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1.
Disabil Health J ; 17(3): 101633, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38664150

RESUMO

BACKGROUND: Autistic adults and those with other developmental disabilities (DD) have increased depressive symptoms and decreased activity engagement when compared to those with no DD. Few studies explore activities related to depressive symptoms in autistic people and those with other DD during adolescence. OBJECTIVE: The objectives of this analysis were to describe depressive symptoms and activity engagement among autistic adolescents and those with other DD and no DD and explore types of activities associated with depressive symptoms, stratified by study group. METHODS: Parents of adolescents completed a multi-site case-control study of autism and other DD when their child was 2-5 years of age and a follow-up survey when their child was 12-16 years of age. Questions asked about the adolescent's current diagnoses, depressive symptoms (i.e., diagnosis, medication use, or symptoms), and engagement in club, social, sport, vocational, volunteer, and other organized activities. RESULTS: Autistic adolescents (N = 238) and those with other DD (N = 222) were significantly more likely to have depressive symptoms than adolescents with no DD (N = 406), (31.9 %, 30.6 %, and 15.0 % respectively). Lower percentages of autistic adolescents participated in activities than peers with other DD, who had lower percentages than peers with no DD. Participation in sports was associated with lower likelihood of depressive symptoms in all groups. CONCLUSIONS: Autistic adolescents and those with other DD are at increased risk for depressive symptoms and reduced activity engagement. Participation in sports may be especially important for adolescent mental health regardless of disability status. Implications for public health education and intervention are discussed.


Assuntos
Transtorno Autístico , Depressão , Deficiências do Desenvolvimento , Humanos , Adolescente , Feminino , Masculino , Depressão/epidemiologia , Depressão/psicologia , Deficiências do Desenvolvimento/psicologia , Deficiências do Desenvolvimento/complicações , Estudos de Casos e Controles , Transtorno Autístico/psicologia , Transtorno Autístico/complicações , Criança , Pessoas com Deficiência/psicologia , Pessoas com Deficiência/estatística & dados numéricos , Pais/psicologia , Pré-Escolar , Inquéritos e Questionários , Participação Social/psicologia , Esportes/psicologia , Esportes/estatística & dados numéricos
2.
JAACAP Open ; 2(1): 36-44, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38533351

RESUMO

Objective: Many children with autism spectrum disorder (ASD) and other developmental disabilities (DD) transitioned to telehealth services due to the COVID-19 pandemic. Our objectives were to describe reductions in allied and behavioral healthcare services and receipt of caregiver training to deliver services at home because of COVID-19 for children with ASD and other DD, and factors associated with worse response to remote delivery of services for children with ASD. Method: Prior to the pandemic, children 2 to 5 years of age were enrolled in a multi-site case-control study and completed a developmental assessment. Caregivers completed questionnaires on child behavior problems and ASD symptoms. Children were classified as having ASD vs another DD based on standardized diagnostic measures. Subsequently, caregivers completed a survey during January to June 2021 to assess how COVID-19 affected children and families. Results: Caregivers reported that most children with ASD and other DD had a decrease in service hours (50.0%-76.9% by service type) during the COVID-19 pandemic. Children with ASD were significantly more likely to experience reduced speech/language therapy than children with other DD. Receipt of caregiver training to deliver services at home ranged from 38.1% to 57.4% by service type. Among children with ASD, pre-pandemic problems with internalizing behaviors and social communication/interaction were associated with worse response to behavioral telehealth but no other common therapies. Conclusion: Our study demonstrates the caregiver-reported impacts of COVID-19 on remote delivery of allied and behavioral healthcare services for children with ASD and other DD. Considerations for caregiver support and remote delivery of services are provided.

