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1.
Early Child Educ J ; : 1-13, 2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36373063

RESUMO

Early childhood care and education providers provide instruction to diverse learners, including children with developmental delays, but often lack training in the use of evidence-based instructional strategies to support children's meaningful learning engagement. This preliminary study examined effects of the Early Achievements for Child Care Providers professional development program with and without generalization training on center-based child care providers (N = 12). Outcomes assessed included providers' implementation fidelity, knowledge, and self-efficacy as well as children's (N = 43) social-communication skills and engagement in shared book reading. Results demonstrated that providers trained in a generalization context made larger gains in implementation fidelity in a generalization context; no other significant between-group differences were found for providers. Children in both groups made comparable, significant gains. Findings suggest that explicit generalization training is needed for providers to achieve fidelity when transferring newly learned evidence-based practices to additional classroom instructional contexts, but a brief interval of implementation likely is insufficient to differentially benefit child outcomes. Researchers should elicit providers' perceptions when designing professional development programs to maximize feasibility of investing additional time and resources for generalization training.

2.
Adm Policy Ment Health ; 48(2): 266-278, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32653973

RESUMO

When parents and teachers align their practices across home and school, it may optimize services for children with autism spectrum disorder (ASD). Partners in School is a multi-faceted implementation strategy designed to improve ASD services in schools. The goal is to increase parents' and teachers' use of evidence-based practices (EBPs) and to align those EBPs across settings. We piloted Partners in School with 49 parent-teacher dyads to assess administration and the factors associated with reported fidelity to the model. Specifically, we measured the number of intervention steps both parents and teachers completed (reported alignment) and the characteristics associated with intervention alignment. Partners in School involves parent-teacher participation in a pre-consultation interview, an in-person consultation meeting, active implementation of the same EBPs in their respective settings, and a post-consultation interview. Parents and teachers also completed surveys pre- and post-consultation. On average, parents and teachers completed approximately five EBP steps on their own in their respective settings (i.e., at home or at school). Of these five steps, parents and teachers both completed three of the same EBPs steps, on average. Different factors were related to reported alignment for parents versus teachers; however, a similarity noted for both parents and teachers was that communication variables were associated with reported alignment. Our findings indicate the important role of communication in aligning stakeholders for ASD service delivery models.


Assuntos
Transtorno do Espectro Autista , Transtorno do Espectro Autista/terapia , Criança , Comunicação , Prática Clínica Baseada em Evidências , Humanos , Pais , Professores Escolares , Instituições Acadêmicas
3.
Dev Psychopathol ; 32(4): 1217-1229, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32928316

RESUMO

Infant siblings of children with autism spectrum disorder (ASD) exhibit greater heterogeneity in behavioral presentation and outcomes relative to infants at low familial risk (LR), yet there is limited understanding of the diverse developmental profiles that characterize these infants. We applied a hierarchical agglomerative cluster analysis approach to parse developmental heterogeneity in 420 toddlers with heightened (HR) and low (LR) familial risk for ASD using measures of four dimensions of development: language, social, play, and restricted and repetitive behaviors (RRB). Results revealed a two-cluster solution. Comparisons of clusters revealed significantly lower language, social, and play performance, and higher levels of restricted and repetitive behaviors in Cluster 1 relative to Cluster 2. In Cluster 1, 25% of children were later diagnosed with ASD compared to 8% in Cluster 2. Comparisons within Cluster 1 between subgroups of toddlers having ASD+ versus ASD- 36-month outcomes revealed significantly lower functioning in the ASD+ subgroup across cognitive, motor, social, language, symbolic, and speech dimensions. Findings suggest profiles of early development associated with resiliency and vulnerability to later ASD diagnosis, with multidimensional developmental lags signaling vulnerability to ASD diagnosis.


Assuntos
Transtorno do Espectro Autista , Pré-Escolar , Análise por Conglomerados , Humanos , Lactente , Risco , Irmãos
4.
Int Rev Psychiatry ; 30(1): 25-39, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29537331

RESUMO

With advances in the field's ability to identify autism spectrum disorders (ASD) at younger ages, the need for information about the evidence-base for early intervention continues to rise. This review of the ASD early intervention (EI) literature focuses on efficacy studies published within the past 15 years. The neurodevelopmental context for early intervention, timing of initiating intervention, primary intervention approaches, and predictors of treatment outcomes are discussed. The evidence indicates that young children with ASD benefit from EI, and their parents learn to implement child-responsive engagement strategies when a parent-coaching intervention is provided. Evidence supports combining parent-mediated and direct clinician-implemented intervention to maximize child developmental gains. Clinical practice recommendations are presented, based on the literature reviewed.


