1. Bonnard-Couton V, Lubrano S, Tosello AL, Serret S, Askenazy-Gittard F. {{[Autism spectrum disorders, a pilot parent-child unit]}}. {Soins Pediatrie, puericulture}. 2018; 39(305): 37-41.
Today, it is possible to work on the developmental trajectory of autism spectrum disorders. Due to brain plasticity, the earlier the treatment, the greater the benefits. A pilot unit has been created in a day hospital, offering a quick and intensive approach, between 18 and 36 months, focused on parental skills.
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2. Brignell A, May T, Morgan AT, Williams K. {{Predictors and growth in receptive vocabulary from 4 to 8 years in children with and without autism spectrum disorder: A population-based study}}. {Autism : the international journal of research and practice}. 2018: 1362361318801617.
Few studies have examined growth and predictors of receptive vocabulary in children with autism spectrum disorder. Here we aimed to compare receptive vocabulary from 4 to 8 years and identify predictors of receptive vocabulary, at 8 years, in children with and without autism spectrum disorder. Participants were drawn from a nationally representative population-based study with two cohorts recruited at birth (N = 4983) and kindergarten (N = 5107). Receptive vocabulary growth was compared for children with and without autism spectrum disorder at 4 (n = 188, n = 7136), 6 (n = 215, n = 7297) and 8 (n = 216, n = 7408) years. Predictors of receptive vocabulary were analysed. Estimated mean receptive vocabulary scores for children without autism spectrum disorder were 2.3 units higher than the autism spectrum disorder group across three time points. This difference was significant (p = 0.004; 95% confidence interval 0.769-3.927). Children with and without autism spectrum disorder progressed at a similar pace. There was no significant difference between the proportions of children with and without autism spectrum disorder who had stable, improving and declining trajectories. Age was the only significant predictor of greater receptive vocabulary growth in children with autism spectrum disorder. Baseline receptive language and nonverbal IQ were significant predictors of receptive vocabulary ability at 8 years. These findings inform prognostic advice given to families on language outcomes.
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3. Canali G, Goutebroze L. {{CNTNAP2 Heterozygous Missense Variants: Risk Factors for Autism Spectrum Disorder and/or Other Pathologies?}}. {Journal of experimental neuroscience}. 2018; 12: 1179069518809666.
The CNTNAP2 gene has been proposed to be one of the major susceptibility genes for neurodevelopmental disorders, in which numerous heterozygous missense variants have been identified in patients with autism spectrum disorder (ASD). The contribution of these variants to the manifestations of ASD is however highly controversial because numerous heterozygous missense variants have also been identified in control subjects. In a recent study, we set up a sensitive developmental in vitro cell assay to clarify the potential functional impact of these variants in a heterozygous Cntnap2 background relevant for CNTNAP2 heterozygosity in patients with ASD. We showed that the cell adhesion glycoprotein Caspr2 encoded by CNTNAP2 plays a dose-dependent role in cortical neuron axon growth and provided a proof of principle that some variants have functional consequences, either a loss of function or a dominant-negative effect. This indicates that phenotypes mimicking CNTNAP2 heterozygous and homozygous null mutation may exist in humans. Our observations further suggest that more variants than originally expected could be functionally deleterious and induce a high heterogeneity of phenotypes at the scale of the whole brain. This raises the interesting possibility that CNTNAP2 heterozygous missense variants could define an overall endophenotype shaping a risk for ASD and questions whether, beyond ASD, the variants could contribute to the development of other neurodevelopmental disorders and/or genetically less complex pathologies.
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4. Ceranoglu TA, Wozniak J, Fried R, Galdo M, Hoskova B, Fong MD, Biederman J, Joshi G. {{A Retrospective Chart Review of Buspirone for the Treatment of Anxiety in Psychiatrically Referred Youth with High-Functioning Autism Spectrum Disorder}}. {Journal of child and adolescent psychopharmacology}. 2018.