3.
J Dev Behav Pediatr ; 45(1): e31-e38, 2024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-38364085

RESUMO

OBJECTIVE: Understanding how the COVID-19 pandemic affected children with disabilities is essential for future public health emergencies. We compared children with autism spectrum disorder (ASD) with those with another developmental disability (DD) and from the general population (POP) regarding (1) missed or delayed appointments for regular health/dental services, immunizations, and specialty services; (2) reasons for difficulty accessing care; and (3) use of remote learning and school supports. METHOD: Caregivers of children previously enrolled in the Study to Explore Early Development, a case-control study of children with ASD implemented during 2017 to 2020, were recontacted during January-June 2021 to learn about services during March-December 2020. Children were classified as ASD, DD, or POP during the initial study and were aged 3.4 to 7.5 years when their caregivers were recontacted during the pandemic. RESULTS: Over half of all children missed or delayed regular health/dental appointments (58.4%-65.2%). More children in the ASD versus DD and POP groups missed or delayed specialty services (75.7%, 58.3%, and 22.8%, respectively) and reported difficulties obtaining care of any type because of issues using telehealth and difficulty wearing a mask. During school closures, a smaller proportion of children with ASD versus another DD were offered live online classes (84.3% vs 91.1%), while a larger proportion had disrupted individualized education programs (50.0% vs 36.2%). CONCLUSION: Minimizing service disruptions for all children and ensuring continuity of specialty care for children with ASD is essential for future public health emergencies. Children may need additional services to compensate for disruptions during the pandemic.


Assuntos
Transtorno do Espectro Autista , COVID-19 , Criança , Humanos , Pré-Escolar , Transtorno do Espectro Autista/epidemiologia , Transtorno do Espectro Autista/terapia , Deficiências do Desenvolvimento/epidemiologia , Deficiências do Desenvolvimento/terapia , Pandemias , Estudos de Casos e Controles , Emergências , COVID-19/epidemiologia
4.
Cereb Cortex ; 33(13): 8546-8556, 2023 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-37106572

RESUMO

Autism spectrum disorder (ASD) is associated with episodic memory impairment. However, episodic memories include a variety of contextual details, and it is difficult to solely rely on behavioral data to assess how specifically (i.e. event-specific reinstatement) an event is remembered. We applied encoding-retrieval representational similarity (ERS) analysis to EEG data to assess event-specific ERS for object-context associations in a sample of 34 adults (17 with, 17 without ASD). Participants studied objects presented alongside 2 contextual features: scene/color, and attention was directed toward one object-context relationship. At retrieval, memory was assessed for the object and both contexts. Behavioral results revealed no group differences in item or context memory performance. ERS results revealed group temporal differences in reinstatement. Results may indicate differences in both encoding (i.e. fewer perceptual details) and retrieval (i.e. ineffectively skipping through memory fragments) in ASD and should be further investigated in studies modulating the perceptual detail required for memory decisions. Results highlight the utility of ERS as a methodology used to evaluate episodic reinstatement even in the absence of behavioral differences in memory performance.


Assuntos
Transtorno do Espectro Autista , Memória Episódica , Adulto , Humanos , Rememoração Mental , Atenção , Cognição
5.
Neuroimage ; 247: 118851, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-34954026

RESUMO

Previous studies have attempted to separate single trial neural responses for events a person is likely to remember from those they are likely to forget using machine learning classification methods. Successful single trial classification holds potential for translation into the clinical realm for real-time detection of memory and other cognitive states to provide real-time interventions (i.e., brain-computer interfaces). However, most of these studies-and classification analyses in general- do not make clear if the chosen methodology is optimally suited for the classification of memory-related brain states. To address this problem, we systematically compared different methods for every step of classification (i.e., feature extraction, feature selection, classifier selection) to investigate which methods work best for decoding episodic memory brain states-the first analysis of its kind. Using an adult lifespan sample EEG dataset collected during performance of an episodic context encoding and retrieval task, we found that no specific feature type (including Common Spatial Pattern (CSP)-based features, mean, variance, correlation, features based on AR model, entropy, phase, and phase synchronization) outperformed others consistently in distinguishing different memory classes. However, extracting all of these feature types consistently outperformed extracting only one type of feature. Additionally, the combination of filtering and sequential forward selection was the optimal method to select the effective features compared to filtering alone or performing no feature selection at all. Moreover, although all classifiers performed at a fairly similar level, LASSO was consistently the highest performing classifier compared to other commonly used options (i.e., naïve Bayes, SVM, and logistic regression) while naïve Bayes was the fastest classifier. Lastly, for multiclass classification (i.e., levels of context memory confidence and context feature perception), generalizing the binary classification using the binary decision tree performed better than the voting or one versus rest method. These methods were shown to outperform alternative approaches for three orthogonal datasets (i.e., EEG working memory, EEG motor imagery, and MEG working memory), supporting their generalizability. Our results provide an optimized methodological process for classifying single-trial neural data and provide important insight and recommendations for a cognitive neuroscientist's ability to make informed choices at all stages of the classification process for predicting memory and other cognitive states.