Assuntos
Transtorno do Espectro Autista/reabilitação , Terapia Comportamental/métodos , Intervenção Educacional Precoce/métodos , Intervenção Médica Precoce/métodos , Avaliação de Resultados em Cuidados de Saúde , Criança , Pré-Escolar , Humanos , Lactente
5.
J Child Psychol Psychiatry ; 56(9): 988-98, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25921776

RESUMO

BACKGROUND: The diagnosis of autism spectrum disorder (ASD) made before age 3 has been found to be remarkably stable in clinic- and community-ascertained samples. The stability of an ASD diagnosis in prospectively ascertained samples of infants at risk for ASD due to familial factors has not yet been studied, however. The American Academy of Pediatrics recommends intensive surveillance and screening for this high-risk group, which may afford earlier identification. Therefore, it is critical to understand the stability of an ASD diagnosis made before age 3 in young children at familial risk. METHODS: Data were pooled across seven sites of the Baby Siblings Research Consortium. Evaluations of 418 later-born siblings of children with ASD were conducted at 18, 24, and 36 months of age and a clinical diagnosis of ASD or Not ASD was made at each age. RESULTS: The stability of an ASD diagnosis at 18 months was 93% and at 24 months was 82%. There were relatively few children diagnosed with ASD at 18 or 24 months whose diagnosis was not confirmed at 36 months. There were, however, many children with ASD outcomes at 36 months who had not yet been diagnosed at 18 months (63%) or 24 months (41%). CONCLUSIONS: The stability of an ASD diagnosis in this familial-risk sample was high at both 18 and 24 months of age and comparable with previous data from clinic- and community-ascertained samples. However, almost half of the children with ASD outcomes were not identified as being on the spectrum at 24 months and did not receive an ASD diagnosis until 36 months. Thus, longitudinal follow-up is critical for children with early signs of social-communication difficulties, even if they do not meet diagnostic criteria at initial assessment. A public health implication of these data is that screening for ASD may need to be repeated multiple times in the first years of life. These data also suggest that there is a period of early development in which ASD features unfold and emerge but have not yet reached levels supportive of a diagnosis.


Assuntos
Transtorno do Espectro Autista/diagnóstico , Diagnóstico Precoce , Predisposição Genética para Doença , Irmãos , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , Risco
6.
Child Dev ; 85(6): 2218-31, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24978128

RESUMO

Atypical motor behaviors are common among children with autism spectrum disorders (ASD). However, little is known about onset and functional implications of differences in early motor development among infants later diagnosed with ASD. Two prospective experiments were conducted to investigate motor skills among 6-month-olds at increased risk (high risk) for ASD (N1  = 129; N2  = 46). Infants were assessed using the Mullen Scales of Early Learning (MSEL) and during toy play. Across both experiments, high-risk infants exhibited less mature object manipulation in a highly structured (MSEL) context and reduced grasping activity in an unstructured (free-play) context than infants with no family history of ASD. Longitudinal assessments suggest that between 6 and 10 months, grasping activity increases in high-risk infants.


Assuntos
Transtornos Globais do Desenvolvimento Infantil/fisiopatologia , Desenvolvimento Infantil/fisiologia , Atividade Motora/fisiologia , Destreza Motora/fisiologia , Jogos e Brinquedos/psicologia , Feminino , Humanos , Lactente , Masculino , Risco
7.
Child Dev ; 84(2): 429-42, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23110514

RESUMO

Retrospective studies indicate 2 major classes of autism spectrum disorder (ASD) onset: early and later, after a period of relatively healthy development. This prospective, longitudinal study examined social, language, and motor trajectories in 235 children with and without a sibling with autism, ages 6-36 months. Children were grouped as: ASD identified by 14 months, ASD identified after 14 months, and no ASD. Despite groups' initial similar developmental level at 6 months, ASD groups exhibited atypical trajectories thereafter. Impairment from 14 to 24 months was greater in the Early-ASD than the Later-ASD group, but comparable at 36 months. Developmental plateau and regression occurred in some children with ASD, regardless of timing of ASD diagnosis. Findings indicate a preclinical phase of varying duration for ASD.


