Impaired ability to organize information in individuals with autism spectrum disorders and their siblings.

PubMed

Sumiyoshi, Chika; Kawakubo, Yuki; Suga, Motomu; Sumiyoshi, Tomiki; Kasai, Kiyoto

2011-03-01

Despite rigorous research on disturbances of executive function and social cognition in autism spectrum disorders (ASD), little information has been available concerning higher cognitive functions, such as the ability to focus and associate relevant features to form categories, or 'organizing of information'. The purpose of this study was to investigate this issue by using the Wisconsin Card Sorting Test (WCST) and the Verbal Learning Task (VLT). Cognitive assessments were conducted in 22 individuals with ASD, 14 non-affected siblings, and 15 age-matched control subjects. Overall, individuals with ASD performed significantly worse on the WCST and VLT compared to their siblings and normal control subjects. Although siblings performed generally well on both tasks, they exhibited similar degree of perseverative responses in the WCST compared to the probands. A linear increase of the memory organization score in the VLT was also absent in siblings as well as the ASD group. These results suggest an impaired ability to organize information is one of the cognitive endophenotypes for ASD. Copyright © 2010 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

A Proton Magnetic Resonance Spectroscopic Study in Autism Spectrum Disorder Using a 3-Tesla Clinical Magnetic Resonance Imaging (MRI) System: The Anterior Cingulate Cortex and the Left Cerebellum.

PubMed

Ito, Hiromichi; Mori, Kenji; Harada, Masafumi; Hisaoka, Sonoka; Toda, Yoshihiro; Mori, Tatsuo; Goji, Aya; Abe, Yoko; Miyazaki, Masahito; Kagami, Shoji

2017-07-01

The pathophysiology of autism spectrum disorder (ASD) is not fully understood. We used proton magnetic resonance spectroscopy to investigate metabolite concentration ratios in the anterior cingulate cortex and left cerebellum in ASD. In the ACC and left cerebellum studies, the ASD group and intelligence quotient- and age-matched control group consisted of 112 and 114 subjects and 65 and 45 subjects, respectively. In the ASD group, γ-aminobutyric acid (GABA)+/ creatine/phosphocreatine (Cr) was significantly decreased in the anterior cingulate cortex, and glutamate (Glu)/Cr was significantly increased and GABA+/Cr was significantly decreased in the left cerebellum compared to those in the control group. In addition, both groups showed negative correlations between Glu/Cr and GABA+/Cr in the left cerebellum, and positive correlations between GABA+/Cr in the anterior cingulate cortex and left cerebellum. ASD subjects have hypoGABAergic alterations in the anterior cingulate cortex and hyperglutamatergic/hypoGABAergic alterations in the left cerebellum.

Risk factors for anterior traumatic dental injury in children and adolescents with autism spectrum disorders: a case-control study.

PubMed

Habibe, R C H; Ortega, A O L; Guaré, R O; Diniz, M B; Santos, M T B R

2016-04-01

This was to assess and compare risk factors for traumatic dental injury (TDI) among children/adolescents with and without autism spectrum disorders (ASD). The study consisted of 122 children and adolescents (98 males, 24 females), 61 with ASD (study group) and 61 without ASD (control group, CG). Dental injuries were determined according to Andreaseńss classification. The cause, location and type of activity at the time of trauma were recorded from patient/carer recollection. Subjects with ASD presented higher percentages of TDI in routine activities (P = 0.003), falling while walking and episodes of self-harm (P = 0.007) in the individual's own residence (P = 0.036). TDI prevalence in the ASD group was higher (39.3%) than in the CG (26.2%) though not significant, (P = 0.123). Girls with ASD presented a significantly higher TDI percentage (50.0%) compared with girls from the CG (8.3%) (P = 0.024). Enamel fracture was the most frequent type of TDI for both groups (P = 0.292). The teeth most commonly affected were #11 and #21 for both groups. Children and adolescents with ASD exhibit different risk factors for TDI compared with those without ASD, and girls with ASD are more prone than boys.

Salivary biomarker levels and oral health status of children with autistic spectrum disorders: a comparative study.

PubMed

Bhandary, S; Hari, N

2017-04-01

To evaluate the oral health status, salivary flow rate, pH and buffering capacity in children with autistic spectrum disorders (ASD) in comparison to their healthy siblings. A total of 30 subjects with ASD and 30 normal healthy siblings between the ages of 6-12 years of both genders attending various special schools and hospitals of Mangalore, India were recruited. Estimation of salivary pH, flow rate and buffering capacity were performed and oral health status was assessed using the WHO oral assessment form for children (World Health Organization in Oral health surveys: basic methods, World Health Organization, Geneva, 2013). The oral hygiene of the subjects was assessed using the oral hygiene index-simplified. Dental erosive lesions, presence of mucosal lesions and dental trauma were recorded for both the study and the control groups. It was observed that salivary pH and buffering capacity were lower in children with ASD than their healthy siblings, the dental caries incidence was higher in ASD children when compared to their healthy siblings and oral hygiene was fair with gingival bleeding in children with ASD. This study clearly indicates a need for better home care measures, parent, caregiver and institutional education on the importance of oral well-being among children with ASD.

Developmental differences in intra-individual variability in children with ADHD and ASD.

PubMed

van Belle, Janna; van Hulst, Branko M; Durston, Sarah

2015-12-01

Intra-individual variability reflects temporal variation within an individual's performance on a cognitive task. Children with developmental disorders, such as ADHD and ASD show increased levels of intra-individual variability. In typical development, intra-individual variability decreases sharply between the ages 6 and 20. The tight link between intra-individual variability and age has led to the suggestion that it may be marker of neural development. As there is accumulating evidence that ADHD and ASD are characterised by atypical neurodevelopmental trajectories, we set out to explore developmental changes in intra-individual variability in subjects with ADHD and ASD. We used propensity score matching to match a cross-sectional sample of children with ADHD, ASD and control subjects (N = 405, aged 6-19 years old) for age, IQ and gender. We used ex-Gaussian distribution parameters to characterise intra-individual variability on fast responses (sigma) and slow responses (tau). Results showed that there was a similar decrease in mean response times with age across groups, and an interaction between age and group for measures of variability, where there was a much lower rate of change in the variability parameters (sigma and tau) for subjects with ASD compared with the other two groups. Subjects with ADHD had higher intra-individual variability, reflected by both sigma and tau, but the rate of decrease in variability with age was similar to that of the controls. These results suggest that subjects with ADHD, ASD and controls differ in the rate at which intra-individual variability decreases during development, and support the idea that intra-individual variability may be a marker of neural development, mimicking the neurodevelopmental changes in these disorders. © 2015 Association for Child and Adolescent Mental Health.

Mosaic epigenetic dysregulation of ectodermal cells in autism spectrum disorder.

PubMed

Berko, Esther R; Suzuki, Masako; Beren, Faygel; Lemetre, Christophe; Alaimo, Christine M; Calder, R Brent; Ballaban-Gil, Karen; Gounder, Batya; Kampf, Kaylee; Kirschen, Jill; Maqbool, Shahina B; Momin, Zeineen; Reynolds, David M; Russo, Natalie; Shulman, Lisa; Stasiek, Edyta; Tozour, Jessica; Valicenti-McDermott, Maria; Wang, Shenglong; Abrahams, Brett S; Hargitai, Joseph; Inbar, Dov; Zhang, Zhengdong; Buxbaum, Joseph D; Molholm, Sophie; Foxe, John J; Marion, Robert W; Auton, Adam; Greally, John M

2014-01-01

DNA mutational events are increasingly being identified in autism spectrum disorder (ASD), but the potential additional role of dysregulation of the epigenome in the pathogenesis of the condition remains unclear. The epigenome is of interest as a possible mediator of environmental effects during development, encoding a cellular memory reflected by altered function of progeny cells. Advanced maternal age (AMA) is associated with an increased risk of having a child with ASD for reasons that are not understood. To explore whether AMA involves covert aneuploidy or epigenetic dysregulation leading to ASD in the offspring, we tested a homogeneous ectodermal cell type from 47 individuals with ASD compared with 48 typically developing (TD) controls born to mothers of ≥35 years, using a quantitative genome-wide DNA methylation assay. We show that DNA methylation patterns are dysregulated in ectodermal cells in these individuals, having accounted for confounding effects due to subject age, sex and ancestral haplotype. We did not find mosaic aneuploidy or copy number variability to occur at differentially-methylated regions in these subjects. Of note, the loci with distinctive DNA methylation were found at genes expressed in the brain and encoding protein products significantly enriched for interactions with those produced by known ASD-causing genes, representing a perturbation by epigenomic dysregulation of the same networks compromised by DNA mutational mechanisms. The results indicate the presence of a mosaic subpopulation of epigenetically-dysregulated, ectodermally-derived cells in subjects with ASD. The epigenetic dysregulation observed in these ASD subjects born to older mothers may be associated with aging parental gametes, environmental influences during embryogenesis or could be the consequence of mutations of the chromatin regulatory genes increasingly implicated in ASD. The results indicate that epigenetic dysregulatory mechanisms may complement and interact with DNA mutations in the pathogenesis of the disorder.

Cortical and Subcortical Brain Morphometry Differences Between Patients With Autism Spectrum Disorder and Healthy Individuals Across the Lifespan: Results From the ENIGMA ASD Working Group.

PubMed

van Rooij, Daan; Anagnostou, Evdokia; Arango, Celso; Auzias, Guillaume; Behrmann, Marlene; Busatto, Geraldo F; Calderoni, Sara; Daly, Eileen; Deruelle, Christine; Di Martino, Adriana; Dinstein, Ilan; Duran, Fabio Luis Souza; Durston, Sarah; Ecker, Christine; Fair, Damien; Fedor, Jennifer; Fitzgerald, Jackie; Freitag, Christine M; Gallagher, Louise; Gori, Ilaria; Haar, Shlomi; Hoekstra, Liesbeth; Jahanshad, Neda; Jalbrzikowski, Maria; Janssen, Joost; Lerch, Jason; Luna, Beatriz; Martinho, Mauricio Moller; McGrath, Jane; Muratori, Filippo; Murphy, Clodagh M; Murphy, Declan G M; O'Hearn, Kirsten; Oranje, Bob; Parellada, Mara; Retico, Alessandra; Rosa, Pedro; Rubia, Katya; Shook, Devon; Taylor, Margot; Thompson, Paul M; Tosetti, Michela; Wallace, Gregory L; Zhou, Fengfeng; Buitelaar, Jan K

2018-04-01

Neuroimaging studies show structural differences in both cortical and subcortical brain regions in children and adults with autism spectrum disorder (ASD) compared with healthy subjects. Findings are inconsistent, however, and it is unclear how differences develop across the lifespan. The authors investigated brain morphometry differences between individuals with ASD and healthy subjects, cross-sectionally across the lifespan, in a large multinational sample from the Enhancing Neuroimaging Genetics Through Meta-Analysis (ENIGMA) ASD working group. The sample comprised 1,571 patients with ASD and 1,651 healthy control subjects (age range, 2-64 years) from 49 participating sites. MRI scans were preprocessed at individual sites with a harmonized protocol based on a validated automated-segmentation software program. Mega-analyses were used to test for case-control differences in subcortical volumes, cortical thickness, and surface area. Development of brain morphometry over the lifespan was modeled using a fractional polynomial approach. The case-control mega-analysis demonstrated that ASD was associated with smaller subcortical volumes of the pallidum, putamen, amygdala, and nucleus accumbens (effect sizes [Cohen's d], 0.13 to -0.13), as well as increased cortical thickness in the frontal cortex and decreased thickness in the temporal cortex (effect sizes, -0.21 to 0.20). Analyses of age effects indicate that the development of cortical thickness is altered in ASD, with the largest differences occurring around adolescence. No age-by-ASD interactions were observed in the subcortical partitions. The ENIGMA ASD working group provides the largest study of brain morphometry differences in ASD to date, using a well-established, validated, publicly available analysis pipeline. ASD patients showed altered morphometry in the cognitive and affective parts of the striatum, frontal cortex, and temporal cortex. Complex developmental trajectories were observed for the different regions, with a developmental peak around adolescence. These findings suggest an interplay in the abnormal development of the striatal, frontal, and temporal regions in ASD across the lifespan.

Neuroimaging in autism spectrum disorders: 1H-MRS and NIRS study.

PubMed

Mori, Kenji; Toda, Yoshihiro; Ito, Hiromichi; Mori, Tatsuo; Mori, Keiko; Goji, Aya; Hashimoto, Hiroko; Tani, Hiroe; Miyazaki, Masahito; Harada, Masafumi; Kagami, Shoji

2015-01-01

Using proton magnetic resonance spectroscopy ((1)H-MRS), we measured chemical metabolites in the left amygdala and the bilateral orbito-frontal cortex (OFC) in children with autism spectrum disorders (ASD). The concentrations of N-acetylaspartate (NAA) in these regions of ASD were significantly decreased compared to those in the control group. In the autistic patients, the NAA concentrations in these regions correlated with their social quotient. These findings suggest the presence of neuronal dysfunction in the amygdala and OFC in ASD. Dysfunction in the amygdala and OFC may contribute to the pathogenesis of ASD. We performed a near-infrared spectroscopy (NIRS) study to evaluate the mirror neuron system in children with ASD. The concentrations of oxygenated hemoglobin (oxy-Hb) were measured with frontal probes using a 34-channel NIRS machine while the subjects imitated emotional facial expressions. The increments in the concentration of oxy-Hb in the pars opercularis of the inferior frontal gyrus in autistic subjects were significantly lower than those in the controls. However, the concentrations of oxy-Hb in this area were significantly elevated in autistic subjects after they were trained to imitate emotional facial expressions. The results suggest that mirror neurons could be activated by repeated imitation in children with ASD.

Autism Spectrum Disorder and intact executive functioning.

PubMed

Ferrara, R; Ansermet, F; Massoni, F; Petrone, L; Onofri, E; Ricci, P; Archer, T; Ricci, S

2016-01-01

Earliest notions concerning autism (Autism Spectrum Disorders, ASD) describe the disturbance in executive functioning. Despite altered definition, executive functioning, expressed as higher cognitive skills required complex behaviors linked to the prefrontal cortex, are defective in autism. Specific difficulties in children presenting autism or verbal disabilities at executive functioning levels have been identified. Nevertheless, the developmental deficit of executive functioning in autism is highly diversified with huge individual variation and may even be absent. The aim of the present study to examine the current standing of intact executive functioning intact in ASD. Analysis of ASD populations, whether high-functioning, Asperger's or autism Broad Phenotype, studied over a range of executive functions including response inhibition, planning, cognitive flexibility, cognitive inhibition, and alerting networks indicates an absence of damage/impairment compared to the typically-developed normal control subjects. These findings of intact executive functioning in ASD subjects provide a strong foundation on which to construct applications for growth environments and the rehabilitation of autistic subjects.

Brief Report: Significant Differences in Perceived Odor Pleasantness Found in Children with ASD

ERIC Educational Resources Information Center

Hrdlicka, Michal; Vodicka, Jan; Havlovicova, Marketa; Urbanek, Tomas; Blatny, Marek; Dudova, Iva

2011-01-01

The aim of our study was to explore possible differences in estimation of odor pleasantness in children with autism spectrum disorders (ASD) compared to controls. Thirty-five patients with Asperger's syndrome and high functioning autism (mean age 10.8 [plus or minus] 3.6 years; 31 boys) were compared with 35 healthy control subjects (mean age 10.4…

Impairment in face processing in autism spectrum disorder: a developmental perspective.

PubMed

Greimel, Ellen; Schulte-Rüther, Martin; Kamp-Becker, Inge; Remschmidt, Helmut; Herpertz-Dahlmann, Beate; Konrad, Kerstin

2014-09-01

Findings on face identity and facial emotion recognition in autism spectrum disorder (ASD) are inconclusive. Moreover, little is known about the developmental trajectory of face processing skills in ASD. Taking a developmental perspective, the aim of this study was to extend previous findings on face processing skills in a sample of adolescents and adults with ASD. N = 38 adolescents and adults (13-49 years) with high-functioning ASD and n = 37 typically developing (TD) control subjects matched for age and IQ participated in the study. Moreover, n = 18 TD children between the ages of 8 and 12 were included to address the question whether face processing skills in ASD follow a delayed developmental pattern. Face processing skills were assessed using computerized tasks of face identity recognition (FR) and identification of facial emotions (IFE). ASD subjects showed impaired performance on several parameters of the FR and IFE task compared to TD control adolescents and adults. Whereas TD adolescents and adults outperformed TD children in both tasks, performance in ASD adolescents and adults was similar to the group of TD children. Within the groups of ASD and control adolescents and adults, no age-related changes in performance were found. Our findings corroborate and extend previous studies showing that ASD is characterised by broad impairments in the ability to process faces. These impairments seem to reflect a developmentally delayed pattern that remains stable throughout adolescence and adulthood.

Salivary miRNA profiles identify children with autism spectrum disorder, correlate with adaptive behavior, and implicate ASD candidate genes involved in neurodevelopment.

PubMed

Hicks, Steven D; Ignacio, Cherry; Gentile, Karen; Middleton, Frank A

2016-04-22

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder that lacks adequate screening tools, often delaying diagnosis and therapeutic interventions. Despite a substantial genetic component, no single gene variant accounts for >1 % of ASD incidence. Epigenetic mechanisms that include microRNAs (miRNAs) may contribute to the ASD phenotype by altering networks of neurodevelopmental genes. The extracellular availability of miRNAs allows for painless, noninvasive collection from biofluids. In this study, we investigated the potential for saliva-based miRNAs to serve as diagnostic screening tools and evaluated their potential functional importance. Salivary miRNA was purified from 24 ASD subjects and 21 age- and gender-matched control subjects. The ASD group included individuals with mild ASD (DSM-5 criteria and Autism Diagnostic Observation Schedule) and no history of neurologic disorder, pre-term birth, or known chromosomal abnormality. All subjects completed a thorough neurodevelopmental assessment with the Vineland Adaptive Behavior Scales at the time of saliva collection. A total of 246 miRNAs were detected and quantified in at least half the samples by RNA-Seq and used to perform between-group comparisons with non-parametric testing, multivariate logistic regression and classification analyses, as well as Monte-Carlo Cross-Validation (MCCV). The top miRNAs were examined for correlations with measures of adaptive behavior. Functional enrichment analysis of the highest confidence mRNA targets of the top differentially expressed miRNAs was performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID), as well as the Simons Foundation Autism Database (AutDB) of ASD candidate genes. Fourteen miRNAs were differentially expressed in ASD subjects compared to controls (p <0.05; FDR <0.15) and showed more than 95 % accuracy at distinguishing subject groups in the best-fit logistic regression model. MCCV revealed an average ROC-AUC value of 0.92 across 100 simulations, further supporting the robustness of the findings. Most of the 14 miRNAs showed significant correlations with Vineland neurodevelopmental scores. Functional enrichment analysis detected significant over-representation of target gene clusters related to transcriptional activation, neuronal development, and AutDB genes. Measurement of salivary miRNA in this pilot study of subjects with mild ASD demonstrated differential expression of 14 miRNAs that are expressed in the developing brain, impact mRNAs related to brain development, and correlate with neurodevelopmental measures of adaptive behavior. These miRNAs have high specificity and cross-validated utility as a potential screening tool for ASD.

A stable pattern of EEG spectral coherence distinguishes children with autism from neuro-typical controls - a large case control study.

PubMed

Duffy, Frank H; Als, Heidelise

2012-06-26

The autism rate has recently increased to 1 in 100 children. Genetic studies demonstrate poorly understood complexity. Environmental factors apparently also play a role. Magnetic resonance imaging (MRI) studies demonstrate increased brain sizes and altered connectivity. Electroencephalogram (EEG) coherence studies confirm connectivity changes. However, genetic-, MRI- and/or EEG-based diagnostic tests are not yet available. The varied study results likely reflect methodological and population differences, small samples and, for EEG, lack of attention to group-specific artifact. Of the 1,304 subjects who participated in this study, with ages ranging from 1 to 18 years old and assessed with comparable EEG studies, 463 children were diagnosed with autism spectrum disorder (ASD); 571 children were neuro-typical controls (C). After artifact management, principal components analysis (PCA) identified EEG spectral coherence factors with corresponding loading patterns. The 2- to 12-year-old subsample consisted of 430 ASD- and 554 C-group subjects (n = 984). Discriminant function analysis (DFA) determined the spectral coherence factors' discrimination success for the two groups. Loading patterns on the DFA-selected coherence factors described ASD-specific coherence differences when compared to controls. Total sample PCA of coherence data identified 40 factors which explained 50.8% of the total population variance. For the 2- to 12-year-olds, the 40 factors showed highly significant group differences (P < 0.0001). Ten randomly generated split half replications demonstrated high-average classification success (C, 88.5%; ASD, 86.0%). Still higher success was obtained in the more restricted age sub-samples using the jackknifing technique: 2- to 4-year-olds (C, 90.6%; ASD, 98.1%); 4- to 6-year-olds (C, 90.9%; ASD 99.1%); and 6- to 12-year-olds (C, 98.7%; ASD, 93.9%). Coherence loadings demonstrated reduced short-distance and reduced, as well as increased, long-distance coherences for the ASD-groups, when compared to the controls. Average spectral loading per factor was wide (10.1 Hz). Classification success suggests a stable coherence loading pattern that differentiates ASD- from C-group subjects. This might constitute an EEG coherence-based phenotype of childhood autism. The predominantly reduced short-distance coherences may indicate poor local network function. The increased long-distance coherences may represent compensatory processes or reduced neural pruning. The wide average spectral range of factor loadings may suggest over-damped neural networks.

Serum Oxytocin Levels and an Oxytocin Receptor Gene Polymorphism (rs2254298) Indicate Social Deficits in Children and Adolescents with Autism Spectrum Disorders

PubMed Central

Yang, Shuhan; Dong, Xiaopeng; Guo, Xuan; Han, Yu; Song, Hanbing; Gao, Lei; Dai, Wei; Su, Yuanyuan; Zhang, Xin

2017-01-01

The neuropeptide oxytocin (OT) and its receptor (OXTR) have been predicted to be involved in the regulation of social functioning in autism spectrum disorders (ASD). Objective of the study was to investigate serum OT levels and the OXTR rs2254298 polymorphism in Chinese Han children and adolescents with ASD as well as to identify their social deficits relevant to the oxytocinergic system. We tested serum OT levels using ELISA in 55 ASD subjects and 110 typically developing (TD) controls as well as genotyped the OXTR rs2254298 polymorphism using PCR-RFLP in 100 ASD subjects and 232 TD controls. Autistic symptoms were assessed by the Autism Behavior Checklist (ABC) and the Childhood Autism Rating Scale (CARS). There were no significant associations between OXTR rs2254298 polymorphism and ASD, serum OT levels and age, as well as serum OT levels and intelligent quotient (IQ) in both ASD and TD groups. However, ASD subjects exhibited elevated serum OT levels compared to TD controls and positive correlations between serum OT levels and “adaptation to change score” in the CARS and CARS total scores. Moreover, in the ASD group, significant relationships were revealed between the single-nucleotide polymorphism (SNP) rs2254298 and serum OT levels, the category “stereotypes and object use” in the ABC and the category “adaptation to change” in the CARS. These findings indicated that individuals with ASD may exhibit a dysregulation in OT on the basis of changes in OXTR gene expression as well as environmentally induced alterations of the oxytocinergic system to determine their social deficits. PMID:28484366

Depletion of Stercobilin in Fecal Matter from a Mouse Model of Autism Spectrum Disorders

PubMed Central

Sekera, Emily R.; Rudolph, Heather L.; Carro, Stephen D.; Morales, Michael J.; Bett, Glenna C. L.; Rasmusson, Randall L.; Wood, Troy D.

2017-01-01

Introduction Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders lacking a clinical biomarker for diagnosis. Emerging evidence shows that intestinal microflora from ASD subjects can be distinguished from controls, suggesting metabolite differences due to the action of intestinal microbes may provide a means for identifying potential biomarkers for ASD. Objectives The aim of this study was to determine if quantitative differences in levels of stercobilin and stercobilinogen, metabolites produced by biological action of intestinal microflora, exist in the fecal matter between an ASD mouse model population and controls. Methods Pairs of fecal samples were collected from two mouse groups, an ASD model group with Timothy syndrome 2 (TS2-NEO) and a gender-matched control group. After centrifugation, supernatant was spiked with an 18O-labeled stercobilin isotopomer and subjected to solid phase extraction for processing. Extracted samples were spotted on a stainless steel plate and subjected to matrix-assisted laser desorption and ionization mass spectrometry using dihydroxybenzoic acid as the matrix (n = 5). Peak areas for bilins and 18O-stercobilin isotopomers were determined in each fecal sample. Results A 40–45% depletion in stercobilin in TS2-NEO fecal samples compared with controls was observed with p < 0.05; a less dramatic depletion was observed for stercobilinogen. Conclusions The results show that stercobilin depletion in feces is observed for an ASD mouse model vs. controls. This may help to explain recent observations of a less diverse microbiome in humans with ASD and may prove helpful in developing a clinical ASD biomarker. PMID:29147105

Differential immune responses and microbiota profiles in children with autism spectrum disorders and co-morbid gastrointestinal symptoms.