Assuntos
Eletroencefalografia/métodos , Memória Episódica , Adulto , Idoso , Teorema de Bayes , Interfaces Cérebro-Computador , Conjuntos de Dados como Assunto , Feminino , Humanos , Masculino , Rememoração Mental , Pessoa de Meia-Idade
6.
Sci Rep ; 11(1): 20482, 2021 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-34650189

RESUMO

Research on memory in autism spectrum disorder (ASD) finds increased difficulty encoding contextual associations in episodic memory and suggests executive dysfunction (e.g., selective attention, cognitive flexibility) and deficient metacognitive monitoring as potential contributing factors. Findings from our lab suggest that age-related impairments in selective attention contribute to those in context memory accuracy and older adults tended to show dependence in context memory accuracy between relevant and irrelevant context details (i.e., hyper-binding). Using an aging framework, we tested the effects of selective attention on context memory in a sample of 23 adults with ASD and 23 typically developed adults. Participants studied grayscale objects flanked by two types of contexts (color, scene) on opposing sides and were told to attend to only one object-context relationship, ignoring the other context. At test, participants made object and context recognition decisions and judgment of confidence decisions allowing for an evaluation of context memory performance, hyper-binding, and metacognitive performance for context judgments in a single task. Results showed that adults with ASD performed similarly to typically developed adults on all measures. These findings suggest that context memory performance is not always disrupted in adults with ASD, even when demands on selective attention are high. We discuss the need for continued research to evaluate episodic memory in a wider variety of adults with ASD.


Assuntos
Atenção , Transtorno do Espectro Autista/psicologia , Rememoração Mental , Adulto , Cognição , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reconhecimento Psicológico
7.
MMWR Morb Mortal Wkly Rep ; 70(17): 605-611, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33914722

RESUMO

Persons identified in early childhood as having autism spectrum disorder (autism) often have co-occurring health problems that extend into adolescence (1-3). Although only limited data exist on their health and use of health care services as they transition to adolescence, emerging data suggest that a minority of these persons receive recommended guidance* from their primary care providers (PCPs) starting at age 12 years to ensure a planned transition from pediatric to adult health care (4,5). To address this gap in data, researchers analyzed preliminary data from a follow-up survey of parents and guardians of adolescents aged 12-16 years who previously participated in the Study to Explore Early Development (https://www.cdc.gov/ncbddd/autism/seed.html). The adolescents were originally studied at ages 2-5 years and identified at that age as having autism (autism group) or as general population controls (control group). Adjusted prevalence ratios (aPRs) that accounted for differences in demographic characteristics were used to compare outcomes between groups. Adolescents in the autism group were more likely than were those in the control group to have physical difficulties (21.2% versus 1.6%; aPR = 11.6; 95% confidence interval [CI] = 4.2-31.9), and to have additional mental health or other conditions† (one or more condition: 63.0% versus 28.9%; aPR = 1.9; 95% CI = 1.5-2.5). Adolescents in the autism group were more likely to receive mental health services (41.8% versus 22.1%; aPR = 1.8, 95% CI = 1.3-2.6) but were also more likely to have an unmet medical or mental health service need§ (11.0% versus 3.2%; aPR = 3.1; 95% CI = 1.1-8.8). In both groups, a small percentage of adolescents (autism, 7.5%; control, 14.1%) received recommended health care transition (transition) guidance. These findings are consistent with previous research (4,5) indicating that few adolescents receive the recommended transition guidance and suggest that adolescents identified with autism in early childhood are more likely than adolescents in the general population to have unmet health care service needs. Improved provider training on the heath care needs of adolescents with autism and coordination of comprehensive programs¶ to meet their needs can improve delivery of services and adherence to recommended guidance for transitioning from pediatric to adult health care.