Assuntos
Transtornos Globais do Desenvolvimento Infantil/fisiopatologia , Desenvolvimento Infantil/fisiologia , Idioma , Destreza Motora/fisiologia , Comportamento Social , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos Prospectivos , Testes Psicológicos , Irmãos , Fatores de Tempo
8.
Lang Speech Hear Serv Sch ; 54(4): 1295-1307, 2023 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-37699196

RESUMO

PURPOSE: Speech-language pathologists (SLPs) have multiple roles and responsibilities related to language and literacy instruction in schools. The purpose of this exploratory, qualitative study was to analyze school-based SLPs' perceptions related to effective language and early literacy instruction for pre-K children with developmental language disorder (DLD). The goal of this study was to inform development of a new language and early literacy professional development program for inclusive pre-K teachers. METHOD: Eight school-based SLPs participated in a 1-hr virtual focus group conducted via Zoom recording technology. The researchers used a conventional content analysis approach to analyze the focus group data and identify themes from the discussion. RESULTS: The researchers developed two themes: (a) SLPs identified repeated exposure to books, peer interaction, and teaching vocabulary with visual supports and props as key elements of language and literacy instruction that can be integrated into a variety of contexts, and (b) SLPs want more time with parents and teachers to support their book reading and model specific language strategies. CONCLUSIONS: SLPs identified several instructional practices inclusive pre-K teachers could be taught to use during professional development programs to support the emergent literacy development of children with DLD. They also discussed the need for ongoing collaboration between SLPs, caregivers, and teachers to maximize children's early language and literacy experiences. Future research should explore the impact of partnerships with caregivers and teachers on children's language and literacy outcomes.


Assuntos
Transtornos do Desenvolvimento da Linguagem , Patologia da Fala e Linguagem , Criança , Humanos , Alfabetização , Fala , Patologistas , Idioma , Transtornos do Desenvolvimento da Linguagem/terapia , Patologia da Fala e Linguagem/educação
9.
Front Hum Neurosci ; 17: 1211676, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37662636

RESUMO

Autism spectrum disorder (ASD) is an increasingly prevalent and heterogeneous neurodevelopmental condition, characterized by social communicative differences, and a combination of repetitive behaviors, focused interests, and sensory sensitivities. Early speech and language delays are characteristic of young autistic children and are one of the first concerns reported by parents; often before their child's second birthday. Elucidating the neural mechanisms underlying these delays has the potential to improve early detection and intervention efforts. To fill this gap, this systematic review aimed to synthesize evidence on early neurobiological correlates and predictors of speech and language development across different neuroimaging modalities in infants with and without a family history of autism [at an elevated (EL infants) and low likelihood (LL infants) for developing autism, respectively]. A comprehensive, systematic review identified 24 peer-reviewed articles published between 2012 and 2023, utilizing structural magnetic resonance imaging (MRI; n = 2), functional MRI (fMRI; n = 4), functional near-infrared spectroscopy (fNIRS; n = 4), and electroencephalography (EEG; n = 14). Three main themes in results emerged: compared to LL infants, EL infants exhibited (1) atypical language-related neural lateralization; (2) alterations in structural and functional connectivity; and (3) mixed profiles of neural sensitivity to speech and non-speech stimuli, with some differences detected as early as 6 weeks of age. These findings suggest that neuroimaging techniques may be sensitive to early indicators of speech and language delays well before overt behavioral delays emerge. Future research should aim to harmonize experimental paradigms both within and across neuroimaging modalities and additionally address the feasibility, acceptability, and scalability of implementing such methodologies in non-academic, community-based settings.

10.
Autism ; 27(7): 1856-1875, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-36802822

RESUMO

LAY ABSTRACT: The topic of how parents react (e.g., how they talk and act) to their child with autism or elevated likelihood of autism, often called parent responsiveness, has been studied by researchers for over 50 years. Many methods for measuring behaviors around parent responsiveness have been created depending on what researchers were interested in discovering. For example, some include only the behaviors that the parent does/says in reacting to something the child does/says. Other systems look at all behaviors in a period of time between child and parent (e.g., who talked/acted first, how much the child or parent said/did). The purpose of this article was to provide a summary of how and what researchers looked at around parent responsiveness, describe the strengths and barriers of these approaches, and suggest a "best practices" method of looking at parent responsiveness. The model suggested could make it more possible to look across studies to compare study methods and results. The model could be used in the future by researchers, clinicians, and policymakers to provide more effective services to children and their families.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Criança , Humanos , Pais
11.
J Autism Dev Disord ; 53(4): 1305-1318, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34859339