OBJECTIVES: Anxiety disorders (ADs) are commonly associated with high-functioning Autism Spectrum Disorder (HF-ASD) and often worsen with age. Buspirone is a commonly prescribed anxiolytic drug with a favorable tolerability profile that may offer potential benefits in anxiety management for patients with HF-ASD. This study examines inadequately explored tolerability and effectiveness of buspirone in treating ADs comorbid with high-functioning ASD. METHODS: A retrospective chart review of a 1-year period was conducted in psychiatrically referred population of HF-ASD youth with AD (age 8-17 years) who were treated with buspirone (N = 31). Information on the demographics and treatment history was recorded. Effectiveness was assessed through the Clinical Global Impressions Scale (CGI) severity (CGI-S) and improvement (CGI-I) scores noted by the treating clinician. RESULTS: A total of 31 patients were prescribed buspirone during the determined period, at a mean dose of 41.61 +/- 24.10 mg for an average duration of 272 +/- 125 days. Change in the CGI-S mean scores with treatment suggests an overall improvement in the severity of anxiety symptoms (MT1 = 4.9 +/- 0.7; MT2 = 2.8 +/- 0.87; p < 0.001). Significant improvement in anxiety symptoms (CGI-I Lien vers le texte intégral (Open Access ou abonnement)
5. Cvejic RC, Arnold SRC, Foley KR, Trollor JN. {{Neuropsychiatric profile and psychotropic medication use in adults with autism spectrum disorder: results from the Australian Longitudinal Study of Adults with Autism}}. {BJPsych open}. 2018; 4(6): 461-6.
Background: Children and adolescents with autism spectrum disorder (ASD) are a highly medicated group. Few studies have examined the neuropsychiatric profile and patterns of psychotropic medication use among adults with ASD. Aims: To describe and compare the neuropsychiatric profile and psychotropic medication use in a cohort of adults with ASD and non-autistic controls. Method: Baseline data from a survey-based, longitudinal study of adults with ASD in Australia. Participants were 188 adults with ASD and 115 controls aged 25-80 years. Results: ASD was associated with increased odds of psychotropic medication use even when controlling for the presence of any neurological or psychiatric disorder. There were no corresponding indications for 14.4% of psychotropic medications prescribed to adults with ASD. Conclusions: This study found substantial psychotropic prescribing for adults with ASD. Patterns of psychotropic medication use may reflect prescribing for behavioural indications despite limited evidence to support this practice. Declaration of interest: None.
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6. Dawson G, Campbell K, Hashemi J, Lippmann SJ, Smith V, Carpenter K, Egger H, Espinosa S, Vermeer S, Baker J, Sapiro G. {{Atypical postural control can be detected via computer vision analysis in toddlers with autism spectrum disorder}}. {Scientific reports}. 2018; 8(1): 17008.
Evidence suggests that differences in motor function are an early feature of autism spectrum disorder (ASD). One aspect of motor ability that develops during childhood is postural control, reflected in the ability to maintain a steady head and body position without excessive sway. Observational studies have documented differences in postural control in older children with ASD. The present study used computer vision analysis to assess midline head postural control, as reflected in the rate of spontaneous head movements during states of active attention, in 104 toddlers between 16-31 months of age (Mean = 22 months), 22 of whom were diagnosed with ASD. Time-series data revealed robust group differences in the rate of head movements while the toddlers watched movies depicting social and nonsocial stimuli. Toddlers with ASD exhibited a significantly higher rate of head movement as compared to non-ASD toddlers, suggesting difficulties in maintaining midline position of the head while engaging attentional systems. The use of digital phenotyping approaches, such as computer vision analysis, to quantify variation in early motor behaviors will allow for more precise, objective, and quantitative characterization of early motor signatures and potentially provide new automated methods for early autism risk identification.
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7. Hagerman R, Jacquemont S, Berry-Kravis E, Des Portes V, Stanfield A, Koumaras B, Rosenkranz G, Murgia A, Wolf C, Apostol G, von Raison F. {{Mavoglurant in Fragile X Syndrome: Results of two open-label, extension trials in adults and adolescents}}. {Scientific reports}. 2018; 8(1): 16970.
