitate and encourage research to better understand the FMR1 premutation and its impact on human health, to facilitate clinical trial readiness by identifying and characterising diverse cohorts of individuals interested in study participation, and to build community and collaboration among carriers, family members, researchers and clinicians around the world. Here, we describe the development and content of the IFXPR, characterise its first 747 registrants from 32 countries and invite investigators to apply for recruitment support for their project(s). With larger numbers, increased diversity and potentially the future clinical characterisation of registrants, the IFXPR will contribute to a more comprehensive and accurate understanding of the fragile X premutation in human health and support treatment studies.

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9. Jonkman KM, Back E, Begeer S. Predicting intervention use in autistic children: Demographic and autism-specific characteristics. Autism;2022 (Jun 13):13623613221102748.

Autism is a condition that is characterised by social communication difficulties and restrictive and repetitive behaviours or interests. Autism can present in many different ways and various interventions are available. Some interventions are conventional, and they are recommended to be used for children with autism (guideline therapies) or for other disorders such as anxiety or attention-deficit hyperactivity disorder (mainstream therapies or medication), while others are less conventional (other therapies or medication, they are discouraged, unknown or alternative). Little is known about who chooses which intervention. This study found that most autistic children use some kind of intervention. Children who attend special education or have an additional diagnosis (other than autism) tend to receive more therapies, while children with a lower IQ receive fewer therapies. Older children, children with a higher IQ and girls are more likely to use conventional (mainstream or guideline) therapies. Children whose parents have a lower educational level are more likely to have used conventional medication. Whereas, children with more sensory issues (e.g. sensitivity to sound, smell or movement) were more likely to have used unconventional medication. This study found that other autism-related characteristics such as the number of autism symptoms, social skills and repetitive and restrictive behaviours were not related to the interventions used. More treatments focussed on multiple problems should be available for children with autism who have additional difficulties.

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10. Joshi G, Wilens TE. Pharmacotherapy of Attention-Deficit/Hyperactivity Disorder in Individuals with Autism Spectrum Disorder. Child Adolesc Psychiatr Clin N Am;2022 (Jul);31(3):449-468.

Attention-deficit/hyperactivity disorder (ADHD) is the most frequent comorbid disorder that is observed at a higher rate and with greater morbidity in higher intellectually functioning populations with autism. Up to 85% of the populations with autism and 15% of individuals with ADHD suffer from a reciprocal comorbidity that is highly under-recognized in intellectually capable populations. Limited empirical evidence is available on the response of anti-ADHD agents in autism populations with ADHD. In autism spectrum disorder (ASD) populations, response to methylphenidate for the treatment of hyperactivity is worse than typically expected in the presence of the intellectual disability. The anti-ADHD response to atomoxetine in autism populations is worse than typically expected although tolerability is similar to that observed in the typicals. The hyperactivity response to guanfacine treatment in predominantly intellectually impaired populations with ASD is as robust as observed in the typicals although tolerability was worse than typically expected. Further trials are warranted to document the extent of atypical anti-ADHD response in intellectually capable populations with autism.

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11. King G, Smart E, Bowman L, Pinto M. Social participation interventions targeting relational outcomes for young people with physical and developmental disabilities: an umbrella review and narrative synthesis. Disabil Rehabil;2022 (Jun 12):1-14.

Purpose: To synthesize knowledge about social participation interventions targeting relational outcomes for young people with physical and developmental disabilities.Method: An umbrella review with a narrative synthesis was conducted to integrate findings of review articles examining social participation interventions targeting relational outcomes (e.g., peer interaction and friendships). Six databases were searched to identify reviews published between 2010 and 2021.Results: Five reviews were identified, examining participation interventions, social/community integration interventions, recreational sport programs, online peer mentorship programs, and augmentative and alternative communication interventions to promote social interaction with peers. Interventions associated with improvements in relational outcomes included group-based programs, programs involving personalized goals, arts-based programs, and multi-component social communication interventions. Recommendations for future research included better description of interventions to identify active ingredients and key mechanisms, measurement of participants’ experiences, and the need for interventions to be aligned with the nature of the outcomes examined. Preliminary intervention principles are proposed to guide the design of social participation interventions: individualizing, contextualizing, and immersion in social settings.Conclusions: There are multiple pathways by which to influence the relational outcomes of young people with disabilities. There are implications for the design of social participation interventions based on an ecological/experiential and relational perspective.IMPLICATIONS FOR REHABILITATIONImprovements in relational outcomes are associated with participation in group-based programs, programs involving personalized goals, arts-based programs, and multi-component social communication interventions.Three evidence-informed principles can help guide the design of social participation interventions: (1) personalizing, (2) contextualizing, and (3) immersion in social settings.Greater attention to aligning the nature of intervention with desired outcomes is needed to more effectively measure and promote relational outcomes.