RESUMO

Discernment of possible sex-based variations in presentations of autism spectrum disorder (ASD) symptoms is limited by smaller female samples with ASD and confounds with ASD ascertainment. A large national cohort of individuals with autism, SPARK, allowed parent report data to be leveraged to examine whether intrinsic child characteristics and extrinsic factors differentially impact males and females with ASD. Small but consistent sex differences in individuals with ASD emerged related to both intrinsic and extrinsic factors, with different markers for males and females. Language concerns in males may make discernment of ASD more straightforward, while early motor concerns in females may hamper diagnosis as such delays are not identified within traditional ASD diagnostic criteria.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Humanos , Masculino , Criança , Feminino , Adolescente , Transtorno do Espectro Autista/diagnóstico , Transtorno do Espectro Autista/epidemiologia , Caracteres Sexuais , Idioma , Fatores Sexuais
12.
J Child Psychol Psychiatry ; 53(9): 986-96, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22574686

RESUMO

BACKGROUND: Siblings of children with autism (sibs-A) are at increased genetic risk for autism spectrum disorders (ASD) and milder impairments. To elucidate diversity and contour of early developmental trajectories exhibited by sibs-A, regardless of diagnostic classification, latent class modeling was used. METHODS: Sibs-A (N = 204) were assessed with the Mullen Scales of Early Learning from age 6 to 36 months. Mullen T scores served as dependent variables. Outcome classifications at age 36 months included: ASD (N = 52); non-ASD social/communication delay (broader autism phenotype; BAP; N = 31); and unaffected (N = 121). Child-specific patterns of performance were studied using latent class growth analysis. Latent class membership was then related to diagnostic outcome through estimation of within-class proportions of children assigned to each diagnostic classification. RESULTS: A 4-class model was favored. Class 1 represented accelerated development and consisted of 25.7% of the sample, primarily unaffected children. Class 2 (40.0% of the sample), was characterized by normative development with above-average nonverbal cognitive outcome. Class 3 (22.3% of the sample) was characterized by receptive language, and gross and fine motor delay. Class 4 (12.0% of the sample), was characterized by widespread delayed skill acquisition, reflected by declining trajectories. Children with an outcome diagnosis of ASD were spread across Classes 2, 3, and 4. CONCLUSIONS: Results support a category of ASD that involves slowing in early non-social development. Receptive language and motor development is vulnerable to early delay in sibs-A with and without ASD outcomes. Non-ASD sibs-A are largely distributed across classes depicting average or accelerated development. Developmental trajectories of motor, language, and cognition appear independent of communication and social delays in non-ASD sibs-A.


Assuntos
Transtorno Autístico/diagnóstico , Desenvolvimento Infantil/fisiologia , Irmãos/psicologia , Transtorno Autístico/genética , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Modelos Psicológicos , Fenótipo , Escalas de Graduação Psiquiátrica
13.
Front Psychiatry ; 13: 805686, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35370852

RESUMO

Given the importance of early detection, it is critical to understand the non-linearity in manifestation of ASD before age 24 months, when ASD symptoms are beginning to consolidate, through the age of 36 months when stability of ASD diagnosis is reportedly high into school-age when increased demands may challenge previously successful compensatory processes and permit first ASD detection. We employed a prospective, longitudinal design focused on children with an older sibling with ASD (n = 210) who received diagnostic evaluations at mean ages of 15.4 months (Time 1), 36.6 months (Time 2), and 5.7 years (Time 3) to examine: (1) diagnostic stability, (2) developmental trajectories associated with different patterns of ASD vs. non-ASD classifications, and (3) predictors of classification group over time. Clinical best estimate (CBE) diagnosis of ASD or non-ASD was made at each time point. Linear mixed-effects models were implemented to examine differences in developmental trajectories of stable and dynamic diagnostic groups. Multinomial logistic regression analyses were used to examine predictors of the likelihood of belonging to each CBE diagnostic classification group. Results revealed that sensitivity and stability of an ASD diagnosis significantly increased from Time 1 (sensitivity: 52%; stability: 63%) to Time 2 (sensitivity: 86%; stability: 68%). Different developmental trajectories of autism symptom severity and non-verbal and verbal IQ were observed across groups, with differences first observed at Time 1 and becoming more pronounced through Time 3. Presence of restricted and repetitive behaviors as well as limitations in initiation of joint attention and expressive language skills differentially predicted the likelihood of belonging to the different CBE diagnostic classification groups. Results suggest that ASD symptoms may emerge or attenuate over time, with some children meeting diagnosis at follow-up, and other children no longer meeting diagnostic criteria. From a systems perspective, diagnostic non-linearity may be viewed as a dynamic developmental process, where emergent properties arising from various biological, genetic, and experiential factors interact, culminating in phenotypic phenomena that change over time. Clinical implications include extending universal ASD and social communication screening into school-age, supporting families' understanding of diagnostic shifts, and ensuring unbiased diagnostic decision-making when following children with ASD.