Fragile X syndrome (FXS) is the most common monogenic cause of inherited intellectual and developmental disabilities. Mavoglurant, a selective metabotropic glutamate receptor subtype-5 antagonist, has shown positive neuronal and behavioral effects in preclinical studies, but failed to demonstrate any behavioral benefits in two 12-week, randomized, placebo-controlled, double-blind, phase IIb studies in adults and adolescents with FXS. Here we report the long-term safety (primary endpoint) and efficacy (secondary endpoint) results of the open-label extensions. Adolescent (n = 119, aged 12-19 years) and adult (n = 148, aged 18-45 years) participants received up to 100 mg bid mavoglurant for up to 34 months. Both extension studies were terminated prematurely due to lack of proven efficacy in the core studies. Mavoglurant was well tolerated with no new safety signal. Five percent of adults and 16.9 percent of adolescents discontinued treatment due to adverse events. Gradual and consistent behavioral improvements as measured by the ABC-CFX scale were observed, which were numerically superior to those seen in the placebo arm of the core studies. These two extension studies confirm the long-term safety of mavoglurant in FXS, but further investigations are required to determine whether and under which conditions the significant preclinical results obtained with mGluR5 inhibition can translate to humans.
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8. Li G, Liu M, Sun Q, Shen D, Wang L. {{Early Diagnosis of Autism Disease by Multi-channel CNNs}}. {Machine learning in medical imaging MLMI (Workshop)}. 2018; 11046: 303-9.
Currently there are still no early biomarkers to detect infants with risk of autism spectrum disorder (ASD), which is mainly diagnosed based on behavior observations at three or four years old. Since intervention efforts may miss a critical developmental window after 2 years old, it is significant to identify imaging-based biomarkers for early diagnosis of ASD. Although some methods using magnetic resonance imaging (MRI) for brain disease prediction have been proposed in the last decade, few of them were developed for predicting ASD in early age. Inspired by deep multi-instance learning, in this paper, we propose a patch-level data-expanding strategy for multi-channel convolutional neural networks to automatically identify infants with risk of ASD in early age. Experiments were conducted on the National Database for Autism Research (NDAR), with results showing that our proposed method can significantly improve the performance of early diagnosis of ASD.
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9. Lin CW, Lin HY, Lo YC, Chen YJ, Hsu YC, Chen YL, Tseng WI, Gau SS. {{Alterations in white matter microstructure and regional volume are related to motor functions in boys with autism spectrum disorder}}. {Progress in neuro-psychopharmacology & biological psychiatry}. 2018.
BACKGROUND: Altered inter-regional structural connectivity related to higher cognitive functions has been commonly reported in individuals with autism spectrum disorder (ASD). However, whether these alterations similarly involve cortico-cerebellar motor circuitries remains largely elusive. METHODS: Using a cross-modality approach accounting for in-scanner motion levels, we investigated white matter (WM) properties in motor circuits of 55 boys with ASD (aged 8-18years) and 68 age-matched typically developing boys. Regional WM volumes in the primary motor, supplementary motor, somatosensory, and cerebellar areas were investigated using voxel-based morphometry. Diffusion spectrum imaging tractography was used to estimate WM integrity of the corticospinal, cortico-ponto-cerebellar (including fronto-ponto-cerebellar and parieto-ponto-cerebellar), and dentato-rubro-thalamo-cortical tracts. The reaction time test in the Cambridge Neuropsychological Test Automated Battery was used to assess motor performances. RESULTS: Boys with ASD had shorter movement time, increased WM volumes in the left somatosensory area, but decreased generalized fractional anisotropy value in the left parieto-ponto-cerebellar tract, compared to controls. A positive correlation between movement time and microstructural properties of the left parieto-ponto-cerebellar tract was found in boys with ASD. CONCLUSIONS: As the first study to demonstrate altered WM properties in the left somatosensory area, and its descending pathway connecting to the cerebellum in ASD, current results may highlight a potential new target of interventions for motor performance in ASD.
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10. Nadig A, Flanagan T, White K, Bhatnagar S. {{Results of a RCT on a Transition Support Program for Adults with ASD: Effects on Self-Determination and Quality of Life}}. {Autism research : official journal of the International Society for Autism Research}. 2018.
