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1.
Artículo en Inglés | MEDLINE | ID: mdl-39237004

RESUMEN

BACKGROUND: Reduced social attention - looking at faces - is one of the most common manifestations of social difficulty in autism central to social development. Although reduced social attention is well-characterized in autism, qualitative differences in how social attention unfolds across time remains unknown. METHODS: We used a computational modeling (i.e., hidden Markov modeling) approach to assess and compare the spatiotemporal dynamics of social attention in a large, well-characterized sample of autistic (n = 280) and neurotypical (n = 120) children (ages 6-11) that completed three social eye-tracking assays across three longitudinal time points (Baseline, 6 weeks, 24 weeks). RESULTS: Our analysis supported the existence of two common eye movement patterns that emerged across three ET assays. A focused pattern was characterized by small face regions of interest, which had high probability of capturing fixations early in visual processing. In contrast, an exploratory pattern was characterized by larger face regions of interest, with lower initial probability of fixation, and more non-social regions of interest. In the context of social perception, autistic children showed significantly more exploratory eye movement patterns than neurotypical children across all social perception assays and all three longitudinal time points. Eye movement patterns were associated with clinical features of autism, including adaptive function, face recognition, and autism symptom severity. CONCLUSIONS: Decreased likelihood of precisely looking to faces early in social visual processing may be an important feature of autism that was associated with autism-related symptomology and may reflect less visual sensitivity to face information.

2.
Clin Neurophysiol ; 165: 55-63, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38959536

RESUMEN

OBJECTIVE: Electroencephalography (EEG) measures of visual evoked potentials (VEPs) provide a targeted approach for investigating neural circuit dynamics. This study separately analyses phase-locked (evoked) and non-phase-locked (induced) gamma responses within the VEP to comprehensively investigate circuit differences in autism. METHODS: We analyzed VEP data from 237 autistic and 114 typically developing (TD) children aged 6-11, collected through the Autism Biomarkers Consortium for Clinical Trials (ABC-CT). Evoked and induced gamma (30-90 Hz) responses were separately quantified using a wavelet-based time-frequency analysis, and group differences were evaluated using a permutation-based clustering procedure. RESULTS: Autistic children exhibited reduced evoked gamma power but increased induced gamma power compared to TD peers. Group differences in induced responses showed the most prominent effect size and remained statistically significant after excluding outliers. CONCLUSIONS: Our study corroborates recent research indicating diminished evoked gamma responses in children with autism. Additionally, we observed a pronounced increase in induced power. Building upon existing ABC-CT findings, these results highlight the potential to detect variations in gamma-related neural activity, despite the absence of significant group differences in time-domain VEP components. SIGNIFICANCE: The contrasting patterns of decreased evoked and increased induced gamma activity in autistic children suggest that a combination of different EEG metrics may provide a clearer characterization of autism-related circuitry than individual markers alone.


Asunto(s)
Trastorno Autístico , Electroencefalografía , Potenciales Evocados Visuales , Ritmo Gamma , Humanos , Potenciales Evocados Visuales/fisiología , Masculino , Niño , Femenino , Ritmo Gamma/fisiología , Trastorno Autístico/fisiopatología , Electroencefalografía/métodos , Estimulación Luminosa/métodos
3.
Autism Res ; 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39080977

RESUMEN

This preliminary study sought to assess biomarkers of attention using electroencephalography (EEG) and eye tracking in two ultra-rare monogenic populations associated with autism spectrum disorder (ASD). Relative to idiopathic ASD (n = 12) and neurotypical comparison (n = 49) groups, divergent attention profiles were observed for the monogenic groups, such that individuals with DYRK1A (n = 9) exhibited diminished auditory attention condition differences during an oddball EEG paradigm whereas individuals with SCN2A (n = 5) exhibited diminished visual attention condition differences noted by eye gaze tracking when viewing social interactions. Findings provide initial support for alignment of auditory and visual attention markers in idiopathic ASD and neurotypical development but not monogenic groups. These results support ongoing efforts to develop translational ASD biomarkers within the attention domain.

