Pubmed du 09/06/20

mardi 9 juin 2020

1. Bellon-Harn ML, Ni J, Manchaiah V. Twitter usage about autism spectrum disorder. Autism ;2020 (Jun 6):1362361320923173.

Stakeholders within autism spectrum disorder communities use Twitter for specific purposes. The goal of this study was to characterize patterns and themes of tweet content and sentiment and intercommunications between users sending and retweeting content to their respective user networks. The study used cross-sectional analysis of data generated from Twitter. Twitter content, sentiment, users, and community networks were examined from a sample of tweets with the highest Twitter reach and the lowest Twitter reach. Results indicate that Twitter content from both samples was primarily related to empowerment and support. Differences between the number of tweets originating from an individual in the lowest reach sample (i.e. 41%) as compared to the individuals in the highest reach sample (i.e. 18%) were noted. The number of users belonging to an advocacy subcommunity was substantially larger than a clinical and research subcommunity. Results provide insight into the presuppositions of individuals with autism spectrum disorder, their families and significant others, and other stakeholders.

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2. Eigsti IM, Fein DA, Dumont-Mathieu T. A Response to the "Challenging Cases" Article, "Questioning a Previous Autism Spectrum Disorder Diagnosis : Can You ’Lose’ the Diagnosis ?". J Dev Behav Pediatr ;2020 (Jun 5)

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3. Feng C, Zhao J, Ji F, Su L, Chen Y, Jiao J. TCF20 dysfunction leads to cortical neurogenesis defects and autistic-like behaviors in mice. EMBO Rep ;2020 (Jun 8):e49239.

Recently, de novo mutations of transcription factor 20 (TCF20) were found in patients with autism by large-scale exome sequencing. However, how TCF20 modulates brain development and whether its dysfunction causes ASD remain unclear. Here, we show that TCF20 deficits impair neurogenesis in mouse. TCF20 deletion significantly reduces the number of neurons, which leads to abnormal brain functions. Furthermore, transcriptome analysis and ChIP-qPCR reveal that the DNA demethylation factor TDG is a downstream target gene of TCF20. As a nonspecific DNA demethylation factor, TDG potentially affects many genes. Combined TDG ChIP-seq and GO analysis of TCF20 RNA-Seq identifies T-cell factor 4 (TCF-4) as a common target. TDG controls the DNA methylation level in the promoter area of TCF-4, affecting TCF-4 expression and modulating neural differentiation. Overexpression of TDG or TCF-4 rescues the deficient neurogenesis of TCF20 knockdown brains. Together, our data reveal that TCF20 is essential for neurogenesis and we suggest that defects in neurogenesis caused by TCF20 loss are associated with ASD.

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4. Frank HE, Kagan ER, Storch EA, Wood JJ, Kerns CM, Lewin AB, Small BJ, Kendall PC. Accommodation of Anxiety in Youth with Autism Spectrum Disorder : Results from the TAASD Study. J Clin Child Adolesc Psychol ;2020 (Jun 8):1-11.

OBJECTIVE : Accommodation, or the ways in which families modify their routines and expectations in response to a child’s anxiety, is common and interferes with anxiety treatment outcomes. However, little research has examined family accommodation among youth with autism spectrum disorder and anxiety. The current study aimed to (a) identify pre-treatment correlates of accommodation, (b) examine changes in accommodation after treatment, and (c) assess relationships between accommodation and post-treatment anxiety severity. METHOD : The sample consisted of 167 youth (mean age = 9.90 years ; 79.6% male ; 18% Latinx) with clinically significant anxiety and a diagnosis of autism spectrum disorder who were enrolled in a randomized clinical trial comparing two cognitive behavioral therapy interventions for anxiety and treatment-as-usual. Participants were evaluated for symptom severity and family accommodation at pre- and post-treatment. RESULTS : Results indicated that clinician-rated anxiety severity and parent-rated externalizing behaviors and autism spectrum disorder severity significantly predicted pre-treatment accommodation. Accommodation significantly decreased from pre- to post-treatment and non-responders showed significantly higher accommodation at post-treatment compared to responders. Finally, youth with higher pre-treatment accommodation had higher post-treatment anxiety. CONCLUSIONS : Findings indicate that accommodation for anxiety is common among youth with autism spectrum disorder and anxiety. Furthermore, accommodation is implicated in treatment outcomes and should be targeted in treatment for youth with autism spectrum disorder and anxiety.