PubMed

Rose, Destanie R; Yang, Houa; Serena, Gloria; Sturgeon, Craig; Ma, Bing; Careaga, Milo; Hughes, Heather K; Angkustsiri, Kathy; Rose, Melissa; Hertz-Picciotto, Irva; Van de Water, Judy; Hansen, Robin L; Ravel, Jacques; Fasano, Alessio; Ashwood, Paul

2018-05-01

Many studies have reported the increased presence of gastrointestinal (GI) symptoms in children with autism spectrum disorders (ASD). Altered microbiome profiles, pro-inflammatory responses and impaired intestinal permeability have been observed in children with ASD and co-morbid GI symptoms, yet few studies have compared these findings to ASD children without GI issues or similarly aged typical developing children. The aim of this study was to determine whether there are biological signatures in terms of immune dysfunction and microbiota composition in children with ASD with GI symptoms. Children were enrolled in one of four groups: ASD and GI symptoms of irregular bowel habits (ASD GI ), children with ASD but without current or previous GI symptoms (ASD NoGI ), typically developing children with GI symptoms (TD GI ) and typically developing children without current or previous GI symptoms (TD NoGI ). Peripheral blood mononuclear cells (PBMC) were isolated from the blood, stimulated and assessed for cytokine production, while stool samples were analyzed for microbial composition. Following Toll-Like receptor (TLR)-4 stimulation, the ASD GI group produced increased levels of mucosa-relevant cytokines including IL-5, IL-15 and IL-17 compared to ASD NoGI . The production of the regulatory cytokine TGFβ1 was decreased in the ASD GI group compared with both the ASD NoGI and TD NoGI groups. Analysis of the microbiome at the family level revealed differences in microbiome composition between ASD and TD children with GI symptoms; furthermore, a predictive metagenome functional content analysis revealed that pathways were differentially represented between ASD and TD subjects, independently of the presence of GI symptoms. The ASD GI also showed an over-representation of the gene encoding zonulin, a molecule regulating gut permeability, compared to the other groups. Overall our findings suggest that children with ASD who experience GI symptoms have an imbalance in their immune response, possibly influenced by or influencing metagenomic changes, and may have a propensity to impaired gut barrier function which may contribute to their symptoms and clinical outcome. Copyright © 2018 Elsevier Inc. All rights reserved.

Asian sand dust aggregate causes atopic dermatitis-like symptoms in Nc/Nga mice.

PubMed

Takeshita, Sayaka; Tokunaga, Takahiro; Tanabe, Yoshiko; Arinami, Tadao; Ichinose, Takamichi; Noguchi, Emiko

2015-01-01

Asian sand dust (ASD) originates from the arid and semiarid areas of China, and epidemiologic studies have shown that ASD exposure is associated with various allergic and respiratory symptoms. However, few studies have been performed to assess the relationship between skin inflammation and ASD exposure. Twelve-week-old NC/Nga mice were divided into 6 groups (n = 8 for each group): hydrophilic petrolatum only (control); hydrophilic petrolatum plus ASD (ASD); hydrophilic petrolatum and heat inactivated-ASD (H-ASD); Dermatophagoides farinae extract (Df); Df and ASD (Df + ASD), and; Df and H-ASD (Df + H-ASD). The NC/Nga mice in each group were subjected to treatment twice a week for 4 weeks. We evaluated skin lesions by symptoms, pathologic changes, and serum IgE levels. ASD alone did not induce atopic dermatitis (AD)-like skin symptoms. However, Df alone, Df + H-ASD and Df + ASD all induced AD-like symptoms, and dermatitis scores in the group of Df + ASD group were significantly greater than that of the Df group (P = 0.0011 at day 21; and P = 0.017 at day 28). Mean serum IgE was markedly increased in the Df and Df + ASD groups, compared to the ASD and control groups (P < 0.0001), and serum IgE levels in the Df + ASD group were significantly higher compared to the Df group (P = 0.003). ASD alone did not cause AD-like symptoms in NC/Nga mice. However, AD-like symptoms induced by Df, a major allergen, were enhanced by adding ASD. Although no epidemiological studies have been conducted for the association between ASD and symptoms of dermatitis, our data suggest that it is likely that ASD may contribute to the exacerbation of not only respiratory symptoms, but also skin diseases, in susceptible individuals.

Social cognition in autism is associated with the neurodevelopment of the posterior superior temporal sulcus.

PubMed

Hotier, S; Leroy, F; Boisgontier, J; Laidi, C; Mangin, J-F; Delorme, R; Bolognani, F; Czech, C; Bouquet, C; Toledano, E; Bouvard, M; Petit, J; Mishchenko, M; d'Albis, M-A; Gras, D; Gaman, A; Scheid, I; Leboyer, M; Zalla, T; Houenou, J

2017-11-01

The posterior superior temporal sulcus (pSTS) plays a critical role in the 'social brain'. Its neurodevelopment and relationship with the social impairment in autism spectrum disorders (ASD) are not well understood. We explored the relationship between social cognition and the neurodevelopment of the pSTS in ASD. We included 44 adults with high-functioning ASD and 36 controls. We assessed their performances on the 'Reading the mind in the eyes' test (for 34 of 44 subjects with ASD and 30 of 36 controls), their fixation time on the eyes with eye tracking (for 35 of 44 subjects with ASD and 30 of 36 controls) and the morphology of the caudal branches of the pSTS (length and depth), markers of the neurodevelopment, with structural MRI. The right anterior caudal ramus of the pSTS was significantly longer in patients with ASD compared with controls (52.6 mm vs. 38.3 mm; P = 1.4 × 10 -3 ; Cohen's d = 0.76). Its length negatively correlated with fixation time on the eyes (P = 0.03) in the ASD group and with the 'Reading the mind in the eyes' test scores in both groups (P = 0.03). Our findings suggest that the neurodevelopment of the pSTS is related to the ASD social impairments. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Prevalence of attention deficit hyperactivity disorder and/or autism spectrum disorder and its relation to lifestyle in female college students.

PubMed

Takahashi, Keizo; Miyatake, Nobuyuki; Kurato, Risa; Takahashi, Nobuko

2016-11-01

The aim of this study was to explore the prevalence of attention deficit hyperactivity disorder (ADHD) and/or autism spectrum disorder (ASD) and its relation to lifestyle in female college students. A total of 375 female college students (19.2 ± 1.3 years) among 439 students were enrolled in this cross-sectional study. Using a self-reported questionnaire, we measured the prevalence of ADHD using the ADHD Self-Report Scale-v1.1 (ASRS) and the prevalence of ASD using the Autism-Spectrum Quotient (AQ). In addition, lifestyle choices such as medications, physical activity, cigarette smoking, alcohol drinking and sleeping habits were also evaluated. The suspected prevalence of ADHD was 102 students (27.2 %) and the suspected prevalence of ASD was 4 students (1.1 %). Only one student (0.3 %) was thought to have both ADHD and ASD. Subjects with suspected ADHD had higher AQ scores compared with those without suspected ADHD. There were no unhealthy lifestyle choices in subjects with suspected ADHD and/or ASD. The prevalence of suspected ADHD and/or ASD may be relatively high even among female college students in Japan.

Developmental changes in face visual scanning in autism spectrum disorder as assessed by data-based analysis

PubMed Central

Amestoy, Anouck; Guillaud, Etienne; Bouvard, Manuel P.; Cazalets, Jean-René

2015-01-01

Individuals with autism spectrum disorder (ASD) present reduced visual attention to faces. However, contradictory conclusions have been drawn about the strategies involved in visual face scanning due to the various methodologies implemented in the study of facial screening. Here, we used a data-driven approach to compare children and adults with ASD subjected to the same free viewing task and to address developmental aspects of face scanning, including its temporal patterning, in healthy children, and adults. Four groups (54 subjects) were included in the study: typical adults, typically developing children, and adults and children with ASD. Eye tracking was performed on subjects viewing unfamiliar faces. Fixations were analyzed using a data-driven approach that employed spatial statistics to provide an objective, unbiased definition of the areas of interest. Typical adults expressed a spatial and temporal strategy for visual scanning that differed from the three other groups, involving a sequential fixation of the right eye (RE), left eye (LE), and mouth. Typically developing children, adults and children with autism exhibited similar fixation patterns and they always started by looking at the RE. Children (typical or with ASD) subsequently looked at the LE or the mouth. Based on the present results, the patterns of fixation for static faces that mature from childhood to adulthood in typical subjects are not found in adults with ASD. The atypical patterns found after developmental progression and experience in ASD groups appear to remain blocked in an immature state that cannot be differentiated from typical developmental child patterns of fixation. PMID:26236264

Central Coherence Theory and the Interpretation of Picture Materials: Toward an Assessment of Autistic Spectrum Disorder.

ERIC Educational Resources Information Center

Worth, Sarah

2003-01-01

This study compared responses of 16 pupils either with or without autistic spectrum disorder (ASD) and matched for gender and verbal ability. Subjects' responses to various pictures were categorized. Results suggested errors made by the two groups differed both quantitatively and qualitatively. Errors made by pupils with ASD were largely…

Head Circumferences in Twins with and without Autism Spectrum Disorders

ERIC Educational Resources Information Center

Froehlich, Wendy; Cleveland, Sue; Torres, Andrea; Phillips, Jennifer; Cohen, Brianne; Torigoe, Tiffany; Miller, Janet; Fedele, Angie; Collins, Jack; Smith, Karen; Lotspeich, Linda; Croen, Lisa A.; Ozonoff, Sally; Lajonchere, Clara; Grether, Judith K.; Hallmayer, Joachim

2013-01-01

To determine the genetic relationship between head circumference (HC) and Autism Spectrum Disorders (ASDs). Twin pairs with at least one twin with an ASD were assessed. HCs in affected and unaffected individuals were compared, as were HC correlations in monozygotic and dizygotic pairs. 404 subjects, ages 4-18, were included. 20% of males and 27%…

Dysfunctions in brain networks supporting empathy: An fMRI study in adults with autism spectrum disorders

PubMed Central

Schulte-Rüther, Martin; Greimel, Ellen; Markowitsch, Hans J.; Kamp-Becker, Inge; Remschmidt, Helmut; Fink, Gereon R.; Piefke, Martina

2010-01-01

The present study aimed at identifying dysfunctions in brain networks that may underlie disturbed empathic behavior in autism spectrum disorders (ASD). During functional magnetic resonance imaging, subjects were asked to identify the emotional state observed in a facial stimulus (other-task) or to evaluate their own emotional response (self-task). Behaviorally, ASD subjects performed equally to the control group during the other-task, but showed less emotionally congruent responses in the self-task. Activations in brain regions related to theory of mind were observed in both groups. Activations of the medial prefrontal cortex (MPFC) were located in dorsal subregions in ASD subjects and in ventral areas in control subjects. During the self-task, ASD subjects activated an additional network of frontal and inferior temporal areas. Frontal areas previously associated with the human mirror system were activated in both tasks in control subjects, while ASD subjects recruited these areas during the self-task only. Activations in the ventral MPFC may provide the basis for one's “emotional bond” with other persons’ emotions. Such atypical patterns of activation may underlie disturbed empathy in individuals with ASD. Subjects with ASD may use an atypical cognitive strategy to gain access to their own emotional state in response to other people's emotions. PMID:20945256

Dysfunctions in brain networks supporting empathy: an fMRI study in adults with autism spectrum disorders.

PubMed

Schulte-Rüther, Martin; Greimel, Ellen; Markowitsch, Hans J; Kamp-Becker, Inge; Remschmidt, Helmut; Fink, Gereon R; Piefke, Martina

2011-01-01

The present study aimed at identifying dysfunctions in brain networks that may underlie disturbed empathic behavior in autism spectrum disorders (ASD). During functional magnetic resonance imaging, subjects were asked to identify the emotional state observed in a facial stimulus (other-task) or to evaluate their own emotional response (self-task). Behaviorally, ASD subjects performed equally to the control group during the other-task, but showed less emotionally congruent responses in the self-task. Activations in brain regions related to theory of mind were observed in both groups. Activations of the medial prefrontal cortex (MPFC) were located in dorsal subregions in ASD subjects and in ventral areas in control subjects. During the self-task, ASD subjects activated an additional network of frontal and inferior temporal areas. Frontal areas previously associated with the human mirror system were activated in both tasks in control subjects, while ASD subjects recruited these areas during the self-task only. Activations in the ventral MPFC may provide the basis for one's "emotional bond" with other persons' emotions. Such atypical patterns of activation may underlie disturbed empathy in individuals with ASD. Subjects with ASD may use an atypical cognitive strategy to gain access to their own emotional state in response to other people's emotions.

Cognitive Control in Autism Spectrum Disorders

PubMed Central

Solomon, Marjorie; Ozonoff, Sally; Cummings, Neil; Carter, Cameron

2009-01-01

Cognitive control refers to the ability to flexibly allocate mental resources to guide thoughts and actions in light of internal goals. Given the behavioral inflexibility exhibited by individuals with autism spectrum disorders (ASDs), it would appear they experience cognitive control deficits. Cognitive correlates of this behavioral inflexibility have been elusive in previous investigations. Study goals were to investigate deficits in cognitive control in ASDs; to explore its developmental trajectory; and to test whether control deficits are related to symptoms of inflexible thoughts and/or behaviors, and attention symptoms. Thirty-one children and adolescents aged 8 to17 with ASDs and 32 age, IQ, and gender matched control subjects completed cognitive, diagnostic, and behavorial assessments, as well as a measure of cognitive control involving overcoming a prepotent response tendency. Compared with typically developing control subjects, individuals with ASDs exhibited deficits in cognitive control. Younger children with ASDs did not demonstrate age related improvements in cognitive control. Modest relationships between cognitive control, IQ, and attention problems were found for the sample. Only the relationship between cognitive control and Full Scale IQ survived correction for multiple comparisons. PMID:18093787

Brain-Derived Neurotrophic Factor Levels in Autism: A Systematic Review and Meta-Analysis.

PubMed

Saghazadeh, Amene; Rezaei, Nima

2017-04-01

Brain-derived neurotrophic factor (BDNF) plays an important role in activity-dependent synaptic plasticity. Altered blood BDNF levels have been frequently identified in people with autism spectrum disorders (ASD). There are however wide discrepancies in the evidence. Therefore, we performed the present systematic review and meta-analysis aimed at qualitative and quantitative synthesis of studies that measured blood BDNF levels in ASD and control subjects. Observational studies were identified through electronic database searching and also hand-searching of reference lists of relevant articles. A total of 183 papers were initially identified for review and eventually twenty studies were included in the meta-analysis. A meta-analysis of blood BDNF in 887 patients with ASD and 901 control subjects demonstrated significantly higher BDNF levels in ASD compared to controls with the SMD of 0.47 (95% CI 0.07-0.86, p = 0.02). In addition subgroup meta-analyses were performed based on the BDNF specimen. The present meta-analysis study led to conclusion that BDNF might play role in autism initiation/ propagation and therefore it can be considered as a possible biomarker of ASD.

A stable pattern of EEG spectral coherence distinguishes children with autism from neuro-typical controls - a large case control study

PubMed Central

2012-01-01

Background The autism rate has recently increased to 1 in 100 children. Genetic studies demonstrate poorly understood complexity. Environmental factors apparently also play a role. Magnetic resonance imaging (MRI) studies demonstrate increased brain sizes and altered connectivity. Electroencephalogram (EEG) coherence studies confirm connectivity changes. However, genetic-, MRI- and/or EEG-based diagnostic tests are not yet available. The varied study results likely reflect methodological and population differences, small samples and, for EEG, lack of attention to group-specific artifact. Methods Of the 1,304 subjects who participated in this study, with ages ranging from 1 to 18 years old and assessed with comparable EEG studies, 463 children were diagnosed with autism spectrum disorder (ASD); 571 children were neuro-typical controls (C). After artifact management, principal components analysis (PCA) identified EEG spectral coherence factors with corresponding loading patterns. The 2- to 12-year-old subsample consisted of 430 ASD- and 554 C-group subjects (n = 984). Discriminant function analysis (DFA) determined the spectral coherence factors' discrimination success for the two groups. Loading patterns on the DFA-selected coherence factors described ASD-specific coherence differences when compared to controls. Results Total sample PCA of coherence data identified 40 factors which explained 50.8% of the total population variance. For the 2- to 12-year-olds, the 40 factors showed highly significant group differences (P < 0.0001). Ten randomly generated split half replications demonstrated high-average classification success (C, 88.5%; ASD, 86.0%). Still higher success was obtained in the more restricted age sub-samples using the jackknifing technique: 2- to 4-year-olds (C, 90.6%; ASD, 98.1%); 4- to 6-year-olds (C, 90.9%; ASD 99.1%); and 6- to 12-year-olds (C, 98.7%; ASD, 93.9%). Coherence loadings demonstrated reduced short-distance and reduced, as well as increased, long-distance coherences for the ASD-groups, when compared to the controls. Average spectral loading per factor was wide (10.1 Hz). Conclusions Classification success suggests a stable coherence loading pattern that differentiates ASD- from C-group subjects. This might constitute an EEG coherence-based phenotype of childhood autism. The predominantly reduced short-distance coherences may indicate poor local network function. The increased long-distance coherences may represent compensatory processes or reduced neural pruning. The wide average spectral range of factor loadings may suggest over-damped neural networks. PMID:22730909

The fears, phobias and anxieties of children with autism spectrum disorders and Down syndrome: comparisons with developmentally and chronologically age matched children.

PubMed

Evans, David W; Canavera, Kristin; Kleinpeter, F Lee; Maccubbin, Elise; Taga, Ken

2005-01-01

This study compared the fears and behavior problems of 25 children with an autism spectrum disorder (ASD), 43 children with Down syndrome (DS), 45 mental age (MA) matched children, and 37 chronologically age (CA) matched children. Children's fears, phobias, anxieties and behavioral problems were assessed using parent reports. Significant differences emerged across the diagnostic groups on a variety of fears. Children with ASD were reported to have more situation phobias and medical fears, but fewer fears of harm/injury compared to all other groups. The groups also differed in terms of the pattern of correlations between fears, phobias, anxieties and behavior problems. For children with ASD, fears, phobias and anxieties were closely related to problem behaviors, whereas fears, phobias, and anxieties were less related to behavioral symptoms for the other groups of subjects. Such findings suggest that children with ASD exhibit a distinct profile of fear and anxiety compared to other mental age and chronologically age-matched children, and these fears are related to the symptoms associated with ASD.

Repetitive behavior profiles: Consistency across autism spectrum disorder cohorts and divergence from Prader-Willi syndrome.

PubMed

Flores, Cindi G; Valcante, Gregory; Guter, Steve; Zaytoun, Annette; Wray, Emily; Bell, Lindsay; Jacob, Suma; Lewis, Mark H; Driscoll, Daniel J; Cook, Edwin H; Kim, Soo-Jeong

2011-12-01

Restricted and repetitive behavior (RRB) is a group of heterogeneous maladaptive behaviors. RRB is one of the key diagnostic features of autism spectrum disorders (ASDs) and also commonly observed in Prader-Willi syndrome (PWS). In this study, we assessed RRB using the Repetitive Behavior Scale-Revised (RBS-R) in two ASD samples (University of Illinois at Chicago [UIC] and University of Florida [UF]) and one PWS sample. We compared the RBS-R item endorsements across three ASD cohorts (UIC, UF and an ASD sample from Lam, The Repetitive Behavior Scale-Revised: independent validation and the effect of subject variables, PhD thesis, 2004), and a PWS sample. We also compared the mean RBS-R subscale/sum scores across the UIC, UF and PWS samples; across the combined ASD (UIC + UF), PWS-deletion and PWS-disomy groups; and across the combined ASD sample, PWS subgroup with a Social Communication Questionnaire (SCQ) score ≥15, and PWS subgroup with a SCQ score <15. Despite the highly heterogeneous nature, the three ASD samples (UIC, UF and Lam's) showed a similar pattern of the RBS-R endorsements, and the mean RBS-R scores were not different between the UIC and UF samples. However, higher RRB was noted in the ASD sample compared with the PWS sample, as well as in the PWS subgroup with a SCQ score ≥15 compared with the PWS subgroup with a SCQ score <15. Study limitations include a small sample size, a wide age range of our participants, and not controlling for potential covariates. A future replication study using a larger sample and further investigation into the genetic bases of overlapping ASD and RRB phenomenology are needed, given the higher RRB in the PWS subgroup with a SCQ score ≥15.

Social memory, amnesia, and autism: brain oxytocin secretion is regulated by NAD+ metabolites and single nucleotide polymorphisms of CD38.

PubMed

Higashida, Haruhiro; Yokoyama, Shigeru; Huang, Jian-Jun; Liu, Li; Ma, Wen-Jie; Akther, Shirin; Higashida, Chiharu; Kikuchi, Mitsuru; Minabe, Yoshio; Munesue, Toshio

2012-11-01

Previously, we demonstrated that CD38, a transmembrane protein with ADP-ribosyl cyclase activity, plays a critical role in mouse social behavior by regulating the release of oxytocin (OXT), which is essential for mutual recognition. When CD38 was disrupted, social amnesia was observed in Cd38 knockout mice. The autism spectrum disorders (ASDs), characterized by defects in reciprocal social interaction and communication, occur either sporadically or in a familial pattern. However, the etiology of ASDs remains largely unknown. Therefore, the theoretical basis for pharmacological treatments has not been established. Hence, there is a rationale for investigating single nucleotide polymorphisms (SNPs) in the human CD38 gene in ASD subjects. We found several SNPs in this gene. The SNP rs3796863 (C>A) was associated with high-functioning autism (HFA) in American samples from the Autism Gene Resource Exchange. Although this finding was partially confirmed in low-functioning autism subjects in Israel, it has not been replicated in Japanese HFA subjects. The second SNP of interest, rs1800561 (4693C>T), leads to the substitution of an arginine (R) at codon 140 by tryptophan (W; R140W) in CD38. This mutation was found in four probands of ASD and in family members of three pedigrees with variable levels of ASD or ASD traits. The plasma levels of OXT in ASD subjects with the R140W allele were lower than those in ASD subjects lacking this allele. The OXT levels were unchanged in healthy subjects with or without this mutation. One proband with the R140W allele receiving intranasal OXT for approximately 3years showed improvement in areas of social approach, eye contact and communication behaviors, emotion, irritability, and aggression. Five other ASD subjects with mental deficits received nasal OXT for various periods; three subjects showed improved symptoms, while two showed little or no effect. These results suggest that SNPs in CD38 may be possible risk factors for ASD by abrogating OXT function and that some ASD subjects can be treated with OXT in preliminary clinical trials. Copyright © 2012 Elsevier Ltd. All rights reserved.

Decreased plasma agmatine levels in autistic subjects.

PubMed

Esnafoglu, Erman; İrende, İlhan

2018-04-01

Agmatine is a polyamine endogenously synthesized from arginine and is considered to be a new neurotransmitter. Agmatine has been implicated in the pathophysiology of several diseases such as anxiety disorder, depression, and schizophrenia. Agmatine also possesses anticonvulsant, neuroprotective, antiapoptotic, antioxidant, anxiolytic, and antidepressant effects. Furthermore, agmatine inhibits the nitric oxide synthase enzyme and exerts antagonist effects on NMDA, alpha-2, and imidazoline receptors. Considering these characteristics, the present study investigated whether agmatine plays a role in the pathogenesis of autistic spectrum disorders (ASDs). Therefore, plasma agmatine levels were evaluated in 34 patients with ASD and 28 non-ASD controls. Plasma agmatine levels were measured using the HPLC method. The study found remarkably lower agmatine levels in patients with ASD compared with the non-ASD control group (p < 0.001). These findings support the notion that agmatine might contribute to the pathogenesis of ASD and may serve as a new target for treatment.

Cerebro-cerebellar Resting-State Functional Connectivity in Children and Adolescents with Autism Spectrum Disorder.

PubMed

Khan, Amanda J; Nair, Aarti; Keown, Christopher L; Datko, Michael C; Lincoln, Alan J; Müller, Ralph-Axel

2015-11-01

The cerebellum plays important roles in sensori-motor and supramodal cognitive functions. Cellular, volumetric, and functional abnormalities of the cerebellum have been found in autism spectrum disorders (ASD), but no comprehensive investigation of cerebro-cerebellar connectivity in ASD is available. We used resting-state functional connectivity magnetic resonance imaging in 56 children and adolescents (28 subjects with ASD, 28 typically developing subjects) 8-17 years old. Partial and total correlation analyses were performed for unilateral regions of interest (ROIs), distinguished in two broad domains as sensori-motor (premotor/primary motor, somatosensory, superior temporal, and occipital) and supramodal (prefrontal, posterior parietal, and inferior and middle temporal). There were three main findings: 1) Total correlation analyses showed predominant cerebro-cerebellar functional overconnectivity in the ASD group; 2) partial correlation analyses that emphasized domain specificity (sensori-motor vs. supramodal) indicated a pattern of robustly increased connectivity in the ASD group (compared with the typically developing group) for sensori-motor ROIs but predominantly reduced connectivity for supramodal ROIs; and 3) this atypical pattern of connectivity was supported by significantly increased noncanonical connections (between sensori-motor cerebral and supramodal cerebellar ROIs and vice versa) in the ASD group. Our findings indicate that sensori-motor intrinsic functional connectivity is atypically increased in ASD, at the expense of connectivity supporting cerebellar participation in supramodal cognition. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Melatonin and circadian rhythms in autism: Case report.