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12. Kiyono T, Ando S, Morishima R, Fujikawa S, Kanata S, Morimoto Y, Endo K, Yamasaki S, Usami S, Hiraiwa-Hasegawa M, Nishida A, Kasai K. Sex-based differences in the longitudinal association between autistic traits and positive psychotic experiences in adolescents: A population-based cohort study. Schizophr Res;2022 (Jun 10);246:1-6.

Previous reports have suggested a cross-sectional association between autistic traits and psychotic experiences (PEs) in adolescents. However, while both autistic traits and PEs show sex-related differences, no studies have directly assessed whether such differences exist in the longitudinal association between autistic traits and PEs. Using a population-based adolescent cohort sample (n = 3007), we tested whether the longitudinal association between autistic traits and positive PEs was affected by sex-based differences using regression analyses. Autistic traits were assessed at 12 years old (timepoint 1 [T1]), and PEs were assessed at 12 and 14 years old (T1 and T2). Subsequently, we tested whether subdomains of autistic traits (difficulties in social interaction, communication, imagination, attention to detail, and attention switching) were associated with subtypes of PEs (auditory hallucinations, visual hallucinations, and delusions) using structural equation modeling, after controlling for PEs at T1, socio-economic status, school performance and parents’ psychiatric disorders. After controlling for PEs at T1, we did not find any associations between autistic traits at T1 and PEs at T2 in both sexes. There was no significant positive or negative association between all subdomains of autistic traits and subtypes of PEs in both sexes. Autistic traits do not seem to predict future PEs in general adolescents regardless of sex.

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13. Li J, Wang H, Qing W, Liu F, Zeng N, Wu F, Shi Y, Gao X, Cheng M, Li H, Shen W, Meng F, He Y, Chen M, Li Z, Zhou H, Wang Q. Congenitally underdeveloped intestine drives autism-related gut microbiota and behavior. Brain Behav Immun;2022 (Jun 14)

Autism spectrum disorder (ASD) is a neurological and developmental disorder accompanied by gut dysbiosis and gastrointestinal symptoms in most cases, while how autism-related gut microbiota occurs and its relationship with intestinal dysfunction in ASD remains unclear. Using a valproic acid (VPA)-induced ASD mouse model, we showed a congenitally immature intestine of VPA-exposed mice accompanied by prominent oxidative stress and inflammation. Of note, the gut microbiota composition of VPA-exposed mice resembled that of control mice within 24 h after birth; however, their gut microbiota compositions differed on postnatal days 7 and 21. Oral administration of superoxide dismutase (SOD) to attenuate intestinal oxidative stress either before weaning or during juvenile restored the autism-associated gut microbiota, leading to the amelioration of autism-related behaviors. These findings collectively suggest the congenitally underdeveloped intestine as an early driving force shaping the autism-associated gut microbiota and host neurodevelopment through enhancing oxidative stress.

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14. Liu X, Wang Z, Zhang X, Zhang D, Yang Q, Hu P, Li F. LncRNA MEG3 activates CDH2 expression by recruitment of EP300 in valproic acid-induced autism spectrum disorder. Neurosci Lett;2022 (Jun 11);783:136726.

LncRNAs partake in the biological processes contributing to development of autism spectrum disorder (ASD). The aim of the present study is to investigate the effects of lncRNA maternally expressed gene 3 (MEG3) on viability and apoptosis of hippocampal neurons from ASD rats. Rats with ASD were induced using valproic acid (VPA) with normal saline (NS) as control. We performed microarray analysis on hippocampal tissues of NS rats and ASD rats to screen the differentially expressed lncRNAs. MEG3 loss in rats alleviated the impairment of learning and memory abilities induced by VPA, and promoted neuronal viability and inhibited apoptosis. MEG3 could recruit the transcription factor E1A binding protein p300 (EP300) in the nucleus and promote the cadherin 2 (CDH2) expression. CDH2 depletion in rats ameliorated the impairment of learning and memory capacities in ASD rats. After upregulation of CDH2 in neurons with sh-MEG3, we found diminished viability and increased apoptosis in hippocampal neurons of ASD rats. Taken together, MEG3 supports activation of CDH2 via EP300, thus repressing the viability of hippocampal neurons. Therefore, MEG3 upregulation may be partially responsible for the pathogenesis of ASD.