Few evidence-based services exist for people with Autism Spectrum Disorder (ASD) as they transition into adulthood, particularly those that foster appreciation of one’s own goals and strengths. We developed a transition service for adults with ASD (without Intellectual Disability), and conducted a randomized controlled trial (RCT) focusing on self-report of Quality of Life and Self-Determination outcomes. Thirty participants aged 18-29 were randomized to immediate or delayed intervention, with 26 participants analyzed after 4 were lost to follow-up. Curriculum was tailored to participants’ self-expressed needs in three areas: social communication, self-determination, and working with others. Groups of four-to-six participants with ASD and two facilitators met weekly for 10 weeks. Positive intervention effects were observed on self-report of Quality of Life; the intervention group scored on average 2 points higher than the control group, 95% CI [-0.2, 3.9]. Positive effects were also observed on the Self Determination Scale (Interpersonal Cognitive Problem-Solving subdomain), where the intervention group scored 2 points higher than control group 95% CI [0.082, 3.4]. In addition, participants rated skills targeted by the curriculum 6 points higher after versus before intervention, 95% CI [3.7, 8.6]. This was echoed by a subset of parents rating their child’s skills as seven points higher after versus before intervention, 95% CI [1, 14]. Autism Research 2018. (c) 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: These findings indicate that it is possible to increase Self-Determination and subjective Quality of Life in adults with ASD through a brief group-format service, and provide a model for doing so. Self-Determination abilities are linked to improved adult outcomes in individuals with other disabilities. These often overlooked factors should be incorporated in programming for adults with ASD as they transition to adulthood.
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11. O’Brolchain F. {{Autonomy Benefits and Risks of Assistive Technologies for Persons With Intellectual and Developmental Disabilities}}. {Frontiers in public health}. 2018; 6: 296.
This paper explores the ways in which assistive technologies (ATs) can both promote and undermine the autonomy of Persons with Intellectual and Developmental Disabilities (PIDD). Following an initial discussion of ATs for PIDD, I examine the specific issues of autonomy for PIDD. I outline the ways in which ATs can boost autonomy, of PIDD, focusing on knowledge, authenticity, and liberty. Following that I suggest that ATs are not necessarily beneficial in terms of autonomy and examine ways that they might be used to undermine the autonomy of PIDD, specifically the categories of knowledge, authenticity, and liberty. I conclude by suggesting that the development of ATs requires ethical oversight.
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12. Osorio AAC, Russowsky Brunoni A. {{Transcranial direct current stimulation in children with autism spectrum disorder: a systematic scoping review}}. {Developmental medicine and child neurology}. 2018.
AIM: Our aim was to review available studies which test transcranial direct current stimulation (tDCS) to reduce symptom severity in children with autism spectrum disorder (ASD). METHOD: We performed a systematic scoping review in PubMed and PsychINFO databases for studies employing tDCS in children and adolescents with ASD. RESULTS: We found five studies (two small randomized controlled studies, one experimental study, one quasi-experimental study, and one case study) reporting positive effects of tDCS in ASD symptom reduction. Study design varied greatly and sample size ranged from 1 to 20 patients. INTERPRETATION: Preliminary evidence is encouraging of the potential usefulness of tDCS for treatment of ASD in children and adolescents. It suggests tentative support for reductions in symptom severity and, according to parental reports and clinical observations, improvements in some aspects of language. However, the evidence is sparse and of low quality, so the true effect of tDCS is likely to be substantially different from the estimate of effect in this review. Therefore, future randomized controlled trials are needed to draw conclusions regarding tDCS efficacy in paediatric samples with ASD. WHAT THIS PAPER ADDS: There is low confidence in the estimate of effect, but tentatively encouraging results warrant further investigation.
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13. Pagalan L, Bickford C, Weikum W, Lanphear B, Brauer M, Lanphear N, Hanley GE, Oberlander TF, Winters M. {{Association of Prenatal Exposure to Air Pollution With Autism Spectrum Disorder}}. {JAMA pediatrics}. 2018.