4.
Autism Res ; 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38984666

RESUMEN

One of the candidate genes related to language variability in individuals with Autism Spectrum Disorder (ASD) is the contactin-associated protein-like 2 gene (CNTNAP2), a member of the Neurexin family. However, due to the different assessment tools used, it is unknown whether the polymorphisms of the CNTNAP2 gene are linked to structural language skills or more general communication abilities. A total of 302 youth aged 7 to 18 years participated in the present study: 131 verbal youth with ASD (62 female), 130 typically developing (TD) youth (64 female), and 41 unaffected siblings (US) of youth with ASD (25 female). Blood samples were collected to obtain genomic DNA and processed by the Rutgers University Cell and Data Repository or using standard protocols (Gentra Puregene Blood DNA extraction kit; Qiagen). Language and verbal communication skills were screened with the Clinical Evaluation of Language Fundamental-4 (CELF-4) and Vineland-II Communication domain, subsequently. The results showed that the polymorphism of CNTNAP2 (SNP rs2710102) was related to structural language abilities, such that participants carrying the A-allele had lower language skills in comparison to the G-allele homozygotes. No relationship was found between the polymorphism of CNTNAP2 and more general communication abilities. Although the study revealed genetic mechanisms that are associated with CELF-4 measures but not Vineland-II in youth with ASD, follow-up studies are needed that will include measures of language and communication that are less correlated to each other as well as will include a group of minimally and/or non-verbal individuals with ASD.

5.
J Autism Dev Disord ; 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38809474

RESUMEN

Specialized multidisciplinary supports are important for long-term outcomes for autistic youth. Although family and child factors predict service utilization in autism, little is known with respect to youth with rare, autism-associated genetic variants, who frequently have increased psychiatric, developmental, and behavioral needs. We investigate the impact of family factors on service utilization to determine whether caregiver (autistic features, education, income) and child (autistic features, sex, age, IQ, co-occurring conditions) factors predicted service type (e.g., speech, occupational, behavioral) and intensity (hours/year) among children with autism-associated variants (N = 125), some of whom also had a confirmed ASD diagnosis. Analyses revealed variability in the types of services used across a range of child demographic, behavioral, and mental health characteristics. Speech therapy was the most received service (87.2%). Importantly, behavior therapy was the least received service and post-hoc analyses revealed that use of this therapy was uniquely predicted by ASD diagnosis. However, once children received a particular service, there was largely comparable intensity of services, independent of caregiver and child factors. Findings suggest that demographic and clinical factors impact families' ability to obtain services, with less impact on the intensity of services received. The low receipt of therapies that specifically address core support needs in autism (i.e., behavior therapy) indicates more research is needed on the availability of these services for youth with autism-associated variants, particularly for those who do not meet criteria for an ASD diagnosis but do demonstrate elevated and impactful child autistic features as compared to the general population.

6.
Mol Autism ; 15(1): 19, 2024 05 07.
Artículo en Inglés | MEDLINE | ID: mdl-38711098

RESUMEN

BACKGROUND: Most children with Autism Spectrum Disorder (ASD) have co-occurring language impairments and some of these autism-specific language difficulties are also present in their non-autistic first-degree relatives. One of the possible neural mechanisms associated with variability in language functioning is alterations in cortical gamma-band oscillations, hypothesized to be related to neural excitation and inhibition balance. METHODS: We used a high-density 128-channel electroencephalography (EEG) to register brain response to speech stimuli in a large sex-balanced sample of participants: 125 youth with ASD, 121 typically developing (TD) youth, and 40 unaffected siblings (US) of youth with ASD. Language skills were assessed with Clinical Evaluation of Language Fundamentals. RESULTS: First, during speech processing, we identified significantly elevated gamma power in ASD participants compared to TD controls. Second, across all youth, higher gamma power was associated with lower language skills. Finally, the US group demonstrated an intermediate profile in both language and gamma power, with nonverbal IQ mediating the relationship between gamma power and language skills. LIMITATIONS: We only focused on one of the possible neural contributors to variability in language functioning. Also, the US group consisted of a smaller number of participants in comparison to the ASD or TD groups. Finally, due to the timing issue in EEG system we have provided only non-phase-locked analysis. CONCLUSIONS: Autistic youth showed elevated gamma power, suggesting higher excitation in the brain in response to speech stimuli and elevated gamma power was related to lower language skills. The US group showed an intermediate pattern of gamma activity, suggesting that the broader autism phenotype extends to neural profiles.