Assuntos
Transtorno Autístico/epidemiologia , Nível de Saúde , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Adolescente , Feminino , Humanos , Masculino , Estados Unidos/epidemiologia
8.
eNeuro ; 8(1)2021.
Artigo em Inglês | MEDLINE | ID: mdl-33436445

RESUMO

Episodic memories are multidimensional, including simple and complex features. How we successful encode and recover these features in time, whether these temporal dynamics are preserved across age, even under conditions of reduced memory performance, and the role of attention on these temporal dynamics is unknown. In the current study, we applied time-resolved multivariate decoding to oscillatory electroencephalography (EEG) in an adult lifespan sample to investigate the temporal order of successful encoding and recognition of simple and complex perceptual context features. At encoding, participants studied pictures of black and white objects presented with both color (low-level/simple) and scene (high-level/complex) context features and subsequently made context memory decisions for both features. Attentional demands were manipulated by having participants attend to the relationship between the object and either the color or scene while ignoring the other context feature. Consistent with hierarchical visual perception models, simple visual features (color) were successfully encoded earlier than were complex features (scenes). These features were successfully recognized in the reverse temporal order. Importantly, these temporal dynamics were both dependent on whether these context features were in the focus of one's attention, and preserved across age, despite age-related context memory impairments. These novel results support the idea that episodic memories are encoded and retrieved successively, likely dependent on the input and output pathways of the medial temporal lobe (MTL), and attentional influences that bias activity within these pathways across age.


Assuntos
Longevidade , Memória Episódica , Adulto , Atenção , Mapeamento Encefálico , Humanos , Imageamento por Ressonância Magnética , Lobo Temporal , Percepção Visual
9.
MMWR Morb Mortal Wkly Rep ; 69(34): 1156-1160, 2020 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-32853187

RESUMO

Clinical guidelines recommend that primary care providers (PCPs) provide guidance and support to ensure a planned transition from pediatric to adult health care for adolescents, beginning at age 12 years (1). However, most adolescents do not receive the recommended health care transition planning (2). This is particularly concerning for adolescents with diagnosed mental, behavioral, and developmental disorders (MBDDs) (3), who account for approximately 20% of U.S. adolescents (4). Childhood MBDDs are linked to increased long-term morbidity and mortality; timely health care transition planning might mitigate adverse outcomes (5,6). CDC analyzed pooled, parent-reported data from the 2016 and 2017 National Survey of Children's Health (NSCH), comparing adolescents, aged 12-17 years, with and without MBDDs on a composite measure and specific indicators of recommended health care transition planning by PCPs. Overall, approximately 15% of adolescents received recommended health care transition planning: 15.8% (95% confidence interval [CI] = 14.1%-17.5%) of adolescents with MBDDs, compared with 14.2% (95% CI = 13.2%-15.3%) of adolescents without MBDDs. Relative to peers without MBDDs and after adjusting for age, adolescents with anxiety were 36% more likely to receive recommended health care transition planning, and those with depression were 69% more likely; adolescents with autism spectrum disorder (ASD) were 35% less likely to receive such transition planning, and those with developmental delay* were 25% less likely. Fewer than 20% of adolescents with MBDDs receiving current treatment met the transition measure. These findings suggest that a minority of adolescents with MBDDs receive recommended transition planning, indicating a potential missed public health opportunity to prevent morbidity and mortality in a population at high risk for health care disengagement (1). Improving access to comprehensive and coordinated programs and services,† as well as increasing provider training concerning adolescents' unique mental and physical health care needs (7), could help increase the number of adolescents benefiting from successful health care transitions (4).