PubMed

Zuculo, Gabriela Melloni; Gonçalves, Bruno S B; Brittes, Clay; Menna-Barreto, Luiz; Pinato, Luciana

2017-01-01

Among the most co-occurring conditions in autism spectrum disorders (ASD), there are sleep disorders which may exacerbate associated behavioral disorders and lead to intensification of existing autistic symptoms. Several studies investigating the use of melatonin in the treatment of sleep disorders in ASD have shown comparative efficiency in sleep with little or no side effects. Here we report a case of ASD with non-24-hour rhythm and the effect of melatonin in circadian parameters by actigraphy. Visual analysis of the first 10 days recorded and the periodogram suggest that this patient showed a non-24-hour rhythm. This ASD subject showed before melatonin administration an activity/rest rhythm lower than 24 hours. The results show that melatonin increased approximately 4.7 times the regularity of circadian activity rhythm and resting staying on average between 00:00 and 06:00 and showed positive effects in improving the quality of sleep and behavior. So, the actigraphy showed an ASD subject with a non-24-hour activity/rest rhythm which changed this rhythm to a 24-hour rhythm after melatonin administration. This result reinforces the prospect of therapy with melatonin for synchronization (increased regularity) of endogenous rhythms and improve sleep quality and hence behavior and indicates the actigraphy as a choice tool to characterize several parameters of the activity/rest rhythm of ASD individuals.

Exon resequencing of H3K9 methyltransferase complex genes, EHMT1, EHTM2 and WIZ, in Japanese autism subjects.

PubMed

Balan, Shabeesh; Iwayama, Yoshimi; Maekawa, Motoko; Toyota, Tomoko; Ohnishi, Tetsuo; Toyoshima, Manabu; Shimamoto, Chie; Esaki, Kayoko; Yamada, Kazuo; Iwata, Yasuhide; Suzuki, Katsuaki; Ide, Masayuki; Ota, Motonori; Fukuchi, Satoshi; Tsujii, Masatsugu; Mori, Norio; Shinkai, Yoichi; Yoshikawa, Takeo

2014-01-01

Histone H3 methylation at lysine 9 (H3K9) is a conserved epigenetic signal, mediating heterochromatin formation by trimethylation, and transcriptional silencing by dimethylation. Defective GLP (Ehmt1) and G9a (Ehmt2) histone lysine methyltransferases, involved in mono and dimethylation of H3K9, confer autistic phenotypes and behavioral abnormalities in animal models. Moreover, EHMT1 loss of function results in Kleefstra syndrome, characterized by severe intellectual disability, developmental delays and psychiatric disorders. We examined the possible role of histone methyltransferases in the etiology of autism spectrum disorders (ASD) and suggest that rare functional variants in these genes that regulate H3K9 methylation may be associated with ASD. Since G9a-GLP-Wiz forms a heteromeric methyltransferase complex, all the protein-coding regions and exon/intron boundaries of EHMT1, EHMT2 and WIZ were sequenced in Japanese ASD subjects. The detected variants were prioritized based on novelty and functionality. The expression levels of these genes were tested in blood cells and postmortem brain samples from ASD and control subjects. Expression of EHMT1 and EHMT2 isoforms were determined by digital PCR. We identified six nonsynonymous variants: three in EHMT1, two in EHMT2 and one in WIZ. Two variants, the EHMT1 ankyrin repeat domain (Lys968Arg) and EHMT2 SET domain (Thr961Ile) variants were present exclusively in cases, but showed no statistically significant association with ASD. The EHMT2 transcript expression was significantly elevated in the peripheral blood cells of ASD when compared with control samples; but not for EHMT1 and WIZ. Gene expression levels of EHMT1, EHMT2 and WIZ in Brodmann area (BA) 9, BA21, BA40 and the dorsal raphe nucleus (DoRN) regions from postmortem brain samples showed no significant changes between ASD and control subjects. Nor did expression levels of EHMT1 and EHMT2 isoforms in the prefrontal cortex differ significantly between ASD and control groups. We identified two novel rare missense variants in the EHMT1 and EHMT2 genes of ASD patients. We surmise that these variants alone may not be sufficient to exert a significant effect on ASD pathogenesis. The elevated expression of EHMT2 in the peripheral blood cells may support the notion of a restrictive chromatin state in ASD, similar to schizophrenia.

The neonatal levels of TSB, NSE and CK-BB in autism spectrum disorder from Southern China.

PubMed

Lv, Meng-Na; Zhang, Hong; Shu, Yi; Chen, Shan; Hu, Yuan-Yuan; Zhou, Min

2016-01-01

Background" Autism spectrum disorder (ASD) is a serious neurodevelopmental disorder that impairs a child's ability to communicate with others. It also includes restricted repetitive behaviors, interests and activities. Symptoms manifest before the age of 3. In the previous studies, we found structural abnormalities of the temporal lobe cortex. High spine densities were most commonly found in ASD subjects with lower levels of cognitive functioning. In the present study, we retrospectively analyzed medical records in relation to the neonatal levels of total serum bilirubin (TSB), neuron-specific enolase (NSE), creatine kinase brain band isoenzyme (CK-BB), and neonatal behavior in ASD patients from Southern China. A total of 80 patients with ASD (ASD group) were screened for this retrospective study. Among them, 34 were low-functioning ASD (L-ASD group) and 46 were high-functioning ASD (H-ASD group). Identification of the ASD cases was confirmed with a Revised Autism Diagnostic Inventory. For comparison with ASD cases, 80 normal neonates (control group) were selected from the same period. Biochemical parameters, including TSB, NSE and CK-BB in the neonatal period and medical records on neonatal behavior were collected. The levels of serum TSB, NSE and CK-BB in the ASD group were significantly higher when compared with those from the control group (P < 0.01, or P < 0.05). The amounts of serum TSB, NSE and CK-BB in the L-ASD group were significantly higher when compared with those in the H-ASD group (P < 0.01, or P < 0.05). The Neonatal Behavioral Assessment Scale (NBAS) scores in the ASD group were significantly lower than that in the control group (P < 0.05). Likewise, the NBAS scores in the L-ASD group were significantly lower than that in the H-ASD group (P < 0.05). There was no association between serum TSB, NSE, CK-BB and NBAS scores (P > 0.05) in the ASD group. The neonatal levels of TSB, NSE and CK-BB in ASD from Southern China were significantly higher than those of healthy controls. These findings need to be investigated thoroughly by future studies with large sample.

The neonatal levels of TSB, NSE and CK-BB in autism spectrum disorder from Southern China

PubMed Central

Lv, Meng-na; Shu, Yi; Chen, Shan; Hu, Yuan-yuan; Zhou, Min

2016-01-01

Abstract Background" Autism spectrum disorder (ASD) is a serious neurodevelopmental disorder that impairs a child’s ability to communicate with others. It also includes restricted repetitive behaviors, interests and activities. Symptoms manifest before the age of 3. In the previous studies, we found structural abnormalities of the temporal lobe cortex. High spine densities were most commonly found in ASD subjects with lower levels of cognitive functioning. In the present study, we retrospectively analyzed medical records in relation to the neonatal levels of total serum bilirubin (TSB), neuron-specific enolase (NSE), creatine kinase brain band isoenzyme (CK-BB), and neonatal behavior in ASD patients from Southern China. Methods: A total of 80 patients with ASD (ASD group) were screened for this retrospective study. Among them, 34 were low-functioning ASD (L-ASD group) and 46 were high-functioning ASD (H-ASD group). Identification of the ASD cases was confirmed with a Revised Autism Diagnostic Inventory. For comparison with ASD cases, 80 normal neonates (control group) were selected from the same period. Biochemical parameters, including TSB, NSE and CK-BB in the neonatal period and medical records on neonatal behavior were collected. Results: The levels of serum TSB, NSE and CK-BB in the ASD group were significantly higher when compared with those from the control group (P < 0.01, or P < 0.05). The amounts of serum TSB, NSE and CK-BB in the L-ASD group were significantly higher when compared with those in the H-ASD group (P < 0.01, or P < 0.05). The Neonatal Behavioral Assessment Scale (NBAS) scores in the ASD group were significantly lower than that in the control group (P < 0.05). Likewise, the NBAS scores in the L-ASD group were significantly lower than that in the H-ASD group (P < 0.05). There was no association between serum TSB, NSE, CK-BB and NBAS scores (P > 0.05) in the ASD group. Conclusions: The neonatal levels of TSB, NSE and CK-BB in ASD from Southern China were significantly higher than those of healthy controls. These findings need to be investigated thoroughly by future studies with large sample. PMID:28123815

Differential methylation at the RELN gene promoter in temporal cortex from autistic and typically developing post-puberal subjects.

PubMed

Lintas, Carla; Sacco, Roberto; Persico, Antonio M

2016-01-01

Reelin plays a pivotal role in neurodevelopment and in post-natal synaptic plasticity and has been implicated in the pathogenesis of autism spectrum disorder (ASD). The reelin (RELN) gene expression is significantly decreased in ASD, both in the brain and peripherally. Methylation at the RELN gene promoter is largely triggered at puberty, and hypermethylation has been found in post-mortem brains of schizophrenic and bipolar patients. In this study, we assessed RELN gene methylation status in post-mortem temporocortical tissue samples (BA41/42 or 22) of six pairs of post-puberal individuals with ASD and typically developing subjects, matched for sex (male:female, M:F = 5:1), age, and post-mortem interval. ASD patients display a significantly higher number of methylated CpG islands and heavier methylation in the 5' region of the RELN gene promoter, spanning from -458 to -223 bp, whereas controls have more methylated CpG positions and greater extent of methylation at the 3' promoter region, spanning from -222 to +1 bp. The most upstream promoter region (-458 to -364 bp) is methylated only in ASD brains, while the most downstream region (-131 to +1 bp) is methylated exclusively in control brains. Within this general framework, three different methylation patterns are discernible, each correlated with different extents of reduction in reelin gene expression among ASD individuals compared to controls. The methylation pattern is different in ASD and control post-mortem brains. ASD-specific CpG positions, located in the most upstream gene promoter region, may exert a functional role potentially conferring ASD risk by blunting RELN gene expression.

Decreased levels of serum fibroblast growth factor-2 in children with autism spectrum disorder.

PubMed

Esnafoglu, Erman; Ayyıldız, Sema Nur

2017-11-01

The neurodevelopment and functioning of the central nervous system, and especially the cerebral cortex, have basic importance to understand neuropsychiatric disorders like autism. Fibroblast growth factor-2 (FGF-2) plays a very important role in the development and functioning of the cortex. FGF-2 is related to developmental processes in the central nervous system such as neurogenesis, migration, differentiation and survival. This study researched the serum FGF-2 levels in children with autism spectrum disorder (ASD). With this aim, 60 ASD children and 40 healthy controls were compared. We applied a sociodemographic form and the Childhood Autism Rating Scale (CARS) to each subject with their family to assess the severity of autism. Additionally, all subjects had routine laboratory tests performed. Serum samples were studied with ELISA. The results found that serum FGF-2 levels were statistically significantly low in the patient group compared to the healthy control group (p value 0.003). Additionally there was a statistically significant negative correlation identified between serum FGF-2 levels and CARS score for all subjects (r = -0.300; p = 0.02). In conclusion, FGF-2 may contribute to the etiopathogenesis of ASD. Copyright © 2017 Elsevier B.V. All rights reserved.

Idiosyncratic Brain Activation Patterns Are Associated with Poor Social Comprehension in Autism

PubMed Central

Tyszka, J. Michael; Adolphs, Ralph; Kennedy, Daniel P.

2015-01-01

Autism spectrum disorder (ASD) features profound social deficits but neuroimaging studies have failed to find any consistent neural signature. Here we connect these two facts by showing that idiosyncratic patterns of brain activation are associated with social comprehension deficits. Human participants with ASD (N = 17) and controls (N = 20) freely watched a television situation comedy (sitcom) depicting seminaturalistic social interactions (“The Office”, NBC Universal) in the scanner. Intersubject correlations in the pattern of evoked brain activation were reduced in the ASD group—but this effect was driven entirely by five ASD subjects whose idiosyncratic responses were also internally unreliable. The idiosyncrasy of these five ASD subjects was not explained by detailed neuropsychological profile, eye movements, or data quality; however, they were specifically impaired in understanding the social motivations of characters in the sitcom. Brain activation patterns in the remaining ASD subjects were indistinguishable from those of control subjects using multiple multivariate approaches. Our findings link neurofunctional abnormalities evoked by seminaturalistic stimuli with a specific impairment in social comprehension, and highlight the need to conceive of ASD as a heterogeneous classification. PMID:25855192

Serotonin and the neural processing of facial emotions in adults with autism: an fMRI study using acute tryptophan depletion.

PubMed

Daly, Eileen M; Deeley, Quinton; Ecker, Christine; Craig, Michael; Hallahan, Brian; Murphy, Clodagh; Johnston, Patrick; Spain, Debbie; Gillan, Nicola; Brammer, Michael; Giampietro, Vincent; Lamar, Melissa; Page, Lisa; Toal, Fiona; Cleare, Anthony; Surguladze, Simon; Murphy, Declan G M

2012-10-01

People with autism spectrum disorders (ASDs) have lifelong deficits in social behavior and differences in behavioral as well as neural responses to facial expressions of emotion. The biological basis to this is incompletely understood, but it may include differences in the role of neurotransmitters such as serotonin, which modulate facial emotion processing in health. While some individuals with ASD have significant differences in the serotonin system, to our knowledge, no one has investigated its role during facial emotion processing in adults with ASD and control subjects using acute tryptophan depletion (ATD) and functional magnetic resonance imaging. To compare the effects of ATD on brain responses to primary facial expressions of emotion in men with ASD and healthy control subjects. Double-blind, placebo-controlled, crossover trial of ATD and functional magnetic resonance imaging to measure brain activity during incidental processing of disgust, fearful, happy, and sad facial expressions. Institute of Psychiatry, King's College London, and South London and Maudsley National Health Service Foundation Trust, England. Fourteen men of normal intelligence with autism and 14 control subjects who did not significantly differ in sex, age, or overall intelligence. Blood oxygenation level-dependent response to facial expressions of emotion. Brain activation was differentially modulated by ATD depending on diagnostic group and emotion type within regions of the social brain network. For example, processing of disgust faces was associated with interactions in medial frontal and lingual gyri, whereas processing of happy faces was associated with interactions in middle frontal gyrus and putamen. Modulation of the processing of facial expressions of emotion by serotonin significantly differs in people with ASD compared with control subjects. The differences vary with emotion type and occur in social brain regions that have been shown to be associated with group differences in serotonin synthesis/receptor or transporter density.

Perceptual reasoning predicts handwriting impairments in adolescents with autism

PubMed Central

Fuentes, Christina T.; Mostofsky, Stewart H.; Bastian, Amy J.

2010-01-01

Background: We have previously shown that children with autism spectrum disorder (ASD) have specific handwriting deficits consisting of poor form, and that these deficits are predicted by their motor abilities. It is not known whether the same handwriting impairments persist into adolescence and whether they remain linked to motor deficits. Methods: A case-control study of handwriting samples from adolescents with and without ASD was performed using the Minnesota Handwriting Assessment. Samples were scored on an individual letter basis in 5 categories: legibility, form, alignment, size, and spacing. Subjects were also administered an intelligence test and the Physical and Neurological Examination for Subtle (Motor) Signs (PANESS). Results: We found that adolescents with ASD, like children, show overall worse performance on a handwriting task than do age- and intelligence-matched controls. Also comparable to children, adolescents with ASD showed motor impairments relative to controls. However, adolescents with ASD differ from children in that Perceptual Reasoning Indices were significantly predictive of handwriting performance whereas measures of motor skills were not. Conclusions: Like children with ASD, adolescents with ASD have poor handwriting quality relative to controls. Despite still demonstrating motor impairments, in adolescents perceptual reasoning is the main predictor of handwriting performance, perhaps reflecting subjects' varied abilities to learn strategies to compensate for their motor impairments. GLOSSARY ASD = autism spectrum disorder; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders, 4th edition; PANESS = Physical and Neurological Examination for Subtle (Motor) Signs; PRI = Perceptual Reasoning Index; WASI = Wechsler Abbreviated Scale of Intelligence; WISC = Wechsler Intelligence Scale for Children IV. PMID:21079184

Adult Autism Subthreshold Spectrum (AdAS Spectrum): Validation of a questionnaire investigating subthreshold autism spectrum.

PubMed

Dell'Osso, L; Gesi, C; Massimetti, E; Cremone, I M; Barbuti, M; Maccariello, G; Moroni, I; Barlati, S; Castellini, G; Luciano, M; Bossini, L; Rocchetti, M; Signorelli, M; Aguglia, E; Fagiolini, A; Politi, P; Ricca, V; Vita, A; Carmassi, C; Maj, M

2017-02-01

Increasing literature has shown the usefulness of a dimensional approach to autism. The present study aimed to determine the psychometric properties of the Adult Autism Subthreshold Spectrum (AdAS Spectrum), a new questionnaire specifically tailored to assess subthreshold forms of autism spectrum disorder (ASD) in adulthood. 102 adults endorsing at least one DSM-5 symptom criterion for ASD (ASDc), 143 adults diagnosed with a feeding and eating disorder (FED), and 160 subjects with no mental disorders (CTL), were recruited from 7 Italian University Departments of Psychiatry and administered the following: SCID-5, Autism-Spectrum Quotient (AQ), Ritvo Autism and Asperger Diagnostic Scale 14-item version (RAADS-14), and AdAS Spectrum. The AdAS Spectrum demonstrated excellent internal consistency for the total score (Kuder-Richardson's coefficient=.964) as well as for five out of seven domains (all coefficients>.80) and sound test-retest reliability (ICC=.976). The total and domain AdAS Spectrum scores showed a moderate to strong (>.50) positive correlation with one another and with the AQ and RAADS-14 total scores. ASDc subjects reported significantly higher AdAS Spectrum total scores than both FED (p<.001) and CTL (p<.001), and significantly higher scores on the Childhood/adolescence, Verbal communication, Empathy, Inflexibility and adherence to routine, and Restricted interests and rumination domains (all p<.001) than FED, while on all domains compared to CTL. CTL displayed significantly lower total and domain scores than FED (all p<.001). A significant effect of gender emerged for the Hyper- and hyporeactivity to sensory input domain, with women showing higher scores than men (p=.003). A Diagnosis* Gender interaction was also found for the Verbal communication (p=.019) and Empathy (p=.023) domains. When splitting the ASDc in subjects with one symptom criterion (ASD 1 ) and those with a ASD, and the FED in subjects with no ASD symptom criteria (FED 0 ) and those with one ASD symptom criterion (FED 1 ) , a gradient of severity in AdAS Spectrum scores from CTL subjects to ASD patients, across FED 0 , ASD 1 , FED 1 was shown. The AdAS Spectrum showed excellent internal consistency and test-retest reliability and strong convergent validity with alternative dimensional measures of ASD. The questionnaire performed differently among the three diagnostic groups and enlightened some significant effects of gender in the expression of autistic traits. Copyright © 2016 Elsevier Inc. All rights reserved.

Neonatal hyperbilirubinemia and risk of autism spectrum disorders.

PubMed

Croen, Lisa A; Yoshida, Cathleen K; Odouli, Roxana; Newman, Thomas B

2005-02-01

To investigate the association between neonatal hyperbilirubinemia and autism spectrum disorders (ASD). We conducted a large case-control study nested within the cohort of singleton term infants born between 1995 and 1998 at a northern California Kaiser Permanente hospital. Case subjects (n = 338) were children with an ASD diagnosis recorded in Kaiser Permanente outpatient databases; control subjects (n = 1817) were children without an ASD diagnosis, who were randomly sampled and frequency-matched to case subjects according to gender, birth year, and birth hospital. Approximately 28% of case and control subjects received > or =1 bilirubin test in the first 30 days of life. No case-control differences were observed for maximal bilirubin levels of > or =15 mg/dL (10.1% vs 12.1%), > or =20 mg/dL (2.1% vs 2.5%), or > or =25 mg/dL (0.3% vs 0.2%). Compared with children whose maximal neonatal bilirubin levels were <15 mg/dL or not measured, children with any degree of bilirubin level elevation were not at increased risk of ASD, after adjustment for gender, birth facility, maternal age, maternal race/ethnicity, maternal education, and gestational age (for bilirubin levels of 15-19.9 mg/dL: odds ratio: 0.7; 95% confidence interval: 0.5-1.2; for bilirubin levels of 20-24.9 mg/dL: odds ratio: 0.7; 95% confidence interval: 0.3-1.6; for bilirubin levels of > or =25 mg/dL: odds ratio: 1.1; 95% confidence interval: 0.1-11.2). These data suggest that neonatal hyperbilirubinemia is not a risk factor for ASD.

An Exploratory Trial of Transdermal Nicotine for Aggression and Irritability in Adults with Autism Spectrum Disorder.

PubMed

Lewis, Alan S; van Schalkwyk, Gerrit Ian; Lopez, Mayra Ortiz; Volkmar, Fred R; Picciotto, Marina R; Sukhodolsky, Denis G

2018-03-13

Nicotinic acetylcholine receptors (nAChRs), particularly the α7 nAChR, are implicated in the pathophysiology of both autism spectrum disorder (ASD) and aggressive behavior. We explored the feasibility, tolerability, and preliminary efficacy of targeting nAChRs using transdermal nicotine to reduce aggressive symptoms in adults with ASD. Eight subjects were randomized in a double-blind crossover trial of 7 mg transdermal nicotine or placebo, each for 1 week. All participants tolerated nicotine treatment well. Five subjects contributed data to the primary outcome, Aberrant Behavior Checklist-Irritability (ABC-I) subscale change from baseline, which was improved by nicotine compared to placebo. Sleep ratings were also improved by nicotine and correlated with ABC-I improvement. These findings support further investigation of nAChR agonists for aggression and sleep in ASD.

Multi-frequency localization of aberrant brain activity in autism spectrum disorder.

PubMed

Xiang, Jing; Korostenskaja, Milena; Molloy, Cynthia; deGrauw, Xinyao; Leiken, Kimberly; Gilman, Carley; Meinzen-Derr, Jareen; Fujiwara, Hisako; Rose, Douglas F; Mitchell, Terry; Murray, Donna S

2016-01-01

The abnormality of intrinsic brain activity in autism spectrum disorders (ASDs) is still inconclusive. Contradictory results have been found pointing towards hyper-activity or hypo-activity in various brain regions. The present research aims to investigate the spatial and spectral signatures of aberrant brain activity in an unprecedented frequency range of 1-2884 Hz at source levels in ASD using newly developed methods. Seven ASD subjects and age- and gender-matched controls were studied using a high-sampling rate magnetoencephalography (MEG) system. Brain activity in delta (1-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), beta (12-30 Hz), low gamma (30-55 Hz), high gamma (65-90 Hz), ripples (90-200 Hz), high-frequency oscillations (HFOs, 200-1000 Hz), and very high-frequency oscillations (VHFOs, 1000-2884 Hz) was volumetrically localized and measured using wavelet and beamforming. In comparison to controls, ASD subjects had significantly higher odds of alpha activity (8-12 Hz) in the sensorimotor cortex (mu rhythm), and generally high-frequency activity (90-2884 Hz) in the frontal cortex. The source power of HFOs (200-1000 Hz) in the frontal cortex in ASD was significantly elevated as compared with controls. The results suggest that ASD has significantly altered intrinsic brain activity in both low- and high-frequency ranges. Increased intrinsic high-frequency activity in the frontal cortex may play a key role in ASD. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Adolescent boys with autism spectrum disorder growing up: follow-up of self-reported sexual experience.

PubMed

Dewinter, J; Vermeiren, R; Vanwesenbeeck, I; Van Nieuwenhuizen, Ch

2016-09-01

Systematic research on sexual development in adolescents with autism spectrum disorder (ASD) remains scant, notwithstanding the often-suggested relation between ASD, atypical, and even sexually offensive behaviours. This study compared follow-up data related to lifetime sexual experience (LTSE) in a homogeneous group of adolescent boys with ASD (n = 30), aged 16-20, with a matched group of boys in the general population (n = 60). Most boys in the ASD and control groups reported masturbation and having experienced an orgasm. The proportion of boys with ASD that had no partnered sexual experience was larger than in the control group. This difference was mostly explained by significantly fewer boys with ASD, compared with controls, who reported experience with kissing and petting; no significant differences emerged relating to more intimate partnered sexual experiences. The results suggest the existence of a subgroup of boys who have not (yet) entered the arena of partnered sexual experiences-a finding in line with research in adult samples. There were no differences relating to sexual abuse or coercion. Exploration of the partnered experiences revealed a variety of types of partners, mostly of comparable age. Several boys with ASD had not anticipated their sexual debut. Although they felt ready for it, some boys reported regret afterward. The hypothesised sexual developmental trajectories are subject to further research, but the sexual experience in this sample and the assumed developmental differences indicate the need for early, attuned, and comprehensive sexuality-related education and communication.

Autism traits in the RASopathies.

PubMed

Adviento, Brigid; Corbin, Iris L; Widjaja, Felicia; Desachy, Guillaume; Enrique, Nicole; Rosser, Tena; Risi, Susan; Marco, Elysa J; Hendren, Robert L; Bearden, Carrie E; Rauen, Katherine A; Weiss, Lauren A

2014-01-01

Mutations in Ras/mitogen-activated protein kinase (Ras/MAPK) pathway genes lead to a class of disorders known as RASopathies, including neurofibromatosis type 1 (NF1), Noonan syndrome (NS), Costello syndrome (CS), and cardio-facio-cutaneous syndrome (CFC). Previous work has suggested potential genetic and phenotypic overlap between dysregulation of Ras/MAPK signalling and autism spectrum disorders (ASD). Although the literature offers conflicting evidence for association of NF1 and autism, there has been no systematic evaluation of autism traits in the RASopathies as a class to support a role for germline Ras/MAPK activation in ASDs. We examined the association of autism traits with NF1, NS, CS and CFC, comparing affected probands with unaffected sibling controls and subjects with idiopathic ASDs using the qualitative Social Communication Questionnaire (SCQ) and the quantitative Social Responsiveness Scale (SRS). Each of the four major RASopathies showed evidence for increased qualitative and quantitative autism traits compared with sibling controls. Further, each RASopathy exhibited a distinct distribution of quantitative social impairment. Levels of social responsiveness show some evidence of correlation between sibling pairs, and autism-like impairment showed a male bias similar to idiopathic ASDs. Higher prevalence and severity of autism traits in RASopathies compared to unaffected siblings suggests that dysregulation of Ras/MAPK signalling during development may be implicated in ASD risk. Evidence for sex bias and potential sibling correlation suggests that autism traits in the RASopathies share characteristics with autism traits in the general population and clinical ASD population and can shed light on idiopathic ASDs.