Asunto(s)
Trastorno del Espectro Autista , Electroencefalografía , Ritmo Gamma , Humanos , Trastorno del Espectro Autista/fisiopatología , Trastorno del Espectro Autista/psicología , Masculino , Femenino , Adolescente , Niño , Lenguaje , Familia , Hermanos
7.
J Neurodev Disord ; 16(1): 15, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38622540

RESUMEN

BACKGROUND: Neurodevelopmental conditions such as intellectual disability (ID) and autism spectrum disorder (ASD) can stem from a broad array of inherited and de novo genetic differences, with marked physiological and behavioral impacts. We currently know little about the psychiatric phenotypes of rare genetic variants associated with ASD, despite heightened risk of psychiatric concerns in ASD more broadly. Understanding behavioral features of these variants can identify shared versus specific phenotypes across gene groups, facilitate mechanistic models, and provide prognostic insights to inform clinical practice. In this paper, we evaluate behavioral features within three gene groups associated with ID and ASD - ADNP, CHD8, and DYRK1A - with two aims: (1) characterize phenotypes across behavioral domains of anxiety, depression, ADHD, and challenging behavior; and (2) understand whether age and early developmental milestones are associated with later mental health outcomes. METHODS: Phenotypic data were obtained for youth with disruptive variants in ADNP, CHD8, or DYRK1A (N = 65, mean age = 8.7 years, 40% female) within a long-running, genetics-first study. Standardized caregiver-report measures of mental health features (anxiety, depression, attention-deficit/hyperactivity, oppositional behavior) and developmental history were extracted and analyzed for effects of gene group, age, and early developmental milestones on mental health features. RESULTS: Patterns of mental health features varied by group, with anxiety most prominent for CHD8, oppositional features overrepresented among ADNP, and attentional and depressive features most prominent for DYRK1A. For the full sample, age was positively associated with anxiety features, such that elevations in anxiety relative to same-age and same-sex peers may worsen with increasing age. Predictive utility of early developmental milestones was limited, with evidence of early language delays predicting greater difficulties across behavioral domains only for the CHD8 group. CONCLUSIONS: Despite shared associations with autism and intellectual disability, disruptive variants in ADNP, CHD8, and DYRK1A may yield variable psychiatric phenotypes among children and adolescents. With replication in larger samples over time, efforts such as these may contribute to improved clinical care for affected children and adolescents, allow for earlier identification of emerging mental health difficulties, and promote early intervention to alleviate concerns and improve quality of life.


Asunto(s)
Trastorno del Espectro Autista , Discapacidad Intelectual , Trastornos del Neurodesarrollo , Adolescente , Niño , Femenino , Humanos , Masculino , Trastorno del Espectro Autista/complicaciones , Proteínas de Unión al ADN/genética , Proteínas de Homeodominio/genética , Discapacidad Intelectual/genética , Discapacidad Intelectual/complicaciones , Salud Mental , Proteínas del Tejido Nervioso/genética , Trastornos del Neurodesarrollo/genética , Trastornos del Neurodesarrollo/complicaciones , Calidad de Vida , Factores de Transcripción/genética
9.
BMC Ophthalmol ; 24(1): 133, 2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38532367

RESUMEN

BACKGROUND: To describe and analyze the real-life refractive, functional and safety outcomes of the Clareon® intraocular lens (IOL) after 3 years. METHODS: Data was collected retrospectively for observational purposes between July 2017 and December 2019 in the ophthalmology department of Desgenettes military hospital in Lyon, France. Eyes that underwent cataract surgery with Claeron® implantation were consecutively included. Patients with a systemic or ocular condition that could affect the visual outcome were excluded. Postoperative corrected (CDVA) and uncorrected (UDVA) distance visual acuities as well as capsule and IOL transparency were assessed at 1 month and 3 years. RESULTS: A total of 326 eyes were analyzed at one month and 191 eyes were reassessed at the 3-year follow-up visit. At 3 years, the mean CDVA was 0.003 LogMAR (95% confidence interval [CI]: -0.003 to -0.01) and the mean UDVA was 0.075 (95% CI: 0.054 to 0.095). Three quarters of the patients had an UDVA ≥ 0.097 logMAR (20/25 Snellen equivalent) and 50% had an UDVA ≥ 0 (20/20). The absence of glistening was reported in 95.3% of cases and 4.7% [9] of patients experienced a clinically significant posterior capsular opacification (PCO) for which Nd:YAG treatment was required. CONCLUSIONS: This real-life study reports high-performance and stable long-term refractive outcomes of the Clareon® IOL with good safety in terms of PCO and glistening.