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5. Fu Y, Zhang J, Li Y, Shi J, Zou Y, Guo H, Yao Z, Wang Y, Hu B. A novel pipeline leveraging surface-based features of small subcortical structures to classify individuals with autism spectrum disorder. Prog Neuropsychopharmacol Biol Psychiatry ;2020 (Jun 5):109989.

Autism spectrum disorder (ASD) is accompanied with widespread impairment in social-emotional functioning. Classification of ASD using sensitive morphological features derived from structural magnetic resonance imaging (MRI) of the brain may help us to better understand ASD-related mechanisms and improve related automatic diagnosis. Previous studies using T1 MRI scans in large heterogeneous ABIDE dataset with typical development (TD) controls reported poor classification accuracies (around 60%). This may because they only considered surface-based morphometry (SBM) as scalar estimates (such as cortical thickness and surface area) and ignored the neighboring intrinsic geometry information among features. In recent years, the shape-related SBM achieves great success in discovering the disease burden and progression of other brain diseases. However, when focusing on local geometry information, its high dimensionality requires careful treatment in its application to machine learning. To address the above challenges, we propose a novel pipeline for ASD classification, which mainly includes the generation of surface-based features, patch-based surface sparse coding and dictionary learning, Max-pooling and ensemble classifiers based on adaptive optimizers. The proposed pipeline may leverage the sensitivity of brain surface morphometry statistics and the efficiency of sparse coding and Max-pooling. By introducing only the surface features of bilateral hippocampus that derived from 364 male subjects with ASD and 381 age-matched TD males, this pipeline outperformed five recent MRI-based ASD classification studies with >80% accuracy in discriminating individuals with ASD from TD controls. Our results suggest shape-related SBM features may further boost the classification performance of MRI between ASD and TD.

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6. Gevi F, Belardo A, Zolla L. A metabolomics approach to investigate urine levels of neurotransmitters and related metabolites in autistic children. Biochim Biophys Acta Mol Basis Dis ;2020 (Jun 5):165859.

Since recently metabolic abnormalities in autistic children have been associated with ASD disturbs, the aim of this study is to determine the neurotransmitter levels in urine samples of autistic children and to analyse the altered metabolic pathway involved in their production. Thus, ASD-specific urinary metabolomic patterns were explored in 40 ASD children and 40 matched controls using untargeted metabolomics through UHPLC-mass spectrometry (Q-exactive analyser), and by using XCMS Metlin software for data interpretation. Through this new advanced technique, a more considerable number of urinary altered metabolites were recorded in autistic children, than in the previous investigations, which allowed us to collect metabolites involved in neurotransmitter production. In these subjects, a high amount of dopamine was revealed and an increased amount of homovanillic acid, to the detriment of noradrenaline and adrenaline production, as well as MHPG and vanillylmandelic acid, which were found lower. This indicates that the accumulation of dopamine is not due to its greater production, but its lesser biotransformation into noradrenaline, due to the blockage of the dopamine β-hydroxylase enzyme by 4-cresol and vitamin C, both found in high quantities in autistic subjects. Finally, a decreased amount of the active form of vitamin B6, pyridoxal phosphate (P5P), implicated in biotransformation of glutamate into γ-aminobutyric acid (GABA), was also detected, justifying the lower levels of latter. All of these alterations are correlated with a peculiar intestinal microbiome in autistic subjects, supporting the idea of a microbiota-gut-brain axis, then altered levels of neurotransmitters and altered neuronal transmission exist.

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7. Glennon JM, D’Souza H, Mason L, Karmiloff-Smith A, Thomas MSC. Visuo-attentional correlates of Autism Spectrum Disorder (ASD) in children with Down syndrome : A comparative study with children with idiopathic ASD. Res Dev Disabil ;2020 (Jun 4) ;104:103678.

