IACC Top Papers

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

Source: 
Pediatrics
Date Published: 
June 23, 2014
Abstract: 

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.

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

Source: 
Child and Adolescent Psychiatry
Date Published: 
March 13, 2014
Abstract: 

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 children’s response to treatment.

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

Source: 
BMC Neurology
Date Published: 
May 15, 2014
Abstract: 

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.

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

Source: 
Nature Genetics
Date Published: 
May 25, 2014
Abstract: 

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.

The Familial Risk of Autism

Source: 
JAMA
Date Published: 
May 7, 2014
Abstract: 

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.

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

Source: 
Pediatrics
Date Published: 
June 23, 2014
Abstract: 

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.

Elevated Fetal Steroidogenic Activity in Autism

Source: 
Molecular Psychiatry
Date Published: 
June 3, 2014
Abstract: 

"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 Δ4 sex steroids (progesterone, 17α-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."

Network Inefficiencies in Autism Spectrum Disorder at 24 Months

Source: 
Translational Psychiatry
Date Published: 
May 6, 2014
Abstract: 

"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."

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

Source: 
Journal of Autism and Developmental Disorders
Date Published: 
June 27, 2014
Abstract: 

"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."

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

Source: 
Autism Research and Treatment
Date Published: 
June 22, 2014
Abstract: 

"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."