Research by Topic: IACC Top Papers

Limited Fine Motor and Grasping Skills in 6-Month-Old Infants at High Risk for Autism

Published June 30, 2014 in Child Development

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

http://www.ncbi.nlm.nih.gov/pubmed/?term=%22Child+development%22%5BJournal%5D++limited+fine+motor+and+grasping+skills

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Brief Report: Assessment of Early Sensory Processing in Infants at High-Risk of Autism Spectrum Disorder

Published June 27, 2014 in Journal of Autism and Developmental Disorders

“This study assessed sensory processing differences between 24-month infants at high-risk of autism spectrum disorder (ASD), each with an older sibling with ASD, and low-risk infants with no family history of ASD. Sensory processing differences were assessed using the Infant/Toddler Sensory Profile, a parent-reported measure. Groups were compared based on 3-year outcomes: (a) high-risk infants subsequently diagnosed with ASD; (b) high-risk infants without an ASD diagnosis; and (c) low-risk infants without an ASD diagnosis. Analyses showed that high-risk infants diagnosed with ASD have more difficulty with auditory processing (i.e., responses to auditory stimuli) and lower registration (i.e., lacking sensation awareness) compared to controls. Thus, behavioral responses to sensory input represent early risk markers of ASD, particularly in high-risk infants.”

http://www.ncbi.nlm.nih.gov/pubmed/?term=%22Journal+of+autism+and+developmental+disorders%22%5BJournal%5D+Brief+Report%3A+Assessment+of+Early+Sensory+Processing+in+INfatns+at+High+Risk+of+ASD

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Caregiver-Mediated Intervention for Low-Resourced Preschoolers With Autism: An RCT

Published June 23, 2014 in Pediatrics

This study is among the first randomized trials comparing 2 active interventions with a large sample of low-resourced families. Results suggest improvements in core autism deficits of joint engagement, joint attention, and symbolic play with relatively brief, caregiver-mediated interventions, but additional support is necessary to maintain and generalize these gains over time.

http://pediatrics.aappublications.org/content/early/2014/06/17/peds.2013-3229.abstract

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Autism Spectrum Disorders and Race, Ethnicity, and Nativity: A Population-Based Study

Published June 23, 2014 in Pediatrics

OBJECTIVE:Our understanding of the influence of maternal race/ethnicity and nativity and childhood autistic disorder (AD) in African Americans/blacks, Asians, and Hispanics in the United States is limited. Phenotypic differences in the presentation of childhood AD in minority groups may indicate etiologic heterogeneity or different thresholds for diagnosis. We investigated whether the risk of developing AD and AD phenotypes differed according to maternal race/ethnicity and nativity.METHODS:Children born in Los Angeles County with a primary AD diagnosis at ages 3 to 5 years during 1998-2009 were identified and linked to 1995-2006 California birth certificates (7540 children with AD from a cohort of 1?626?354 births). We identified a subgroup of children with AD and a secondary diagnosis of mental retardation and investigated heterogeneity in language and behavior.RESULTS:We found increased risks of being diagnosed with AD overall and specifically with comorbid mental retardation in children of foreign-born mothers who were black, Central/South American, Filipino, and Vietnamese, as well as among US-born Hispanic and African American/black mothers, compared with US-born whites. Children of US African American/black and foreign-born black, foreign-born Central/South American, and US-born Hispanic mothers were at higher risk of exhibiting an AD phenotype with both severe emotional outbursts and impaired expressive language than children of US-born whites.CONCLUSIONS:Maternal race/ethnicity and nativity are associated with offspring’s AD diagnosis and severity. Future studies need to examine factors related to nativity and migration that may play a role in the etiology as well as identification and diagnosis of AD in children.

http://www.ncbi.nlm.nih.gov/pubmed/24958588

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Computer Vision Tools for Low-Cost and Noninvasive Measurement of Autism-Related Behaviors in Infants

Published June 22, 2014 in Autism Research and Treatment

“The early detection of developmental disorders is key to child outcome, allowing interventions to be initiated which promote development and improve prognosis. Research on autism spectrum disorder (ASD) suggests that behavioral signs can be observed late in the first year of life. Many of these studies involve extensive frame-by-frame video observation and analysis of a child’s natural behavior. Although nonintrusive, these methods are extremely time-intensive and require a high level of observer training; thus, they are burdensome for clinical and large population research purposes. This work is a first milestone in a long-term project on non-invasive early observation of children in order to aid in risk detection and research of neurodevelopmental disorders. We focus on providing low-cost computer vision tools to measure and identify ASD behavioral signs based on components of the Autism Observation Scale for Infants (AOSI). In particular, we develop algorithms to measure responses to general ASD risk assessment tasks and activities outlined by the AOSI which assess visual attention by tracking facial features. We show results, including comparisons with expert and nonexpert clinicians, which demonstrate that the proposed computer vision tools can capture critical behavioral observations and potentially augment the clinician’s behavioral observations obtained from real in-clinic assessments.”

