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Sensory differences are included in the DSM-5 criteria of autism for the first time, yet it is unclear how they relate to neural indicators of perception. We studied early brain signatures of perception and examined their relationship to sensory behaviors and autistic traits. Thirteen autistic children and 13 Typically Developing (TD) children matched on age and nonverbal IQ participated in a passive oddball task, during which P1 habituation and P1 and MMN discrimination were evoked by pure tones. Autistic children had less neural habituation than the TD comparison group, and the MMN, but not P1, mapped on to sensory overresponsivity. Findings highlight the significance of temporal and contextual factors in neural information processing as it relates to autistic traits and sensory behaviors.
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Transtorno do Espectro Autista , Transtorno Autístico , Criança , Humanos , Transtorno Autístico/diagnóstico , Eletroencefalografia , Estimulação Acústica , Habituação Psicofisiológica/fisiologia , Transtorno do Espectro Autista/diagnóstico , Encéfalo , Percepção Auditiva/fisiologia , Potenciais Evocados Auditivos/fisiologiaRESUMO
BACKGROUND: Differences in responding to sensory stimuli, including sensory hyperreactivity (HYPER), hyporeactivity (HYPO), and sensory seeking (SEEK) have been observed in autistic individuals across sensory modalities, but few studies have examined the structure of these "supra-modal" traits in the autistic population. METHODS: Leveraging a combined sample of 3868 autistic youth drawn from 12 distinct data sources (ages 3-18 years and representing the full range of cognitive ability), the current study used modern psychometric and meta-analytic techniques to interrogate the latent structure and correlates of caregiver-reported HYPER, HYPO, and SEEK within and across sensory modalities. Bifactor statistical indices were used to both evaluate the strength of a "general response pattern" factor for each supra-modal construct and determine the added value of "modality-specific response pattern" scores (e.g., Visual HYPER). Bayesian random-effects integrative data analysis models were used to examine the clinical and demographic correlates of all interpretable HYPER, HYPO, and SEEK (sub)constructs. RESULTS: All modality-specific HYPER subconstructs could be reliably and validly measured, whereas certain modality-specific HYPO and SEEK subconstructs were psychometrically inadequate when measured using existing items. Bifactor analyses supported the validity of a supra-modal HYPER construct (ωH = .800) but not a supra-modal HYPO construct (ωH = .653), and supra-modal SEEK models suggested a more limited version of the construct that excluded some sensory modalities (ωH = .800; 4/7 modalities). Modality-specific subscales demonstrated significant added value for all response patterns. Meta-analytic correlations varied by construct, although sensory features tended to correlate most with other domains of core autism features and co-occurring psychiatric symptoms (with general HYPER and speech HYPO demonstrating the largest numbers of practically significant correlations). LIMITATIONS: Conclusions may not be generalizable beyond the specific pool of items used in the current study, which was limited to caregiver report of observable behaviors and excluded multisensory items that reflect many "real-world" sensory experiences. CONCLUSION: Of the three sensory response patterns, only HYPER demonstrated sufficient evidence for valid interpretation at the supra-modal level, whereas supra-modal HYPO/SEEK constructs demonstrated substantial psychometric limitations. For clinicians and researchers seeking to characterize sensory reactivity in autism, modality-specific response pattern scores may represent viable alternatives that overcome many of these limitations.
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Transtorno Autístico , Adolescente , Humanos , Teorema de Bayes , Cognição , Análise de Dados , FenótipoRESUMO
The current study examined factorial invariance of the Center for Epidemiologic Studies Depression Scale-Revised (CESD-R) and the Depression Anxiety Stress Scales-21 (DASS-21) using a convenience sample of 434 adults surveyed though Amazon Mechanical Turk. Participants were sorted into two groups based on their score on the Autism-Spectrum Quotient. Results indicated that the CESD-R did not demonstrate configural invariance. The DASS-21 demonstrated evidence of scalar invariance, indicating cross-group equality in factor loadings and factor intercepts. Findings suggest that the DASS-21 measures symptoms of depression, anxiety, and stress consistently across individuals with high and low levels of ASD-related traits, whereas the CESD-R may not be valid when assessing symptoms of depression in those with a high level of ASD-related traits.