Importance: The etiology of autism spectrum disorder (ASD) is poorly understood, but prior studies suggest associations with airborne pollutants. Objective: To evaluate the association between prenatal exposures to airborne pollutants and ASD in a large population-based cohort. Design, Setting, and Participants: This population-based cohort encompassed nearly all births in Metro Vancouver, British Columbia, Canada, from 2004 through 2009, with follow-up through 2014. Children were diagnosed with ASD using a standardized assessment with the Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule. Monthly mean exposures to particulate matter with a diameter less than 2.5 microm (PM2.5), nitric oxide (NO), and nitrogen dioxide (NO2) at the maternal residence during pregnancy were estimated with temporally adjusted, high-resolution land use regression models. The association between prenatal air pollution exposures and the odds of developing ASD was evaluated using logistic regression adjusted for child sex, birth month, birth year, maternal age, maternal birthplace, and neighborhood-level urbanicity and income band. Data analysis occurred from June 2016 to May 2018. Exposures: Mean monthly concentrations of ambient PM2.5, NO, and NO2 at the maternal residence during pregnancy, calculated retrospectively using temporally adjusted, high-resolution land use regression models. Main Outcomes and Measures: Autism spectrum disorder diagnoses based on standardized assessment of the Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule. The hypothesis being tested was formulated during data collection. Results: In a cohort of 132256 births, 1307 children (1.0%) were diagnosed with ASD by the age of 5 years. The final sample size for the PM2.5-adjusted model was 129439 children, and for NO and NO2, it was 129436 children; of these, 1276 (1.0%) were diagnosed with ASD. Adjusted odds ratios for ASD per interquartile range (IQR) were not significant for exposure to PM2.5 during pregnancy (1.04 [95% CI, 0.98-1.10] per 1.5 mug/m3 increase [IQR] in PM2.5) or NO2 (1.06 [95% CI, 0.99-1.12] per 4.8 ppb [IQR] increase in NO2) but the odds ratio was significant for NO (1.07 [95% CI, 1.01-1.13] per 10.7 ppb [IQR] increase in NO). Odds ratios for male children were 1.04 (95% CI, 0.98-1.10) for PM2.5; 1.09 (95% CI, 1.02-1.15) for NO; and 1.07 (95% CI, 1.00-1.13) for NO2. For female children, they were for 1.03 (95% CI, 0.90-1.18) for PM2.5; 0.98 (95% CI, 0.83-1.13) for NO; and 1.00 (95% CI, 0.86-1.16) for NO2. Conclusions and Relevance: In a population-based birth cohort, we detected an association between exposure to NO and ASD but no significant association with PM2.5 and NO2.
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14. Serur Y, Sofrin Frumer D, Daon K, Sobol-Havia D, Weinberger R, Shulman C, Gothelf D. {{Psychiatric disorders and autism in young children with 22q11.2 deletion syndrome compared to children with idiopathic autism}}. {European psychiatry : the journal of the Association of European Psychiatrists}. 2018; 55: 116-21.
BACKGROUND: The 22q11.2 deletion syndrome (22q11DS) is a neurogenetic condition characterized by high rates of psychiatric disorders. To our knowledge, this is the first study to assess psychiatric disorders in young children with 22q11DS using a structured psychiatric diagnostic interview, and one of few studies to use the complete gold standard diagnostic evaluation to examine the prevalence of autism spectrum disorder (ASD) in young children with 22q11DS and compare it to a matched control group with iASD. METHODS: We identified the psychiatric disorders and autistic phenotype of young children with 22q11DS (age 3-8 years) and compared them with those of age and sex-matched children with idiopathic autism (iASD). We used the gold standard psychiatric and ASD assessments including the Autism Diagnostic Interview-Revised (ADI-R), the Autism Diagnostic Observation Schedule (ADOS) and a clinical examination by a child psychiatrist. RESULTS: Eighty-four percent of the children with 22q11DS had at least one psychiatric disorder, including anxiety disorders and ADHD, and 16% met strict criteria for ASD. Children with 22q11DS and ASD symptoms had less severe overall ASD symptoms than those with iASD. Children with 22q11DS, regardless of ASD diagnosis, were characterized by repetitive restricted behaviors. CONCLUSIONS: Our results highlight the need to screen for psychiatric disorders in 22q11DS and treat them already in preschool years.