http://www.hindawi.com/journals/aurt/2014/935686/

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Elevated Fetal Steroidogenic Activity in Autism

Published June 3, 2014 in Molecular Psychiatry

“Autism affects males more than females, giving rise to the idea that the influence of steroid hormones on early fetal brain development may be one important early biological risk factor. We identified all amniotic fluid samples of males born between 1993 and 1999 who later received diagnoses of autism, Asperger syndrome or PDD-NOS (pervasive developmental disorder not otherwise specified) (n=128) compared with matched typically developing controls. Concentration levels of ?4 sex steroids (progesterone, 17?-hydroxy-progesterone, androstenedione and testosterone) and cortisol were measured with liquid chromatography tandem mass spectrometry. All hormones were positively associated with each other and principal component analysis confirmed that one generalized latent steroidogenic factor was driving much of the variation in the data. The autism group showed elevations across all hormones on this latent generalized steroidogenic factor (Cohen’s d=0.37, P=0.0009) and this elevation was uniform across ICD-10 diagnostic label. These results provide the first direct evidence of elevated fetal steroidogenic activity in autism. Such elevations may be important as epigenetic fetal programming mechanisms and may interact with other important pathophysiological factors in autism.”

http://www.ncbi.nlm.nih.gov/pubmed/24888361?dopt=Abstract

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Brain-Expressed Exons Under Purifying Selection are Enriched for De Novo Mutations in Autism Spectrum Disorder

Published May 25, 2014 in Nature Genetics

A universal challenge in genetic studies of autism spectrum disorders is determining whether a given DNA sequence alteration will manifest as disease. Among different population controls, we observed, for specific exons, an inverse correlation between exon expression level in brain and burden of rare missense mutations. For genes that harbor de novo mutations predicted to be deleterious, we found that specific critical exons were significantly enriched in individuals with ASD relative to their siblings without ASD. Furthermore, our analysis of genes with high exonic expression in brain and low burden of rare mutations demonstrated enrichment for known ASD-associated genes and ASD-relevant fragile-X protein targets. Our results suggest that brain-expressed exons under purifying selection should be prioritized in genotype-phenotype studies for ASD and related neurodevelopmental conditions.

http://www.nature.com/ng/journal/v46/n7/full/ng.2980.html

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Corticosteroid Therapy in Regressive Autism: A Retrospective Study of Effects on the Frequency Modulated Auditory Evoked Response (FMAER), Language, and Behavior

Published May 15, 2014 in BMC Neurology

Steroid treatment was associated with a significantly increased FMAER response magnitude, reduction of FMAER response distortion, and improvement in language and behavior scores. This was not observed in the non-treated group. These pilot findings warrant a prospective randomized validation trial of steroid treatment for R-ASD utilizing FMAER, EEG, and standardized ASD, language and behavior measures, and a longer follow-up period. Children with R-ASD, and without concurrent evidence for an epileptic encephalopathy such as the Landau-Kleffner syndrome, who receive steroid therapy, show improvement in a language specific electrophysiological brain function indicator, as measured with the FMAER. Additionally, they appear to show improvement in language and behavior performance. At the level utilized in this study, steroid therapy did not appear to result in recognized, lasting morbidities.

http://www.biomedcentral.com/1471-2377/14/70

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The Familial Risk of Autism

Published May 7, 2014 in JAMA

Among children born in Sweden, the individual risk of ASD and autistic disorder increased with increasing genetic relatedness. Heritability of ASD and autistic disorder were estimated to be approximately 50%. These findings may inform the counseling of families with affected children.

http://jama.jamanetwork.com/article.aspx?articleid=1866100

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Network Inefficiencies in Autism Spectrum Disorder at 24 Months