Assuntos
Deficiências do Desenvolvimento/terapia , Transtornos Mentais/terapia , Apoio Social , Transição para Assistência do Adulto/organização & administração , Adolescente , Criança , Deficiências do Desenvolvimento/epidemiologia , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Masculino , Transtornos Mentais/epidemiologia , Estados Unidos/epidemiologia
10.
Clin Genet ; 96(3): 199-206, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31038196

RESUMO

Autism spectrum disorder (ASD) is a highly heterogeneous genetic disorder with strong evidence of ASD-association currently available only for a small number of genes. This makes it challenging to identify the underlying genetic cause in many cases of ASD, and there is a continuing need for further discovery efforts. We sequenced whole genomes of 119 deeply phenotyped ASD probands in order to identify likely pathogenic variants. We prioritized variants found in each subject by predicted damage, population frequency, literature evidence, and phenotype concordance. We used Sanger sequencing to determine the inheritance status of high-priority variants where possible. We report five novel de novo damaging variants as well as several likely damaging variants of unknown inheritance; these include two novel de novo variants in the well-established ASD gene SCN2A. The availability of rich phenotypic information and its concordance with the literature allowed us to increase our confidence in pathogenicity of discovered variants, especially in probands without parental DNA. Our results contribute to the documentation of potential pathogenic variants and their associated phenotypes in individuals with ASD.


Assuntos
Transtorno do Espectro Autista/genética , Predisposição Genética para Doença , Variação Genética , Sequenciamento Completo do Genoma , Alelos , Substituição de Aminoácidos , Transtorno do Espectro Autista/diagnóstico , Colúmbia Britânica , Estudos de Coortes , Variações do Número de Cópias de DNA , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Mutação , Fenótipo , Polimorfismo de Nucleotídeo Único
11.
J Autism Dev Disord ; 49(2): 556-568, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30145735

RESUMO

With the increasing prevalence of adults with autism spectrum disorder (ASD), research examining the service experiences of this population is greatly needed. The current study investigated service use, unmet needs, and obstacles to service access for a large sample of adults with ASD. After accounting for various demographic factors known to impact service usage and needs, living situation was a significant predictor of service use, needs, and obstacles to services. Adults with ASD living with family reported less service use, higher unmet need, and more obstacles to accessing services. With more than half of this adult sample living with family, results have clear public policy implications to support the increasing population of adults with ASD living with aging caregivers.


Assuntos
Transtorno do Espectro Autista/epidemiologia , Utilização de Instalações e Serviços/estatística & dados numéricos , Necessidades e Demandas de Serviços de Saúde/normas , Adulto , Transtorno do Espectro Autista/reabilitação , Criança , Família , Feminino , Humanos , Masculino , Características de Residência , Condições Sociais
12.
Neuroimage ; 181: 95-107, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-29991445

RESUMO

Emerging evidence has suggested that the tendency for older adults to bind too much contextual information during encoding (i.e., hyper-binding) may contribute to poorer memory for relevant contextual information during retrieval. While these findings are consistent with theories of age-related declines in selective attention and inhibitory control, the degree to which older adults are able to selectively attend to relevant contextual information during encoding is unknown. To better understand the neural dynamics associated with selective attention during encoding, the current study applied multivariate pattern analyses (MVPA) to oscillatory EEG in order to track moment-to-moment shifts of attention between relevant and irrelevant contextual information during encoding. Young and older adults studied pictures of objects in the presence of two contextual features: a color and a scene, and their attention was directed to the object's relationship with one of those contexts (i.e., target context). Results showed that patterns of oscillatory power successfully predicted whether selective attention was directed to a scene or color, across age groups. Individual differences in overall classification performance were associated with individual differences in target context memory accuracy during retrieval. However, changes in classification performance within a trial, suggestive of fluctuations in selective attention, predicted individual differences in hyper-binding. To the best of our knowledge, this is the first study to use MPVA techniques to decode attention during episodic encoding and the impact of attentional shifts toward distracting information on age-related context memory impairments and hyper-binding. These results are consistent with the as-of-yet unsubstantiated theory that age-related declines in context memory may be attributable to poorer selective attention and/or greater inhibitory deficits in older adults.