The effects of mandated health insurance benefits for autism on out-of-pocket costs and access to treatment.

PubMed

Chatterji, Pinka; Decker, Sandra L; Markowitz, Sara

2015-01-01

As of 2014, 37 states have passed mandates requiring many private health insurance policies to cover diagnostic and treatment services for autism spectrum disorders (ASDs). We explore whether ASD mandates are associated with out-of-pocket costs, financial burden, and cost or insurance-related problems with access to treatment among privately insured children with special health care needs (CSHCNs). We use difference-in-difference and difference-in-difference-in-difference approaches, comparing pre--post mandate changes in outcomes among CSHCN who have ASD versus CSHCN other than ASD. Data come from the 2005 to 2006 and the 2009 to 2010 waves of the National Survey of CSHCN. Based on the model used, our findings show no statistically significant association between state ASD mandates and caregivers' reports about financial burden, access to care, and unmet need for services. However, we do find some evidence that ASD mandates may have beneficial effects in states in which greater percentages of privately insured individuals are subject to the mandates. We caution that we do not study the characteristics of ASD mandates in detail, and most ASD mandates have gone into effect very recently during our study period.

Long-Range Reduced Predictive Information Transfers of Autistic Youths in EEG Sensor-Space During Face Processing.

PubMed

Khadem, Ali; Hossein-Zadeh, Gholam-Ali; Khorrami, Anahita

2016-03-01

The majority of previous functional/effective connectivity studies conducted on the autistic patients converged to the underconnectivity theory of ASD: "long-range underconnectivity and sometimes short-rang overconnectivity". However, to the best of our knowledge the total (linear and nonlinear) predictive information transfers (PITs) of autistic patients have not been investigated yet. Also, EEG data have rarely been used for exploring the information processing deficits in autistic subjects. This study is aimed at comparing the total (linear and nonlinear) PITs of autistic and typically developing healthy youths during human face processing by using EEG data. The ERPs of 12 autistic youths and 19 age-matched healthy control (HC) subjects were recorded while they were watching upright and inverted human face images. The PITs among EEG channels were quantified using two measures separately: transfer entropy with self-prediction optimality (TESPO), and modified transfer entropy with self-prediction optimality (MTESPO). Afterwards, the directed differential connectivity graphs (dDCGs) were constructed to characterize the significant changes in the estimated PITs of autistic subjects compared with HC ones. By using both TESPO and MTESPO, long-range reduction of PITs of ASD group during face processing was revealed (particularly from frontal channels to right temporal channels). Also, it seemed the orientation of face images (upright or upside down) did not modulate the binary pattern of PIT-based dDCGs, significantly. Moreover, compared with TESPO, the results of MTESPO were more compatible with the underconnectivity theory of ASD in the sense that MTESPO showed no long-range increase in PIT. It is also noteworthy that to the best of our knowledge it is the first time that a version of MTE is applied for patients (here ASD) and it is also its first use for EEG data analysis.

Altered metabolites in the plasma of autism spectrum disorder: a capillary electrophoresis time-of-flight mass spectroscopy study.

PubMed

Kuwabara, Hitoshi; Yamasue, Hidenori; Koike, Shinsuke; Inoue, Hideyuki; Kawakubo, Yuki; Kuroda, Miho; Takano, Yosuke; Iwashiro, Norichika; Natsubori, Tatsunobu; Aoki, Yuta; Kano, Yukiko; Kasai, Kiyoto

2013-01-01

Clinical diagnosis and severity of autism spectrum disorders (ASD) are determined by trained clinicians based on clinical evaluations of observed behaviors. As such, this approach is inevitably dependent on the expertise and subjective assessment of those administering the clinical evaluations. There is a need to identify objective biological markers associated with diagnosis or clinical severity of the disorder. To identify novel candidate metabolites as potential biomarkers for ASD, the current study applied capillary electrophoresis time-of-flight mass spectroscopy (CE-TOFMS) for high-throughput profiling of metabolite levels in the plasma of 25 psychotropic-naïve adult males with high-functioning ASD and 28 age-matched typically-developed control subjects. Ten ASD participants and ten age-matched controls were assigned in the first exploration set, while 15 ASD participants and 18 controls were included in the second replication set. By CE-TOFMS analysis, a total of 143 metabolites were detected in the plasma of the first set. Of these, 17 metabolites showed significantly different relative areas between the ASD participants and the controls (p<0.05). Of the 17 metabolites, we consistently found that the ASD participants had significantly high plasma levels of arginine (p = 0.024) and taurine (p = 0.018), and significantly low levels of 5-oxoproline (p<0.001) and lactic acid (p = 0.031) compared with the controls in the second sample set. Further confirmatory analysis using quantification of absolute metabolite concentrations supported the robustness of high arginine (p = 0.001) and low lactic acid (p = 0.003) in the combined sample (n = 53). The present study identified deviated plasma metabolite levels associated with oxidative stress and mitochondrial dysfunction in individuals with ASD.

Altered Metabolites in the Plasma of Autism Spectrum Disorder: A Capillary Electrophoresis Time-of-Flight Mass Spectroscopy Study

PubMed Central

Kuwabara, Hitoshi; Yamasue, Hidenori; Koike, Shinsuke; Inoue, Hideyuki; Kawakubo, Yuki; Kuroda, Miho; Takano, Yosuke; Iwashiro, Norichika; Natsubori, Tatsunobu; Aoki, Yuta; Kano, Yukiko; Kasai, Kiyoto

2013-01-01

Clinical diagnosis and severity of autism spectrum disorders (ASD) are determined by trained clinicians based on clinical evaluations of observed behaviors. As such, this approach is inevitably dependent on the expertise and subjective assessment of those administering the clinical evaluations. There is a need to identify objective biological markers associated with diagnosis or clinical severity of the disorder. To identify novel candidate metabolites as potential biomarkers for ASD, the current study applied capillary electrophoresis time-of-flight mass spectroscopy (CE-TOFMS) for high-throughput profiling of metabolite levels in the plasma of 25 psychotropic-naïve adult males with high-functioning ASD and 28 age-matched typically-developed control subjects. Ten ASD participants and ten age-matched controls were assigned in the first exploration set, while 15 ASD participants and 18 controls were included in the second replication set. By CE-TOFMS analysis, a total of 143 metabolites were detected in the plasma of the first set. Of these, 17 metabolites showed significantly different relative areas between the ASD participants and the controls (p<0.05). Of the 17 metabolites, we consistently found that the ASD participants had significantly high plasma levels of arginine (p = 0.024) and taurine (p = 0.018), and significantly low levels of 5-oxoproline (p<0.001) and lactic acid (p = 0.031) compared with the controls in the second sample set. Further confirmatory analysis using quantification of absolute metabolite concentrations supported the robustness of high arginine (p = 0.001) and low lactic acid (p = 0.003) in the combined sample (n = 53). The present study identified deviated plasma metabolite levels associated with oxidative stress and mitochondrial dysfunction in individuals with ASD. PMID:24058493

A meta-analysis of imitation abilities in individuals with autism spectrum disorders.

PubMed

Edwards, Laura A

2014-06-01

Although imitation impairments are often reported in individuals with autism spectrum disorders (ASD), previous work has not yet determined whether these impairments are significant, specific to ASD, and present across the entire spectrum. This report of 53 studies on imitation in ASD seeks to determine whether individuals with ASD show significant imitation deficits, the magnitude of these deficits, and whether they are specific to ASD. Using standard meta-analytic techniques in a random-effects model, the data reviewed suggest that individuals with ASD show deficits in imitation, performing on average 0.81 SDs below individuals without ASD on imitation tasks. This deficit was specific to the condition of having ASD. Moderator analyses revealed that the average Autism Diagnostic Observation Schedule (ADOS) scores of groups of ASD participants were significantly and strongly negatively associated with the imitation abilities of these subjects, but average participant IQ was not associated with imitation abilities. Study setting, novelty of actions, format of imitation tasks (live vs. not), number of actions to imitate, or verbal prompts were not found to significantly affect the sizes of the imitation differences between individuals with and without ASD. The manner in which imitation was operationalized, however, had significant effects on whether imitation deficits were found between individuals with and without ASD. In tests that measured imitation of both form and end points, participants with ASD showed significant deficits compared with those without ASD; on tests of end point emulation only, individuals with ASD showed no deficits. © 2014 International Society for Autism Research, Wiley Periodicals, Inc.

Brain Volumetric Correlates of Autism Spectrum Disorder Symptoms in Attention Deficit/Hyperactivity Disorder

PubMed Central

O’Dwyer, Laurence; Tanner, Colby; van Dongen, Eelco V.; Greven, Corina U.; Bralten, Janita; Zwiers, Marcel P.; Franke, Barbara; Oosterlaan, Jaap; Heslenfeld, Dirk; Hoekstra, Pieter; Hartman, Catharina A.; Rommelse, Nanda; Buitelaar, Jan K.

2014-01-01

Autism spectrum disorder (ASD) symptoms frequently occur in subjects with attention deficit/hyperactivity disorder (ADHD). While there is evidence that both ADHD and ASD have differential structural correlates, no study to date has investigated these structural correlates within a framework that robustly accounts for the phenotypic overlap between the two disorders. The presence of ASD symptoms was measured by the parent-reported Children’s Social and Behavioural Questionnaire (CSBQ) in ADHD subjects (n = 180), their unaffected siblings (n = 118) and healthy controls (n = 146). ADHD symptoms were assessed by a structured interview (K-SADS-PL) and the Conners’ ADHD questionnaires. Whole brain T1-weighted MPRAGE images were acquired and the structural MRI correlates of ASD symptom scores were analysed by modelling ASD symptom scores against white matter (WM) and grey matter (GM) volumes using mixed effects models which controlled for ADHD symptom levels. ASD symptoms were significantly elevated in ADHD subjects relative to both controls and unaffected siblings. ASD scores were predicted by the interaction between WM and GM volumes. Increasing ASD score was associated with greater GM volume. Equivocal results from previous structural studies in ADHD and ASD may be due to the fact that comorbidity has not been taken into account in studies to date. The current findings stress the need to account for issues of ASD comorbidity in ADHD. PMID:24979066

Clinical outcomes of neonatal onset proximal versus distal urea cycle disorders do not differ.

PubMed

Ah Mew, Nicholas; Krivitzky, Lauren; McCarter, Robert; Batshaw, Mark; Tuchman, Mendel

2013-02-01

To compare the clinical course and outcome of patients diagnosed with one of 4 neonatal-onset urea cycle disorders (UCDs): deficiency of carbamyl phosphate synthase 1 (CPSD), ornithine transcarbamylase (OTCD), argininosuccinate synthase (ASD), or argininosuccinate lyase (ALD). Clinical, biochemical, and neuropsychological data from 103 subjects with neonatal-onset UCDs were derived from the Longitudinal Study of Urea Cycle Disorders, an observational protocol of the Urea Cycle Disorders Consortium, one of the Rare Disease Clinical Research Networks. Some 88% of the subjects presented clinically by age 7 days. Peak ammonia level was 963 μM in patients with proximal UCDs (CPSD or OTCD), compared with 589 μM in ASD and 573 μM in ALD. Roughly 25% of subjects with CPSD or OTCD, 18% of those with ASD, and 67% of those with ALD had a "honeymoon period," defined as the time interval from discharge from initial admission to subsequent admission for hyperammonemia, greater than 1 year. The proportion of patients with a poor outcome (IQ/Developmental Quotient <70) was greatest in ALD (68%), followed by ASD (54%) and CPSD/OTCD (47%). This trend was not significant, but was observed in both patients aged <4 years and those aged ≥ 4 years. Poor cognitive outcome was not correlated with peak ammonia level or duration of initial admission. Neurocognitive outcomes do not differ between patients with proximal UCDs and those with distal UCDs. Factors other than hyperammonemia may contribute to poor neurocognitive outcome in the distal UCDs. Copyright © 2013 Mosby, Inc. All rights reserved.

Individuals with autism spectrum disorder show abnormalities during initial and subsequent phases of precision gripping

PubMed Central

Magnon, Grant C.; White, Stormi P.; Greene, Rachel K.; Vaillancourt, David E.

2014-01-01

Sensorimotor impairments are common in autism spectrum disorder (ASD), but they are not well understood. Here we examined force control during initial pulses and the subsequent rise, sustained, and relaxation phases of precision gripping in 34 individuals with ASD and 25 healthy control subjects. Participants pressed on opposing load cells with their thumb and index finger while receiving visual feedback regarding their performance. They completed 2- and 8-s trials during which they pressed at 15%, 45%, or 85% of their maximum force. Initial pulses guided by feedforward control mechanisms, sustained force output controlled by visual feedback processes, and force relaxation rates all were examined. Control subjects favored an initial pulse strategy characterized by a rapid increase in and then relaxation of force when the target force was low (Type 1). When the target force level or duration of trials was increased, control subjects transitioned to a strategy in which they more gradually increased their force, paused, and then increased their force again. Individuals with ASD showed a more persistent bias toward the Type 1 strategy at higher force levels and during longer trials, and their initial force output was less accurate than that of control subjects. Patients showed increased force variability compared with control subjects when attempting to sustain a constant force level. During the relaxation phase, they showed reduced rates of force decrease. These findings suggest that both feedforward and feedback motor control mechanisms are compromised in ASD and these deficits may contribute to the dyspraxia and sensorimotor abnormalities often seen in this disorder. PMID:25552638

A large-scale survey of the novel 15q24 microdeletion syndrome in autism spectrum disorders identifies an atypical deletion that narrows the critical region

PubMed Central

2010-01-01

Background The 15q24 microdeletion syndrome has been recently described as a recurrent, submicroscopic genomic imbalance found in individuals with intellectual disability, typical facial appearance, hypotonia, and digital and genital abnormalities. Gene dosage abnormalities, including copy number variations (CNVs), have been identified in a significant fraction of individuals with autism spectrum disorders (ASDs). In this study we surveyed two ASD cohorts for 15q24 abnormalities to assess the frequency of genomic imbalances in this interval. Methods We screened 173 unrelated subjects with ASD from the Central Valley of Costa Rica and 1336 subjects with ASD from 785 independent families registered with the Autism Genetic Resource Exchange (AGRE) for CNVs across 15q24 using oligonucleotide arrays. Rearrangements were confirmed by array comparative genomic hybridization and quantitative PCR. Results Among the patients from Costa Rica, an atypical de novo deletion of 3.06 Mb in 15q23-q24.1 was detected in a boy with autism sharing many features with the other 13 subjects with the 15q24 microdeletion syndrome described to date. He exhibited intellectual disability, constant smiling, characteristic facial features (high anterior hairline, broad medial eyebrows, epicanthal folds, hypertelorism, full lower lip and protuberant, posteriorly rotated ears), single palmar crease, toe syndactyly and congenital nystagmus. The deletion breakpoints are atypical and lie outside previously characterized low copy repeats (69,838-72,897 Mb). Genotyping data revealed that the deletion had occurred in the paternal chromosome. Among the AGRE families, no large 15q24 deletions were observed. Conclusions From the current and previous studies, deletions in the 15q24 region represent rare causes of ASDs with an estimated frequency of 0.1 to 0.2% in individuals ascertained for ASDs, although the proportion might be higher in sporadic cases. These rates compare with a frequency of about 0.3% in patients ascertained for unexplained intellectual disability and congenital anomalies. This atypical deletion reduces the minimal interval for the syndrome from 1.75 Mb to 766 kb, implicating a reduced number of genes (15 versus 38). Sequencing of genes in the 15q24 interval in large ASD and intellectual disability samples may identify mutations of etiologic importance in the development of these disorders. PMID:20678247

Deficits in motor abilities and developmental fractionation of imitation performance in high-functioning autism spectrum disorders.

PubMed

Biscaldi, Monica; Rauh, Reinhold; Irion, Lisa; Jung, Nikolai H; Mall, Volker; Fleischhaker, Christian; Klein, Christoph

2014-07-01

The co-occurrence of motor and imitation disabilities often characterises the spectrum of deficits seen in patients with autism spectrum disorders (ASD). Whether these seemingly separate deficits are inter-related and whether, in particular, motor deficits contribute to the expression of imitation deficits is the topic of the present study and was investigated by comparing these deficits' cross-sectional developmental trajectories. To that end, different components of motor performance assessed in the Zurich Neuromotor Assessment and imitation abilities for facial movements and non-meaningful gestures were tested in 70 subjects (aged 6-29 years), including 36 patients with high-functioning ASD and 34 age-matched typically developed (TD) participants. The results show robust deficits in probands with ASD in timed motor performance and in the quality of movement, which are all independent of age, with one exception. Only diadochokinesis improves moderately with increasing age in ASD probands. Imitation of facial movements and of non-meaningful hand, finger, hand finger gestures not related to social context or tool use is also impaired in ASD subjects, but in contrast to motor performance this deficit overall improves with age. A general imitation factor, extracted from the highly inter-correlated imitation tests, is differentially correlated with components of neuromotor performance in ASD and TD participants. By developmentally fractionating developmentally stable motor deficits from developmentally dynamic imitation deficits, we infer that imitation deficits are primarily cognitive in nature.

Mind-Reading in Young Adults with ASD: Does Structure Matter?

ERIC Educational Resources Information Center

Ponnet, Koen; Buysse, Ann; Roeyers, Herbert; De Clercq, Armand

2008-01-01

This study further elaborates on the mind-reading impairments of young adults with autism spectrum disorder (ASD). The hypothesis is that differences in mind-reading abilities between subjects with ASD and control subjects become more apparent when they have to infer thoughts and feelings of other persons in a less structured or more chaotic…

Novel rare variations of the oxytocin receptor (OXTR) gene in autism spectrum disorder individuals.

PubMed

Liu, Xiaoxi; Kawashima, Minae; Miyagawa, Taku; Otowa, Takeshi; Latt, Khun Zaw; Thiri, Myo; Nishida, Hisami; Sugiyama, Toshiro; Tsurusaki, Yoshinori; Matsumoto, Naomichi; Mabuchi, Akihiko; Tokunaga, Katsushi; Sasaki, Tsukasa

2015-01-01

The oxytocin receptor (OXTR) gene has been implicated as a risk gene for autism spectrum disorder (ASD)-a neurodevelopmental disorder with essential features of impairments in social communication and reciprocal interaction. The genetic associations between common variations in OXTR and ASD have been reported in multiple ethnic populations. However, little is known about the distribution of rare variations within OXTR in ASD patients. In this study, we resequenced the full length of OXTR in 105 ASD individuals using an approach that combined the power of next-generation sequencing technology, long-range PCR and DNA pooling. We demonstrated that rare variants with minor allele frequency as low as 0.05% could be reliably detected by our method. We identified 28 novel variants including potential functional variants in the intron region and one rare missense variant (R150S). We subsequently performed Sanger sequencing and validated five novel variants located in previously suggested candidate regions in ASD individuals. Further sequencing of 312 healthy subjects showed that the burden of rare variants is significantly higher in ASDs compared with healthy individuals. Our results support that the rare variation in OXTR gene might be involved in ASD.

The effect of gender on the neuroanatomy of children with autism spectrum disorders: a support vector machine case-control study.

PubMed

Retico, Alessandra; Giuliano, Alessia; Tancredi, Raffaella; Cosenza, Angela; Apicella, Fabio; Narzisi, Antonio; Biagi, Laura; Tosetti, Michela; Muratori, Filippo; Calderoni, Sara

2016-01-01

Genetic, hormonal, and environmental factors contribute since infancy to sexual dimorphism in regional brain structures of subjects with typical development. However, the neuroanatomical differences between male and female children with autism spectrum disorders (ASD) are an intriguing and still poorly investigated issue. This study aims to evaluate whether the brain of young children with ASD exhibits sex-related structural differences and if a correlation exists between clinical ASD features and neuroanatomical underpinnings. A total of 152 structural MRI scans were analysed. Specifically, 76 young children with ASD (38 males and 38 females; 2-7 years of age; mean = 53 months, standard deviation = 17 months) were evaluated employing a support vector machine (SVM)-based analysis of the grey matter (GM). Group comparisons consisted of 76 age-, gender- and non-verbal-intelligence quotient-matched children with typical development or idiopathic developmental delay without autism. For both genders combined, SVM showed a significantly increased GM volume in young children with ASD with respect to control subjects, predominantly in the bilateral superior frontal gyrus (Brodmann area -BA- 10), bilateral precuneus (BA 31), bilateral superior temporal gyrus (BA 20/22), whereas less GM in patients with ASD was found in right inferior temporal gyrus (BA 37). For the within gender comparisons (i.e., females with ASD vs. controls and males with ASD vs. controls), two overlapping regions in bilateral precuneus (BA 31) and left superior frontal gyrus (BA 9/10) were detected. Sex-by-group analyses revealed in males with ASD compared to matched controls two male-specific regions of increased GM volume (left middle occipital gyrus-BA 19-and right superior temporal gyrus-BA 22). Comparisons in females with and without ASD demonstrated increased GM volumes predominantly in the bilateral frontal regions. Additional regions of significantly increased GM volume in the right anterior cingulate cortex (BA 32) and right cerebellum were typical only of females with ASD. Despite the specific behavioural correlates of sex-dimorphism in ASD, brain morphology as yet remains unclear and requires future dedicated investigations. This study provides evidence of structural brain gender differences in young children with ASD that possibly contribute to the different phenotypic disease manifestations in males and females.

Theta and Alpha Oscillation Impairments in Autistic Spectrum Disorder Reflect Working Memory Deficit.

PubMed

Larrain-Valenzuela, Josefina; Zamorano, Francisco; Soto-Icaza, Patricia; Carrasco, Ximena; Herrera, Claudia; Daiber, Francisca; Aboitiz, Francisco; Billeke, Pablo

2017-10-30

A dysfunction in the excitatory-inhibitory (E/I) coordination in neuronal assembly has been proposed as a possible neurobiological mechanism of Autistic Spectrum Disorder (ASD). However, the potential impact of this mechanism in cognitive performance is not fully explored. Since the main consequence of E/I dysfunction is an impairment in oscillatory activity and its underlying cognitive computations, we assessed the electroencephalographic activity of ASD and typically developing (TD) subjects during a working-memory task. We found that ASD subjects committed more errors than TD subjects. Moreover, TD subjects demonstrated a parametric modulation in the power of alpha and theta band while ASD subjects did not demonstrate significant modulations. The preceding leads to significant differences between the groups in both the alpha power placed on the occipital cortex and the theta power placed on the left premotor and the right prefrontal cortex. The impaired theta modulation correlated with autistic symptoms. The results indicated that ASD may present an alteration in the recruitment of the oscillatory activity during working-memory, and this alteration could be related to the physiopathology of the disorder.

Receiver operating characteristic curve analysis of the Child Behavior Checklist and Teacher’s Report Form for assessing autism spectrum disorder in preschool-aged children

PubMed Central

Bara, Tiago S; Farias, Antonio C; Felden, Erico PG; Cordeiro, Mara L

2018-01-01

Background Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social, behavioral, and communication impairments with an estimated prevalence of 1 in 68 school-aged children. There is a need for objective and easily applicable instruments for early identification of autistic children to enable initiation of early interventions during a very sensitive period of brain development and, consequently, optimize prognosis. Here, we tested the utility of the Child Behavior Checklist (CBCL) and the Caregiver-Teacher’s Report Form (C-TRF) scales for assessing ASD in Brazil, where ASD screening research is emergent. Subjects and methods A total of 70 children (2–5 years old, both sexes) were enrolled, including an ASD group (n=39) and a non-ASD control group (n=31). The preschool versions of the CBCL and C-TRF were applied. The CBCL and C-TRF results were compared between the ASD and non-ASD control groups with Mann–Whitney U tests and receiver operating characteristic analyses. Results The CBCL and C-TRF were found to have moderate accuracy for the dimensions withdrawn and autism spectrum problems, and to correlate with each other. Conclusion The CBCL and C-TRF may aid in early ASD detection. PMID:29343961

Autistic children and anesthesia: is their perioperative experience different?