Published May 6, 2014 in Translational Psychiatry

“Autism spectrum disorder (ASD) is a developmental disorder defined by behavioral symptoms that emerge during the first years of life. Associated with these symptoms are differences in the structure of a wide array of brain regions, and in the connectivity between these regions. However, the use of cohorts with large age variability and participants past the generally recognized age of onset of the defining behaviors means that many of the reported abnormalities may be a result of cascade effects of developmentally earlier deviations. This study assessed differences in connectivity in ASD at the age at which the defining behaviors first become clear. There were 113 24-month-old participants at high risk for ASD, 31 of whom were classified as ASD, and 23 typically developing 24-month-old participants at low risk for ASD. Utilizing diffusion data to obtain measures of the length and strength of connections between anatomical regions, we performed an analysis of network efficiency. Our results showed significantly decreased local and global efficiency over temporal, parietal and occipital lobes in high-risk infants classified as ASD, relative to both low- and high-risk infants not classified as ASD. The frontal lobes showed only a reduction in global efficiency in Broca’s area. In addition, these same regions showed an inverse relation between efficiency and symptom severity across the high-risk infants. The results suggest delay or deficits in infants with ASD in the optimization of both local and global aspects of network structure in regions involved in processing auditory and visual stimuli, language and nonlinguistic social stimuli.”

http://www.ncbi.nlm.nih.gov/pubmed/24802306

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The cost-effectiveness of supported employment for adults with autism in the United Kingdom

Published April 29, 2014 in Autism: the international journal of research and practice

"Adults with autism face high rates of unemployment. Supported employment enables individuals with autism to secure and maintain a paid job in a regular work environment. The objective of this study was to assess the cost-effectiveness of supported employment compared with standard care (day services) for adults with autism in the United Kingdom. The analysis […]

http://www.ncbi.nlm.nih.gov/pubmed/?term=24126866

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Comparing cognitive outcomes among children with autism spectrum disorders receiving community-based early intervention in one of three placements

Published April 18, 2014 in Autism: the international journal of research and practice

"Little comparative research examines which community-based preschool intervention placements produce the best outcomes for which children with autism spectrum disorders. Autism-specific placements can provide intensive evidence-based care; however, inclusion settings provide interaction with typically developing peers, the importance of which is increasingly recognized. This study examined the association between early intervention placement in three settings […]

http://www.ncbi.nlm.nih.gov/pubmed/?term=23188885

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Communication Interventions for Minimally Verbal Children With Autism: A Sequential Multiple Assignment Randomized Trial

Published March 13, 2014 in Child and Adolescent Psychiatry

Minimally verbal school-aged children can make significant and rapid gains in spoken spontaneous language with a novel, blended intervention that focuses on joint engagement and play skills and incorporates an SGD. Future studies should further explore the tailoring design used in this study to better understand childrens response to treatment.

http://www.jaacap.com/article/S0890-8567(14)00163-4/abstract

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Effects of a Self-Monitoring Device on Socially Relevant Behaviors in Adolescents with Asperger Disorder: A Pilot Study

Published January 22, 2014 in Assistive Technology

This article reports the results of two case studies. Two middle school-aged participants with high-functioning autism spectrum disorders were taught to self-monitor behaviors impacting their social acceptance by peers in their general education settings: oral self-stimulatory behaviors and conversation skills. Results indicate that the intervention was effective to some degree with both participants. As a result of the self-monitoring intervention, one participant decreased self-stimulatory behaviors; however, his data were highly variable throughout the study though lower on average during intervention than in baseline. The other participant’s targeted skills in communication were only slightly improved. Self-monitoring using a vibrating reminder appears to be a low-cost intervention with high levels of social acceptability, low training requirements for teachers or students, and no social stigma.

http://www.ncbi.nlm.nih.gov/pubmed/24020153

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Oxytocin enhances brain function in children with autism

Published December 24, 2013 in Proceedings of the National Academy of Sciences

"Following intranasal administration of oxytocin (OT), we measured, via functional MRI, changes in brain activity during judgments of socially (Eyes) and nonsocially (Vehicles) meaningful pictures in 17 children with high-functioning autism spectrum disorder (ASD). OT increased activity in the striatum, the middle frontal gyrus, the medial prefrontal cortex, the right orbitofrontal cortex, and the left […]

http://www.ncbi.nlm.nih.gov/pubmed/?term=24297883

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Microbiota Modulate Behavioral and Physiological Abnormalities Associated with Neurodevelopmental Disorders