Assuntos
Envelhecimento/fisiologia , Ritmo alfa/fisiologia , Atenção/fisiologia , Ritmo beta/fisiologia , Córtex Cerebral/fisiologia , Eletroencefalografia/métodos , Memória Episódica , Rememoração Mental/fisiologia , Percepção Visual/fisiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Percepção de Cores/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reconhecimento Visual de Modelos/fisiologia , Adulto Jovem
13.
J Autism Dev Disord ; 48(8): 2870-2878, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29551006

RESUMO

Research suggests that individuals with autism spectrum disorder (ASD) have significant difficulties with adaptive behavior skills including daily living and functional communication skills. Few studies have examined the developmental trajectory of adaptive behavior across childhood and adolescence. The present study examined longitudinal trajectories of adaptive behavior in a community-based clinic sample of 186 individuals with ASD. The overall pattern indicated an initial increase in adaptive behavior during early childhood followed by a plateau in skills during adolescence for individuals of all IQ groups. Given the importance of adaptive behavior for employment and quality of life, this study emphasizes the importance of targeting adaptive behavior during adolescence to insure continued gains.


Assuntos
Adaptação Psicológica , Transtorno do Espectro Autista/fisiopatologia , Desenvolvimento Infantil , Adolescente , Transtorno do Espectro Autista/psicologia , Criança , Pré-Escolar , Feminino , Humanos , Masculino
14.
J Autism Dev Disord ; 47(10): 3204-3219, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28730417

RESUMO

Little is known about age-related cognitive differences in autism spectrum disorder (ASD). However, given the overlap in cognitive impairments in ASD to those seen in typical aging, it is possible that adults with ASD will face even greater cognitive difficulties as they age. The current study used a cross-sectional design to examine age-related cognitive differences in adults with ASD and age and IQ-matched adults with typical development (age range 30-67 years). Results indicated that both age and diagnosis were related to poorer cognitive performance. However, adults with ASD exhibited pronounced age effects on measures related to executive functioning compared to adults with typical development, suggesting that aging in ASD may disproportionately affect specific cognitive processes.


Assuntos
Transtorno do Espectro Autista/diagnóstico , Transtorno do Espectro Autista/psicologia , Cognição , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/psicologia , Adolescente , Adulto , Fatores Etários , Idoso , Cognição/fisiologia , Estudos Transversais , Função Executiva/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos/normas
15.
Hum Mutat ; 37(8): 719-26, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27158917

RESUMO

Identifying variants causal for complex genetic disorders is challenging. With the advent of whole-exome and whole-genome sequencing, computational tools are needed to explore and analyze the list of variants for further validation. Correlating genetic variants with subject phenotype is crucial for the interpretation of the disease-causing mutations. Often such work is done by teams of researchers who need to share information and coordinate activities. To this end, we have developed a powerful, easy to use Web application, ASPIREdb, which allows researchers to search, organize, analyze, and visualize variants and phenotypes associated with a set of human subjects. Investigators can annotate variants using publicly available reference databases and build powerful queries to identify subjects or variants of interest. Functional information and phenotypic associations of these genes are made accessible as well. Burden analysis and additional reporting tools allow investigation of variant properties and phenotype characteristics. Projects can be shared, allowing researchers to work collaboratively to build queries and annotate the data. We demonstrate ASPIREdb's functionality using publicly available data sets, showing how the software can be used to accomplish goals that might otherwise require specialized bioinformatics expertise. ASPIREdb is available at http://aspiredb.chibi.ubc.ca.