BACKGROUND : Children with Down syndrome (DS) are at increased likelihood of Autism Spectrum Disorder (ASD) relative to the general population. To better understand the nature of this comorbidity, we examined the visuo-attentional processes associated with autistic trait expression in children with DS, focusing specifically on attentional disengagement and visual search performance. METHOD : We collected eye-tracking data from children with DS (n = 15) and children with idiopathic ASD (iASD, n = 16) matched according to chronological age. Seven children with DS had a formal clinical diagnosis of ASD (DS+ASD). RESULTS : In children with iASD, but not DS, higher autistic trait levels were associated with decreased temporal facilitation on a gap-overlap task, implying increased visuospatial orienting efficiency. In all cases, higher autistic trait levels were associated with improved visual search performance according to decreased target detection latency. On a visual search task, children with DS+ASD outperformed their peers with DS-ASD, mirroring the phenotypic advantage associated with iASD. We found no evidence of a relationship between attentional disengagement and visual search performance, providing preliminary evidence of a differentiation in terms of underlying visuo-attentional mechanism. CONCLUSION : We illustrate the value of progressing beyond insensitive behavioural measures of phenotypic description to examine, in a more fine-grained way, the attentional features associated with ASD comorbidity in children with DS.

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8. Graziano C, Despang P, Palombo F, Severi G, Posar A, Cassio A, Pippucci T, Isidori F, Matthes J, Bonora E. A New Homozygous CACNB2 Mutation has Functional Relevance and Supports a Role for Calcium Channels in Autism Spectrum Disorder. J Autism Dev Disord ;2020 (Jun 6)

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9. Guy J, Ng-Cordell E, Doherty BR, Duta M, Scerif G. Understanding attention, memory and social biases in fragile X syndrome : Going below the surface with a multi-method approach. Res Dev Disabil ;2020 (May 16) ;104:103693.

Fragile X syndrome (FXS) is characterised by atypical social behaviours, such as gaze aversion. However, it remains unclear whether, or if so how, these behaviours affect cognitive processing and influence memory. We asked children with FXS (N = 16) and typically developing children (TD ; N = 46) to explore naturalistic scenes containing social and non-social salient items unrelated to their task at hand (searching for a simple target object). We also assessed children’s memory for target locations. We complemented behavioural responses with eye-tracking data for the subset of participants who managed to comply with calibration and the demands of the experimental testing session (6 children with FXS and 43 TD children). Children with FXS performed well at the experimental task, and showed similar accuracy and speed in locating targets in natural scenes to children of equivalent verbal abilities. They also learned target locations over blocks, but their memory of target locations was not as precise as that of comparison children. In addition, children with FXS initially directed few first looks to salient social items within the scenes, but these looks increased over blocks. Like TD children, children with FXS also dwelled gaze upon social items while recalling target locations from memory. Individual differences in everyday social characteristics also related to gaze and behavioural measures. In conclusion, experimental approaches can highlight cognitive underpinnings of atypical social behaviour in FXS, pinpointing both similarities and differences to TD individuals.

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10. Hill JR, Ziviani J, Driscoll C. "The connection just happens" : Therapists’ perspectives of canine-assisted occupational therapy for children on the autism spectrum. Aust Occup Ther J ;2020 (Jun 8)

INTRODUCTION : The inclusion of a therapy dog has been suggested as a means of facilitating therapy engagement for children on the autism spectrum within occupational therapy sessions. The aim of this study was to seek an understanding of possible benefits and challenges of this practice from the perspectives of occupational therapists, trained in canine-assisted therapy. METHOD : This study adopted an interpretive descriptive design. Six therapists participated in a semi-structured, telephone interview to describe their experience of working as canine-assisted occupational therapists with children on the autism spectrum. An inductive thematic analysis was used to analyse the data. RESULTS : Two overarching themes emerged. The first captured how therapists incorporated their therapy dog into sessions to accelerate children’s initial motivation to engage within the therapy process. Specifically, therapists discussed how involving their therapy dog facilitated the development of a secure relationship, supported autonomous task involvement and increased children’s sense of confidence. Second, they identified challenges inherent in their practice, such as the therapist’s ability to maintain a goal-directed focus when including a therapy dog. Beyond the challenges within their own practice sessions, therapists reflected on issues thought to impact the occupational therapy profession since starting practice as a canine-assisted occupational therapist. CONCLUSION : Findings from this study contribute to the current understanding of how occupational therapists incorporate therapy dogs into their practice with children on the autism spectrum. The specific challenges noted by the therapists highlighted the importance of canine-assisted occupational therapy being viewed as an advanced scope of practice within Australia and, therefore, the need for training and practice guidelines to be established.