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15. Lv H, Gu X, Shan X, Zhu T, Ma B, Zhang HT, Bambini-Junior V, Zhang T, Li WG, Gao X, Li F. Nanoformulated Bumetanide Ameliorates Social Deficiency in BTBR Mice Model of Autism Spectrum Disorder. Front Immunol;2022;13:870577.

Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder with few medication options. Bumetanide, an FDA-approved diuretic, has been proposed as a viable candidate to treat core symptoms of ASD, however, neither the brain region related to its effect nor the cell-specific mechanism(s) is clear. The availability of nanoparticles provides a viable way to identify pharmacological mechanisms for use in ASD. Here, we found that treatment with bumetanide, in a systemic and medial prefrontal cortex (mPFC) region-specific way, attenuated social deficits in BTBR mice. Furthermore, using poly (ethylene glycol)-poly(l-lactide) (PEG-PLA) nanoparticles [NP(bumetanide)], we showed that the administration of NP(bumetanide) in a mPFC region-specific way also alleviated the social deficits of BTBR mice. Mechanistically, the behavioral effect of NP(bumetanide) was dependent on selective microglia-specific targeting in the mPFC. Pharmacological depletion of microglia significantly reduced the effect of nanoencapsulation and depletion of microglia alone did not improve the social deficits in BTBR mice. These findings suggest the potential therapeutic capabilities of nanotechnology for ASD, as well as the relevant link between bumetanide and immune cells.

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16. Mills WR, Huffman MM, Roosa J, Pitzen K, Boyd R, Schraer B, Poltavski D. Provision of Home-Based Primary Care to Individuals With Intellectual and/or Developmental Disability Is Associated With a Lower Hospitalization Rate Than a Traditional Primary Care Model. J Am Med Dir Assoc;2022 (Jun 14)

OBJECTIVES: The objective of this study was to determine if providing home-based primary care (HBPC) to individuals with intellectual and/or developmental disabilities (IDDs) was associated with a lower hospitalization rate than a control group receiving traditional primary care. DESIGN AND INTERVENTION: Individuals with IDDs living in supported residential settings in Ohio were offered HBPC. Individuals electing HBPC made up the intervention group. Those who did not opt for HBPC continued to receive traditional primary care services and made up the control group. Hospitalizations were tracked in both groups. SETTING AND PARTICIPANTS: The 757 study participants had IDD diagnoses and received residential support services throughout the study period. METHODS: Annualized hospitalization rate was determined in both groups and was compared using generalized estimating equations while controlling for patients’ age and hospitalization rate in the year prior to the study. RESULTS: The results showed that group membership had a significant effect on the hospitalization rate (Wald χ(2) = 20.71, P < .01). Being in the control group was associated with a 2.12-fold increase in annual hospitalization rate for a given patient. The overall population hospitalization rate was 329 hospitalizations per 1000 per year in the HBPC-receiving individuals and 619 hospitalizations per 1000 per year in the control group. CONCLUSIONS AND IMPLICATIONS: We found that individuals with IDDs receiving HBPC were hospitalized at a lower rate than a control group receiving traditional primary care. Expanding access to HBPC may be a worthwhile priority for organizations that support individuals with IDDs.

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17. Mohan A, Roberts JA. Accommodating Developmental Disabilities in the Social Determinants of Health:: A Brief Inquiry into the Applicability of Metrics to the Lives of Individuals with Developmental Disabilities in Delaware. Dela J Public Health;2022 (May);8(2):50-55.