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15. Tejada MI, Elcoroaristizabal X, Ibarluzea N, Botella MP, de la Hoz AB, Ocio I. {{A novel nonsense homozygous variant in the NLGN1 gene found in a pair of monozygotic twin brothers with intellectual disability and autism}}. {Clinical genetics}. 2018.
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16. Thirumanickam A, Raghavendra P, McMillan JM, van Steenbrugge W. {{Effectiveness of video-based modelling to facilitate conversational turn taking of adolescents with autism spectrum disorder who use AAC}}. {Augmentative and alternative communication (Baltimore, Md : 1985)}. 2018: 1-12.
This study evaluated and compared the effectiveness of packaged video modelling (VM) and video self-modelling (VSM) interventions to develop conversational behaviors with four adolescents with autism spectrum disorder (ASD) who used augmentative and alternative communication (AAC). The study was conducted using an alternating treatments design nested within a multiple baseline design. The intervention effect was measured using Robust-Improvement Rate Difference (R-IRD). The results demonstrated that, overall, video-based modelling used in conjunction with a system of least prompts was effective in promoting conversation skills in adolescents with ASD who used AAC. Without the systematic instruction, R-IRD indicated that these techniques yielded only small to moderate intervention effects. The findings demonstrated the necessity of systematic instruction for this group of participants. This investigation provides preliminary evidence to support the use of packaged video-based modelling interventions to develop conversation skills in adolescents with ASD who use AAC systems.
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17. Varman DR, Soria-Ortiz MB, Martinez-Torres A, Reyes-Haro D. {{GABArho3 expression in lobule X of the cerebellum is reduced in the valproate model of autism}}. {Neuroscience letters}. 2018; 687: 158-63.
Autism spectrum disorder (ASD) is a group of developmental disorders characterized by social interaction deficits, communication impairments, and stereotyped and repetitive behaviors. Additionally, impairments in the GABAergic circuitry have been associated with ASD. Several studies have shown that dysfunction of the cerebellum is a hallmark of ASD, and postmortem studies in humans reported a reduced density of Purkinje cells (PCs) together with an abnormal expression of GABAA subunits, among which GABArho3 is expressed in early postnatal development, forms homomeric receptors with high affinity to the agonist (GABA EC50 approximately 3 muM) and desensitize very little upon activation. Thus, we tested if the expression of GABArho3 was modified by prenatal exposure to valproate (VPA), a well-known murine model of autism. The latency to find the nest increased in VPA-treated mice when compared to controls at postnatal day 8 (P8). Immunofluorescence studies showed a reduced expression of GABArho3 in Purkinje cells (PCs) and ependymal glial cells (EGCs) from lobule X of VPA-treated mice. Finally, the expression of GABArho3 increases linearly throughout normal development of the cerebellum, but this pattern is disrupted in the VPA model of autism. We conclude that the expression of GABArho3 is reduced in PCs and EGCs from lobule X of the cerebellum in the VPA model of autism. Thus, GABArho3 may be a relevant marker for ASD etiology.
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18. Vazquez LM, Khanlou N, Davidson D, Aidarus F. {{Strategies to Promote the Inclusion of Young Adults With Developmental Disabilities in Community-Based Health Studies}}. {Qualitative health research}. 2018: 1049732318808249.
We discuss strategies to promote the inclusion of people with developmental disabilities (DDs) in qualitative community-based research studies. Strategies were applied in three projects conducted between 2012 and 2017 that addressed issues of socioeconomic challenges, discrimination, and exclusion of children and young adults with developmental disabilities (YADD). Strategies included partnership with community organizations; inclusion of YADD, family caregivers (FCs), and service providers in advisory committees (ACs); and strategies to accommodate YADD. As part of our contribution, we discuss issues of invisibility and exclusion of individuals with DDs who have « low » functioning capacities. There is a need to review studies sampling inclusion criteria as they may constitute a barrier for participation. Preference for sampling « high » functioning individuals may reinforce exclusion in research, and replicate broader patterns of socioeconomic exclusion of individuals with disabilities. Our discussion of inclusive research is informed by critical disability studies and the underlying principle « nothing about us without us. »