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Background Differences in responding to sensory stimuli, including sensory hyperreactivity (HYPER), hyporeactivity (HYPO), and sensory seeking (SEEK) have been observed in autistic individuals across sensory modalities, but few studies have examined the structure of these "supra-modal" traits in the autistic population. Methods Leveraging a combined sample of 3,868 autistic youth drawn from 12 distinct data sources (ages 3-18 years and representing the full range of cognitive ability), the current study used modern psychometric and meta-analytic techniques to interrogate the latent structure and correlates of caregiver-reported HYPER, HYPO, and SEEK within and across sensory modalities. Bifactor statistical indices were used to both evaluate the strength of a "general response pattern" factor for each supra-modal construct and determine the added value of "modality-specific response pattern" scores (e.g., Visual HYPER). Bayesian random-effects integrative data analysis models were used to examine the clinical and demographic correlates of all interpretable HYPER, HYPO and SEEK (sub)constructs. Results All modality-specific HYPER subconstructs could be reliably and validly measured, whereas certain modality-specific HYPO and SEEK subconstructs were psychometrically inadequate when measured using existing items. Bifactor analyses unambiguously supported the validity of a supra-modal HYPER construct (ω H = .800), whereas a coherent supra-modal HYPO construct was not supported (ω H = .611), and supra-modal SEEK models suggested a more limited version of the construct that excluded some sensory modalities (ω H = .799; 4/7 modalities). Within each sensory construct, modality-specific subscales demonstrated substantial added value beyond the supra-modal score. Meta-analytic correlations varied by construct, although sensory features tended to correlate most strongly with other domains of core autism features and co-occurring psychiatric symptoms. Certain subconstructs within the HYPO and SEEK domains were also associated with lower adaptive behavior scores. Limitations: Conclusions may not be generalizable beyond the specific pool of items used in the current study, which was limited to parent-report of observable behaviors and excluded multisensory items that reflect many "real-world" sensory experiences. Conclusion Psychometric issues may limit the degree to which some measures of supra-modal HYPO/SEEK can be interpreted. Depending on the research question at hand, modality-specific response pattern scores may represent a valid alternative method of characterizing sensory reactivity in autism.
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This study characterizes the subcortical auditory brainstem response (speech-ABR) and cortical auditory processing (P1 and Mismatch Negativity; MMN) to speech sounds and their relationship to autistic traits and sensory features within the same group of autistic children (n = 10) matched on age and non-verbal IQ to their typically developing (TD) peers (n = 21). No speech-ABR differences were noted, but autistic individuals had larger P1 and faster MMN responses. Correlations revealed that larger P1 amplitudes and MMN responses were associated with greater autistic traits and more sensory features. These findings highlight the complexity of the auditory system and its relationships to behaviours in autism, while also emphasizing the importance of measurement and developmental matching.
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BACKGROUND: Omalizumab has been found to improve outcomes in patients with chronic spontaneous urticaria (CSU). Idiopathic angioedema (IAE) is increasingly being recognized as a condition with similar underlying mechanisms as CSU and a form of CSU. We hypothesized that add-on therapy with omalizumab would benefit patients with uncontrolled IAE. OBJECTIVE: To study the safety and efficacy of omalizumab for the treatment of IAE in adults. METHODS: We conducted a randomized, placebo-controlled trial to study the efficacy of omalizumab in adults with 2 or more episodes of angioedema (AE) in the past 6 months for which no clinical or laboratory cause of AE could be found. A total of 10 patients were randomized on a 1:1 basis to receive omalizumab 300 mg subcutaneously or placebo every 4 weeks for 24 weeks with a 12-week follow-up period. The primary endpoint was the change in the Angioedema Activity Score. Secondary endpoints included the Angioedema Quality of Life Questionnaire, the Visual Analogue Scale, and the number of angioedema episodes per month. RESULTS: We observed improvement in the Angioedema Activity Score (-2.93 ln odds; 95% confidence interval [CI], -4.84 to -1.02; P = .003), Visual Analogue Scale (-3.49 ln odds; 95% CI, -6.58 to -0.40; P = .03), Angioedema Quality of Life Questionnaire (-9.43 score; 95% CI, -17.63 to -1.24; P = .03), and number of angioedema episodes per month (-1.93 ln count; 95% CI, -3.23 to -0.63; P = .005) in patients who received omalizumab vs placebo. CONCLUSION: This study provides preliminary prospective evidence that omalizumab improves outcomes in patients with IAE. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02966314. CLINICALTRIALS: gov URL:https://clinicaltrials.gov/ct2/show/NCT02966314?term=omalizumab&cond=Angioedema&draw=2&rank=1.
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Angioedema , Antialérgicos , Urticária Crônica , Urticária , Adulto , Humanos , Omalizumab/efeitos adversos , Urticária/tratamento farmacológico , Qualidade de Vida , Estudos Prospectivos , Doença Crônica , Angioedema/induzido quimicamente , Resultado do TratamentoRESUMO
Data science advances in behavioral signal processing and machine learning hold the promise to automatically quantify clinically meaningful behaviors that can be applied to a large amount of data. The objective of this study was to identify an automated behavioral marker of treatment response in social communication in children with autism spectrum disorder (ASD). First, using an automated computational method, we successfully derived the amount of time it took for a child with ASD and an adult social partner (N pairs = 210) to respond to each other while they were engaged in conversation bits ("latency") using recordings of brief, natural social interactions. Then, we measured changes in latency at pre- and post-interventions. Children with ASD who were receiving interventions showed significantly larger reduction in latency compared to those who were not receiving interventions. There was also a significant group difference in the changes in latency for adult social partners. Results suggest that the automated measure of latency derived from natural social interactions is a scalable and objective method to quantify treatment response in children with ASD.