This commentary outlines the methods and findings of a preliminary study examining the fitness of the Social Determinants of Health in their current conceptualizations for accommodating the specific and general experiences of individuals with developmental disabilities and suggests recommendations for both additional research and policy interventions. The study is based on research conducted with individuals with intellectual and developmental disabilities living in Delaware and other stakeholders working in this community. There is currently extensive literature concerning the validity and importance of including the social determinants of health in healthcare decision-making, but very little research exists around the intersection of developmental disabilities and these determinants. This commentary provides additional detail and added emphasis to calls previously made in this Journal to align social determinants with developmental disabilities and the importance of considering the SDOH in policy measures aimed at supporting this population. The ultimate aim of the work presented here is to explore how the State’s interest in putting the SDOH to work generally can be aligned to accommodate the needs and interests of individuals with I/DD and to identify future research and policy interventions in support of these efforts.

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18. Mutluer T, Aslan Genç H, Özcan Morey A, Yapici Eser H, Ertinmaz B, Can M, Munir K. Population-Based Psychiatric Comorbidity in Children and Adolescents With Autism Spectrum Disorder: A Meta-Analysis. Front Psychiatry;2022;13:856208.

Psychiatric comorbidity in autism spectrum disorder (ASD) is a subject of critical scientific importance, affecting the quality of life, prognosis, and functional outcomes. The prevalence of psychiatric disorders vary considerably according to variables such as index subject characteristics, study setting, sampling frame, diagnostic methods used, as well as country of geographic origin. To date, most studies comprise clinical or treatment referral samples in tertiary care or subjects enrolled in clinical trials and genetic cohort collections. Such samples carry the potential for overestimation of both the frequency and severity of psychiatric comorbidity. A systematic literature search was performed using PubMed and Web of Science databases restricted to population-based study publications in the English between May 1, 2015, and May 31, 2020. A comprehensive keyword list was generated to investigate co-occurrence of psychiatric disorders in children and adolescents with ASD. A wide range of DSM-5 based disorders such as anxiety, mood, ADHD, intellectual disability/intellectual developmental disorder, eating/feeding, gender dysphoria and sleep-wake disorders were assessed. Initial search revealed a total of 1674 articles after removal of duplicates. Two independent researchers conducted a parallel-blinded screening process to identify the eligible studies based on titles and abstracts; 39 studies were analyzed in the current review. The main findings show prevalence estimates of 22.9% (95% CI: 17.7- 29.2) for intellectual disability; 26.2% (22-31) for attention-deficit hyperactivity disorder; 11.1% (8.6-14.1) for anxiety disorders; 19.7% (11.9-30.7) for sleep disorders; 7% (5.2- 9.3) for disruptive disorders; 2% (1.3- 3.1) for bipolar disorders; 2.7% (1.8- 4.2) for depression; 1.8% (0.4-8.7) for obsessive-compulsive disorder; and 0.6% (0.3-1.1) for psychosis. Psychiatric comorbidity in population-based studies is lower than in clinical and referred samples. However, our results also indicate that the frequency of psychiatric comorbidity in children and adolescents with ASD in the population context is considerable, without the influence of referral bias implicit in clinical and treatment samples. There is a need for better targeted diagnostic tools to detect psychiatric comorbidity in children and youth in future population-based studies, as an essential component in providing care as well as new insights into the nature and mechanisms of its underlying associations. SYSTEMATIC REVIEW REGISTRATION: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42021234464].

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19. Park S, Zikopoulos B, Yazdanbakhsh A. Visual Illusion Susceptibility in Autism: A Neural Model. Eur J Neurosci;2022 (Jun 14)

While atypical sensory perception is reported among individuals with autism spectrum disorder (ASD), the underlying neural mechanisms of autism that give rise to disruptions in sensory perception remain unclear. We developed a neural model with key physiological, functional, and neuroanatomical parameters to investigate mechanisms underlying the range of representations of visual illusions related to orientation perception in typically developed (TD) subjects compared to individuals with ASD. Our results showed that two theorized autistic traits, excitation/inhibition imbalance and weakening of top-down modulation, could be potential candidates for reduced susceptibility to some visual illusions. Parametric correlation between cortical suppression, balance of excitation/inhibition, feedback from higher visual areas on one hand, and susceptibility to a class of visual illusions related to orientation perception on the other hand, provide the opportunity to investigate the contribution and complex interactions of distinct sensory processing mechanisms in ASD. The novel approach used in this study can be used to link behavioral, functional, and neuropathological studies, estimate and predict perceptual and cognitive heterogeneity in ASD, and form a basis for the development of novel diagnostics and therapeutics.

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20. Rhinn M, Zapata-Bodalo I, Klein A, Plassat JL, Knauer-Meyer T, Keyes WM. Aberrant induction of p19Arf-mediated cellular senescence contributes to neurodevelopmental defects. PLoS Biol;2022 (Jun);20(6):e3001664.