Published December 19, 2013 in Cell

Neurodevelopmental disorders, including autism spectrum disorder (ASD), are defined by core behavioral impairments; however, subsets of individuals display a spectrum of gastrointestinal (GI) abnormalities. We demonstrate GI barrier defects and microbiota alterations in the maternal immune activation (MIA) mouse model that is known to display features of ASD. Oral treatment of MIA offspring with the human commensal Bacteroides fragilis corrects gut permeability, alters microbial composition, and ameliorates defects in communicative, stereotypic, anxiety-like and sensorimotor behaviors. MIA offspring display an altered serum metabolomic profile, and B. fragilis modulates levels of several metabolites. Treating naive mice with a metabolite that is increased by MIA and restored by B. fragilis causes certain behavioral abnormalities, suggesting that gut bacterial effects on the host metabolome impact behavior. Taken together, these findings support a gut-microbiome-brain connection in a mouse model of ASD and identify a potential probiotic therapy for GI and particular behavioral symptoms in human neurodevelopmental disorders.

http://www.cell.com/abstract/S0092-8674(13)01473-6

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Attention to Eyes is Present but in Decline in 2-6-Month-Old Infants Later Diagnosed with Autism

Published December 19, 2013 in Nature

Deficits in eye contact have been a hallmark of autism since the condition’s initial description. They are cited widely as a diagnostic feature and figure prominently in clinical instruments; however, the early onset of these deficits has not been known. Here we show in a prospective longitudinal study that infants later diagnosed with autism spectrum disorders (ASDs) exhibit mean decline in eye fixation from 2 to 6 months of age, a pattern not observed in infants who do not develop ASD. These observations mark the earliest known indicators of social disability in infancy, but also falsify a prior hypothesis: in the first months of life, this basic mechanism of social adaptive action–eye looking–is not immediately diminished in infants later diagnosed with ASD; instead, eye looking appears to begin at normative levels prior to decline. The timing of decline highlights a narrow developmental window and reveals the early derailment of processes that would otherwise have a key role in canalizing typical social development. Finally, the observation of this decline in eye fixation–rather than outright absence–offers a promising opportunity for early intervention that could build on the apparent preservation of mechanisms subserving reflexive initial orientation towards the eyes.

http://www.ncbi.nlm.nih.gov/pubmed/24196715

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Coexpression networks implicate human midfetal deep cortical projection neurons in the pathogenesis of autism

Published November 21, 2013 in Cell

"As techniques for studying the human genome have advanced, an increasing number of genes are being associated with ASD; it is important to find the connections between these ASD-linked genes in order to understand how they may contribute to ASD. A new resource called the BrainSpan1 atlas provides researchers with three dimensional maps showing when […]

http://www.ncbi.nlm.nih.gov/pubmed/?term=24267886

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Parents’ First Concerns about Toddlers with Autism Spectrum Disorder: Effect of Sibling Status.

Published November 11, 2013 in Autism

Symptoms of autism spectrum disorders may appear as early as 6 months, but parent concern, which can precipitate evaluation, often lags significantly. The presence of typical or atypical older siblings can change parents’ sensitivity to departures from typical development. This study investigated type and age of parent’s first concerns in toddlers with autism spectrum disorder, prior to diagnosis. Participants had (1) at least one older sibling with autism spectrum disorder (Sibs-ASD); (2) only typically developing older siblings (Sibs-TD), or (3) were only/oldest (No-Sibs). Specific autism spectrum disorder diagnoses and symptom severity were similar among groups. Developmentally, No-Sibs showed the largest delays, followed by Sibs-TD, followed by Sibs-ASD. Mean age of first concern was 16 months for No-Sibs, 14 months for Sibs-TD, and 10 months for Sibs-ASD. Age of first concern differed significantly by group, even after controlling for mother’s age and education. Concern about language was prevalent in all groups. Thus, the presence of an older child with typical or, especially, atypical development was associated with earlier concerns for the affected child, despite milder developmental delays. These findings underscore the importance of encouraging parents to report concerns to pediatricians, routine standardized screening for autism spectrum disorder, and the need for pediatrician vigilance, especially for only or oldest children.

http://www.ncbi.nlm.nih.gov/pubmed/24216070

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Gastrointestinal problems in children with autism, developmental delays or typical development

Published November 6, 2013 in Journal of Autism and Developmental Disororders

"To compare gastrointestinal (GI) problems among children with: (1) autism spectrum disorder (ASD), (2) developmental delay (DD) and (3) typical development (TD), GI symptom frequencies were obtained for 960 children from the Childhood Autism Risks from Genetics and Environment (CHARGE) study. We also examined scores on five Aberrant Behavior Checklist (ABC) subscales comparing ASD children […]

http://www.ncbi.nlm.nih.gov/pubmed/?term=24193577

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Gastrointestinal problems in children with autism, developmental delays or typical development