PubMed

Arnold, Brook; Elliott, Anila; Laohamroonvorapongse, Dean; Hanna, John; Norvell, Daniel; Koh, Jeffrey

2015-11-01

Children with autism spectrum disorders (ASD) are an increasingly common patient population in the perioperative setting. Children with ASD present with abnormal development in social interaction, communication, and stereotyped patterns of behavior and may be more prone to elevated perioperative anxiety. The perioperative experience for these patients is complex and presents a unique challenge for clinicians. The aim of the current study was to provide a further understanding of the premedication patterns and perioperative experiences of children with ASD in comparison to children without ASD. Using a retrospective cohort study design, medical records were evaluated for patients with and without ASD undergoing general anesthesia for dental rehabilitation from 2006-2011. The following objectives were measured and compared: (i) premedication patterns and (ii) complications, pain, anesthetic type, PACU time, and time to discharge. To compare categorical variables, the chi-square test was used. Bivariate and multivariable analyses were performed to control for potential confounding as a result of baseline differences between the two groups. A total of 121 ASD patients and 881 non-ASD patients were identified. When controlling for age, weight, and gender, children in the ASD group were more likely to have nonstandard premedication types (P < 0.0001), while children without ASD were more likely to have standard premedication types (P < 0.0001). No significant group differences were identified in regards to the other outcome measures. Other than a significant difference in the premedication type and route, we found that children with ASD seemed to have similar perioperative experiences as non-ASD subjects. It was especially interesting to find that their postoperative period did not pose any special challenges. There is much to be learned about this unique patient population, and a more in-depth prospective evaluation is warranted to help better delineate the best approach to caring for these patients. © 2015 John Wiley & Sons Ltd.

Cognitive endophenotypes of attention deficit/hyperactivity disorder and intra-subject variability in patients with autism spectrum disorder.

PubMed

Biscaldi, M; Bednorz, N; Weissbrodt, K; Saville, C W N; Feige, B; Bender, S; Klein, C

2016-07-01

Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) have previously been studied mainly in isolation from each other. However the two conditions may be aetiologically related and thus show overlap in aetiologically relevant functions. In order to address this question of potential aetiological overlap between ADHD and ASD, the present study set out to investigate putative endophenotypes of ADHD in N=33 typically developing (TD) children and N=28 patients with ASD that were (ASD+) or were not (ASD-) co-morbid for ADHD. With regard to both the cognitive endophenotype candidates (working memory, inhibition, temporal processing) and intra-subject variability (ISV) the pattern of abnormalities was inconsistent. Furthermore, the overall profile of ASD-TD differences was extremely similar to the pattern of differences between the ASD+ and ASD- sub-groups, suggesting that any abnormalities found were due to the comorbid ASD subgroup. This held in particular for ISV, which did not show in patients with ASD the task-general increase that is common in ADHD samples. Altogether, the present results do not support the hypothesis of aetiological overlap between ASD and ADHD. Copyright © 2016 Elsevier B.V. All rights reserved.

Analysis of gait symmetry during over-ground walking in children with autism spectrum disorder.

PubMed

Eggleston, Jeffrey D; Harry, John R; Hickman, Robbin A; Dufek, Janet S

2017-06-01

Gait symmetry is utilized as an indicator of neurologic function. Healthy gait often exhibits minimal asymmetries, while pathological gait exhibits exaggerated asymmetries. The purpose of this study was to examine symmetry of mechanical gait parameters during over-ground walking in children with Autism Spectrum Disorder (ASD). Kinematic and kinetic data were obtained from 10 children (aged 5-12 years) with ASD. The Model Statistic procedure (α=0.05) was used to compare gait related parameters between limbs. Analysis revealed children with ASD exhibit significant lower extremity joint position and ground reaction force asymmetries throughout the gait cycle. The observed asymmetries were unique for each subject. These data do not support previous research relative to gait symmetry in children with ASD. Many individuals with ASD do not receive physical therapy interventions, however, precision medicine based interventions emphasizing lower extremity asymmetries may improve gait function and improve performance during activities of daily living. Copyright © 2017 Elsevier B.V. All rights reserved.

Neural correlates of moral reasoning in autism spectrum disorder

PubMed Central

Schneider, Karla; Pauly, Katharina D.; Gossen, Anna; Mevissen, Lea; Michel, Tanja M.; Gur, Ruben C.; Schneider, Frank

2013-01-01

In our study, we tried to clarify whether patients with autism spectrum disorder (ASD) reveal different moral decision patterns as compared to healthy subjects and whether common social interaction difficulties in ASD are reflected in altered brain activation during different aspects of moral reasoning. 28 patients with high-functioning ASD and 28 healthy subjects matched for gender, age and education took part in an event-related functional magnetic resonance imaging study. Participants were confronted with textual dilemma situations followed by proposed solutions to which they could agree or disagree. On a neural level, moral decision making was associated with activation in anterior medial prefrontal regions, the temporo-parietal junction and the precuneus for both groups. However, while patients and healthy controls did not exhibit significant behavioral differences, ASD patients showed decreased activation in limbic regions, particularly the amygdala, as well as increased activation in the anterior and the posterior cingulate gyrus during moral reasoning. Alterations of brain activation in patients might thus indicate specific impairments in empathy. However, activation increases in brain regions associated with the ‘default mode network’ and self-referential cognition also provide evidence for an altered way of patients’ cerebral processing with regard to decision making based on social information. PMID:22569187

Neurobiology of Sensory Overresponsivity in Youth With Autism Spectrum Disorders.

PubMed

Green, Shulamite A; Hernandez, Leanna; Tottenham, Nim; Krasileva, Kate; Bookheimer, Susan Y; Dapretto, Mirella

2015-08-01

More than half of youth with autism spectrum disorders (ASDs) have sensory overresponsivity (SOR), an extreme negative reaction to sensory stimuli. However, little is known about the neurobiological basis of SOR, and there are few effective treatments. Understanding whether SOR is due to an initial heightened sensory response or to deficits in regulating emotional reactions to stimuli has important implications for intervention. To determine differences in brain responses, habituation, and connectivity during exposure to mildly aversive sensory stimuli in youth with ASDs and SOR compared with youth with ASDs without SOR and compared with typically developing control subjects. Functional magnetic resonance imaging was used to examine brain responses and habituation to mildly aversive auditory and tactile stimuli in 19 high-functioning youths with ASDs and 19 age- and IQ-matched, typically developing youths (age range, 9-17 years). Brain activity was related to parents' ratings of children's SOR symptoms. Functional connectivity between the amygdala and orbitofrontal cortex was compared between ASDs subgroups with and without SOR and typically developing controls without SOR. The study dates were March 2012 through February 2014. Relative increases in blood oxygen level-dependent signal response across the whole brain and within the amygdala during exposure to sensory stimuli compared with fixation, as well as correlation between blood oxygen level-dependent signal change in the amygdala and orbitofrontal cortex. The mean age in both groups was 14 years and the majority in both groups (16 of 19 each) were male. Compared with neurotypical control participants, participants with ASDs displayed stronger activation in primary sensory cortices and the amygdala (P < .05, corrected). This activity was positively correlated with SOR symptoms after controlling for anxiety. The ASDs with SOR subgroup had decreased neural habituation to stimuli in sensory cortices and the amygdala compared with groups without SOR. Youth with ASDs without SOR showed a pattern of amygdala downregulation, with negative connectivity between the amygdala and orbitofrontal cortex (thresholded at z > 1.70, P < .05). Results demonstrate that youth with ASDs and SOR show sensorilimbic hyperresponsivity to mildly aversive tactile and auditory stimuli, particularly to multiple modalities presented simultaneously, and show that this hyperresponsivity is due to failure to habituate. In addition, findings suggest that a subset of youth with ASDs can regulate their responses through prefrontal downregulation of amygdala activity. Implications for intervention include minimizing exposure to multiple sensory modalities and building coping strategies for regulating emotional response to stimuli.

Psychiatric and psychosocial problems in adults with normal-intelligence autism spectrum disorders.

PubMed

Hofvander, Björn; Delorme, Richard; Chaste, Pauline; Nydén, Agneta; Wentz, Elisabet; Ståhlberg, Ola; Herbrecht, Evelyn; Stopin, Astrid; Anckarsäter, Henrik; Gillberg, Christopher; Råstam, Maria; Leboyer, Marion

2009-06-10

Individuals with autism spectrum disorders (ASDs) often display symptoms from other diagnostic categories. Studies of clinical and psychosocial outcome in adult patients with ASDs without concomitant intellectual disability are few. The objective of this paper is to describe the clinical psychiatric presentation and important outcome measures of a large group of normal-intelligence adult patients with ASDs. Autistic symptomatology according to the DSM-IV-criteria and the Gillberg & Gillberg research criteria, patterns of comorbid psychopathology and psychosocial outcome were assessed in 122 consecutively referred adults with normal intelligence ASDs. The subjects consisted of 5 patients with autistic disorder (AD), 67 with Asperger's disorder (AS) and 50 with pervasive developmental disorder not otherwise specified (PDD NOS). This study group consists of subjects pooled from two studies with highly similar protocols, all seen on an outpatient basis by one of three clinicians. Core autistic symptoms were highly prevalent in all ASD subgroups. Though AD subjects had the most pervasive problems, restrictions in non-verbal communication were common across all three subgroups and, contrary to current DSM criteria, so were verbal communication deficits. Lifetime psychiatric axis I comorbidity was very common, most notably mood and anxiety disorders, but also ADHD and psychotic disorders. The frequency of these diagnoses did not differ between the ASD subgroups or between males and females. Antisocial personality disorder and substance abuse were more common in the PDD NOS group. Of all subjects, few led an independent life and very few had ever had a long-term relationship. Female subjects more often reported having been bullied at school than male subjects. ASDs are clinical syndromes characterized by impaired social interaction and non-verbal communication in adulthood as well as in childhood. They also carry a high risk for co-existing mental health problems from a broad spectrum of disorders and for unfavourable psychosocial life circumstances. For the next revision of DSM, our findings especially stress the importance of careful examination of the exclusion criterion for adult patients with ASDs.

Color Vision Losses in Autism Spectrum Disorders

PubMed Central

Zachi, Elaine C.; Costa, Thiago L.; Barboni, Mirella T. S.; Costa, Marcelo F.; Bonci, Daniela M. O.; Ventura, Dora F.

2017-01-01

Autism spectrum disorders (ASDs) are neurodevelopmental conditions characterized by impairments in social/communication abilities and restricted behaviors. The present study aims to examine color vision discrimination in ASD children and adolescents without intellectual disability. The participants were also subdivided in order to compare color vision thresholds of autistic participants and those who achieved diagnostic criteria for Asperger Syndrome (AS). Nine subjects with autism, 11 participants with AS and 36 typically developing children and adolescents participated in the study. Color vision was assessed by the Cambridge Color Test (CCT). The Trivector protocol was administered to determine color discrimination thresholds along the protan, deutan, and tritan color confusion lines. Data from ASD participants were compared to tolerance limits for 90% of the population with 90% probability obtained from controls thresholds. Of the 20 ASD individuals examined, 6 (30%) showed color vision losses. Elevated color discrimination thresholds were found in 3/9 participants with autism and in 3/11 AS participants. Diffuse and tritan deficits were found. Mechanisms for chromatic losses may be either at the retinal level and/or reflect reduced cortical integration. PMID:28713324

Novel Genetic Variants of Sporadic Atrial Septal Defect (ASD) in a Chinese Population Identified by Whole-Exome Sequencing (WES)

PubMed Central

Liu, Yong; Cao, Yu; Li, Yaxiong; Lei, Dongyun; Li, Lin; Hou, Zong Liu; Han, Shen; Meng, Mingyao; Shi, Jianlin; Zhang, Yayong; Wang, Yi; Niu, Zhaoyi; Xie, Yanhua; Xiao, Benshan; Wang, Yuanfei; Li, Xiao; Yang, Lirong

2018-01-01

Background Recently, mutations in several genes have been described to be associated with sporadic ASD, but some genetic variants remain to be identified. The aim of this study was to use whole-exome sequencing (WES) combined with bioinformatics analysis to identify novel genetic variants in cases of sporadic congenital ASD, followed by validation by Sanger sequencing. Material/Methods Five Han patients with secundum ASD were recruited, and their tissue samples were analyzed by WES, followed by verification by Sanger sequencing of tissue and blood samples. Further evaluation using blood samples included 452 additional patients with sporadic secundum ASD (212 male and 240 female patients) and 519 healthy subjects (252 male and 267 female subjects) for further verification by a multiplexed MassARRAY system. Bioinformatic analyses were performed to identify novel genetic variants associated with sporadic ASD. Results From five patients with sporadic ASD, a total of 181,762 genomic variants in 33 exon loci, validated by Sanger sequencing, were selected and underwent MassARRAY analysis in 452 patients with ASD and 519 healthy subjects. Three loci with high mutation frequencies, the 138665410 FOXL2 gene variant, the 23862952 MYH6 gene variant, and the 71098693 HYDIN gene variant were found to be significantly associated with sporadic ASD (P<0.05); variants in FOXL2 and MYH6 were found in patients with isolated, sporadic ASD (P<5×10−4). Conclusions This was the first study that demonstrated variants in FOXL2 and HYDIN associated with sporadic ASD, and supported the use of WES and bioinformatics analysis to identify disease-associated mutations. PMID:29505555

Novel Genetic Variants of Sporadic Atrial Septal Defect (ASD) in a Chinese Population Identified by Whole-Exome Sequencing (WES).

PubMed

Liu, Yong; Cao, Yu; Li, Yaxiong; Lei, Dongyun; Li, Lin; Hou, Zong Liu; Han, Shen; Meng, Mingyao; Shi, Jianlin; Zhang, Yayong; Wang, Yi; Niu, Zhaoyi; Xie, Yanhua; Xiao, Benshan; Wang, Yuanfei; Li, Xiao; Yang, Lirong; Wang, Wenju; Jiang, Lihong

2018-03-05

BACKGROUND Recently, mutations in several genes have been described to be associated with sporadic ASD, but some genetic variants remain to be identified. The aim of this study was to use whole-exome sequencing (WES) combined with bioinformatics analysis to identify novel genetic variants in cases of sporadic congenital ASD, followed by validation by Sanger sequencing. MATERIAL AND METHODS Five Han patients with secundum ASD were recruited, and their tissue samples were analyzed by WES, followed by verification by Sanger sequencing of tissue and blood samples. Further evaluation using blood samples included 452 additional patients with sporadic secundum ASD (212 male and 240 female patients) and 519 healthy subjects (252 male and 267 female subjects) for further verification by a multiplexed MassARRAY system. Bioinformatic analyses were performed to identify novel genetic variants associated with sporadic ASD. RESULTS From five patients with sporadic ASD, a total of 181,762 genomic variants in 33 exon loci, validated by Sanger sequencing, were selected and underwent MassARRAY analysis in 452 patients with ASD and 519 healthy subjects. Three loci with high mutation frequencies, the 138665410 FOXL2 gene variant, the 23862952 MYH6 gene variant, and the 71098693 HYDIN gene variant were found to be significantly associated with sporadic ASD (P<0.05); variants in FOXL2 and MYH6 were found in patients with isolated, sporadic ASD (P<5×10^-4). CONCLUSIONS This was the first study that demonstrated variants in FOXL2 and HYDIN associated with sporadic ASD, and supported the use of WES and bioinformatics analysis to identify disease-associated mutations.

Absence of age-related prefrontal NAA change in adults with autism spectrum disorders.

PubMed

Aoki, Y; Abe, O; Yahata, N; Kuwabara, H; Natsubori, T; Iwashiro, N; Takano, Y; Inoue, H; Kawakubo, Y; Gonoi, W; Sasaki, H; Murakami, M; Katsura, M; Nippashi, Y; Takao, H; Kunimatsu, A; Matsuzaki, H; Tsuchiya, K J; Kato, N; Kasai, K; Yamasue, H

2012-10-23

Atypical trajectory of brain growth in autism spectrum disorders (ASDs) has been recognized as a potential etiology of an atypical course of behavioral development. Numerous neuroimaging studies have focused on childhood to investigate atypical age-related change of brain structure and function, because it is a period of neuron and synapse maturation. Recent studies, however, have shown that the atypical age-related structural change of autistic brain expands beyond childhood and constitutes neural underpinnings for lifelong difficulty to behavioral adaptation. Thus, we examined effects of aging on neurochemical aspects of brain maturation using 3-T proton magnetic resonance spectroscopy ((1)H-MRS) with single voxel in the medial prefrontal cortex (PFC) in 24 adult men with non-medicated high-functioning ASDs and 25 age-, IQ- and parental-socioeconomic-background-matched men with typical development (TD). Multivariate analyses of covariance demonstrated significantly high N-acetylaspartate (NAA) level in the ASD subjects compared with the TD subjects (F=4.83, P=0.033). The low NAA level showed a significant positive correlation with advanced age in the TD group (r=-0.618, P=0.001), but was not evident among the ASD individuals (r=0.258, P=0.223). Fisher's r-to-z transformation showed a significant difference in the correlations between the ASD and TD groups (Z=-3.23, P=0.001), which indicated that the age-NAA relationship was significantly specific to people with TD. The current (1)H-MRS study provided new evidence that atypical age-related change of neurochemical aspects of brain maturation in ASD individuals expands beyond childhood and persists during adulthood.

Relationship between absolute and relative ratios of glutamate, glutamine and GABA and severity of autism spectrum disorder.

PubMed

Al-Otaish, Hanoof; Al-Ayadhi, Laila; Bjørklund, Geir; Chirumbolo, Salvatore; Urbina, Mauricio A; El-Ansary, Afaf

2018-06-01

Autism spectrum disorder (ASD) is a neurodevelopmental pathology characterized by an impairment in social interaction, communication difficulties, and repetitive behaviors. Glutamate signaling abnormalities are thought to be considered as major etiological mechanisms leading to ASD. The search for amino-acidic catabolytes related to glutamate in patients with different levels of ASD might help current research to clarify the mechanisms underlying glutamate signaling and its disorders, particularly in relation to ASD. In the present study, plasma levels of the amino acids and their derivatives glutamate, glutamine, and γ-aminobutyric acid (GABA), associated with their relative ratios, were evaluated using an enzyme-linked immunosorbent assay (ELISA) technique in 40 male children with ASD and in 38 age- and gender-matched neurotypical health controls. The Social Responsiveness Scale (SRS) was used to evaluate social cognition, and the Childhood Autism Rating Scale (CARS) was used to assess subjects' behaviors. Children with ASD exhibited a significant elevation of plasma GABA and glutamate/glutamine ratio, as well as significantly lower levels of plasma glutamine and glutamate/GABA ratios compared to controls. No significant correlation was found between glutamate levels and the severity of autism, measured by CARS and SRS. In receiver operating characteristic (ROC) curve analysis, the area under the curve for GABA compared to other parameters was close to one, indicating its potential use as a biomarker. Glutamine appeared as the best predictive prognostic markers in the present study. The results of the present study indicate a disturbed balance between GABAergic and glutamatergic neurotransmission in ASD. The study also indicates that an increased plasma level of GABA can be potentially used as an early diagnostic biomarker for ASD.

Vitamin D status in autism spectrum disorders and the efficacy of vitamin D supplementation in autistic children.

PubMed

Saad, Khaled; Abdel-Rahman, Ahmed A; Elserogy, Yasser M; Al-Atram, Abdulrahman A; Cannell, John J; Bjørklund, Geir; Abdel-Reheim, Mohamed K; Othman, Hisham A K; El-Houfey, Amira A; Abd El-Aziz, Nafisa H R; Abd El-Baseer, Khaled A; Ahmed, Ahmed E; Ali, Ahmed M

2016-10-01

Autism spectrum disorder (ASD) is a developmental disorder characterized by pervasive deficits in social interaction, impairment in verbal and non-verbal communication, and stereotyped patterns of interests and activities. Vitamin-D deficiency was previously reported in autistic children. However, the data on the relationship between vitamin D deficiency and the severity of autism are limited. We performed a case-controlled cross-sectional analysis conducted on 122 ASD children, to assess their vitamin D status compared to controls and the relationship between vitamin D deficiency and the severity of autism. We also conducted an open trial of vitamin D supplementation in ASD children. Fifty-seven percent of the patients in the present study had vitamin D deficiency, and 30% had vitamin D insufficiency. The mean 25-OHD levels in patients with severe autism were significantly lower than those in patients with mild/moderate autism. Serum 25-OHD levels had significant negative correlations with Childhood Autism Rating Scale (CARS) scores. Of the ASD group, 106 patients with low-serum 25-OHD levels (<30 ng/ml) participated in the open label trial. They received vitamin D3 (300 IU/kg/day not to exceed 5000 IU/day) for 3 months. Eighty-three subjects completed 3 months of daily vitamin D treatment. Collectively, 80.72% (67/83) of subjects who received vitamin D3 treatment had significantly improved outcome, which was mainly in the sections of the CARS and aberrant behavior checklist subscales that measure behavior, stereotypy, eye contact, and attention span. Vitamin D is inexpensive, readily available and safe. It may have beneficial effects in ASD subjects, especially when the final serum level is more than 40 ng/ml. UMIN-CTR Study Design: trial Number: R000016846.

Head circumference and body growth in autism spectrum disorders.

PubMed

Fukumoto, Aya; Hashimoto, Toshiaki; Mori, Kenji; Tsuda, Yoshimi; Arisawa, Kokichi; Kagami, Shoji

2011-08-01

Research has shown that there is a relationship between increased head circumference and autism spectrum disorders (ASD). This study examined this relationship during the first year of life in subjects with ASD. We compared 280 children with ASD and 609 controls. In the ASD-male group, increases were observed in head circumference from 3 to 12months, in height from 3 to 9months, and in body weight from 3 to 6 and 12months. On the other hand, in the ASD-female group increases in head circumference, in body height, and in body weight were only observed at 3months. After adjusting for height, weight, and age, only the head circumference in the male ASD group was significantly increased from 6 to 9months after birth, reaching a peak at 6months after birth. No difference was found in the female ASD group. Although body overgrowth in the ASD group also started early after birth, the increase in head circumference was more marked than that in body growth. The values of physical measurements in the first year may be useful, minimally invasive parameters for the early detection of autism in combination with observing the timing of certain behaviors such as smiling, eye contact, crawling, pointing, and joint attention. Copyright © 2010 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Levels of Soluble Adhesion Molecules PECAM-1 and P-Selectin are Decreased in Children with Autism Spectrum Disorder

PubMed Central

Onore, Charity E.; Nordahl, Christine Wu; Young, Gregory S.; Van de Water, Judy A.; Rogers, Sally J.; Ashwood, Paul

2012-01-01

Background Although the etiopathology of Autism Spectrum Disorder (ASD) is not clear there is increasing evidence that dysfunction in the immune system affects many children with ASD. Findings of immune dysfunction in ASD include increases in inflammatory cytokines, chemokines and microglial activity in brain tissue and CSF, as well as abnormal peripheral immune cell function. Methods Adhesion molecules, such as platelet endothelial adhesion molecule-1 (PECAM-1), intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), P-Selectin, and L-Selectin, function to facilitate leukocyte transendothelial migration. We assessed concentrations of soluble adhesion molecules, sPECAM-1, sICAM-1, sVCAM-1, sP-Selectin, and sL-Selectin in the plasma of 49 participants with ASD, and 31 typically developing controls of the same age, all of whom were enrolled as part of the Autism Phenome Project (APP). Behavioral assessment, the levels of soluble adhesion molecules, head circumference and MRI measurements of brain volume were compared in the same subjects. Results Levels of sPECAM-1 and sP-Selectin were significantly reduced in the ASD group compared to typically developing controls (p < 0.02). Soluble PECAM-1 levels were negatively associated with repetitive behavior and abnormal brain growth in children with ASD (p=0.03). Conclusions As adhesion molecules modulate the permeability and signaling at the blood brain barrier as well as leukocyte infiltration into the CNS, current data suggests a role for these molecules in the complex pathophysiology of ASD. PMID:22717029

[Does the Fragmented Images Test measure locally oriented visual processing in autism spectrum disorders?].

PubMed

Scheurich, Armin; Fellgiebel, Andreas; Müller, Mattias J; Poustka, Fritz; Bölte, Sven

2010-03-01

The cognitive phenotype of autism spectrum disorders (ASD) is characterized among other things by local processing (weak central coherence). It was examined whether a test that measures identification of fragmented pictures (FBT) is able to seize this preference for local processing. The FBT performance of 15 patients with ASD, 16 with depression, 16 with schizophrenia and of 16 control subjects was compared. In addition, two tests well known to be sensitive to local processing were assessed, namely the Embedded Figures Test (EFT) and the Block Design Test (BDT). ASD patients demonstrated a preference for local processing. Difficulties in global processing, or more specifically in gestalt perception (FBT), were accompanied by good performance on the EFT and BDT as expected. Controlling for age and nonverbal intelligence (ANCOVA) reduced differences to trends. However, the calculation of difference scores (i.e., subtraction of FBT from EFT performance) resulted in significant differences between ASD and control groups even after controlling for of age and intelligence. The FBT is a suitable exploratory test of local visual processing in ASD. In particular, a difference criterion can be generated (FBT vs. EFT) that discriminates between ASD and clinical as well as healthy control groups.

Perceived Intensity of Emotional Point-Light Displays Is Reduced in Subjects with ASD

ERIC Educational Resources Information Center

Krüger, Britta; Kaletsch, Morten; Pilgramm, Sebastian; Schwippert, Sven-Sören; Hennig, Jürgen; Stark, Rudolf; Lis, Stefanie; Gallhofer, Bernd; Sammer, Gebhard; Zentgraf, Karen; Munzert, Jörn

2018-01-01

One major characteristic of autism spectrum disorder (ASD) is problems with social interaction and communication. The present study explored ASD-related alterations in perceiving emotions expressed via body movements. 16 participants with ASD and 16 healthy controls observed video scenes of human interactions conveyed by point-light displays. They…

Barriers to dental care for children with autism spectrum disorder.