Valproic acid (VPA) is a widely prescribed drug to treat epilepsy, bipolar disorder, and migraine. If taken during pregnancy, however, exposure to the developing embryo can cause birth defects, cognitive impairment, and autism spectrum disorder. How VPA causes these developmental defects remains unknown. We used embryonic mice and human organoids to model key features of VPA drug exposure, including exencephaly, microcephaly, and spinal defects. In the malformed tissues, in which neurogenesis is defective, we find pronounced induction of cellular senescence in the neuroepithelial (NE) cells. Critically, through genetic and functional studies, we identified p19Arf as the instrumental mediator of senescence and microcephaly, but, surprisingly, not exencephaly and spinal defects. Together, these findings demonstrate that misregulated senescence in NE cells can contribute to developmental defects.

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21. Roberts MY, Sone BJ, Jones M, Grauzer J, Sudec L, Stern YS, Kwok E, Losh M, Kaat A. One size does not fit all for parent-mediated autism interventions: A randomized clinical trial. Autism;2022 (Jun 13):13623613221102736.

Parent-mediated interventions support parents’ use of language facilitation strategies to improve their autistic child’s communication and language development. To improve the effectiveness of parent-mediated interventions, it is important to individualize interventions. This article evaluates how different components of parent-mediated interventions and mothers’ learning styles influence the effectiveness of the intervention. In a randomized clinical trial, mothers were taught to use one of two types of language facilitation strategies: responsive and directive. Mothers’ learning styles were characterized by the Broad Autism Phenotype (BAP) and their natural tendency to use language facilitation strategies before intervention. Findings suggest that it was easier for all mothers (irrespective of learning style) to use responsive strategies compared to directive strategies. In addition, mothers with learning styles that were not consistent with the BAP were more likely to benefit from the intervention if they did not naturally use strategies before the intervention. In contrast, mothers with learning styles that were consistent with the BAP were more likely to benefit from the intervention if they did naturally use strategies before the intervention. Teaching mothers to use responsive strategies results in greater strategy use. Consideration of BAP and mothers’ natural use of language facilitation strategies may inform intervention individualization.

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22. Schröder SS, Danner UN, Spek AA, van Elburg AA. Problematic eating behaviours of autistic women-A scoping review. Eur Eat Disord Rev;2022 (Jun 14)

AIM: Eating and feeding behaviours of autistic individuals and related consequences have been mainly investigated in autistic children or in autistic adults with intellectual disabilities. Behaviours such as food selectivity or food neophobia have been shown to persist into adolescence and adulthood and are associated with aversive consequences. However, much less is known about the eating behaviours of autistic adults without intellectual disabilities, especially those of women. By means of a scoping review, we aim to assess the extent of the scientific literature on what is known about the eating behaviours of these women and the possible consequences of such eating behaviour. METHOD: Medline, Cochrane, PubMed and PsycInfo databases were searched according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: Five studies met the eligibility criteria and were included in this review. Autistic women not only reported high levels of eating behaviour frequently seen in autism spectrum disorders (ASD), but also high levels of disordered eating behaviour, similar to that of women with eating disorders. CONCLUSIONS: Autistic women seem to exhibit high levels of eating behaviour frequently seen in ASD as well as disordered eating behaviour. Future research needs to shed light on what underlies these problematic eating behaviours, in order to help to adapt current treatment modalities to meet the unique needs of these women.

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23. Sheng Z, Liu Q, Cheng C, Li M, Barash J, Kofke WA, Shen Y, Xie Z. Fentanyl induces autism-like behaviours in mice by hypermethylation of the glutamate receptor gene Grin2b. Br J Anaesth;2022 (Jun 11)