Published November 6, 2013 in Journal of Autism and Developmental Disororders

"To compare gastrointestinal (GI) problems among children with: (1) autism spectrum disorder (ASD), (2) developmental delay (DD) and (3) typical development (TD), GI symptom frequencies were obtained for 960 children from the Childhood Autism Risks from Genetics and Environment (CHARGE) study. We also examined scores on five Aberrant Behavior Checklist (ABC) subscales comparing ASD children […]

http://www.ncbi.nlm.nih.gov/pubmed/?term=24193577

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Psychotropic Medication Use and Polypharmacy in Children with Autism Spectrum Disorders

Published November 1, 2013 in Pediatrics

The objectives of this study were to examine rates and predictors of psychotropic use and multiclass polypharmacy among commercially insured children with autism spectrum disorders. Despite minimal evidence of the effectiveness or appropriateness of multidrug treatment of ASD, psychotropic medications are commonly used, singly and in combination, for ASD and its co-occurring conditions. Our results indicate the need to develop standards of care around the prescription of psychotropic medications to children with ASD.

http://www.ncbi.nlm.nih.gov/pubmed/24144704

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SHANK3 and IGF1 Restore Synaptic Deficits in Neurons from 22q13 Seletion Syndrome Patients

Published October 16, 2013 in Nature

Phelan-McDermid syndrome (PMDS) is a complex neurodevelopmental disorder characterized by global developmental delay, severely impaired speech, intellectual disability, and an increased risk of autism spectrum disorders (ASDs). PMDS is caused by heterozygous deletions of chromosome 22q13.3. Among the genes in the deleted region is SHANK3, which encodes a protein in the postsynaptic density (PSD). Rare mutations in SHANK3 have been associated with idiopathic ASDs, non-syndromic intellectual disability, and schizophrenia. Although SHANK3 is considered to be the most likely candidate gene for the neurological abnormalities in PMDS patients, the cellular and molecular phenotypes associated with this syndrome in human neurons are unknown. We generated induced pluripotent stem (iPS) cells from individuals with PMDS and autism and used them to produce functional neurons. We show that PMDS neurons have reduced SHANK3 expression and major defects in excitatory, but not inhibitory, synaptic transmission. Excitatory synaptic transmission in PMDS neurons can be corrected by restoring SHANK3 expression or by treating neurons with insulin-like growth factor 1 (IGF1). IGF1 treatment promotes formation of mature excitatory synapses that lack SHANK3 but contain PSD95 and N-methyl-D-aspartate (NMDA) receptors with fast deactivation kinetics. Our findings provide direct evidence for a disruption in the ratio of cellular excitation and inhibition in PMDS neurons, and point to a molecular pathway that can be recruited to restore it.

http://www.ncbi.nlm.nih.gov/pubmed/24132240

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“In the Driver’s Seat”: Parent Perceptions of Choice in a Participant-Directed Medicaid Waiver Program for Young Children with Autism

Published September 22, 2013 in Journal of Autism and Developmental Disorders

This study investigated families’ experience of choice within a participant-directed Medicaid waiver program for young children with autism. Fourteen parents or grandparents participated in in-depth interviews about their experience of choosing personnel, directing in-home services, and managing the $25,000 annual allocation. Key findings included families’ preference to hire providers with whom they have a prior relationship, parent empowerment and differences of opinion about parents as teachers. Professionals implementing participant directed service models could benefit from understanding the strong value parents’ placed on the personalities and interpersonal skills of providers. Parents’ descriptions of directing rather than merely accepting autism services revealed increased confidence in their ability to choose and manage the multiple components of their children’s HCBS autism waiver program.

http://www.ncbi.nlm.nih.gov/pubmed/24057132

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Topoisomerases Facilitate Transcription of Long Genes Linked to Autism

Published September 5, 2013 in Nature

Topoisomerases are expressed throughout the developing and adult brain and are mutated in some individuals with autism spectrum disorder (ASD). However, how topoisomerases are mechanistically connected to ASD is unknown. Here we find that topotecan, a topoisomerase 1 (TOP1) inhibitor, dose-dependently reduces the expression of extremely long genes in mouse and human neurons, including nearly all genes that are longer than 200?kilobases. Expression of long genes is also reduced after knockdown of Top1 or Top2b in neurons, highlighting that both enzymes are required for full expression of long genes. By mapping RNA polymerase II density genome-wide in neurons, we found that this length-dependent effect on gene expression was due to impaired transcription elongation. Interestingly, many high-confidence ASD candidate genes are exceptionally long and were reduced in expression after TOP1 inhibition. Our findings suggest that chemicals and genetic mutations that impair topoisomerases could commonly contribute to ASD and other neurodevelopmental disorders.