Asunto(s)
Opacificación Capsular , Extracción de Catarata , Lentes Intraoculares , Facoemulsificación , Humanos , Implantación de Lentes Intraoculares , Estudios Retrospectivos , Agudeza Visual , Refracción Ocular , Diseño de Prótesis
10.
medRxiv ; 2024 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-38293138

RESUMEN

Neurodevelopmental proteasomopathies represent a distinctive category of neurodevelopmental disorders (NDD) characterized by genetic variations within the 26S proteasome, a protein complex governing eukaryotic cellular protein homeostasis. In our comprehensive study, we identified 23 unique variants in PSMC5 , which encodes the AAA-ATPase proteasome subunit PSMC5/Rpt6, causing syndromic NDD in 38 unrelated individuals. Overexpression of PSMC5 variants altered human hippocampal neuron morphology, while PSMC5 knockdown led to impaired reversal learning in flies and loss of excitatory synapses in rat hippocampal neurons. PSMC5 loss-of-function resulted in abnormal protein aggregation, profoundly impacting innate immune signaling, mitophagy rates, and lipid metabolism in affected individuals. Importantly, targeting key components of the integrated stress response, such as PKR and GCN2 kinases, ameliorated immune dysregulations in cells from affected individuals. These findings significantly advance our understanding of the molecular mechanisms underlying neurodevelopmental proteasomopathies, provide links to research in neurodegenerative diseases, and open up potential therapeutic avenues.

11.
Autism Res ; 17(1): 55-65, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37987233

RESUMEN

Differences in social motivation underlie the core social-communication features of autism according to several theoretical models, with decreased social motivation among autistic youth relative to neurotypical peers. However, research on social motivation often relies on caregiver reports and rarely includes firsthand perspectives of children and adolescents with autism. Furthermore, social motivation is typically assumed to be constant across social settings when it may actually vary by social context. Among a sample of 58 verbally fluent youth (8-13 years old; 22 with autism, 36 neurotypical), we examined correspondence between youth and caregiver reports of social motivation with peers and with adults, as well as diagnostic group differences and associations with social outcomes. Results suggest youth and caregivers provide overlapping but distinct information. Autistic youth had lower levels of social motivation relative to neurotypical youth, and reported relatively consistent motivation toward peers and adults. Youth self- and caregiver-report were correlated for motivation toward adults, but not toward peers. Despite low correspondence between self- and caregiver-reported motivation toward peers, autistic youths' self-report corresponded to caregiver-reported social skills and difficulties whereas caregiver-report of peer motivation did not. For neurotypical youth, self- and caregiver-reported motivation toward adults was correlated, but motivation by both reporters was largely independent of broader social outcomes. Findings highlight the unique value of self-report among autistic children and adolescents, and warrant additional work exploring the development, structure, and correlates of social motivation among autistic and neurotypical youth.


Asunto(s)
Trastorno del Espectro Autista , Trastorno Autístico , Niño , Adulto , Humanos , Adolescente , Cuidadores , Motivación , Habilidades Sociales
12.
Dev Psychobiol ; 65(7): e22415, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37860899

RESUMEN

Autistic and comparison individuals differ in resting-state electroencephalography (EEG), such that sex and age explain variability within and between groups. Pubertal maturation and timing may further explain variation, as previous work has suggested alterations in pubertal timing in autistic youth. In a sample from two studies of 181 autistic and 94 comparison youth (8 years to 17 years and 11 months), mixed-effects linear regressions were conducted to assess differences in EEG (midline power for theta, alpha, and beta frequency bands). Alpha power was analyzed as a mediator in the relation between pubertal maturation and timing with autistic traits in the autistic groups to understand the role of puberty in brain-based changes that contribute to functional outcomes. Individuals advanced in puberty exhibited decreased power in all bands. Those who experienced puberty relatively early showed decreased power in theta and beta bands, controlling for age, sex, and diagnosis. Autistic individuals further along in pubertal development exhibited lower social skills. Alpha mediated the relation between puberty and repetitive behaviors. Pubertal maturation and timing appear to play unique roles in the development of cognitive processes for autistic and comparison youth and should be considered in research on developmental variation in resting-state EEG.