BACKGROUND: Environmental factors contribute to autism spectrum disorder. Fentanyl, one of the most widely used opioid analgesics in anaesthesia, can induce neurotoxicity, but its role in autism remains unknown. We determined whether fentanyl induced autism-like behaviours in young mice and the underlying mechanisms. METHODS: Young male and female mice received fentanyl at postnatal days 6, 8, and 10, and performed behavioural tests, including three-chamber social preference, elevated plus maze, grooming behaviour, and open-field test, from postnatal days 30-32. Expression of Grin2b, the gene encoding the GluN2B subunit of the N-methyl-d-aspartate receptor, was assessed in the anterior cingulate cortex of male mice using fluorescence in situ hybridisation histochemistry. We used bisulfite target sequencing to determine Grin2b hypermethylation sites after fentanyl treatment. In the specific activation and rescue experiments, we injected the mu opioid receptor agonist [D-Ala,(2) N-MePhe,(4) Gly-ol]-enkephalin (DAMGO) or Grin2b overexpression lentivirus into the anterior cingulate cortex of male mice. RESULTS: Fentanyl induced autism-like behaviours in both young male and female mice, and downregulated Grin2b expression (0.49-fold [0.08] vs 1.00-fold [0.09]; P<0.01) and GluN2B protein amounts (0.38-fold [0.07] vs 1.00-fold [0.12]; P<0.01) in the anterior cingulate cortex through hypermethylation of Grin2b. The mu-opioid receptor antagonist naloxone and overexpression of Grin2b in anterior cingulate cortex attenuated the fentanyl-induced effects, whereas DAMGO injection into the anterior cingulate cortex induced autism-like behaviours. CONCLUSIONS: These data suggest that fentanyl induces autism-like behaviours in young mice via an epigenetic mechanism. Further research is required to determine possible clinical relevance to autism risk.

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24. Tetnowski JA, Donaher J. Stuttering and Autism Spectrum Disorders: Assessment and Treatment. Semin Speech Lang;2022 (Mar);43(2):117-129.

Dual diagnoses of autism spectrum disorders (ASDs) and stuttering have been reported in the literature, but little is known about how often they co-occur, the best practices for assessment, and even less about intervention. In this article, we gathered the data available on these issues and compiled and analyzed the sparse findings to offer suggestions for assessment and treatment. This article begins with a glossary of terms to promote consistency and understanding. Next, suggestions for assessment are provided along with a work sheet to document fluency breakdowns and monitor change. Suggestions for language and cognitive issues are also provided with a sample worksheet. Finally, an outline and explanation of stuttering/fluency goals for clients with these dual diagnoses are included. Case studies of two individuals who stutter and are diagnosed with ASD are presented to provide exemplars of how to assess and treat individuals with these dual diagnoses. Caveats on how to work with individuals with ASD and fluency disorders, based on our current understanding, are presented in the conclusion.

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25. Thom RP, Palumbo ML, Keary CJ, Hooker JM, McDougle CJ, Ravichandran CT. Prevalence and factors associated with overweight, obesity, and hypertension in a large clinical sample of adults with autism spectrum disorder. Sci Rep;2022 (Jun 13);12(1):9737.

Adults with autism spectrum disorder (ASD) are at risk for excess bodyweight and hypertension, yet the prevalence of and clinical predictors for these health conditions remain unknown. The objective of this study was to assess the prevalence of overweight, obesity, and hypertension in a large clinical sample of adults with a confirmed diagnosis of ASD and to examine potential clinical predictors. This retrospective chart review study included adult subjects (≥ 20 years) with ASD who had been seen within the past 5 years at a multidisciplinary developmental disorders clinic. Data collected from the electronic health record included age, sex, race and ethnicity, cognitive ability, language ability, body mass index (BMI), hypertension, and use of second generation antipsychotic medications (SGAs). Of 622 adults with a confirmed diagnosis of ASD potentially eligible for the study, 483 (78%) had one or more notes in their records from the past 5 years. Those with recent notes were 23% female, 89% White, and had a mean (SD) age of 28.1 (7.1) years. Overall prevalence estimates for adults represented by this predominantly male, White, and young clinical sample were 28% (95% CI 24%, 32%) for overweight (BMI 25-29.9 kg/m(2)), 35% (95% CI 31%, 40%) for obesity (≥ 30 kg/m(2)), and 11% (95% CI 9%, 15%) for hypertension. Controlling for age and sex, intellectual disability (ID) was significantly associated with BMI (p = 0.003) but not hypertension (p = 0.69); those with moderate or more severe ID had a mean BMI that was 2.26 kg/m(2) (95% CI 0.96, 3.57) lower than those with no ID. Controlling for age and sex, neither language ability, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) subtype of autism, nor past or current use of SGAs were significantly associated with BMI or hypertension. The study identified a high prevalence of overweight and obesity in adults with ASD consistent with the prevalence of these medical comorbidities in the U.S. population.