http://www.ncbi.nlm.nih.gov/pubmed/23995680

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Common DNA Methylation Alterations in Multiple Brain Regions in Autism

Published September 3, 2013 in Molecular Psychiatry

Autism spectrum disorders (ASD) are increasingly common neurodevelopmental disorders defined clinically by a triad of features including impairment in social interaction, impairment in communication in social situations and restricted and repetitive patterns of behavior and interests, with considerable phenotypic heterogeneity among individuals. Although heritability estimates for ASD are high, conventional genetic-based efforts to identify genes involved in ASD have yielded only few reproducible candidate genes that account for only a small proportion of ASDs. There is mounting evidence to suggest environmental and epigenetic factors play a stronger role in the etiology of ASD than previously thought. To begin to understand the contribution of epigenetics to ASD, we have examined DNA methylation (DNAm) in a pilot study of postmortem brain tissue from 19 autism cases and 21 unrelated controls, among three brain regions including dorsolateral prefrontal cortex, temporal cortex and cerebellum. We measured over 485?000 CpG loci across a diverse set of functionally relevant genomic regions using the Infinium HumanMethylation450 BeadChip and identified four genome-wide significant differentially methylated regions (DMRs) using a bump hunting approach and a permutation-based multiple testing correction method. We replicated 3/4 DMRs identified in our genome-wide screen in a different set of samples and across different brain regions. The DMRs identified in this study represent suggestive evidence for commonly altered methylation sites in ASD and provide several promising new candidate genes.

http://www.ncbi.nlm.nih.gov/pubmed/23999529

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Integrating Mental Health Services for Mothers of Children With Autism

Published September 1, 2013 in Psychiatric Services

Although up to 40% of mothers of children with autism report clinically significant depressive symptoms, there has been little attention to the mental health needs of parents. Because most autism services for young children rely on active parental engagement to deliver recommended therapies, maternal functioning directly affects the intensity and quality of therapy that children with autism receive. Developing feasible and acceptable strategies to support the mental health of mothers who care for children with autism has the potential to optimize both maternal and child functioning.

http://ps.psychiatryonline.org/article.aspx?articleid=1730565

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Prospective Examination of Visual Attention During Play in Infants at High-Risk for ASD

Published September 1, 2013 in Behavioral Brain Research

Regulation of visual attention is essential to learning about one’s environment. Children with autism spectrum disorder (ASD) exhibit impairments in regulating their visual attention, but little is known about how such impairments develop over time. This prospective longitudinal study is the first to describe the development of components of visual attention, including engaging, sustaining, and disengaging attention, in infants at high-risk of developing ASD (each with an older sibling with ASD). Non-sibling controls and high-risk infant siblings were filmed at 6, 9, 12, 15, 18, 24, and 36 months of age as they engaged in play with small, easily graspable toys. Duration of time spent looking at toy targets before moving the hand toward the target and the duration of time spent looking at the target after grasp were measured. At 36 months of age, an independent, gold standard diagnostic assessment for ASD was conducted for all participants. As predicted, infant siblings subsequently diagnosed with ASD were distinguished by prolonged latency to disengage (‘sticky attention’) by 12 months of age, and continued to show this characteristic at 15, 18, and 24 months of age. The results are discussed in relation to how the development of visual attention may impact later cognitive outcomes of children diagnosed with ASD.

http://europepmc.org/abstract/MED/24004846/reload=0;jsessionid=4pokSXNYgeCg8hZd2lYL.2

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Long-Term Outcomes of Parent-Assisted Social Skills Intervention for High-Functioning Children with Autism Spectrum Disorders

Published August 30, 2013 in Autism

This study aims to evaluate the long-term outcome of Children’s Friendship Training, a parent-assisted social skills intervention for children. Prior research has shown Children’s Friendship Training to be superior to wait-list control with maintenance of gains at 3-month follow-up. Participants were families of children diagnosed with autism spectrum disorder who completed Children’s Friendship Training 1-5 years earlier. They were recruited through mail, phone, and email. Information collected included parent and child completed questionnaires and a phone interview. Data were collected on 24 of 52 potential participants (46%). With an average of 35-month follow-up, participants had a mean age of 12.6 years. Results indicated that participants at follow-up were invited on significantly more play dates, showed less play date conflict, improved significantly in parent-reported social skills and problem behaviors, and demonstrated marginally significant decreases in loneliness when compared to pre-Children’s Friendship Training.