Assuntos
Biologia Computacional/métodos , Variação Genética , Bases de Dados Genéticas , Exoma , Predisposição Genética para Doença , Genoma Humano , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Fenótipo , Navegador
16.
Am J Psychiatry ; 172(11): 1131-40, 2015 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-26238605

RESUMO

OBJECTIVE: Gene expression dysregulation in the brain has been associated with bipolar disorder through candidate gene and microarray expression studies, but questions remain about isoform-specific dysregulation and the role of noncoding RNAs whose importance in the brain has been suggested recently but not yet characterized for bipolar disorder. METHOD: The authors used RNA sequencing, a powerful technique that captures the complexity of gene expression, in postmortem tissue from the anterior cingulate cortex from 13 bipolar disorder case subjects and 13 matched comparison subjects. Differential expression was computed, and a global pattern of downregulation was detected, with 10 transcripts significant at a false discovery rate ≤5%. Importantly, all 10 genes were also replicated in an independent RNA sequencing data set (N=61) from the anterior cingulate cortex. RESULTS: Among the most significant results were genes coding for class A G protein-coupled receptors: SSTR2 (somatostatin receptor 2), CHRM2 (cholinergic receptor, muscarinic 2), and RXFP1 (relaxin/insulin-like family peptide receptor 1). A gene ontology analysis of the entire set of differentially expressed genes pointed to an overrepresentation of genes involved in G protein-coupled receptor regulation. The top genes were followed up by querying the effect of treatment with mood stabilizers commonly prescribed in bipolar disorder, which showed that these drugs modulate expression of the candidate genes. CONCLUSIONS: By using RNA sequencing in the postmortem bipolar disorder brain, an interesting profile of G protein-coupled receptor dysregulation was identified, several new bipolar disorder genes were indicated, and the noncoding transcriptome in bipolar disorder was characterized. These findings have important implications with regard to fine-tuning our understanding of the bipolar disorder brain, as well as for identifying potential new drug target pathways.


Assuntos
Transtorno Bipolar/genética , Regulação da Expressão Gênica/genética , Giro do Cíngulo/metabolismo , RNA Mensageiro/metabolismo , Receptor Muscarínico M2/genética , Receptores Acoplados a Proteínas G/genética , Receptores de Peptídeos/genética , Receptores de Somatostatina/genética , Adulto , Antimaníacos/farmacologia , Transtorno Bipolar/metabolismo , Carbamazepina/farmacologia , Estudos de Casos e Controles , Linhagem Celular , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Técnicas In Vitro , Compostos de Lítio/farmacologia , Masculino , Pessoa de Meia-Idade , Células-Tronco Neurais/efeitos dos fármacos , Células-Tronco Neurais/metabolismo , RNA Mensageiro/efeitos dos fármacos , Reação em Cadeia da Polimerase em Tempo Real , Receptor Muscarínico M2/efeitos dos fármacos , Receptores Acoplados a Proteínas G/efeitos dos fármacos , Receptores de Peptídeos/efeitos dos fármacos , Receptores de Somatostatina/efeitos dos fármacos , Análise de Sequência de RNA , Ácido Valproico/farmacologia
17.
Epigenetics Chromatin ; 7(1): 28, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25493099

RESUMO

BACKGROUND: DNA methylation is thought to play an important role in the regulation of mammalian gene expression, partly based on the observation that a lack of CpG island methylation in gene promoters is associated with high transcriptional activity. However, the CpG island methylation level only accounts for a fraction of the variance in gene expression, and methylation in other domains is hypothesized to play a role. We hypothesized that regions of very high stability in methylation would exist and provide biological insight into the role of methylation both within and outside CpG islands. RESULTS: We set out to identify highly stable regions in the human methylome, based on the subset of CpGs assayed with an Illumina Infinium 450 K array. Using 1,737 samples from 30 publically available studies, we identified 15,224 CpGs that are 'ultrastable' in their state across tissues and developmental stages (974 always methylated; 14,250 always unmethylated). Further analysis of ultrastable CpGs led us to identify a novel subset of CpG islands, 'ravines', which exhibit a markedly consistent pattern of low methylation with highly methylated flanking shores and shelves. We distinguish ravines from other CpG islands characterized by a broader flanking region of low methylation. Interestingly, ravines are associated with higher gene expression compared to typical unmethylated CpG islands, and are more often found near housekeeping genes. CONCLUSIONS: The identification of ultrastable sites in the human methylome led us to identify a subclass of CpG islands characterized by a very stable pattern of methylation encompassing the island and flanking regions, established early in development and maintained through differentiation. This pattern is associated with particularly high levels of gene expression, providing new evidence that methylation beyond the CpG island could play a role in gene expression.