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26. Thomas TR, Koomar T, Casten LG, Tener AJ, Bahl E, Michaelson JJ. Clinical autism subscales have common genetic liabilities that are heritable, pleiotropic, and generalizable to the general population. Transl Psychiatry;2022 (Jun 13);12(1):247.

The complexity of autism’s phenotypic spectra is well-known, yet most genetic research uses case-control status as the target trait. It is undetermined if autistic symptom domain severity underlying this heterogeneity is heritable and pleiotropic with other psychiatric and behavior traits in the same manner as autism case-control status. In N = 6064 autistic children in the SPARK cohort, we investigated the common genetic properties of twelve subscales from three clinical autism instruments measuring autistic traits: the Social Communication Questionnaire (SCQ), the Repetitive Behavior Scale-Revised (RBS-R), and the Developmental Coordination Disorder Questionnaire (DCDQ). Educational attainment polygenic scores (PGS) were significantly negatively correlated with eleven subscales, while ADHD and major depression PGS were positively correlated with ten and eight of the autism subscales, respectively. Loneliness and neuroticism PGS were also positively correlated with many subscales. Significant PGS by sex interactions were found-surprisingly, the autism case-control PGS was negatively correlated in females and had no strong correlation in males. SNP-heritability of the DCDQ subscales ranged from 0.04 to 0.08, RBS-R subscales ranged from 0.09 to 0.24, and SCQ subscales ranged from 0 to 0.12. GWAS in SPARK followed by estimation of polygenic scores (PGS) in the typically-developing ABCD cohort (N = 5285), revealed significant associations of RBS-R subscale PGS with autism-related behavioral traits, with several subscale PGS more strongly correlated than the autism case-control PGS. Overall, our analyses suggest that the clinical autism subscale traits show variability in SNP-heritability, PGS associations, and significant PGS by sex interactions, underscoring the heterogeneity in autistic traits at a genetic level. Furthermore, of the three instruments investigated, the RBS-R shows the greatest evidence of genetic signal in both (1) autistic samples (greater heritability) and (2) general population samples (strongest PGS associations).

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27. Tsuji Y, Matsumoto S, Saito A, Imaizumi S, Yamazaki Y, Kobayashi T, Fujiwara Y, Omori M, Sugawara M. Mediating role of sensory differences in the relationship between autistic traits and internalizing problems. BMC Psychol;2022 (Jun 13);10(1):148.

BACKGROUND: Sensory differences are related to the autistic traits, and previous studies have shown a positive correlation between sensory differences and internalizing problems. In this study, we hypothesized that sensory differences and suffering due to sensory differences mediates the relationships between autistic traits and internalizing problems. METHODS: A total of 346 female Japanese university students completed questionnaires regarding their autistic traits, suffering due to sensory differences, and internalizing problems. Moreover, 114 participants completed a questionnaire related to sensory differences. RESULTS: Autistic traits were correlated with Low Registration and Sensation Avoiding. These sensory differences were also correlated with suffering due to sensory differences and internalizing problems. Moreover, path analysis indicated that the higher the suffering due to Low Registration and Sensation Avoiding was, the greater the internalizing problems in those who showed these sensory differences. CONCLUSIONS: Female university students with serious suffering due to sensory differences may need support in managing their suffering and internalizing problems. Further research will help suggest support that these people require, at school and elsewhere.

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28. Wang SH, Zhang HT, Zou YY, Cheng SM, Zou XB, Chen KY. Efficacy and moderating factors of the Early Start Denver Model in Chinese toddlers with autism spectrum disorder: a longitudinal study. World J Pediatr;2022 (Jun 13)