http://www.ncbi.nlm.nih.gov/pubmed/23996903

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Assessment of Global Functioning in Adolescents with ASD: Utility of the Developmental Disability-Child Global Assessment Scale

Published August 21, 2013 in Autism

Assessment of global functioning is an important consideration in treatment outcome research; yet, there is little guidance on its evidence-based assessment for children with autism spectrum disorders. This study investigated the utility and validity of clinician-rated global functioning using the Developmental Disability-Child Global Assessment Scale in a sample of higher functioning adolescents with autism spectrum disorders and comorbid anxiety disorders enrolled in a randomized controlled trial (n = 30). Pretreatment Developmental Disability-Child Global Assessment Scale scores correlated with severity of autism spectrum disorders core symptoms (r = -.388, p = .034), pragmatic communication (r = .407, p = .032), and verbal ability (r = .449, p = .013) and did not correlate with severity of anxiety symptoms or with parent-reported adaptive behavior. Change in Developmental Disability-Child Global Assessment Scale scores during treatment was associated with autism spectrum disorders symptomatic improvement (r = .414, p = .040) and with improved general communication (r = .499, p = .013). Results support the importance of assessing global functioning in addition to symptom change and treatment response in clinical trials.

http://www.ncbi.nlm.nih.gov/pubmed/23965288

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Selective Serotonin Reuptake Inhibitors for Treating People with Autism Spectrum Disorders

Published August 20, 2013 in Cochrane Collaboration

Autism spectrum disorders (ASD) are characterised by problems with social interaction and communication, as well as repetitive behaviours and limited activities and interests. Selective serotonin reuptake inhibitors (SSRIs) are a class of antidepressants that are sometimes given to reduce anxiety or obsessive?compulsive behaviours. We found nine trials, involving 320 people, which evaluated four SSRIs: fluoxetine, fluvoxamine, fenfluramine and citalopram. Five studies included only children and four studies included only adults. One trial enrolled 149 children, but the other trials were much smaller. We found no trials that evaluated sertraline, paroxetine or escitalopram. There is no evidence to support the use of SSRIs to treat autism in children. There is limited evidence, which is not yet sufficiently robust, to suggest effectiveness of SSRIs in adults with autism. Treatment with an SSRI may cause side effects. Decisions about the use of SSRIs for established clinical indications that may co?occur with autism, such as obsessive?compulsive disorder and depression in adults or children, and anxiety in adults, should be made on a case?by?case basis.

http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0012940/

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Brain-Reactive IgG Correlates with Autoimmunity in Mothers of a Child with an Autism Spectrum Disorder

Published August 20, 2013 in Molecular Psychiatry

It is believed that in utero environmental factors contribute to autism spectrum disorder (ASD). The goal of this study was to demonstrate, using the largest cohort reported so far, that mothers of an ASD child have an elevated frequency of anti-brain antibodies and to assess whether brain reactivity is associated with an autoimmune diathesis of the mother. We screened plasma of 2431 mothers of an ASD child from Simon Simplex Collection and plasma of 653 unselected women of child-bearing age for anti-brain antibodies using immunohistology on mouse brain. Positive and negative plasma from mothers with an ASD child were analyzed for anti-nuclear antibodies and for autoimmune disorders. Mothers of an ASD child were four times more likely to harbor anti-brain antibodies than unselected women of child-bearing age (10.5 vs 2.6%). A second cohort from The Autism Genetic Resource Exchange with multiplex families displayed an 8.8% prevalence of anti-brain antibodies in the mothers of these families. Fifty-three percent of these mothers with anti-brain antibodies also exhibited anti-nuclear autoantibodies compared with 13.4% of mothers of an ASD child without anti-brain antibodies and 15% of control women of child-bearing age. The analysis of ASD mothers with brain-reactive antibodies also revealed an increased prevalence of autoimmune diseases, especially rheumatoid arthritis and systemic lupus erythematosus. This study provides robust evidence that brain-reactive antibodies are increased in mothers of an ASD child and may be associated with autoimmunity. The current study serves as a benchmark and justification for studying the potential pathogenicity of these antibodies on the developing brain. The detailed characterization of the specificity of these antibodies will provide practical benefits for the management and prevention of this disorder.