18.
Front Neurosci ; 7: 5, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23440889

RESUMO

An important goal in neuroscience is to understand gene expression patterns in the brain. The recent availability of comprehensive and detailed expression atlases for mouse and human creates opportunities to discover global patterns and perform cross-species comparisons. Recently we reported that the major source of variation in gene transcript expression in the adult normal mouse brain can be parsimoniously explained as reflecting regional variation in glia to neuron ratios, and is correlated with degree of connectivity and location in the brain along the anterior-posterior axis. Here we extend this investigation to two gene expression assays of adult normal human brains that consisted of over 300 brain region samples, and perform comparative analyses of brain-wide expression patterns to the mouse. We performed principal components analysis (PCA) on the regional gene expression of the adult human brain to identify the expression pattern that has the largest variance. As in the mouse, we observed that the first principal component is composed of two anti-correlated patterns enriched in oligodendrocyte and neuron markers respectively. However, we also observed interesting discordant patterns between the two species. For example, a few mouse neuron markers show expression patterns that are more correlated with the human oligodendrocyte-enriched pattern and vice-versa. In conclusion, our work provides insights into human brain function and evolution by probing global relationships between regional cell type marker expression patterns in the human and mouse brain.

19.
J Autism Dev Disord ; 43(10): 2393-404, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23417264

RESUMO

The present studies examined implicit contextual cueing in adolescents and adults with Autism Spectrum Disorder (ASD). In Study 1, 16 individuals with ASD and 20 matched individuals with typical development completed a contextual cueing task using stimulus-identity cues. In Study 2, 12 individuals with ASD and 16 individuals with typical development completed a revised version of the contextual cueing task, using both stimulus-identity cues and global spatial-configuration cues. The results suggest that when only stimulus-identity cues were provided, individuals with ASD had difficulty with implicit contextual cueing (Study 1). However, when both stimulus-identity and spatial-configuration contextual cues were provided, individuals with ASD demonstrated successful contextual cueing (Study 2). Nuances in implicit learning and clinical implications are discussed.


Assuntos
Transtornos Globais do Desenvolvimento Infantil/psicologia , Sinais (Psicologia) , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Adulto Jovem
20.
J Autism Dev Disord ; 43(7): 1568-83, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23132272

RESUMO

Postural stability is a fundamental aspect of motor ability that allows individuals to sustain and maintain the desired physical position of one's body. The present study examined postural stability in average-IQ adolescents and adults with Autism Spectrum Disorder (ASD). Twenty-six individuals with ASD and 26 age-and-IQ-matched individuals with typical development stood on one leg or two legs with eyes opened or closed on a Wii balance board. Results indicated significant group differences in postural stability during one-legged standing, but there were no significant group differences during two-legged standing. This suggests that static balance during more complex standing postures is impaired in average-IQ individuals with ASD. Further, current ASD symptoms were related to postural stability during two-legged standing in individuals with ASD. Future directions and clinical implications are discussed.


Assuntos
Transtornos Globais do Desenvolvimento Infantil/diagnóstico , Transtornos Globais do Desenvolvimento Infantil/psicologia , Transtornos das Habilidades Motoras/diagnóstico , Transtornos das Habilidades Motoras/psicologia , Equilíbrio Postural , Adolescente , Adulto , Criança , Feminino , Lateralidade Funcional , Humanos , Inteligência , Masculino , Valores de Referência , Comportamento Estereotipado , Suporte de Carga , Adulto Jovem
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