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11. Hu J, Cao L, Li T, Liao B, Dong S, Li P. Interpretable Learning Approaches in Resting-State Functional Connectivity Analysis : The Case of Autism Spectrum Disorder. Comput Math Methods Med ;2020 ;2020:1394830.

Deep neural networks have recently been applied to the study of brain disorders such as autism spectrum disorder (ASD) with great success. However, the internal logics of these networks are difficult to interpret, especially with regard to how specific network architecture decisions are made. In this paper, we study an interpretable neural network model as a method to identify ASD participants from functional magnetic resonance imaging (fMRI) data and interpret results of the model in a precise and consistent manner. First, we propose an interpretable fully connected neural network (FCNN) to classify two groups, ASD versus healthy controls (HC), based on input data from resting-state functional connectivity (rsFC) between regions of interests (ROIs). The proposed FCNN model is a piecewise linear neural network (PLNN) which uses piecewise linear function LeakyReLU as its activation function. We experimentally compared the FCNN model against widely used classification models including support vector machine (SVM), random forest, and two new classes of deep neural network models in a large dataset containing 871 subjects from ABIDE I database. The results show the proposed FCNN model achieves the highest classification accuracy. Second, we further propose an interpreting method which could explain the trained model precisely with a precise linear formula for each input sample and decision features which contributed most to the classification of ASD versus HC participants in the model. We also discuss the implications of our proposed approach for fMRI data classification and interpretation.

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12. Lima JL, Axt G, Teixeira DS, Monteiro D, Cid L, Yamamoto T, Murillo-Rodriguez E, Machado S. Exergames for Children and Adolescents with Autism Spectrum Disorder : An Overview. Clin Pract Epidemiol Ment Health ;2020 ;16:1-6.

Autistic Spectrum Disorder (ASD) is a complex neurodevelopmental disorder associated with various etiologies and characterized by deficits in social interaction, emotional reciprocity, communication, motor skills and cognitive functions. Studies have proposed that limited levels of physical activity and late motor skills and fitness, particularly in children and adolescents with ASD, may accentuate social and emotional deficits. In view of this, exergames, which are active video-games, can be considered a low-cost and safe type of exercise for children and adolescents with ASD, since they are more enjoyable than ordinary physical activities, influencing on treatment adherence. Thus, our study aims to evidence the effects of exergames on physical fitness, cognitive functions, and repetitive behaviors in children and adolescents with ASD. Despite the small number of studies investigating the effects of exergames as new strategy in children and adolescents with ASD, results suggest exergames as potential tool for the treatment of children and adolescents with ASD for improvement in physical fitness, cognitive functions and repetitive behavior. Our review pointed towards the importance of exergames for children and adolescents with ASD. Despite few studies conducted about this issue, we can consider exergames a potential tool to increase physical fitness, cognitive functions and to decrease repetitive behavior in children and adolescents with ASD. Moreover, health professionals should be careful when attempting to help this population, because the current literature is unclear yet about the improvement of ASD features through exergames.

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13. McLay L, Hansen SG, Carnett A, France KG, Blampied NM. Attributions, causal beliefs, and help-seeking behavior of parents of children with autism spectrum disorder and sleep problems. Autism ;2020 (Jun 6):1362361320924216.