PubMed

Barry, S; O'Sullivan, E A; Toumba, K J

2014-04-01

This study examined the problems encountered by children with autism spectrum disorder (ASD), when accessing dental care. This was a cross-sectional, case-control questionnaire study. A piloted questionnaire was developed to identify the main barriers to dental care experienced by patients with ASD in Hull and East Riding. The study group was comprised of parents/carers of children with ASD, and the control group was comprised of parents/carers of age matched healthy, neurotypical children. Results were analysed using Chi-square and Fisher's exact tests where appropriate. Significance was deemed at p < 0.05. Ordinal data was presented using medians and 25th and 75th centiles and compared using Mann-Whitney U test. A piloted questionnaire was developed to identify the main barriers to dental care experienced by patients with ASD in Hull and East Riding. The study group was comprised of parents/carers of children with ASD, and the control group was comprised of parents/carers of age matched healthy, neurotypical children. 112 subjects completed the questionnaire. There was no significant difference in accessing dental care between study and control groups (p = 0.051), although access was perceived as more difficult in the ASD group (p < 0.001). There was a significantly greater perceived difficulty in travelling to the dental surgery in the ASD group. Predicted negative behaviours were more frequent in the ASD group. All suggested interventions were predicted to be helpful in a significantly greater proportion of the ASD group. Difficulties exist for children with ASD in accessing dental care in the Hull and East Riding area.

Health Conditions and Functional Status in Adults with Autism: A Cross-Sectional Evaluation.

PubMed

Fortuna, Robert J; Robinson, Laura; Smith, Tristram H; Meccarello, Jon; Bullen, Beth; Nobis, Kathryn; Davidson, Philip W

2016-01-01

Children and adolescents with autism spectrum disorder (ASD) have many well-known health concerns, yet health conditions in adults with ASD remain poorly defined. To examine health conditions and functional status in adults with ASD and identify factors associated with health and functional status across age cohorts. We collected cross-sectional data from 255 adult subjects aged 18 to 71 years with ASD using the Rochester Health Status Survey IV (RHSS-IV), a 58-item validated survey instrument. We used the National Health and Nutritional Examination Survey and National Health Interview Survey to provide comparative prevalence rates in the general population. Compared to the general population, young adults aged 18-29 with ASD had a substantially higher prevalence of seizure disorder (11.2 % vs. 1.4 %; p = 0.002), depression (16.4 % vs. 6.4 %; p = 0.007), hypertension (12.9 % vs. 6.3 %; p = 0.05), and allergies (39.7 % vs. 8.4 %; p < 0.001). In contrast, young adults with ASD had considerably lower rates of sexually transmitted illness (STI) (0.9 % vs. 4.3 %; p = 0.03), tobacco use (5.2 % vs. 31.9 %; p < 0.001), and alcohol misuse (0.9 % vs. 11.9 %; p < 0.001). Adults 40 and over with ASD also had higher rates of seizure disorder (29.2 % vs. 1.7 %; p < 0.001), lower tobacco use (2.8 % vs. 24.5 %; p < 0.001), and lower alcohol misuse (1.4 % vs. 18.2 %; p < 0.001) compared to the general population. Amongst the 55 % of participants with a documented IQ score, 91 % had an intellectual disability (IQ < 70). Within the cohort aged 40 years old and older, only 54.2 % were independent with eating, 43.0 % independent with dressing, and 43.1 % independent with bathing. Lower IQ and depression were associated with lower functional status. Adults with ASD have a high prevalence of seizure disorders and depression, but low rates of STIs, tobacco use, and alcohol misuse. Within our cohort, the majority of older adults with ASD required some assistance with activities of daily living.

The Ritvo Autism Asperger Diagnostic Scale-Revised (RAADS-R): A Scale to Assist the Diagnosis of Autism Spectrum Disorder in Adults--An International Validation Study

ERIC Educational Resources Information Center

Ritvo, Riva Ariella; Ritvo, Edward R.; Guthrie, Donald; Ritvo, Max J.; Hufnagel, Demetra H.; McMahon, William; Tonge, Bruce; Mataix-Cols, David; Jassi, Amita; Attwood, Tony; Eloff, Johann

2011-01-01

The Ritvo Autism Asperger Diagnostic Scale-Revised (RAADS-R) is a valid and reliable instrument to assist the diagnosis of adults with Autism Spectrum Disorders (ASD). The 80-question scale was administered to 779 subjects (201 ASD and 578 comparisons). All ASD subjects met inclusion criteria: DSM-IV-TR, ADI/ADOS diagnoses and standardized IQ…

Plasma cytokine profiling in sibling pairs discordant for autism spectrum disorder

PubMed Central

2013-01-01

Objective Converging lines of evidence point to the existence of immune dysfunction in autism spectrum disorder (ASD), which could directly affect several key neurodevelopmental processes. Previous studies have shown higher cytokine levels in patients with autism compared with matched controls or subjects with other developmental disorders. In the current study, we used plasma-cytokine profiling for 25 discordant sibling pairs to evaluate whether these alterations occur within families with ASD. Methods Plasma-cytokine profiling was conducted using an array-based multiplex sandwich ELISA for simultaneous quantitative measurement of 40 unique targets. We also analyzed the correlations between cytokine levels and clinically relevant quantitative traits (Vineland Adaptive Behavior Scale in Autism (VABS) composite score, Social Responsiveness Scale (SRS) total T score, head circumference, and full intelligence quotient (IQ)). In addition, because of the high phenotypic heterogeneity of ASD, we defined four subgroups of subjects (those who were non-verbal, those with gastrointestinal issues, those with regressive autism, and those with a history of allergies), which encompass common and/or recurrent endophenotypes in ASD, and tested the cytokine levels in each group. Results None of the measured parameters showed significant differences between children with ASD and their related typically developing siblings. However, specific target levels did correlate with quantitative clinical traits, and these were significantly different when the ASD subgroups were analyzed. It is notable that these differences seem to be attributable to a predisposing immunogenetic background, as no other significant differences were noticed between discordant sibling pairs. Interleukin-1β appears to be the cytokine most involved in quantitative traits and clinical subgroups of ASD. Conclusions In the present study, we found a lack of significant differences in plasma-cytokine levels between children with ASD and in their related non-autistic siblings. Thus, our results support the evidence that the immune profiles of children with autism do not differ from their typically developing siblings. However, the significant association of cytokine levels with the quantitative traits and the clinical subgroups analyzed suggests that altered immune responses may affect core feature of ASD. PMID:23497090

A Discovery Resource of Rare Copy Number Variations in Individuals with Autism Spectrum Disorder

PubMed Central

Prasad, Aparna; Merico, Daniele; Thiruvahindrapuram, Bhooma; Wei, John; Lionel, Anath C.; Sato, Daisuke; Rickaby, Jessica; Lu, Chao; Szatmari, Peter; Roberts, Wendy; Fernandez, Bridget A.; Marshall, Christian R.; Hatchwell, Eli; Eis, Peggy S.; Scherer, Stephen W.

2012-01-01

The identification of rare inherited and de novo copy number variations (CNVs) in human subjects has proven a productive approach to highlight risk genes for autism spectrum disorder (ASD). A variety of microarrays are available to detect CNVs, including single-nucleotide polymorphism (SNP) arrays and comparative genomic hybridization (CGH) arrays. Here, we examine a cohort of 696 unrelated ASD cases using a high-resolution one-million feature CGH microarray, the majority of which were previously genotyped with SNP arrays. Our objective was to discover new CNVs in ASD cases that were not detected by SNP microarray analysis and to delineate novel ASD risk loci via combined analysis of CGH and SNP array data sets on the ASD cohort and CGH data on an additional 1000 control samples. Of the 615 ASD cases analyzed on both SNP and CGH arrays, we found that 13,572 of 21,346 (64%) of the CNVs were exclusively detected by the CGH array. Several of the CGH-specific CNVs are rare in population frequency and impact previously reported ASD genes (e.g., NRXN1, GRM8, DPYD), as well as novel ASD candidate genes (e.g., CIB2, DAPP1, SAE1), and all were inherited except for a de novo CNV in the GPHN gene. A functional enrichment test of gene-sets in ASD cases over controls revealed nucleotide metabolism as a potential novel pathway involved in ASD, which includes several candidate genes for follow-up (e.g., DPYD, UPB1, UPP1, TYMP). Finally, this extensively phenotyped and genotyped ASD clinical cohort serves as an invaluable resource for the next step of genome sequencing for complete genetic variation detection. PMID:23275889

Basic abnormalities in visual processing affect face processing at an early age in autism spectrum disorder.

PubMed

Vlamings, Petra Hendrika Johanna Maria; Jonkman, Lisa Marthe; van Daalen, Emma; van der Gaag, Rutger Jan; Kemner, Chantal

2010-12-15

A detailed visual processing style has been noted in autism spectrum disorder (ASD); this contributes to problems in face processing and has been directly related to abnormal processing of spatial frequencies (SFs). Little is known about the early development of face processing in ASD and the relation with abnormal SF processing. We investigated whether young ASD children show abnormalities in low spatial frequency (LSF, global) and high spatial frequency (HSF, detailed) processing and explored whether these are crucially involved in the early development of face processing. Three- to 4-year-old children with ASD (n = 22) were compared with developmentally delayed children without ASD (n = 17). Spatial frequency processing was studied by recording visual evoked potentials from visual brain areas while children passively viewed gratings (HSF/LSF). In addition, children watched face stimuli with different expressions, filtered to include only HSF or LSF. Enhanced activity in visual brain areas was found in response to HSF versus LSF information in children with ASD, in contrast to control subjects. Furthermore, facial-expression processing was also primarily driven by detail in ASD. Enhanced visual processing of detailed (HSF) information is present early in ASD and occurs for neutral (gratings), as well as for socially relevant stimuli (facial expressions). These data indicate that there is a general abnormality in visual SF processing in early ASD and are in agreement with suggestions that a fast LSF subcortical face processing route might be affected in ASD. This could suggest that abnormal visual processing is causative in the development of social problems in ASD. Copyright © 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

An ontology for Autism Spectrum Disorder (ASD) to infer ASD phenotypes from Autism Diagnostic Interview-Revised data.

PubMed

Mugzach, Omri; Peleg, Mor; Bagley, Steven C; Guter, Stephen J; Cook, Edwin H; Altman, Russ B

2015-08-01

Our goal is to create an ontology that will allow data integration and reasoning with subject data to classify subjects, and based on this classification, to infer new knowledge on Autism Spectrum Disorder (ASD) and related neurodevelopmental disorders (NDD). We take a first step toward this goal by extending an existing autism ontology to allow automatic inference of ASD phenotypes and Diagnostic & Statistical Manual of Mental Disorders (DSM) criteria based on subjects' Autism Diagnostic Interview-Revised (ADI-R) assessment data. Knowledge regarding diagnostic instruments, ASD phenotypes and risk factors was added to augment an existing autism ontology via Ontology Web Language class definitions and semantic web rules. We developed a custom Protégé plugin for enumerating combinatorial OWL axioms to support the many-to-many relations of ADI-R items to diagnostic categories in the DSM. We utilized a reasoner to infer whether 2642 subjects, whose data was obtained from the Simons Foundation Autism Research Initiative, meet DSM-IV-TR (DSM-IV) and DSM-5 diagnostic criteria based on their ADI-R data. We extended the ontology by adding 443 classes and 632 rules that represent phenotypes, along with their synonyms, environmental risk factors, and frequency of comorbidities. Applying the rules on the data set showed that the method produced accurate results: the true positive and true negative rates for inferring autistic disorder diagnosis according to DSM-IV criteria were 1 and 0.065, respectively; the true positive rate for inferring ASD based on DSM-5 criteria was 0.94. The ontology allows automatic inference of subjects' disease phenotypes and diagnosis with high accuracy. The ontology may benefit future studies by serving as a knowledge base for ASD. In addition, by adding knowledge of related NDDs, commonalities and differences in manifestations and risk factors could be automatically inferred, contributing to the understanding of ASD pathophysiology. Copyright © 2015 Elsevier Inc. All rights reserved.

Aggression in children with autism spectrum disorders and a clinic-referred comparison group

PubMed Central

Farmer, Cristan; Butter, Eric; Mazurek, Micah O.; Cowan, Charles; Lainhart, Janet; Cook, Edwin H.; DeWitt, Mary Beth; Aman, Michael

2015-01-01

A gap exists in the literature regarding aggression in autism spectrum disorders (ASD) and how this behavior compares to other groups. In this multisite study, the Children’s Scale for Hostility and Aggression: Reactive/Proactive (C-SHARP) and the Aggression subscale of the Child Behavior Checklist (CBCL) were rated for 414 children with ASD (Autistic Disorder, 69%; PDD-NOS, 24%; Asperger’s Disorder, 7%) and 243 clinic-referred children without ASD, aged 1-21 years (mean age about 7). Participants were not selected for aggressive behavior. Relative to the comparison group, children with ASD were reported to have less aggression and were more likely to be rated as reactive rather than proactive. Among all subjects, sex was not associated with aggression; higher IQ/adaptive behavior and older age were associated with more sophisticated types of aggression while lower scores on IQ, adaptive behavior, and communication measures were associated with more physical aggression. The interaction between demographic variables and diagnosis was significant only for age: younger but not older children with ASD showed less aggression than clinic-referred controls. PMID:24497627

LAMB1 polymorphism is associated with autism symptom severity in Korean autism spectrum disorder patients.

PubMed

Kim, Young Jong; Park, Jin Kyung; Kang, Won Sub; Kim, Su Kang; Park, Hae Jeong; Nam, Min; Kim, Jong Woo

2015-01-01

LAMB1 encodes laminin beta-1, which is expressed during early development of the human nervous system, and could be involved in the pathogenesis of neurodevelopmental disorders. In our study, we aimed to investigate whether single nucleotide polymorphisms (SNPs) in LAMB1 were associated with autism spectrum disorder (ASD) and with related clinical severities of ASD. Two coding SNPs (rs20556 and rs25659) and two intronic SNPs (rs2158836 and rs2237659) were compared between 180 patients with ASD and 147 healthy control subjects using direct sequencing. The Korean version of the Childhood Autism Rating Scale (K-CARS) was used to assess clinical severities. Multiple logistic regression models were employed to analyze genetic data, and associations with symptom severity were tested with the Kruskal-Wallis and the Mann-Whitney U tests. None of the four examined SNPs was associated with ASD risk. However, the GG genotype of rs2158836 was associated with more severe symptoms for the "object use" and "non-verbal communication" measures. The results of our study suggest the association between rs2158836 polymorphisms and symptom severity in ASD.

Transdiagnostic deviant facial recognition for implicit negative emotion in autism and schizophrenia.

PubMed

Ciaramidaro, Angela; Bölte, Sven; Schlitt, Sabine; Hainz, Daniela; Poustka, Fritz; Weber, Bernhard; Freitag, Christine; Walter, Henrik

2018-02-01

Impaired facial affect recognition (FAR) is observed in schizophrenia and autism spectrum disorder (ASD) and has been linked to amygdala and fusiform gyrus dysfunction. ASD patient's impairments seem to be more pronounced during implicit rather than explicit FAR, whereas for schizophrenia data are inconsistent. However, there are no studies comparing both patient groups in an identical design. The aim of this three-group study was to identify (i) whether FAR alterations are equally present in both groups, (ii) whether they are present rather during implicit or explicit FAR, (iii) and whether they are conveyed by similar or disorder-specific neural mechanisms. Using fMRI, we investigated neural activation during explicit and implicit negative and neutral FAR in 33 young-adult individuals with ASD, 20 subjects with paranoid-schizophrenia and 25 IQ- and gender-matched controls individuals. Differences in activation patterns between each clinical group and controls, respectively were found exclusively for implicit FAR in amygdala and fusiform gyrus. In addition, the ASD group additionally showed reduced activations in medial prefrontal cortex (PFC), bilateral dorso-lateral PFC, ventro-lateral PFC, posterior-superior temporal sulcus and left temporo-parietal junction. Although subjects with ASD showed more widespread altered activation patterns, a direct comparison between both patient groups did not show disorder-specific deficits in neither patient group. In summary, our findings are consistent with a common neural deficit during implicit negative facial affect recognition in schizophrenia and autism spectrum disorders. Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.

Immunological characterization and transcription profiling of peripheral blood (PB) monocytes in children with autism spectrum disorders (ASD) and specific polysaccharide antibody deficiency (SPAD): case study.

PubMed

Jyonouchi, Harumi; Geng, Lee; Streck, Deanna L; Toruner, Gokce A

2012-01-07

There exists a small subset of children with autism spectrum disorders (ASD) characterized by fluctuating behavioral symptoms and cognitive skills following immune insults. Some of these children also exhibit specific polysaccharide antibody deficiency (SPAD), resulting in frequent infection caused by encapsulated organisms, and they often require supplemental intravenous immunoglobulin (IVIG) (ASD/SPAD). This study assessed whether these ASD/SPAD children have distinct immunological findings in comparison with ASD/non-SPAD or non-ASD/SPAD children. We describe 8 ASD/SPAD children with worsening behavioral symptoms/cognitive skills that are triggered by immune insults. These ASD/SPAD children exhibited delayed type food allergy (5/8), treatment-resistant seizure disorders (4/8), and chronic gastrointestinal (GI) symptoms (5/8) at high frequencies. Control subjects included ASD children without SPAD (N = 39), normal controls (N = 37), and non-ASD children with SPAD (N = 12). We assessed their innate and adaptive immune responses, by measuring the production of pro-inflammatory and counter-regulatory cytokines by peripheral blood mononuclear cells (PBMCs) in responses to agonists of toll like receptors (TLR), stimuli of innate immunity, and T cell stimulants. Transcription profiling of PB monocytes was also assessed. ASD/SPAD PBMCs produced less proinflammatory cytokines with agonists of TLR7/8 (IL-6, IL-23), TLR2/6 (IL-6), TLR4 (IL-12p40), and without stimuli (IL-1ß, IL-6, and TNF-α) than normal controls. In addition, cytokine production of ASD/SPAD PBMCs in response to T cell mitogens (IFN-γ, IL-17, and IL-12p40) and candida antigen (Ag) (IL-10, IL-12p40) were less than normal controls. ASD/non-SPAD PBMDs revealed similar results as normal controls, while non-ASD/SPAD PBMCs revealed lower production of IL-6, IL-10 and IL-23 with a TLR4 agonist. Only common features observed between ASD/SPAD and non-ASD/SPAD children is lower IL-10 production in the absence of stimuli. Transcription profiling of PB monocytes revealed over a 2-fold up (830 and 1250) and down (653 and 1235) regulation of genes in ASD/SPAD children, as compared to normal (N = 26) and ASD/non-SPAD (N = 29) controls, respectively. Enriched gene expression of TGFBR (p < 0.005), Notch (p < 0.01), and EGFR1 (p < 0.02) pathways was found in the ASD/SPAD monocytes as compared to ASD/non-SPAD controls. The Immunological findings in the ASD/SPAD children who exhibit fluctuating behavioral symptoms and cognitive skills cannot be solely attributed to SPAD. Instead, these findings may be more specific for ASD/SPAD children with the above-described clinical characteristics, indicating a possible role of these immune abnormalities in their neuropsychiatric symptoms.

[Autism spectrum disorders and mu rhythm. A new neurophysiological view].

PubMed

Palau-Baduell, Montserrat; Valls-Santasusana, Antonio; Salvadó-Salvadó, Berta

2011-03-01

Electroencephalographic studies of subjects with autism spectrum disorders (ASD) provide evidences of brain functional aspects in this pathology. Mu rhythm can be reactive in normal population (mu suppression) to both self-movements and to movements performed by others. These reactivities are considered to be related to mirror neurons activity. Subjects with ASD show significant mu suppression to self-movements but they fail to react to the movements performed by others. These findings support the hypothesis of a dysfunctional mirror neurons system in individuals with ASD. Moreover, dysfunction of mirror neurons would be related to social and communicative impairments, cognitive deficits and impairment imitation skills associated with ASD.

Convergence of Genes and Cellular Pathways Dysregulated in Autism Spectrum Disorders

PubMed Central

Pinto, Dalila; Delaby, Elsa; Merico, Daniele; Barbosa, Mafalda; Merikangas, Alison; Klei, Lambertus; Thiruvahindrapuram, Bhooma; Xu, Xiao; Ziman, Robert; Wang, Zhuozhi; Vorstman, Jacob A.S.; Thompson, Ann; Regan, Regina; Pilorge, Marion; Pellecchia, Giovanna; Pagnamenta, Alistair T.; Oliveira, Bárbara; Marshall, Christian R.; Magalhaes, Tiago R.; Lowe, Jennifer K.; Howe, Jennifer L.; Griswold, Anthony J.; Gilbert, John; Duketis, Eftichia; Dombroski, Beth A.; De Jonge, Maretha V.; Cuccaro, Michael; Crawford, Emily L.; Correia, Catarina T.; Conroy, Judith; Conceição, Inês C.; Chiocchetti, Andreas G.; Casey, Jillian P.; Cai, Guiqing; Cabrol, Christelle; Bolshakova, Nadia; Bacchelli, Elena; Anney, Richard; Gallinger, Steven; Cotterchio, Michelle; Casey, Graham; Zwaigenbaum, Lonnie; Wittemeyer, Kerstin; Wing, Kirsty; Wallace, Simon; van Engeland, Herman; Tryfon, Ana; Thomson, Susanne; Soorya, Latha; Rogé, Bernadette; Roberts, Wendy; Poustka, Fritz; Mouga, Susana; Minshew, Nancy; McInnes, L. Alison; McGrew, Susan G.; Lord, Catherine; Leboyer, Marion; Le Couteur, Ann S.; Kolevzon, Alexander; Jiménez González, Patricia; Jacob, Suma; Holt, Richard; Guter, Stephen; Green, Jonathan; Green, Andrew; Gillberg, Christopher; Fernandez, Bridget A.; Duque, Frederico; Delorme, Richard; Dawson, Geraldine; Chaste, Pauline; Café, Cátia; Brennan, Sean; Bourgeron, Thomas; Bolton, Patrick F.; Bölte, Sven; Bernier, Raphael; Baird, Gillian; Bailey, Anthony J.; Anagnostou, Evdokia; Almeida, Joana; Wijsman, Ellen M.; Vieland, Veronica J.; Vicente, Astrid M.; Schellenberg, Gerard D.; Pericak-Vance, Margaret; Paterson, Andrew D.; Parr, Jeremy R.; Oliveira, Guiomar; Nurnberger, John I.; Monaco, Anthony P.; Maestrini, Elena; Klauck, Sabine M.; Hakonarson, Hakon; Haines, Jonathan L.; Geschwind, Daniel H.; Freitag, Christine M.; Folstein, Susan E.; Ennis, Sean; Coon, Hilary; Battaglia, Agatino; Szatmari, Peter; Sutcliffe, James S.; Hallmayer, Joachim; Gill, Michael; Cook, Edwin H.; Buxbaum, Joseph D.; Devlin, Bernie; Gallagher, Louise; Betancur, Catalina; Scherer, Stephen W.

2014-01-01

Rare copy-number variation (CNV) is an important source of risk for autism spectrum disorders (ASDs). We analyzed 2,446 ASD-affected families and confirmed an excess of genic deletions and duplications in affected versus control groups (1.41-fold, p = 1.0 × 10−5) and an increase in affected subjects carrying exonic pathogenic CNVs overlapping known loci associated with dominant or X-linked ASD and intellectual disability (odds ratio = 12.62, p = 2.7 × 10−15, ∼3% of ASD subjects). Pathogenic CNVs, often showing variable expressivity, included rare de novo and inherited events at 36 loci, implicating ASD-associated genes (CHD2, HDAC4, and GDI1) previously linked to other neurodevelopmental disorders, as well as other genes such as SETD5, MIR137, and HDAC9. Consistent with hypothesized gender-specific modulators, females with ASD were more likely to have highly penetrant CNVs (p = 0.017) and were also overrepresented among subjects with fragile X syndrome protein targets (p = 0.02). Genes affected by de novo CNVs and/or loss-of-function single-nucleotide variants converged on networks related to neuronal signaling and development, synapse function, and chromatin regulation. PMID:24768552

Absence of age-related prefrontal NAA change in adults with autism spectrum disorders

PubMed Central

Aoki, Y; Abe, O; Yahata, N; Kuwabara, H; Natsubori, T; Iwashiro, N; Takano, Y; Inoue, H; Kawakubo, Y; Gonoi, W; Sasaki, H; Murakami, M; Katsura, M; Nippashi, Y; Takao, H; Kunimatsu, A; Matsuzaki, H; Tsuchiya, K J; Kato, N; Kasai, K; Yamasue, H

2012-01-01

Atypical trajectory of brain growth in autism spectrum disorders (ASDs) has been recognized as a potential etiology of an atypical course of behavioral development. Numerous neuroimaging studies have focused on childhood to investigate atypical age-related change of brain structure and function, because it is a period of neuron and synapse maturation. Recent studies, however, have shown that the atypical age-related structural change of autistic brain expands beyond childhood and constitutes neural underpinnings for lifelong difficulty to behavioral adaptation. Thus, we examined effects of aging on neurochemical aspects of brain maturation using 3-T proton magnetic resonance spectroscopy (1H-MRS) with single voxel in the medial prefrontal cortex (PFC) in 24 adult men with non-medicated high-functioning ASDs and 25 age-, IQ- and parental-socioeconomic-background-matched men with typical development (TD). Multivariate analyses of covariance demonstrated significantly high N-acetylaspartate (NAA) level in the ASD subjects compared with the TD subjects (F=4.83, P=0.033). The low NAA level showed a significant positive correlation with advanced age in the TD group (r=−0.618, P=0.001), but was not evident among the ASD individuals (r=0.258, P=0.223). Fisher's r-to-z transformation showed a significant difference in the correlations between the ASD and TD groups (Z=−3.23, P=0.001), which indicated that the age–NAA relationship was significantly specific to people with TD. The current 1H-MRS study provided new evidence that atypical age-related change of neurochemical aspects of brain maturation in ASD individuals expands beyond childhood and persists during adulthood. PMID:23092982

Blood-brain barrier and intestinal epithelial barrier alterations in autism spectrum disorders.