14.
Front Psychol ; 13: 936392, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36148115

RESUMO

Delays in early language development are characteristic of young autistic children, and one of the most recognizable first concerns that motivate parents to seek a diagnostic evaluation for their child. Although early language abilities are one of the strongest predictors of long-term outcomes, there is still much to be understood about the role of language impairment in the heterogeneous phenotypic presentation of autism. Using a person-centered, Latent Profile Analysis, we first aimed to identify distinct patterns of language and social communication ability in a clinic-based sample of 498 autistic children, ranging in age from 18 to 60 months (M = 33 mo, SD = 12 mo). Next, a multinomial logistic regression analysis was implemented to examine sociodemographic and child-based developmental differences among the identified language and social communication profiles. Three clinically meaningful profiles were identified from parent-rated and clinician-administered measures: Profile 1 (48% of the sample) "Relatively Low Language and Social Communication Abilities," Profile 2 (34% of the sample) "Relatively Elevated Language and Social Communication Abilities," and Profile 3 (18% of the sample) "Informant Discrepant Language and Relatively Elevated Social Communication Abilities." Overall, young autistic children from the lowest-resource households exhibited the lowest language and social communication abilities, and the lowest non-verbal problem-solving and fine-motor skills, along with more features of attention-deficit/hyperactivity disorder and atypical auditory processing. These findings highlight the need for effective community-based implementation strategies for young autistic children from low-resource households and underrepresented communities to improve access to individualized quality care.

15.
J Child Psychol Psychiatry ; 52(1): 13-21, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21126245

RESUMO

BACKGROUND: Social and communication impairments are core deficits and prognostic indicators of autism. We evaluated the impact of supplementing a comprehensive intervention with a curriculum targeting socially synchronous behavior on social outcomes of toddlers with autism spectrum disorders (ASD). METHODS: Fifty toddlers with ASD, ages 21 to 33 months, were randomized to one of two six-month interventions: Interpersonal Synchrony or Non-Interpersonal Synchrony. The interventions provided identical intensity (10 hours per week in classroom), student-to-teacher ratio, schedule, home-based parent training (1.5 hours per month), parent education (38 hours), and instructional strategies, except the Interpersonal Synchrony condition provided a supplementary curriculum targeting socially engaged imitation, joint attention, and affect sharing; measures of these were primary outcomes. Assessments were conducted pre-intervention, immediately post-intervention, and, to assess maintenance, at six-month follow-up. Random effects models were used to examine differences between groups over time. Secondary analyses examined gains in expressive language and nonverbal cognition, and time effects during the intervention and follow-up periods. RESULTS: A significant treatment effect was found for socially engaged imitation (p = .02), with more than doubling (17% to 42%) of imitated acts paired with eye contact in the Interpersonal Synchrony group after the intervention. This skill was generalized to unfamiliar contexts and maintained through follow-up. Similar gains were observed for initiation of joint attention and shared positive affect, but between-group differences did not reach statistical significance. A significant time effect was found for all outcomes (p < .001); greatest change occurred during the intervention period, particularly in the Interpersonal Synchrony group. CONCLUSIONS: This is the first ASD randomized trial involving toddlers to identify an active ingredient for enhancing socially engaged imitation. Adding social engagement targets to intervention improves short-term outcome at no additional cost to the intervention. The social, language, and cognitive gains in our participants provide evidence for plasticity of these developmental systems in toddlers with ASD. http://www.clinicaltrials.gov/ct2/show/NCT00106210?term = landa&rank = 3.