Asunto(s)
Trastorno Autístico , Humanos , Adolescente , Electroencefalografía , Encéfalo , Pubertad , Habilidades Sociales
13.
JAMA ; 330(9): 854-865, 2023 09 05.
Artículo en Inglés | MEDLINE | ID: mdl-37668621

RESUMEN

Importance: In the US, children with signs of autism often experience more than 1 year of delay before diagnosis and often experience longer delays if they are from racially, ethnically, or economically disadvantaged backgrounds. Most diagnoses are also received without use of standardized diagnostic instruments. To aid in early autism diagnosis, eye-tracking measurement of social visual engagement has shown potential as a performance-based biomarker. Objective: To evaluate the performance of eye-tracking measurement of social visual engagement (index test) relative to expert clinical diagnosis in young children referred to specialty autism clinics. Design, Setting, and Participants: In this study of 16- to 30-month-old children enrolled at 6 US specialty centers from April 2018 through May 2019, staff blind to clinical diagnoses used automated devices to measure eye-tracking-based social visual engagement. Expert clinical diagnoses were made using best practice standardized protocols by specialists blind to index test results. This study was completed in a 1-day protocol for each participant. Main Outcomes and Measures: Primary outcome measures were test sensitivity and specificity relative to expert clinical diagnosis. Secondary outcome measures were test correlations with expert clinical assessments of social disability, verbal ability, and nonverbal cognitive ability. Results: Eye-tracking measurement of social visual engagement was successful in 475 (95.2%) of the 499 enrolled children (mean [SD] age, 24.1 [4.4] months; 38 [8.0%] were Asian; 37 [7.8%], Black; 352 [74.1%], White; 44 [9.3%], other; and 68 [14.3%], Hispanic). By expert clinical diagnosis, 221 children (46.5%) had autism and 254 (53.5%) did not. In all children, measurement of social visual engagement had sensitivity of 71.0% (95% CI, 64.7% to 76.6%) and specificity of 80.7% (95% CI, 75.4% to 85.1%). In the subgroup of 335 children whose autism diagnosis was certain, sensitivity was 78.0% (95% CI, 70.7% to 83.9%) and specificity was 85.4% (95% CI, 79.5% to 89.8%). Eye-tracking test results correlated with expert clinical assessments of individual levels of social disability (r = -0.75 [95% CI, -0.79 to -0.71]), verbal ability (r = 0.65 [95% CI, 0.59 to 0.70]), and nonverbal cognitive ability (r = 0.65 [95% CI, 0.59 to 0.70]). Conclusions and Relevance: In 16- to 30-month-old children referred to specialty clinics, eye-tracking-based measurement of social visual engagement was predictive of autism diagnoses by clinical experts. Further evaluation of this test's role in early diagnosis and assessment of autism in routine specialty clinic practice is warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT03469986.


Asunto(s)
Trastorno Autístico , Tecnología de Seguimiento Ocular , Conducta Social , Percepción Visual , Preescolar , Humanos , Lactante , Instituciones de Atención Ambulatoria , Asiático , Trastorno Autístico/diagnóstico , Trastorno Autístico/fisiopatología , Trastorno Autístico/psicología , Movimientos Oculares/fisiología
14.
Autism Res ; 16(12): 2364-2377, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37776030

RESUMEN

In youth broadly, EEG frontal alpha asymmetry (FAA) associates with affective style and vulnerability to psychopathology, with relatively stronger right activity predicting risk for internalizing and externalizing behaviors. In autistic youth, FAA has been related to ASD diagnostic features and to internalizing symptoms. Among our large, rigorously characterized, sex-balanced participant group, we attempted to replicate findings suggestive of altered FAA in youth with an ASD diagnosis, examining group differences and impact of sex assigned at birth. Second, we examined relations between FAA and behavioral variables (ASD features, internalizing, and externalizing) within autistic youth, examining effects by sex. Third, we explored whether the relation between FAA, autism features, and mental health was informed by maternal depression history. In our sample, FAA did not differ by diagnosis, age, or sex. However, youth with ASD had lower total frontal alpha power than youth without ASD. For autistic females, FAA and bilateral frontal alpha power correlated with social communication features, but not with internalizing or externalizing symptoms. For autistic males, EEG markers correlated with social communication features, and with externalizing behaviors. Exploratory analyses by sex revealed further associations between youth FAA, behavioral indices, and maternal depression history. In summary, findings suggest that individual differences in FAA may correspond to social-emotional and mental health behaviors, with different patterns of association for females and males with ASD. Longitudinal consideration of individual differences across levels of analysis (e.g., biomarkers, family factors, and environmental influences) will be essential to parsing out models of risk and resilience among autistic youth.