http://www.ncbi.nlm.nih.gov/pubmed/23958959

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Maternal Antibodies from Mothers of Children with Autism Alter Brain Growth and Social Behavior Development in the Rhesus Monkey

Published July 9, 2013 in Translational Psychiatry

Antibodies directed against fetal brain proteins of 37 and 73?kDa molecular weight are found in approximately 12% of mothers who have children with autism spectrum disorder (ASD), but not in mothers of typically developing children. This finding has raised the possibility that these immunoglobulin G (IgG) class antibodies cross the placenta during pregnancy and impact brain development, leading to one form of ASD.

http://www.nature.com/tp/journal/v3/n7/full/tp201347a.html

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Maternal Antibodies from Mothers of Children with Autism Alter Brain Growth and Social Behavior Development in the Rhesus Monkey

Published July 9, 2013 in Translational Psychiatry

Antibodies directed against fetal brain proteins of 37 and 73?kDa molecular weight are found in approximately 12% of mothers who have children with autism spectrum disorder (ASD), but not in mothers of typically developing children. This finding has raised the possibility that these immunoglobulin G (IgG) class antibodies cross the placenta during pregnancy and impact brain development, leading to one form of ASD.

http://www.nature.com/tp/journal/v3/n7/full/tp201347a.html

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Comparative Efficacy of LEAP, TEACCH and Non-Model-Specific Special Education Programs for Preschoolers with Autism Spectrum Disorders

Published June 28, 2013 in Journal of Autism and Developmental Disorders

LEAP and TEACCH represent two comprehensive treatment models (CTMs) that have been widely used across several decades to educate young children with autism spectrum disorders. The purpose of this quasi-experimental study was to compare high fidelity LEAP (n = 22) and TEACCH (n = 25) classrooms to each other and a control condition (n = 28), in which teachers in high quality special education programs used non-model-specific practices. A total of 198 children were included in data analysis. Across conditions, children’s performances improved over time. This study raises issues of the replication of effects for CTMs, and whether having access to a high quality special education program is as beneficial as access to a specific CTM.

http://www.ncbi.nlm.nih.gov/pubmed/23812661

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Developmental trajectories in children with and without autism spectrum disorders: the first 3 years

Published March 1, 2013 in Child Development

"Retrospective studies indicate 2 major classes of autism spectrum disorder (ASD) onset: early and later, after a period of relatively healthy development. This prospective, longitudinal study examined social, language, and motor trajectories in 235 children with and without a sibling with autism, ages 6-36 months. Children were grouped as: ASD identified by 14 months, ASD […]

http://www.ncbi.nlm.nih.gov/pubmed/?term=23110514

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Association between maternal use of folic acid supplements and risk of autism spectrum disorders in children

Published February 13, 2013 in Journal of the American Medical Association

The goal of this study was to determine the relationship between the use of prenatal folic acid supplements and presence of autism spectrum disorders in offspring. The study concluded that the use of prenatal folic acid supplements around the time fo conception was associated with a lower risk of autism spectrum disorders. These findings support […]

http://www.ncbi.nlm.nih.gov/pubmed/?term=23403681

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Effectiveness of developmental screening in an urban setting

Published January 1, 2013 in Pediatrics

The goal of this study was to determine whether developmental screening could aid identification of developmental delays, early intervention referrals, and eligibility for early intervention. The study concluded that children who received developmental screening tests were identified for developmental delays, early intervention referrals, and early intervention eligibility services in a more timely fashion than those […]

http://www.ncbi.nlm.nih.gov/pubmed/?term=23248223

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Mutations in BCKD-kinase Lead to a Potentially Treatable Form of Autism with Epilepsy

Published October 19, 2012 in Science

A research team led by Gaia Novarino of the University of California, San Diego, has identified genetic mutations which cause a form of autism that could potentially be treated with dietary supplements.

http://www.ncbi.nlm.nih.gov/pubmed/22956686

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Six Developmental Trajectories Characterize Children With Autism

Published May 1, 2012 in Pediatrics

“OBJECTIVE: The goal of this study was to describe the typical longitudinal developmental trajectories of social and communication functioning in children with autism and to determine the correlates of these trajectories.RESULTS: Six typical patterns of social, communication, and repetitive behavior functioning were identified. These trajectories displayed significant heterogeneity in developmental pathways, and children whose symptoms were least severe at first diagnosis tended to improve more rapidly than those severely affected. “

http://www.ncbi.nlm.nih.gov/pubmed/22473372

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