Assuntos
Terapia Comportamental/métodos , Transtornos Globais do Desenvolvimento Infantil/psicologia , Transtornos Globais do Desenvolvimento Infantil/terapia , Cognição , Comunicação , Comportamento Imitativo , Pais/educação , Transtornos Globais do Desenvolvimento Infantil/diagnóstico , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , Testes Neuropsicológicos , Resultado do Tratamento , Comportamento Verbal
16.
J Speech Lang Hear Res ; 64(9): 3477-3488, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34388006

RESUMO

Purpose Social communication or pragmatic skills are continuously distributed in the general population. Impairment in these skills is associated with two clinical disorders, autism spectrum disorder (ASD) and social (pragmatic) communication disorder. Such impairment can impact a child's peer acceptance, school performance, and current and later mental health. Valid, reliable, examiner-rated observational measures of social communication from a semistructured language sample are needed to detect social communication impairment. We evaluated the psychometrics of an examiner-rated measure of social (pragmatic) communication, the Pragmatic Rating Scale-School Age (PRS-SA). Method The analytic sample consisted of 130 children, ages 7-12 years, from five mutually exclusive groups: ASD (n = 25), language concern (LC; n = 5), ASD + LC (n = 10), social communication impairment only (n = 22), and typically developing (TD; n = 68). All children received language and autism assessments. The PRS-SA was rated separately using video-recorded communication samples from the Autism Diagnostic Observation Schedule. Assessment data were employed to evaluate the psychometrics of the PRS-SA. Analysis of covariance models were used to assess whether the PRS-SA would detect differences in social communication functioning across the five groups. Results The PRS-SA demonstrated strong internal reliability, concurrent validity, and interrater reliability. PRS-SA scores were significantly higher in all groups compared to the TD group and differed significantly in most pairwise comparisons; the ASD + LC group had the highest (more atypical) scores. Conclusions The PRS-SA shows promise as a measure of social communication skills in school-age verbally fluent children with a range of social and language abilities. More research is needed with a larger sample, including a wider age range and geographical diversity, to replicate findings. Supplemental Material https://doi.org/10.23641/asha.15138240.


Assuntos
Transtorno do Espectro Autista , Transtorno do Espectro Autista/diagnóstico , Criança , Comunicação , Humanos , Linguística , Psicometria , Reprodutibilidade dos Testes , Instituições Acadêmicas
17.
Biol Psychiatry ; 87(2): 139-149, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31540669

RESUMO

BACKGROUND: The Xp22.11 locus that encompasses PTCHD1, DDX53, and the long noncoding RNA PTCHD1-AS is frequently disrupted in male subjects with autism spectrum disorder (ASD), but the functional consequences of these genetic risk factors for ASD are unknown. METHODS: To evaluate the functional consequences of PTCHD1 locus deletions, we generated induced pluripotent stem cells (iPSCs) from unaffected control subjects and 3 subjects with ASD with microdeletions affecting PTCHD1-AS/PTCHD1, PTCHD1-AS/DDX53, or PTCHD1-AS alone. Function of iPSC-derived cortical neurons was assessed using molecular approaches and electrophysiology. We also compiled novel and known genetic variants of the PTCHD1 locus to explore the roles of PTCHD1 and PTCHD1-AS in genetic risk for ASD and other neurodevelopmental disorders. Finally, genome editing was used to explore the functional consequences of deleting a single conserved exon of PTCHD1-AS. RESULTS: iPSC-derived neurons from subjects with ASD exhibited reduced miniature excitatory postsynaptic current frequency and N-methyl-D-aspartate receptor hypofunction. We found that 35 ASD-associated deletions mapping to the PTCHD1 locus disrupted exons of PTCHD1-AS. We also found a novel ASD-associated deletion of PTCHD1-AS exon 3 and showed that exon 3 loss altered PTCHD1-AS splicing without affecting expression of the neighboring PTCHD1 coding gene. Finally, targeted disruption of PTCHD1-AS exon 3 recapitulated diminished miniature excitatory postsynaptic current frequency, supporting a role for the long noncoding RNA in the etiology of ASD. CONCLUSIONS: Our genetic findings provide strong evidence that PTCHD1-AS deletions are risk factors for ASD, and human iPSC-derived neurons implicate these deletions in the neurophysiology of excitatory synapses and in ASD-associated synaptic impairment.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Células-Tronco Pluripotentes Induzidas , Transtorno do Espectro Autista/genética , Transtorno Autístico/genética , Humanos , Masculino , Proteínas de Membrana , Neurônios , Sinapses
18.
Infant Behav Dev ; 54: 37-47, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30557704