PubMed

Fiorentino, Maria; Sapone, Anna; Senger, Stefania; Camhi, Stephanie S; Kadzielski, Sarah M; Buie, Timothy M; Kelly, Deanna L; Cascella, Nicola; Fasano, Alessio

2016-01-01

Autism spectrum disorders (ASD) are complex conditions whose pathogenesis may be attributed to gene-environment interactions. There are no definitive mechanisms explaining how environmental triggers can lead to ASD although the involvement of inflammation and immunity has been suggested. Inappropriate antigen trafficking through an impaired intestinal barrier, followed by passage of these antigens or immune-activated complexes through a permissive blood-brain barrier (BBB), can be part of the chain of events leading to these disorders. Our goal was to investigate whether an altered BBB and gut permeability is part of the pathophysiology of ASD. Postmortem cerebral cortex and cerebellum tissues from ASD, schizophrenia (SCZ), and healthy subjects (HC) and duodenal biopsies from ASD and HC were analyzed for gene and protein expression profiles. Tight junctions and other key molecules associated with the neurovascular unit integrity and function and neuroinflammation were investigated. Claudin ( CLDN )-5 and -12 were increased in the ASD cortex and cerebellum. CLDN-3 , tricellulin , and MMP-9 were higher in the ASD cortex. IL-8 , tPA , and IBA-1 were downregulated in SCZ cortex; IL-1b was increased in the SCZ cerebellum. Differences between SCZ and ASD were observed for most of the genes analyzed in both brain areas. CLDN-5 protein was increased in ASD cortex and cerebellum, while CLDN-12 appeared reduced in both ASD and SCZ cortexes. In the intestine, 75% of the ASD samples analyzed had reduced expression of barrier-forming TJ components ( CLDN-1 , OCLN , TRIC ), whereas 66% had increased pore-forming CLDNs ( CLDN-2 , -10 , -15 ) compared to controls. In the ASD brain, there is an altered expression of genes associated with BBB integrity coupled with increased neuroinflammation and possibly impaired gut barrier integrity. While these findings seem to be specific for ASD, the possibility of more distinct SCZ subgroups should be explored with additional studies.

Dynamic characteristic mechanism of atrial septal defect using real-time three-dimensional echocardiography and evaluation of right ventricular functions.

PubMed

Sharen, Gao-Wa; Zhang, Jun; Qin, Chuan; Lv, Qing

2017-02-01

The dynamic characteristics of the area of the atrial septal defect (ASD) were evaluated using the technique of real-time three-dimensional echocardiography (RT 3DE), the potential factors responsible for the dynamic characteristics of the area of ASD were observed, and the overall and local volume and functions of the patients with ASD were measured. RT 3DE was performed on the 27 normal controls and 28 patients with ASD. Based on the three-dimensional data workstations, the area of ASD was measured at P wave vertex, R wave vertex, T wave starting point, and T wave terminal point and in the T-P section. The right atrial volume in the same time phase of the cardiac cycle and the motion displacement distance of the tricuspid annulus in the corresponding period were measured. The measured value of the area of ASD was analyzed. The changes in the right atrial volume and the motion displacement distance of the tricuspid annulus in the normal control group and the ASD group were compared. The right ventricular ejection fractions in the normal control group and the ASD group were compared using the RT 3DE long-axis eight-plane (LA 8-plane) method. Real-time three-dimensional volume imaging was performed in the normal control group and ASD group (n=30). The right ventricular inflow tract, outflow tract, cardiac apex muscular trabecula dilatation, end-systolic volume, overall dilatation, end-systolic volume, and appropriate local and overall ejection fractions in both two groups were measured with the four-dimensional right ventricular quantitative analysis method (4D RVQ) and compared. The overall right ventricular volume and the ejection fraction measured by the LA 8-plane method and 4D RVQ were subjected to a related analysis. Dynamic changes occurred to the area of ASD in the cardiac cycle. The rules for dynamic changes in the area of ASD and the rules for changes in the right atrial volume in the cardiac cycle were consistent. The maximum value of the changes in the right atrial volume occurred in the end-systolic period when the peak of the curve appeared. The minimum value of the changes occurred in the end-systolic period and was located at the lowest point of the volume variation curve. The area variation curve for ASD and the motion variation curve for the tricuspid annulus in the cardiac cycle were the same. The displacement of the tricuspid annulus exhibited directionality. The measured values of the area of ASD at P wave vertex, R wave vertex, T wave starting point, T wave terminal point and in the T-P section were properly correlated with the right atrial volume (P<0.001). The area of ASD and the motion displacement distance of the tricuspid annulus were negatively correlated (P<0.05). The right atrial volumes in the ASD group in the cardiac cycle in various time phases increased significantly as compared with those in the normal control group (P=0.0001). The motion displacement distance of the tricuspid annulus decreased significantly in the ASD group as compared with that in the normal control group (P=0.043). The right ventricular ejection fraction in the ASD group was lower than that in the normal control group (P=0.032). The ejection fraction of the cardiac apex trabecula of the ASD patients was significantly lower than the ejection fractions of the right ventricular outflow tract and inflow tract and overall ejection fraction. The difference was statistically significant (P=0.005). The right ventricular local and overall dilatation and end-systolic volumes in the ASD group increased significantly as compared with those in the normal control group (P=0.031). The aRVEF and the overall ejection fraction decreased in the ASD group as compared with those in the normal control group (P=0.0005). The dynamic changes in the area of ASD and the motion curves for the right atrial volume and tricuspid annulus have the same dynamic characteristics. RT 3DE can be used to accurately evaluate the local and overall volume and functions of the right ventricle. The local and overall volume loads of the right ventricle in the ASD patients increase significantly as compared with those of the normal people. The right ventricular cardiac apex and the overall systolic function decrease.

Concordance of DSM-5 and DSM-IV-TR classifications for autism spectrum disorder.

PubMed

Ohashi, Kei; Mizuno, Yoshifumi; Miyachi, Taishi; Asai, Tomoko; Imaeda, Masayuki; Saitoh, Shinji

2015-12-01

The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) was published in May 2013. Autism spectrum disorder (ASD) has been structured for the three subtypes of pervasive developmental disorder (PDD), but the number of impairment in social and communication dimension is not stated. The subjects were 68 children who visited the Department of Psychology and Development at Nagoya City University Hospital for the first time between the ages of 6 and 15 years old. We retrospectively re-examined the subjects using DSM-IV-TR criteria and DSM-5 criteria with two rules (two of three and one of three on the social and communication dimension) and examined the concordance rate. Forty subjects were diagnosed with PDD, and 28 were not. The mean PDD subject age was 9.4 years, and mean IQ was 84.0 on the Wechsler Intelligence Scale for Children III or 62.7 on the Tanaka-Binet test. Twenty-seven (68%) of the PDD subjects were classified with ASD using DSM-5 criteria when the two of three rule was applied, while 32 (80%) were classified with ASD when the one of three rule was applied. All subjects without PDD were not diagnosed with ASD on DSM-5 criteria. DSM-5 criteria may exclude high functioning and older subjects from ASD because they tend to be atypical. The diagnostic procedure for DSM-5 criteria is ambiguous, especially in high functioning subjects and those diagnosed at an older age. © 2015 Japan Pediatric Society.

[INVITED] Non-intrusive optical imaging of face to probe physiological traits in Autism Spectrum Disorder

NASA Astrophysics Data System (ADS)

Samad, Manar D.; Bobzien, Jonna L.; Harrington, John W.; Iftekharuddin, Khan M.

2016-03-01

Autism Spectrum Disorders (ASD) can impair non-verbal communication including the variety and extent of facial expressions in social and interpersonal communication. These impairments may appear as differential traits in the physiology of facial muscles of an individual with ASD when compared to a typically developing individual. The differential traits in the facial expressions as shown by facial muscle-specific changes (also known as 'facial oddity' for subjects with ASD) may be measured visually. However, this mode of measurement may not discern the subtlety in facial oddity distinctive to ASD. Earlier studies have used intrusive electrophysiological sensors on the facial skin to gauge facial muscle actions from quantitative physiological data. This study demonstrates, for the first time in the literature, novel quantitative measures for facial oddity recognition using non-intrusive facial imaging sensors such as video and 3D optical cameras. An Institutional Review Board (IRB) approved that pilot study has been conducted on a group of individuals consisting of eight participants with ASD and eight typically developing participants in a control group to capture their facial images in response to visual stimuli. The proposed computational techniques and statistical analyses reveal higher mean of actions in the facial muscles of the ASD group versus the control group. The facial muscle-specific evaluation reveals intense yet asymmetric facial responses as facial oddity in participants with ASD. This finding about the facial oddity may objectively define measurable differential markers in the facial expressions of individuals with ASD.

Gender Variance Among Youth with Autism Spectrum Disorders: A Retrospective Chart Review.

PubMed

Janssen, Aron; Huang, Howard; Duncan, Christina

2016-01-01

Purpose: Increasing clinical evidence suggests an overrepresentation of gender variance (GV) among patients with autism spectrum disorders (ASDs). This retrospective chart review aims to contribute to the existing literature on co-occurring ASD and gender dysphoria (GD). We compare the rate of parent-reported GV in patients with an ASD diagnosis to that of parent-reported GV in a normative nonreferred data set. Methods: Child Behavior Checklist (CBCL) charts were collected from 492 children and adolescents (409 natal males and 83 natal females) aged 6-18 years who have received a diagnosis of ASD at the New York University Child Study Center. Parent-reported GV was determined through endorsement of CBCL sex item 110, which assesses the presence of gender-related issues. We calculated the odds ratio of endorsement of item 110 between our ASD sample and the CBCL sample data. Results: The subjects diagnosed with ASD were 7.76 times more likely to report GV than the CBCL sample. This finding was statistically significant. About 5.1% of the patients in the ASD group and 0.7% of the CBCL nonreferred group endorsed sex item 110. 5.1% of natal males and 4.8% of natal females endorsed sex item 110. Neither gender nor age influenced the rate of endorsement. Conclusion: This finding supports the growing research suggesting a heightened co-occurrence rate of ASD and GD. Focus should be placed upon improving our understanding of the nature of this co-occurrence and on gender identity development within the atypical development of ASD.

Altered microstructural connectivity of the superior cerebellar peduncle is related to motor dysfunction in children with autistic spectrum disorders.

PubMed

Hanaie, Ryuzo; Mohri, Ikuko; Kagitani-Shimono, Kuriko; Tachibana, Masaya; Azuma, Junji; Matsuzaki, Junko; Watanabe, Yoshiyuki; Fujita, Norihiko; Taniike, Masako

2013-10-01

Many studies have reported motor impairments in autistic spectrum disorders (ASD). However, the brain mechanism underlying motor impairment in ASD remains unclear. Recent neuroimaging studies have suggested that underconnectivity between the cerebellum and other brain regions contributes to the features of ASD. In this study, we investigated the microstructural integrity of the cerebellar pathways, including the superior, middle, and inferior cerebellar peduncles, of children with and without ASD by using diffusion tensor imaging (DTI) tractography to determine whether the microstructural integrity of the cerebellar pathways is related to motor function in children with ASD. Thirteen children with ASD and 11 age-, gender-, handedness-, and IQ-matched typically developing (TD) controls were enrolled in this study. DTI outcome measurements, such as fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD), for the cerebellar pathways were calculated. The Movement Assessment Battery for Children 2 (M-ABC 2) was used for assessing motor functions. There were no significant differences between the two groups in RD. However, compared to the TD subjects, patients with ASD had a significantly lower FA in the right superior cerebellar peduncle and lower AD in the left superior cerebellar peduncle, in addition to a significantly lower score in ball skills and the total test score of M-ABC 2. There was a significant positive correlation between the total test score of M-ABC 2 and FA in the right superior cerebellar peduncle in the ASD group. These findings suggest that the altered microstructural integrity of the superior cerebellar peduncle may be related to motor impairment in ASD.

[Psychometric attributes of the Spanish version of A-TAC screening scale for autism spectrum disorders].

PubMed

Cubo, E; Sáez Velasco, S; Delgado Benito, V; Ausín Villaverde, V; García Soto, X R; Trejo Gabriel Y Galán, J M; Martín Santidrián, A; Macarrón, J V; Cordero Guevara, J; Benito-León, J; Louis, E D

2011-07-01

As there are no biological markers for Autism Spectrum Disorders (ASD), screening must focus on behaviour and the presence of a markedly abnormal development or a deficiency in verbal and non-verbal social interaction and communication. To evaluate the psychometric attributes of a Spanish version of the autism domain of the Autism-Tics, AD/HD and other Comorbidities Inventory (A-TAC) scale for ASD screening. A total of 140 subjects (43% male, 57% female) aged 6-16, with ASD (n=15), Mental Retardation (n=40), Psychiatric Illness (n=22), Tics (n=12) and controls (n=51), were included for ASD screening. The predictive validity, acceptability, scale assumptions, internal consistency, and precision were analysed. The internal consistency was high (α=0.93), and the standard error was adequate (1.13 [95% CI, -1.08 a 3.34]). The mean scores of the Autism module were higher in patients diagnosed with ASD and mental disability compared to the rest of the patients (P<.001). The area under the curve was 0.96 for the ASD group. The autism domain of the A-TAC scale seems to be a reliable, valid and precise tool for ASD screening in the Spanish school population. Copyright © 2010 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Abnormal Cortical Plasticity in Youth with Autism Spectrum Disorder: A Transcranial Magnetic Stimulation Case-Control Pilot Study.

PubMed

Pedapati, Ernest V; Gilbert, Donald L; Erickson, Craig A; Horn, Paul S; Shaffer, Rebecca C; Wink, Logan K; Laue, Cameron S; Wu, Steve W

2016-09-01

This case-control study investigated the use of a low-intensity repetitive transcranial magnetic stimulation (rTMS) protocol to measure motor cortex (M1) plasticity in youth with autism spectrum disorder (ASD) compared with typically developing children (TDC). We hypothesized that impairments in long-term potentiation-like properties represent a neurophysiological biomarker of abnormal cortical function in ASD. We studied youth with ASD aged 11-18 years and matched controls (TDC). Intermittent theta burst stimulation (iTBS) was delivered to the dominant M1 at an intensity of 70% of resting motor threshold. Suprathreshold single-pulse TMS was performed to compare amplitudes of motor-evoked potentials (MEP) measured from surface electromyography electrodes on a target muscle before (20 pulses) and after (10 pulses/time point) iTBS at predefined timepoints (up to 30 minutes) to measure any potentiation effects. A linear mixed model was used to examine group differences in MEP amplitudes over time following iTBS. Nine youth with ASD (mean age 15.6; 7 males; 6 right-hand dominant) and 9 TDC (mean age 14.5; 5 males; 9 right-hand dominant) participated. All subjects tolerated the procedure well. Both groups had a mean increase in excitability after iTBS for 30 minutes; however, the time course of excitability changes differed (F9,144 = 2.05; p = 0.038). Post-hoc testing identified a significant decrease in amplitude of the ASD group at 20 minutes following iTBS compared with the TDC after correcting for multiple comparisons. In this study, we demonstrate early evidence for a potential physiological biomarker of cortical plasticity in youth with ASD using a rapid low-intensity rTMS protocol with a discriminate measure at 20 minutes following stimulation. The procedure was well tolerated by all 18 participants. Future work will include modification of the protocol to improve the ability to distinguish subtypes of ASD based on behavioral and cognitive testing.

Disruption of Neurexin 1 Associated with Autism Spectrum Disorder

PubMed Central

Kim, Hyung-Goo; Kishikawa, Shotaro; Higgins, Anne W.; Seong, Ihn-Sik; Donovan, Diana J.; Shen, Yiping; Lally, Eric; Weiss, Lauren A.; Najm, Juliane; Kutsche, Kerstin; Descartes, Maria; Holt, Lynn; Braddock, Stephen; Troxell, Robin; Kaplan, Lee; Volkmar, Fred; Klin, Ami; Tsatsanis, Katherine; Harris, David J.; Noens, Ilse; Pauls, David L.; Daly, Mark J.; MacDonald, Marcy E.; Morton, Cynthia C.; Quade, Bradley J.; Gusella, James F.

2008-01-01

Autism is a neurodevelopmental disorder of complex etiology in which genetic factors play a major role. We have implicated the neurexin 1 (NRXN1) gene in two independent subjects who display an autism spectrum disorder (ASD) in association with a balanced chromosomal abnormality involving 2p16.3. In the first, with karyotype 46,XX,ins(16;2)(q22.1;p16.1p16.3)pat, NRXN1 is directly disrupted within intron 5. Importantly, the father possesses the same chromosomal abnormality in the absence of ASD, indicating that the interruption of α-NRXN1 is not fully penetrant and must interact with other factors to produce ASD. The breakpoint in the second subject, with 46,XY,t(1;2)(q31.3;p16.3)dn, occurs ∼750 kb 5′ to NRXN1 within a 2.6 Mb genomic segment that harbors no currently annotated genes. A scan of the NRXN1 coding sequence in a cohort of ASD subjects, relative to non-ASD controls, revealed that amino acid alterations in neurexin 1 are not present at high frequency in ASD. However, a number of rare sequence variants in the coding region, including two missense changes in conserved residues of the α-neurexin 1 leader sequence and of an epidermal growth factor (EGF)-like domain, respectively, suggest that even subtle changes in NRXN1 might contribute to susceptibility to ASD. PMID:18179900

Abnormal transsulfuration metabolism and reduced antioxidant capacity in Chinese children with autism spectrum disorders.

PubMed

Han, Yu; Xi, Qian-qian; Dai, Wei; Yang, Shu-han; Gao, Lei; Su, Yuan-yuan; Zhang, Xin

2015-11-01

Autism spectrum disorder (ASD) is a neurological disorder that presents a spectrum of qualitative impairments in social interaction, communication, as well as restricted and stereotyped behavioral patterns, interests, and activities. Several studies have suggested that the etiology of ASD can be partly explained by oxidative stress. However, the implications of abnormal transsulfuration metabolism and oxidative stress, and their relation with ASD are still unclear. The purpose of this study was to evaluate several transsulfuration pathway metabolites in Chinese participants diagnosed with ASD, to better understand their role in the etiology of this disorder. Fifty children (39 male, 11 female) diagnosed with ASD and 50 age- and gender-matched non-ASD children (i.e., control group) were included in this study. This prospective blinded study was undertaken to assess transsulfuration and oxidative metabolites, including levels of homocysteine (Hcy), cysteine (Cys), total glutathione (tGSH), reduced glutathione (GSH), oxidized glutathione (GSSG), and glutathione ratio (GSH/GSSG). The clinical severity of ASD was evaluated with the Childhood Autism Rating Scale (CARS), and the autistic children's present behavior was measured by the Autism Behavior Checklist (ABC). The results indicated that Hcy and GSSG levels were significantly higher in children diagnosed with ASD, Cys, tGSH and GSH levels as well as the GSH/GSSG ratio showed remarkably lower values in ASD children compared to control subjects. Hcy levels correlated significantly with increasing CARS scores and GSSG levels in children with ASD. Our results suggest that an abnormal transsulfuration metabolism and reduced antioxidant capacity (i.e., hyperhomocysteinemia and increased oxidative stress), and Hcy level appears to have a potentially negative impact on clinical severity of autistic disorder. Copyright © 2015 Elsevier Ltd. All rights reserved.

Associations of acute and chronic stress hormones with cognitive functions in autism spectrum disorder.

PubMed

Ogawa, Shino; Lee, Young-A; Yamaguchi, Yoshie; Shibata, Yuka; Goto, Yukiori

2017-02-20

Extensive studies have reported cognitive abnormalities in neurodevelopmental disorders, such as autism spectrum disorder (ASD). Another line of evidence suggests that stress also affects cognitive functions. In this study, we investigated whether there were associations between stress hormones and cognitive functions in ASD and typically developing (TD) children. Cognitive functions in ASD and TD children were evaluated with a battery of psychological tests for working memory, behavioral flexibility, and social cognition for emotional assessments of others. ASD children exhibited higher hair and salivary cortisol, which reflects chronic and acute stress hormone levels of subjects, respectively, than TD children. Autism-spectrum quotient (AQ) was positively correlated with hair cortisol and the scores of Spence Children's Anxiety Scale in ASD children. In addition, a negative correlation was present between spatial working memory performance and hair cortisol in ASD, but not in TD, children. These results suggest that chronic stress hormone elevation may have relationships with some aspects of cognitive dysfunction in ASD subjects. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Influence of sleep disorders on the behavior of individuals with autism spectrum disorder

PubMed Central

Fadini, Cintia C.; Lamônica, Dionísia A.; Fett-Conte, Agnes C.; Osório, Elaine; Zuculo, Gabriela M.; Giacheti, Célia M.; Pinato, Luciana

2015-01-01

The aim of this study was to investigate the correlation between sleep disorders and the behavior of subjects with autism spectrum disorder (ASD) and control subjects using specific questionnaires. A small percentage (1.8%) of the control subjects had symptoms indicative of sleep-breathing disorders (SBD) and nocturnal sweating. Fifty-nine percent of the subjects with ASD had symptoms indicative of at least one sleep disorder, with SBD the most commonly reported (38%). In the control group, the symptoms of SBD were correlated with social, thought, attentional, aggression, externalizing and behavioral problems. In the ASD group, disorders of arousal (DA) were correlated with thinking problems, and disorders of excessive somnolence were correlated with thinking and behavioral problems. These results suggest that children and adolescents with ASD have a high frequency of sleep disorders, which in turn correlate with some of the behavioral traits that they already exhibit. Furthermore, sleep disturbances, when present in the typically developing children, also correlated with behavioral problems. PMID:26150777

Addressing dental fear in children with autism spectrum disorders: a randomized controlled pilot study using electronic screen media.

PubMed

Isong, Inyang A; Rao, Sowmya R; Holifield, Chloe; Iannuzzi, Dorothea; Hanson, Ellen; Ware, Janice; Nelson, Linda P

2014-03-01

Dental care is a significant unmet health care need for children with autism spectrum disorders (ASD). Many children with ASD do not receive dental care because of fear associated with dental procedures; oftentimes they require general anesthesia for regular dental procedures, placing them at risk of associated complications. Many children with ASD have a strong preference for visual stimuli, particularly electronic screen media. The use of visual teaching materials is a fundamental principle in designing educational programs for children with ASD. To determine if an innovative strategy using 2 types of electronic screen media was feasible and beneficial in reducing fear and uncooperative behaviors in children with ASD undergoing dental visits. We conducted a randomized controlled trial at Boston Children's Hospital dental clinic. Eighty (80) children aged 7 to 17 years with a known diagnosis of ASD and history of dental fear were enrolled in the study. Each child completed 2 preventive dental visits that were scheduled 6 months apart (visit 1 and visit 2). After visit 1, subjects were randomly assigned to 1 of 4 groups: (1) group A, control (usual care); (2) group B, treatment (video peer modeling that involved watching a DVD recording of a typically developing child undergoing a dental visit); (3) group C, treatment (video goggles that involved watching a favorite movie during the dental visit using sunglass-style video eyewear); and (4) group D, treatment (video peer modeling plus video goggles). Subjects who refused or were unable to wear the goggles watched the movie using a handheld portable DVD player. During both visits, the subject's level of anxiety and behavior were measured using the Venham Anxiety and Behavior Scales. Analyses of variance and Fisher's exact tests compared baseline characteristics across groups. Using intention to treat approach, repeated measures analyses were employed to test whether the outcomes differed significantly: (1) between visits 1 and 2 within each group and (2) between each intervention group and the control group over time (an interaction). Between visits 1 and 2, mean anxiety and behavior scores decreased significantly by 0.8 points (P = .03) for subjects within groups C and D. Significant changes were not observed within groups A and B. Mean anxiety and behavior scores did not differ significantly between groups over time, although group A versus C pairwise comparisons showed a trend toward significance (P = .06). These findings suggest that certain electronic screen media technologies may be useful tools for reducing fear and uncooperative behaviors among children with ASD undergoing dental visits. Further studies are needed to assess the efficacy of these strategies using larger sample sizes. Findings from future studies could be relevant for nondental providers who care for children with ASD in other medical settings.

Visual systemizing preference in children with autism: A randomized controlled trial of intranasal oxytocin.

PubMed

Strathearn, Lane; Kim, Sohye; Bastian, D Anthony; Jung, Jennifer; Iyengar, Udita; Martinez, Sheila; Goin-Kochel, Robin P; Fonagy, Peter

2018-05-01

Several studies have suggested that the neuropeptide oxytocin may enhance aspects of social communication in autism. Little is known, however, about its effects on nonsocial manifestations, such as restricted interests and repetitive behaviors. In the empathizing-systemizing theory of autism, social deficits are described along the continuum of empathizing ability, whereas nonsocial aspects are characterized in terms of an increased preference for patterned or rule-based systems, called systemizing. We therefore developed an automated eye-tracking task to test whether children and adolescents with autism spectrum disorder (ASD) compared to matched controls display a visual preference for more highly organized and structured (systemized) real-life images. Then, as part of a randomized, double-blind, placebo-controlled crossover study, we examined the effect of intranasal oxytocin on systemizing preferences in 16 male children with ASD, compared with 16 matched controls. Participants viewed 14 slides, each containing four related pictures (e.g., of people, animals, scenes, or objects) that differed primarily on the degree of systemizing. Visual systemizing preference was defined in terms of the fixation time and count for each image. Unlike control subjects who showed no gaze preference, individuals with ASD preferred to fixate on more highly systemized pictures. Intranasal oxytocin eliminated this preference in ASD participants, who now showed a similar response to control subjects on placebo. In contrast, control participants increased their visual preference for more systemized images after receiving oxytocin versus placebo. These results suggest that, in addition to its effects on social communication, oxytocin may play a role in some of the nonsocial manifestations of autism.