Sleep problems are commonly reported among parents of children with autism spectrum disorder (ASD). Without effective treatment, such problems are unlikely to resolve. To date, we know very little about how and why parents of children with ASD seek help for sleep disturbance. Via an online survey, we gathered information about how parents make sense of their children’s sleep problems, beliefs about their causes, sources of information, and help-seeking behavior. The analysis of responses from 244 parents revealed that parents commonly view sleep problems (a) as a consequence of their child’s ASD, and unlikely to change over time (stable), and (b) as located within the child (intrinsic), stable over time, and difficult to treat. Despite this, parents also rated sleep problems as being important to treat. Eighty-two percent of parents surveyed reported seeking some kind of help for their child’s sleep disturbance, and the average parent had tried six different treatment strategies, most commonly medical approaches (e.g. melatonin). The alignment between parents’ treatment choices and those strategies that are supported by research was poor, but belief in the effectiveness of treatments was closely related to how often the treatment was used. These findings have important implications for parental education and clinical practice in the treatment of sleep problems in children with ASD.

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14. Ozkul Y, Taheri S, Bayram KK, Sener EF, Mehmetbeyoglu E, Öztop DB, Aybuga F, Tufan E, Bayram A, Dolu N, Zararsiz G, Kianmehr L, Beyaz F, Doganyigit Z, Cuzin F, Rassoulzadegan M. A heritable profile of six miRNAs in autistic patients and mouse models. Sci Rep ;2020 (Jun 9) ;10(1):9011.

Autism spectrum disorder (ASD) is a group of developmental pathologies that impair social communication and cause repetitive behaviors. The suggested roles of noncoding RNAs in pathology led us to perform a comparative analysis of the microRNAs expressed in the serum of human ASD patients. The analysis of a cohort of 45 children with ASD revealed that six microRNAs (miR-19a-3p, miR-361-5p, miR-3613-3p, miR-150-5p, miR-126-3p, and miR-499a-5p) were expressed at low to very low levels compared to those in healthy controls. A similar but less pronounced decrease was registered in the clinically unaffected parents of the sick children and in their siblings but never in any genetically unrelated control. Results consistent with these observations were obtained in the blood, hypothalamus and sperm of two of the established mouse models of ASD : valproic acid-treated animals and Cc2d1a(+/-) heterozygotes. In both instances, the same characteristic miRNA profile was evidenced in the affected individuals and inherited together with disease symptoms in the progeny of crosses with healthy animals. The consistent association of these genetic regulatory changes with the disease provides a starting point for evaluating the changes in the activity of the target genes and, thus, the underlying mechanism(s). From the applied societal and medical perspectives, once properly confirmed in large cohorts, these observations provide tools for the very early identification of affected children and progenitors.

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15. Rahman SM, Kundu GK, Akhter S, Ahmed S, Lailatunnessa M, Rahman MM. Childhood Neuro-developmental Disorder (Rett Syndrome) : A Case Report. Mymensingh Med J ;2020 (Apr) ;29(2):460-463.

Rett syndrome is a disorder of early brain development which is clinically characterized by arrested neuro-development. We found one such 5.5 years old girl whose physical and mental development was normal up to 17 months of age, followed by regression. She had lost her already acquired purposeful hand movements, appearance of stereotyped hand movements, along with development of epilepsy. To our knowledge such case is being reported for the first time from Bangladesh. The purpose of this case report is to increase awareness of this syndrome among physicians specially paediatricians, thereby aiding early diagnosis and treatment.

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16. Rio CAC, Nunez-Parra A, Freedman S, Kushner JK, Alexander AL, Restrepo D, Huntsman MM. Disrupted inhibitory plasticity and homeostasis in Fragile X syndrome. Neurobiol Dis ;2020 (Jun 5):104959.

Fragile X Syndrome (FXS) is a neurodevelopmental disorder instigated by the absence of a key translation regulating protein, Fragile X Mental Retardation Protein (FMRP). The loss of FMRP in the CNS leads to abnormal synaptic development, disruption of critical periods of plasticity, and an overall deficiency in proper sensory circuit coding leading to hyperexcitable sensory networks. However, little is known about how this hyperexcitable environment affects inhibitory synaptic plasticity. Here, we show that in vivo layer 2/3 of the primary somatosensory cortex of the Fmr1 KO mouse exhibits basal hyperexcitability and an increase in neuronal firing rate suppression during whisker activation. This aligns with our in vitro data that indicate an increase in GABAergic spontaneous activity, a faulty mGluR-mediated inhibitory input and impaired inhibitory plasticity processes. Specifically, we find that mGluR activation sensitivity is overall diminished in the Fmr1 KO mouse leading to both a decreased spontaneous inhibitory postsynaptic input to principal cells and a disrupted form of inhibitory long-term depression (I-LTD). These data suggest an adaptive mechanism that acts to homeostatically counterbalance the cortical hyperexcitability observed in FXS.