RESUMO

Motor difficulties may be an early Autism Spectrum Disorder (ASD) risk indicator and may predict subsequent expressive language skills. Further understanding of motor functioning in the first year of life in children with ASD is needed. We examined motor skills in 6-month-olds (n = 140) at high and low familial risk for ASD using the Peabody Developmental Motor Scales (Grasping, Visual-Motor Integration, and Stationary subscales). In Study 1, motor skill at 6 months predicted ASD status at 24-36 months; ASD was associated with poorer infant motor skills. In Study 2, motor skill at 6 months predicted expressive language at 30 and 36 months. Findings provide evidence that vulnerability in motor function early in development is present in ASD. Findings highlight the importance of developmental monitoring in high-risk infants and possible cascading effects of early disruption in motor development.


Assuntos
Transtorno do Espectro Autista/diagnóstico , Transtorno do Espectro Autista/psicologia , Desenvolvimento Infantil/fisiologia , Desenvolvimento da Linguagem , Destreza Motora/fisiologia , Transtorno do Espectro Autista/fisiopatologia , Pré-Escolar , Feminino , Humanos , Lactente , Idioma , Transtornos do Desenvolvimento da Linguagem/diagnóstico , Transtornos do Desenvolvimento da Linguagem/fisiopatologia , Transtornos do Desenvolvimento da Linguagem/psicologia , Masculino , Valor Preditivo dos Testes , Fatores de Risco
19.
J Autism Dev Disord ; 49(4): 1352-1365, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30488153

RESUMO

Little empirical evidence exists about school-age pragmatic communication or predictors in siblings at heightened familial risk for ASD (HR) and low-risk (LR) controls. The Pragmatic Rating Scale-School-Age (Landa unpublished) was scored for 49 HR siblings and 18 LR controls at 8-12 years. Social-communication and language measures were collected between 14 and 36 months. At 36-months, siblings were classified as ASD (HR-ASD, n = 15), broad autism phenotype (HR-BAP, n = 19), or typically developing (HR-TD, n = 15). Results revealed a pragmatic continuum with significantly better scores for HR-TD than HR-BAP or HR-ASD, and HR-BAP than HR-ASD. Per regression models including all participants, 14-month joint attention initiations predicted school-age pragmatic communication, as did 24-month social-communication and expressive language scores. Early joint attention, social-communication, and language abilities contribute to later pragmatic functioning.


Assuntos
Transtorno Autístico/epidemiologia , Comunicação , Fenótipo , Comportamento Social , Transtorno de Comunicação Social/epidemiologia , Transtorno Autístico/genética , Transtorno Autístico/psicologia , Criança , Feminino , Humanos , Masculino , Irmãos
20.
J Abnorm Psychol ; 128(1): 69-80, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30628809

RESUMO

Research has identified early appearing differences in gross and fine motor abilities in infants at heightened risk (HR) for autism spectrum disorder (ASD) because they are the younger siblings of children with ASD, and it suggests that such differences may be especially apparent among those HR infants themselves eventually diagnosed with ASD. The present study examined overall and item-level performance on the gross (GM) and fine motor (FM) subscales of the Mullen Scales of Early Learning (MSEL) administered at 6 months to a large, geographically diverse sample of HR infants with varying developmental outcomes (ASD, elevated ADOS without ASD, low ADOS without ASD) and to infants with low ASD risk (low risk [LR]). We also explored whether motor abilities assessed at 6 months predicted ASD symptom severity at 36 months. FM (but not GM) performance distinguished all 3 HR groups from LR infants with the weakest performance observed in the HR-Elevated ADOS children, who exhibited multiple differences from both LR and other HR infants in both gross and fine motor skills. Finally, 6-month FM (but not GM) scores significant predicted 36-month ADOS severity scores in the HR group; but no evidence was found of specific early appearing motor signs associated with a later ASD diagnosis. Vulnerabilities in infants' fine and gross motor skills may have significant consequences for later development not only in the motor domain but in other domains. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Assuntos
Transtorno do Espectro Autista/psicologia , Destreza Motora , Irmãos/psicologia , Transtorno do Espectro Autista/diagnóstico , Pré-Escolar , Feminino , Predisposição Genética para Doença , Humanos , Lactente , Masculino , Fatores de Risco
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