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Transtorno do Espectro Autista , Transtorno do Espectro Autista/terapia , Criança , Comunicação , HumanosRESUMO
OBJECTIVE: This study compared language profiles of children with autism spectrum disorder (ASD) and typically developing (TD) children at kindergarten-entry and investigated whether kindergarten-entry language scores were predictive of concurrent and future academic achievement, peer interactions, and adaptive skills in children with ASD. METHOD: Participants included 97 children (62 children with ASD; 35 TD children) assessed at kindergarten-entry and -exit. Language abilities were assessed using the Children's Communication Checklist-2 (CCC-2). Children with ASD and TD children's language scores were compared at baseline, and the ASD group was followed longitudinally. Regression analyses were performed to compare language scores between ASD and TD groups and to predict concurrent and future functional skills from kindergarten-entry language scores for children with ASD. RESULTS: Children with ASD demonstrated significantly more impairments across all scales of the CCC-2 at kindergarten-entry compared to TD children. Within the ASD group, kindergarten-entry pragmatic language significantly predicted concurrent math and reading achievement. Both syntactic/semantic and pragmatic domains significantly predicted kindergarten-exit reading performance; pragmatics significantly predicted kindergarten-exit math performance. Pragmatics also predicted concurrent and kindergarten-exit peer play. Syntax/semantics significantly predicted concurrent adaptive communication skills, whereas pragmatics significantly predicted concurrent adaptive daily living and socialization skills, as well as kindergarten-exit socialization skills. CONCLUSIONS: School-entry language abilities can serve as a valuable predictor of functional outcomes across the kindergarten year for cognitively-able children with ASD. Results highlight the need to target early language abilities to maximize academic, social, and adaptive skills.
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Transtorno do Espectro Autista , Criança , Humanos , Idioma , Testes Neuropsicológicos , Instituições Acadêmicas , SemânticaRESUMO
BACKGROUND: Autism spectrum disorder (ASD) is a complex neurological condition with increasing prevalence. Few tools accurately predict the developmental trajectory of children with ASD. Such tools would allow clinicians to provide accurate prognoses and track the efficacy of therapeutic interventions. Salivary RNAs that reflect the genetic-environmental interactions underlying ASD may provide objective measures of symptom severity and developmental outcomes. This study investigated whether salivary RNAs previously identified in childhood ASD remain perturbed in older children. We also explored whether RNA candidates changed with therapeutic intervention. METHOD: A case-control design was used to characterize levels of 78 saliva RNA candidates among 96 children (48 ASD, 48 non-ASD, mean age: 11 years). Thirty-one children (22 ASD, 9 non-ASD developmental delay, mean age: 4 years) were followed longitudinally to explore changes of RNA candidates during early intervention. Saliva RNA and standardized behavioral assessments were collected for each participant. Associations between candidate RNAs and behavioral scores were determined in both groups via Spearman Correlation. Changes in candidate RNAs across two time-points were assessed in the younger cohort via Wilcoxon rank-sum test. RESULTS: Seven RNAs were associated with VABS-II and BASC scores in the older group ([R] >0.25, FDR< 0.15). Within the younger cohort, 12 RNAs displayed significant changes over time (FDR< 0.05). Three microRNAs were associated with behavioral scores and changed over time (miR-182-5p, miR-146b-5p, miR-374a-5p). CONCLUSION: Several salivary RNAs are strongly associated with autistic behaviors in older individuals with ASD and change as early as three months after therapy initiation in younger children. These molecules could be used to track treatment effectiveness and provide prognoses. Further validation is necessary.
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Previous studies have suggested that sensory overresponsivity in youth with autism spectrum disorder (ASD) may be due to a failure to habituate to stimuli. We examined the relationship between performance on three tactile psychophysical tasks and the construct of sensory overresponsivity in children with and without ASD. Sensory overresponsivity predicted amplitude discrimination with an adapting stimulus, as well as the effect of adaptation, for ASD youth. Results replicate previous research that children with ASD are less affected by the presence of an adapting stimulus as compared to typically developing children, and further suggest that sensory overresponsivity may be the mechanism underlying the observed lack of an adaptation effect in children with ASD.
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Transtorno do Espectro Autista/fisiopatologia , Discriminação Psicológica , Percepção do Tato , Adaptação Fisiológica , Adolescente , Criança , Feminino , Humanos , MasculinoRESUMO
Eosinophils are the prominent inflammatory cell involved in allergic asthma, atopic dermatitis, eosinophilic esophagitis, and hypereosinophilic syndrome and are found in high numbers in local tissue and/or circulating blood of affected patients. There is recent interest in a family of alarmins, including TSLP, IL-25 and IL-33, that are epithelial-derived and released upon stimulation of epithelial cells. Several genome wide association studies have found SNPs in genes encoding IL-33 to be risk factors for asthma. In two studies examining the direct role of IL-33 in eosinophils, there were differences in eosinophil responses. We sought to further characterize activation of eosinophils with IL-33 compared to activation by other cytokines and chemokines. We assessed IL-33 stimulated adhesion, degranulation, chemotaxis and cell surface protein expression in comparison to IL-3, IL-5, and eotaxin-1 on human eosinophils. Our results demonstrate that IL-33 can produce as potent eosinophil activation as IL-3, IL-5 and eotaxin-1. Thus, when considering specific cytokine targeting strategies, IL-33 will be important to consider for modulating eosinophil function.