Asunto(s)
Trastorno del Espectro Autista , Trastorno Autístico , Recién Nacido , Humanos , Masculino , Femenino , Adolescente , Trastorno Autístico/complicaciones , Caracteres Sexuales , Trastorno del Espectro Autista/psicología , Emociones , Electroencefalografía
15.
Autism Res ; 16(11): 2150-2159, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37749934

RESUMEN

The Selective Social Attention (SSA) task is a brief eye-tracking task involving experimental conditions varying along socio-communicative axes. Traditionally the SSA has been used to probe socially-specific attentional patterns in infants and toddlers who develop autism spectrum disorder (ASD). This current work extends these findings to preschool and school-age children. Children 4- to 12-years-old with ASD (N = 23) and a typically-developing comparison group (TD; N = 25) completed the SSA task as well as standardized clinical assessments. Linear mixed models examined group and condition effects on two outcome variables: percent of time spent looking at the scene relative to scene presentation time (%Valid), and percent of time looking at the face relative to time spent looking at the scene (%Face). Age and IQ were included as covariates. Outcome variables' relationships to clinical data were assessed via correlation analysis. The ASD group, compared to the TD group, looked less at the scene and focused less on the actress' face during the most socially-engaging experimental conditions. Additionally, within the ASD group, %Face negatively correlated with SRS total T-scores with a particularly strong negative correlation with the Autistic Mannerism subscale T-score. These results highlight the extensibility of the SSA to older children with ASD, including replication of between-group differences previously seen in infants and toddlers, as well as its ability to capture meaningful clinical variation within the autism spectrum across a wide developmental span inclusive of preschool and school-aged children. The properties suggest that the SSA may have broad potential as a biomarker for ASD.


Asunto(s)
Trastorno del Espectro Autista , Trastorno Autístico , Lactante , Humanos , Preescolar , Niño , Adolescente , Fijación Ocular , Estudios de Factibilidad , Atención , Biomarcadores , Tomografía Computarizada por Rayos X
16.
Autism Res ; 16(8): 1488-1500, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37497568

RESUMEN

Likely gene-disrupting (LGD) variants in DYRK1A are causative of DYRK1A syndrome and associated with autism spectrum disorder (ASD) and intellectual disability (ID). While many individuals with DYRK1A syndrome are diagnosed with ASD, they may present with a unique profile of ASD traits. We present a comprehensive characterization of the ASD profile in children and young adults with LGDs in DYRK1A. Individuals with LGD variants in DYRK1A (n = 29) were compared to children who had ASD with no known genetic cause, either with low nonverbal IQ (n = 14) or average or above nonverbal IQ (n = 41). ASD was assessed using the ADOS-2, ADI-R, SRS-2, SCQ, and RBS-R. Quantitative score comparisons were conducted, as were qualitative analyses of clinicians' behavioral observations. Diagnosis of ASD was confirmed in 85% and ID was confirmed in 89% of participants with DYRK1A syndrome. Individuals with DYRK1A syndrome showed broadly similar social communication behaviors to children with idiopathic ASD and below-average nonverbal IQ, with specific challenges noted in social reciprocity and nonverbal communication. Children with DYRK1A syndrome also showed high rates of sensory-seeking behaviors. Phenotypic characterization of individuals with DYRK1A syndrome may provide additional information on mechanisms contributing to co-occurring ASD and ID and contribute to the identification of genetic predictors of specific ASD traits.