BACKGROUND: Several studies have shown the effectiveness of the Early Start Denver Model (ESDM), but few studies have explored the long-term efficacy of ESDM. This study aimed to explore the efficacy and moderating factors of ESDM in Chinese toddlers with autism spectrum disorder (ASD) in a longitudinal way. METHODS: A total of 60 toddlers with ASD were recruited and randomly divided into two groups: ESDM group all received 24 weeks intervention; Control group were waiting for intervention. Baseline assessment (T0) was conducted before intervention, including Gesell Developmental Scale (GDS) and Psycho-educational Profile-3rd Edition (PEP-3). All toddlers with ASD were examined in the first assessment (T1) at 6 months and in the second assessment (T2) at 12 months. RESULTS: In T1 assessment, the increments in speech and personal communication development quotient in GDS were significantly larger in the ESDM group than in the control group (P = 0.010, 0.047). In T2 assessment, the ESDM group had higher elevation in cognitive verbal/preverbal (CVP), social reciprocity and characteristic verbal behaviors assessed by PEP-3 (P = 0.021, 0.046, 0.014). In addition, the severity of stereotyped behavior was negatively associated with improvement in CVP. Family income was positively associated with improvement in speech and CVP (all P < 0.05). CONCLUSIONS: ESDM can effectively improve speech and communication in toddlers with ASD after 24-week intervention. More importantly, ESDM can promote cognition and social interaction and can reduce stereotyped verbal behavior in toddlers with ASD in longitudinal observation. The severity of stereotyped behavior and family ecological factors may be considered as affecting the efficacy of ESDM.

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29. Yamamoto S, Isawa S. The Efficacy of Performance Feedback on the Social Niceties of Adolescents With Autism Spectrum Disorder. Behav Anal Pract;2022 (Jun);15(2):466-474.

Individuals with autism spectrum disorder typically experience difficulties in finding and continuing to work. To address this issue, researchers have developed various interventions for these individuals to acquire social skills in the workplace. Social niceties such as saying « excuse me » and « thank you for your time » are especially important to continue work. Interventions that combine various procedures have been shown to be effective, but studies have also pointed out the importance of resource and time efficiency. Thus, this study examined the efficacy of performance feedback alone on the acquisition of these two forms ofsocial niceties. As a result, all participants quickly acquired social niceties.

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30. Zhang Q, Li Q, Yang T, Chen L, Dai Y, Wei H, Wang K, Jia F, Wu L, Hao Y, Li L, Zhang J, Ke X, Yi M, Hong Q, Chen J, Fang S, Wang Y, Wang Q, Jin C, Li T. Neurodevelopmental domain characteristics and their association with core symptoms in preschoolers with autism spectrum disorder in China: a nationwide multicenter study. BMC Psychiatry;2022 (Jun 13);22(1):393.

BACKGROUND: Autism spectrum disorder (ASD) is a group of clinically heterogenic neurodevelopmental disorders, with intellectual disability being one of its common comorbidities. No large-sample, multicenter study has focused on the neurodevelopmental aspect of preschoolers with ASD. This study investigated the neurodevelopmental characteristics of preschoolers with ASD in China and explored the association between them and the core symptoms. METHODS: We enrolled 1019 ASD preschoolers aged 2-7 years old from 13 cities around China between May 2018 and December 2019, and used the revised Children Neuropsychological and Behavior Scale (CNBS-R2016) to assess their neurodevelopment. Their autistic core behaviors were evaluated based on their Social Responsiveness Scale (SRS), Autism Behavior Checklist (ABC), Child Autism Rating Scale (CARS), and communication warning behavior (CWB) scores in the CNBS-R2016. RESULTS: Based on general developmental quotient (GQ) < 70, 68.4% of the preschoolers with ASD had a developmental delay (DD), rated mild in 32.7% of them. The highest DD rate (> 70%) was found in language and personal-social skills, followed by fine motor skills (68.9%). Gross motor skills had the lowest DD rate (34.0%). We found that fine motor, language, and personal-social developmental quotients (DQs) were significantly lower than gross motor skills in no DD (GQ > 70), mild DD (GQ 55-69), and moderate and below DD groups (GQ ≤ 54). Furthermore, the DQs for language and personal-social skills were significantly lower than for gross and fine motor skills in both DD groups. The ABC, SRS, CARS, and CWB scores in the no DD group were the lowest, moderate in the mild DD group, and highest in the moderate and below DD group. Besides, negative correlations were found between the DQs of the four domains and the ABC, SRS, CARS, and CWB scores, of which the language and personal-social skills DQs had the strongest correlations. CONCLUSIONS: Preschoolers with ASD had unbalanced neurodevelopment domain patterns and their neurodevelopmental levels were negatively correlated with the autism core symptoms. Hence, pediatricians should actively evaluate the neurodevelopment of children with ASD and conduct long-term follow-up during their early childhood to promote early diagnosis and develop personalized intervention plans. TRIAL REGISTRATION: ChiCTR2000031194 , registered on 03/23/2020.

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