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17. Umesawa Y, Atsumi T, Chakrabarty M, Fukatsu R, Ide M. GABA Concentration in the Left Ventral Premotor Cortex Associates With Sensory Hyper-Responsiveness in Autism Spectrum Disorders Without Intellectual Disability. Front Neurosci ;2020 ;14:482.

Individuals with autism spectrum disorder (ASD) often exhibit abnormal processing of sensory inputs from multiple modalities and higher-order cognitive/behavioral response to those inputs. Several lines of evidence suggest that altered γ-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the brain, is a central characteristic of the neurophysiology of ASD. The relationship between GABA in particular brain regions and atypical sensory processing in ASD is poorly understood. We therefore employed (1)H magnetic resonance spectroscopy ((1)H-MRS) to examine whether GABA levels in brain regions critical to higher-order motor and/or multiple sensory functions were associated with abnormal sensory responses in ASD. We evaluated atypical sensory processing with a clinically-validated assessment tool. Furthermore, we measured GABA levels in four regions : one each in the primary visual cortex, the left sensorimotor cortex, the left supplementary motor area (SMA), and the left ventral premotor cortex (vPMC). The latter two regions are thought to be involved in executing and coordinating cognitive and behavioral functions in response to multisensory inputs. We found severer sensory hyper-responsiveness in ASD relative to control participants. We also found reduced GABA concentrations in the left SMA but no differences in other regions of interest between ASD and control participants. A correlation analysis revealed a negative association between left vPMC GABA and the severity of sensory hyper-responsiveness across all participants, and the independent ASD group. These findings suggest that reduced inhibitory neurotransmission (reduced GABA) in a higher-order motor area, which modulates motor commands and integrates multiple sensory modalities, may underlie sensory hyper-responsiveness in ASD.

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18. Yaylaci F, Sahbudak B, Citli S, Kilit N. ASD with the Bor Syndrome : A Case Report. Psychopharmacol Bull ;2020 (May 19) ;50(2):45-50.

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19. Zablotsky B, Black LI. Prevalence of Children Aged 3-17 Years With Developmental Disabilities, by Urbanicity : United States, 2015-2018. Natl Health Stat Report ;2020 (Feb)(139):1-7.

Objective-This report examines the prevalence of developmental disabilities among children in both rural and urban areas as well as service utilization among children with developmental issues in both areas. Methods-Data from the 2015-2018 National Health Interview Survey (NHIS) were used to examine the prevalence of 10 parent- or guardian-reported developmental disability diagnoses (attention-deficit/hyperactivity disorder [ADHD], autism spectrum disorder, blindness, cerebral palsy, moderate to profound hearing loss, learning disability, intellectual disability, seizures, stuttering or stammering, and other developmental delays) and service utilization for their child. Prevalence estimates are presented by urbanicity of residence (urban or rural). Bivariate logistic regressions were used to test for differences by urbanicity. Results-Children living in rural areas were more likely to be diagnosed with a developmental disability than children living in urban areas (19.8% compared with 17.4%). Specifically, children living in rural areas were more likely than those in urban areas to be diagnosed with ADHD (11.4% compared with 9.2%) and cerebral palsy (0.5% compared with 0.2%). However, among children with a developmental disability, children living in rural areas were significantly less likely to have seen a mental health professional, therapist, or had a well-child checkup visit in the past year, compared with children living in urban areas. Children with a developmental disability living in rural areas were also significantly less likely to receive Special Educational or Early Intervention Services compared with those living in urban areas. Conclusion-Findings from this study highlight differences in the prevalence of developmental disabilities and use of services related to developmental disabilities by rural and urban residence.

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