Asunto(s)
Trastorno del Espectro Autista , Trastorno Autístico , Discapacidad Intelectual , Humanos , Trastorno del Espectro Autista/complicaciones , Trastorno Autístico/genética , Trastorno Autístico/complicaciones , Discapacidad Intelectual/epidemiología , Discapacidad Intelectual/genética , Discapacidad Intelectual/complicaciones , Fenotipo , Conducta Social , Quinasas DyrK
17.
J Autism Dev Disord ; 2023 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-37031308

RESUMEN

We aimed to identify unique constellations of sensory phenotypes for genetic etiologies associated with diagnoses of autism spectrum disorder (ASD) and intellectual disability (ID). Caregivers reported on sensory behaviors via the Sensory Profile for 290 participants (younger than 25 years of age) with ASD and/or ID diagnoses, of which ~ 70% have a known pathogenic genetic etiology. Caregivers endorsed poor registration (i.e., high sensory threshold, passive behaviors) for all genetic subgroups relative to an "idiopathic" comparison group with an ASD diagnosis and without a known genetic etiology. Genetic profiles indicated prominent sensory seeking in ADNP, CHD8, and DYRK1A, prominent sensory sensitivities in SCN2A, and fewer sensation avoidance behaviors in GRIN2B (relative to the idiopathic ASD comparison group).

18.
Autism Res ; 16(5): 981-996, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36929131

RESUMEN

Clinical trials in autism spectrum disorder (ASD) often rely on clinician rating scales and parent surveys to measure autism-related features and social behaviors. To aid in the selection of these assessments for future clinical trials, the Autism Biomarkers Consortium for Clinical Trials (ABC-CT) directly compared eight common instruments with respect to acquisition rates, sensitivity to group differences, equivalence across demographic sub-groups, convergent validity, and stability over a 6-week period. The sample included 280 children diagnosed with ASD (65 girls) and 119 neurotypical children (36 girls) aged from 6 to 11 years. Full scale IQ for ASD ranged from 60 to 150 and for neurotypical ranged from 86 to 150. Instruments measured clinician global assessment and autism-related behaviors, social communication abilities, adaptive function, and social withdrawal behavior. For each instrument, we examined only the scales that measured social or communication functioning. Data acquisition rates were at least 97.5% at T1 and 95.7% at T2. All scales distinguished diagnostic groups. Some scales significantly differed by participant and/or family demographic characteristics. Within the ASD group, most clinical instruments exhibited weak (≥ |0.1|) to moderate (≥ |0.4|) intercorrelations. Short-term stability was moderate (ICC: 0.5-0.75) to excellent (ICC: >0.9) within the ASD group. Variations in the degree of stability may inform viability for different contexts of use, such as identifying clinical subgroups for trials versus serving as a modifiable clinical outcome. All instruments were evaluated in terms of their advantages and potential concerns for use in clinical trials.


Asunto(s)
Trastorno del Espectro Autista , Trastorno Autístico , Niño , Femenino , Humanos , Habilidades Sociales , Trastorno del Espectro Autista/diagnóstico , Comunicación , Biomarcadores
19.
J Autism Dev Disord ; 53(8): 3220-3229, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35657448

RESUMEN

Visual exploration paradigms involving object arrays have been used to examine salience of social stimuli such as faces in ASD. Recent work suggests performance on these paradigms may associate with clinical features of ASD. We evaluate metrics from a visual exploration paradigm in 4-to-11-year-old children with ASD (n = 23; 18 males) and typical development (TD; n = 23; 13 males). Presented with arrays containing faces and nonsocial stimuli, children with ASD looked less at (p = 0.002) and showed fewer fixations to (p = 0.022) faces than TD children, and spent less time looking at each object on average (p = 0.004). Attention to the screen and faces correlated positively with social and cognitive skills in the ASD group (ps < .05). This work furthers our understanding of objective measures of visual exploration in ASD and its potential for quantifying features of ASD.


Asunto(s)
Trastorno del Espectro Autista , Masculino , Niño , Humanos , Preescolar , Trastorno del Espectro Autista/diagnóstico , Trastorno del Espectro Autista/psicología , Estudios de Factibilidad , Benchmarking , Tomografía Computarizada por Rayos X
20.
J Autism Dev Disord ; 53(4): 1305-1318, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34859339

RESUMEN

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.


Asunto(s)
Trastorno del Espectro Autista , Trastorno Autístico , Humanos , Masculino , Niño , Femenino , Adolescente , Trastorno del Espectro Autista/diagnóstico , Trastorno del Espectro Autista/epidemiología , Caracteres Sexuales , Lenguaje , Factores Sexuales
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