Anatomical differences in the mirror neuron system and social cognition network in autism.

PubMed

Hadjikhani, Nouchine; Joseph, Robert M; Snyder, Josh; Tager-Flusberg, Helen

2006-09-01

Autism spectrum disorder (ASD) is a neurodevelopmental disorder associated with impaired social and emotional skills, the anatomical substrate of which is still unknown. In this study, we compared a group of 14 high-functioning ASD adults with a group of controls matched for sex, age, intelligence quotient, and handedness. We used an automated technique of analysis that accurately measures the thickness of the cerebral cortex and generates cross-subject statistics in a coordinate system based on cortical anatomy. We found local decreases of gray matter in the ASD group in areas belonging to the mirror neuron system (MNS), argued to be the basis of empathic behavior. Cortical thinning of the MNS was correlated with ASD symptom severity. Cortical thinning was also observed in areas involved in emotion recognition and social cognition. These findings suggest that the social and emotional deficits characteristic of autism may reflect abnormal thinning of the MNS and the broader network of cortical areas subserving social cognition.

Brain dynamics in ASD during movie-watching show idiosyncratic functional integration and segregation.

PubMed

Bolton, Thomas A W; Jochaut, Delphine; Giraud, Anne-Lise; Van De Ville, Dimitri

2018-06-01

To refine our understanding of autism spectrum disorders (ASD), studies of the brain in dynamic, multimodal and ecological experimental settings are required. One way to achieve this is to compare the neural responses of ASD and typically developing (TD) individuals when viewing a naturalistic movie, but the temporal complexity of the stimulus hampers this task, and the presence of intrinsic functional connectivity (FC) may overshadow movie-driven fluctuations. Here, we detected inter-subject functional correlation (ISFC) transients to disentangle movie-induced functional changes from underlying resting-state activity while probing FC dynamically. When considering the number of significant ISFC excursions triggered by the movie across the brain, connections between remote functional modules were more heterogeneously engaged in the ASD population. Dynamically tracking the temporal profiles of those ISFC changes and tying them to specific movie subparts, this idiosyncrasy in ASD responses was then shown to involve functional integration and segregation mechanisms such as response inhibition, background suppression, or multisensory integration, while low-level visual processing was spared. Through the application of a new framework for the study of dynamic experimental paradigms, our results reveal a temporally localized idiosyncrasy in ASD responses, specific to short-lived episodes of long-range functional interplays. © 2018 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Mirror neuron dysfunction in autism spectrum disorders.

PubMed

Perkins, Tom; Stokes, Mark; McGillivray, Jane; Bittar, Richard

2010-10-01

Autism spectrum disorders (ASDs) are developmental conditions characterized by deficits in social interaction, verbal and nonverbal communication and obsessive/stereotyped patterns of behaviour. Although there is no reliable neurophysiological marker associated with ASDs, dysfunction of the parieto-frontal mirror neuron system has been suggested as a disturbance linked to the disorder. Mirror neurons (MNs) are visuomotor neurons which discharge both when performing and observing a goal directed action. Research suggests MNs may have a role in imitation, empathy, theory of mind and language. Although the research base is small, evidence from functional MRI, transcranial magnetic stimulation, and an electroencephalographic component called the mu rhythm suggests MNs are dysfunctional in subjects with ASD. These deficits are more pronounced when ASD subjects complete tasks with social relevance, or that are emotional in nature. Promising research has identified that interventions targeting MN related functions such as imitation can improve social functioning in ASDs. Boosting the function of MNs may improve the prognosis of ASDs, and contribute to diagnostic clarity. Copyright 2010 Elsevier Ltd. All rights reserved.

Screening for autism identifies behavioral disorders in children functional defecation disorders.

PubMed

Kuizenga-Wessel, Sophie; Di Lorenzo, Carlo; Nicholson, Lisa M; Butter, Eric M; Ratliff-Schaub, Karen L; Benninga, Marc A; Williams, Kent C

2016-10-01

This study prospectively assessed whether positive screening surveys for autism spectrum disorders (ASDs) in children with functional defecation disorders (FDDs) accurately identify ASD. Parents of children (4-12 years) who met Rome III criteria for functional constipation (FC), FC with fecal incontinence (FI) and functional nonretentive FI (FNRFI) completed two ASD screening surveys. Children with positive screens were referred for psychological evaluation, and a year later, follow-up surveys were conducted. Of the 97 study participants, 30.9 % were diagnosed with FC, 62.9 % with FC with FI, and 6.2 % with FNRFI. ASD surveys were positive for 27 children (27.8 %). New DSM diagnoses were made in 10 out of the 15 children that completed further evaluation. Two (2.1 %) met criteria for ASD, and 12 (12.4 %) met criteria for other behavioral disorders. Average SRS and SCQ-L scores were higher in subjects with FC with FI as compared to FC alone and in those who reported no improvement versus those who reported improvement 1 year later. While positive ASD screening surveys did not correctly identify ASD in the majority, it did help to identify other unrecognized behavioral disorders in children with FDD. High screening scores were more common in children with FC with FI and in children with poorer responses to current medical treatments. •A prior study found that 29 % of children with FDD scored positive on ASD screening questionnaires. •Whether positive screens correctly identify ASD in children with FDD is unknown. What is New: •This study shows that positive ASD screens do not correctly identify ASD in children with FDD. However, the use of ASD screening questionnaires can identify previously unrecognized and untreated behavioral/developmental disorders in children with FDD. •High screening scores are more common in children with FC with FI and in children with poorer responses to current medical treatments.

Can you see it too? Observed and self-rated participation in mainstream schools in students with and without autism spectrum disorders.

PubMed

Falkmer, Marita; Oehlers, Kirsty; Granlund, Mats; Falkmer, Torbjörn

2015-01-01

To examine the degree to which observations can capture perception of participation, observed and self-rated levels of interactions for students with and without autism spectrum disorders (ASD) were explored. Frequencies and levels of involvement in interactions with classmates were observed and compared in 22 students with ASD and 84 of their classmates in mainstream schools, using a standardized protocol. Self-reported participation measurements regarding interactions with classmates and teachers from five questionnaire items were correlated with the observations. In total, 51,516 data points were coded and entered into the analyses, and correlated with 530 questionnaire ratings. Only one weak correlation was found in each group. Compared with classmates, students with ASD participated less frequently, but were not less involved when they actually did. Observations alone do not capture the individuals' perception of participation and are not sufficient if the subjective aspect of participation is to be measured.

ASD Is Not DLI: Individuals With Autism and Individuals With Syntactic DLI Show Similar Performance Level in Syntactic Tasks, but Different Error Patterns.

PubMed

Sukenik, Nufar; Friedmann, Naama

2018-01-01

Do individuals with autism have a developmental syntactic impairment, DLI (formerly known as SLI)? In this study we directly compared the performance of 18 individuals with Autism Spectrum Disorder (ASD) aged 9;0-18;0 years with that of 93 individuals with Syntactic-Developmental Language Impairment (SyDLI) aged 8;8-14;6 (and with 166 typically-developing children aged 5;2-18;1). We tested them using three syntactic tests assessing the comprehension and production of syntactic structures that are known to be sensitive to syntactic impairment: elicitation of subject and object relative clauses, reading and paraphrasing of object relatives, and repetition of complex syntactic structures including Wh questions, relative clauses, topicalized sentences, sentences with verb movement, sentences with A-movement, and embedded sentences. The results were consistent across the three tasks: the overall rate of correct performance on the syntactic tasks is similar for the children with ASD and those with SyDLI. However, once we look closer, they are very different. The types of errors of the ASD group differ from those of the SyDLI group-the children with ASD provide various types of pragmatically infelicitous responses that are not evinced in the SyDLI or in the age equivalent typically-developing groups. The two groups (ASD and SyDLI) also differ in the pattern of performance-the children with SyDLI show a syntactically-principled pattern of impairment, with selective difficulty in specific sentence types (such as sentences derived by movement of the object across the subject), and normal performance on other structures (such as simple sentences). In contrast, the ASD participants showed generalized low performance on the various sentence structures. Syntactic performance was far from consistent within the ASD group. Whereas all ASD participants had errors that can originate in pragmatic/discourse difficulties, seven of them had completely normal syntax in the structures we tested, and were able to produce, understand, and repeat relative clauses, Wh questions, and topicalized sentences. Only one ASD participant showed a syntactically-principled deficit similar to that of individuals with SyDLI. We conclude that not all individuals with ASD have syntactic difficulties, and that even when they fail in a syntactic task, this does not necessarily originate in a syntactic impairment. This shows that looking only at the total score in a syntactic test may be insufficient, and a fuller picture emerges once the performance on different structures and the types of erroneous responses are analyzed.

ASD Is Not DLI: Individuals With Autism and Individuals With Syntactic DLI Show Similar Performance Level in Syntactic Tasks, but Different Error Patterns

PubMed Central

Sukenik, Nufar; Friedmann, Naama

2018-01-01

Do individuals with autism have a developmental syntactic impairment, DLI (formerly known as SLI)? In this study we directly compared the performance of 18 individuals with Autism Spectrum Disorder (ASD) aged 9;0–18;0 years with that of 93 individuals with Syntactic-Developmental Language Impairment (SyDLI) aged 8;8–14;6 (and with 166 typically-developing children aged 5;2–18;1). We tested them using three syntactic tests assessing the comprehension and production of syntactic structures that are known to be sensitive to syntactic impairment: elicitation of subject and object relative clauses, reading and paraphrasing of object relatives, and repetition of complex syntactic structures including Wh questions, relative clauses, topicalized sentences, sentences with verb movement, sentences with A-movement, and embedded sentences. The results were consistent across the three tasks: the overall rate of correct performance on the syntactic tasks is similar for the children with ASD and those with SyDLI. However, once we look closer, they are very different. The types of errors of the ASD group differ from those of the SyDLI group—the children with ASD provide various types of pragmatically infelicitous responses that are not evinced in the SyDLI or in the age equivalent typically-developing groups. The two groups (ASD and SyDLI) also differ in the pattern of performance—the children with SyDLI show a syntactically-principled pattern of impairment, with selective difficulty in specific sentence types (such as sentences derived by movement of the object across the subject), and normal performance on other structures (such as simple sentences). In contrast, the ASD participants showed generalized low performance on the various sentence structures. Syntactic performance was far from consistent within the ASD group. Whereas all ASD participants had errors that can originate in pragmatic/discourse difficulties, seven of them had completely normal syntax in the structures we tested, and were able to produce, understand, and repeat relative clauses, Wh questions, and topicalized sentences. Only one ASD participant showed a syntactically-principled deficit similar to that of individuals with SyDLI. We conclude that not all individuals with ASD have syntactic difficulties, and that even when they fail in a syntactic task, this does not necessarily originate in a syntactic impairment. This shows that looking only at the total score in a syntactic test may be insufficient, and a fuller picture emerges once the performance on different structures and the types of erroneous responses are analyzed. PMID:29670550

Convergence of genes and cellular pathways dysregulated in autism spectrum disorders.

PubMed

Pinto, Dalila; Delaby, Elsa; Merico, Daniele; Barbosa, Mafalda; Merikangas, Alison; Klei, Lambertus; Thiruvahindrapuram, Bhooma; Xu, Xiao; Ziman, Robert; Wang, Zhuozhi; Vorstman, Jacob A S; Thompson, Ann; Regan, Regina; Pilorge, Marion; Pellecchia, Giovanna; Pagnamenta, Alistair T; Oliveira, Bárbara; Marshall, Christian R; Magalhaes, Tiago R; Lowe, Jennifer K; Howe, Jennifer L; Griswold, Anthony J; Gilbert, John; Duketis, Eftichia; Dombroski, Beth A; De Jonge, Maretha V; Cuccaro, Michael; Crawford, Emily L; Correia, Catarina T; Conroy, Judith; Conceição, Inês C; Chiocchetti, Andreas G; Casey, Jillian P; Cai, Guiqing; Cabrol, Christelle; Bolshakova, Nadia; Bacchelli, Elena; Anney, Richard; Gallinger, Steven; Cotterchio, Michelle; Casey, Graham; Zwaigenbaum, Lonnie; Wittemeyer, Kerstin; Wing, Kirsty; Wallace, Simon; van Engeland, Herman; Tryfon, Ana; Thomson, Susanne; Soorya, Latha; Rogé, Bernadette; Roberts, Wendy; Poustka, Fritz; Mouga, Susana; Minshew, Nancy; McInnes, L Alison; McGrew, Susan G; Lord, Catherine; Leboyer, Marion; Le Couteur, Ann S; Kolevzon, Alexander; Jiménez González, Patricia; Jacob, Suma; Holt, Richard; Guter, Stephen; Green, Jonathan; Green, Andrew; Gillberg, Christopher; Fernandez, Bridget A; Duque, Frederico; Delorme, Richard; Dawson, Geraldine; Chaste, Pauline; Café, Cátia; Brennan, Sean; Bourgeron, Thomas; Bolton, Patrick F; Bölte, Sven; Bernier, Raphael; Baird, Gillian; Bailey, Anthony J; Anagnostou, Evdokia; Almeida, Joana; Wijsman, Ellen M; Vieland, Veronica J; Vicente, Astrid M; Schellenberg, Gerard D; Pericak-Vance, Margaret; Paterson, Andrew D; Parr, Jeremy R; Oliveira, Guiomar; Nurnberger, John I; Monaco, Anthony P; Maestrini, Elena; Klauck, Sabine M; Hakonarson, Hakon; Haines, Jonathan L; Geschwind, Daniel H; Freitag, Christine M; Folstein, Susan E; Ennis, Sean; Coon, Hilary; Battaglia, Agatino; Szatmari, Peter; Sutcliffe, James S; Hallmayer, Joachim; Gill, Michael; Cook, Edwin H; Buxbaum, Joseph D; Devlin, Bernie; Gallagher, Louise; Betancur, Catalina; Scherer, Stephen W

2014-05-01

Rare copy-number variation (CNV) is an important source of risk for autism spectrum disorders (ASDs). We analyzed 2,446 ASD-affected families and confirmed an excess of genic deletions and duplications in affected versus control groups (1.41-fold, p = 1.0 × 10(-5)) and an increase in affected subjects carrying exonic pathogenic CNVs overlapping known loci associated with dominant or X-linked ASD and intellectual disability (odds ratio = 12.62, p = 2.7 × 10(-15), ∼3% of ASD subjects). Pathogenic CNVs, often showing variable expressivity, included rare de novo and inherited events at 36 loci, implicating ASD-associated genes (CHD2, HDAC4, and GDI1) previously linked to other neurodevelopmental disorders, as well as other genes such as SETD5, MIR137, and HDAC9. Consistent with hypothesized gender-specific modulators, females with ASD were more likely to have highly penetrant CNVs (p = 0.017) and were also overrepresented among subjects with fragile X syndrome protein targets (p = 0.02). Genes affected by de novo CNVs and/or loss-of-function single-nucleotide variants converged on networks related to neuronal signaling and development, synapse function, and chromatin regulation. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Altered chemical metabolites in the amygdala-hippocampus region contribute to autistic symptoms of autism spectrum disorders.

PubMed

Endo, Taro; Shioiri, Toshiki; Kitamura, Hideaki; Kimura, Teruo; Endo, Sumio; Masuzawa, Naio; Someya, Toshiyuki

2007-11-01

Although several previous studies have been conducted, the neural basis of autism spectrum disorder (ASD) is poorly understood. The objective of the present study was to determine whether individuals with ASD have altered brain chemical metabolites and whether such alterations are related to their autistic symptoms. N-acetylaspartate (NAA)/creatine (Cr) and choline/Cr ratios in the right medial temporal lobe (MTL), medial prefrontal cortex, and cerebellar vermis were measured in 38 individuals with ASD (mean age = 12.9 years), including 12 with autism, 15 with Asperger's Disorder, and 11 with pervasive developmental disorder not otherwise specified (PDD-NOS), and 16 matched healthy control subjects (mean age = 11.5 years) with proton magnetic resonance spectroscopy. Autistic symptoms were assessed by the Childhood Autistic Rating Scale-Tokyo Version. There was a significant group difference for NAA/Cr ratio in the right MTL between the autism, Asperger's Disorder, PDD-NOS, and control groups (p < .001), and the autism group had a significantly lower NAA/Cr ratio compared with the PDD-NOS (p < .001) and control (p < .001) groups. In the ASD group, there was a significant negative correlation between NAA/Cr ratio in the right MTL and their Childhood Autistic Rating Scale-Tokyo Version total scores (r = -.44, p = .01) and subscales of emotional response (r = -.38, p = .02) and listening response (r = -.54, p = .001). The results of the present study suggest that subjects with ASD have abnormalities of neural integrity in the amygdala-hippocampus region that are related to their severity and social impairments.

Brief Report: Atypical expression of distress during the separation phase of the strange situation procedure in infant siblings at high risk for ASD.

PubMed

Esposito, Gianluca; Del Carmen Rostagno, Maria; Venuti, Paola; Haltigan, John D; Messinger, Daniel S

2014-04-01

Previous studies have provided preliminary evidence that disruptions in cry acoustics may be part of an atypical vocal signature of autism early in life. We examined the acoustic characteristics of cries extracted from the separation phase of the strange situation procedure in a sample of toddler of younger siblings of a child with autism spectrum disorder-autism spectrum disorders (ASD) (high risk, HR) and a low risk (LR) group. Cry samples derived from vocal recordings of 15-month-old HR (n = 13) and LR infants (n = 14) were subjected to acoustic analyses. HR toddlers, compared to those with LR, produced cries that were shorter and had a higher fundamental frequency (F0). Three HR toddlers later classified with an ASD at 36 months (autistic disorder in all cases) produced cries that had among the highest F0 and shortest durations. Taken together these results indicate that toddlers at high risk for ASD (and those with an ASD) express atypical patterns of distress in response a social stressor. Implications for early diagnosis and parenting are discussed.

A Statistical Physics Perspective to Understand Social Visual Attention in Autism Spectrum Disorder.

PubMed

Liberati, Alessio; Fadda, Roberta; Doneddu, Giuseppe; Congiu, Sara; Javarone, Marco A; Striano, Tricia; Chessa, Alessandro

2017-08-01

This study investigated social visual attention in children with Autism Spectrum Disorder (ASD) and with typical development (TD) in the light of Brockmann and Geisel's model of visual attention. The probability distribution of gaze movements and clustering of gaze points, registered with eye-tracking technology, was studied during a free visual exploration of a gaze stimulus. A data-driven analysis of the distribution of eye movements was chosen to overcome any possible methodological problems related to the subjective expectations of the experimenters about the informative contents of the image in addition to a computational model to simulate group differences. Analysis of the eye-tracking data indicated that the scanpaths of children with TD and ASD were characterized by eye movements geometrically equivalent to Lévy flights. Children with ASD showed a higher frequency of long saccadic amplitudes compared with controls. A clustering analysis revealed a greater dispersion of eye movements for these children. Modeling of the results indicated higher values of the model parameter modulating the dispersion of eye movements for children with ASD. Together, the experimental results and the model point to a greater dispersion of gaze points in ASD.

The Ritvo Autism Asperger Diagnostic Scale-Revised (RAADS-R): a scale to assist the diagnosis of Autism Spectrum Disorder in adults: an international validation study.

PubMed

Ritvo, Riva Ariella; Ritvo, Edward R; Guthrie, Donald; Ritvo, Max J; Hufnagel, Demetra H; McMahon, William; Tonge, Bruce; Mataix-Cols, David; Jassi, Amita; Attwood, Tony; Eloff, Johann

2011-08-01

The Ritvo Autism Asperger Diagnostic Scale-Revised (RAADS-R) is a valid and reliable instrument to assist the diagnosis of adults with Autism Spectrum Disorders (ASD). The 80-question scale was administered to 779 subjects (201 ASD and 578 comparisons). All ASD subjects met inclusion criteria: DSM-IV-TR, ADI/ADOS diagnoses and standardized IQ testing. Mean scores for each of the questions and total mean ASD vs. the comparison groups' scores were significantly different (p < .0001). Concurrent validity with Constantino Social Responsiveness Scale-Adult = 95.59%. Sensitivity = 97%, specificity = 100%, test-retest reliability r = .987. Cronbach alpha coefficients for the subscales and 4 derived factors were good. We conclude that the RAADS-R is a useful adjunct diagnostic tool for adults with ASD.

Melatonin in children with autistic spectrum disorders: recent and practical data.

PubMed

Doyen, C; Mighiu, D; Kaye, K; Colineaux, C; Beaumanoir, C; Mouraeff, Y; Rieu, C; Paubel, P; Contejean, Y

2011-05-01

Over the last 20 years, melatonin, a pineal hormone synthesized from serotonin, has been implicated in various studies on the autism spectrum disorder (ASD) and altered melatonin levels were detected in subgroups of subjects with ASD. Its effect on sleep disturbances got the attention of clinicians and several investigations were carried out to determine the usefulness and safety of melatonin administration in this disorder. Hypotheses were also raised regarding the possibility that the dysfunctional synthesis and secretion of melatonin detected in subgroups of subjects with ASD may increase the risk as well the severity of ASD. The purpose of this paper is to review our pharmacokinetic knowledge on melatonin and present results from recent studies on sleep disorders in autism, their treatment with melatonin and the impact of melatonin prescription in children with ASD evaluated in a Diagnostic Center for Autism Spectrum Disorder in Paris, France.

Mass spectrometry as a tool for studying autism spectrum disorder.

PubMed

Woods, Alisa G; Ngounou Wetie, Armand G; Sokolowska, Izabela; Russell, Stefanie; Ryan, Jeanne P; Michel, Tanja Maria; Thome, Johannes; Darie, Costel C

2013-01-01

Autism spectrum disorders (ASDs) are increasing in incidence but have an incompletely understood etiology. Tools for uncovering clues to the cause of ASDs and means for diagnoses are valuable to the field. Mass Spectrometry (MS) has been a useful method for evaluating differences between individuals with ASDs versus matched controls. Different biological substances can be evaluated using MS, including urine, blood, saliva, and hair. This technique has been used to evaluate relatively unsupported hypotheses based on introduction of exogenous factors, such as opiate and heavy metal excretion theories of ASDs. MS has also been used to support disturbances in serotonin-related molecules, which have been more consistently observed in ASDs. Serotonergic system markers, markers for oxidative stress, cholesterol system disturbances, peptide hypo-phosphorylation and methylation have been measured using MS in ASDs, although further analyses with larger numbers of subjects are needed (as well as consideration of behavioral data). Refinements in MS and data analysis are ongoing, allowing for the possibility that future studies examining body fluids and specimens from ASD subjects could continue to yield novel insights. This review summarizes MS investigations that have been conducted to study ASD to date and provides insight into future promising applications for this technique, with focus on proteomic studies.

Integration in the Vocational World: How Does It Affect Quality of Life and Subjective Well-Being of Young Adults with ASD

PubMed Central

Gal, Eynat; Selanikyo, Efrat; Bar-Haim Erez, Asnat; Katz, Noomi

2015-01-01

This study aimed to assess whether the perception of quality of life (QOL) and subjective well-being (SWB) of young adults with autism spectrum disorders (ASD) is affected by participation in a comprehensive program. Participants included 25 young adults with ASD who participated in the “Roim Rachok Program” (RRP), where they were trained to become aerial photography interpreters. Following the training period, they served in a designated army unit where they practiced their newly acquired profession. The participants filled out two questionnaires, (a) Quality of Life (QOL-Q) and (b) Personal Well-being Index (PWI), at three points of the intervention: (a) before the course, (b) at the end of the course, and (c) six months after integrating in the designated army unit. Wilcoxon signed ranks tests were used to assess the differences between the reported QOL and SWB at the three points of time. The results suggest that there were no significant differences at the end of the course, compared to its beginning. However, there were significantly improved perception of QOL and SWB during the period between the end of the course and six months after starting work. The results of this study highlight the importance of tailored vocational programs that are adapted to the unique needs and strengths of individuals with ASD. PMID:26404341

Comparing oxytocin and cortisol regulation in a double-blind, placebo-controlled, hydrocortisone challenge pilot study in children with autism and typical development.

PubMed

Corbett, Blythe A; Bales, Karen L; Swain, Deanna; Sanders, Kevin; Weinstein, Tamara A R; Muglia, Louis J

2016-01-01

Children with autism spectrum disorder (ASD) show marked impairment in social functioning and poor adaptation to new and changing contexts, which may be influenced by underlying regulatory processes. Oxytocin (OT) and cortisol are key neuromodulators of biological and behavioral responses, show a synergistic effect, and have been implicated in the neuropathological profile in ASD. However, they are rarely investigated together. The purpose of the pilot study was to evaluate the relationship between cortisol and OT in children with ASD under baseline and physiological stress (hydrocortisone challenge) conditions. Arginine vasopressin (AVP), structurally similar to OT, was also examined. A double-blind, placebo-controlled, randomly assigned, crossover design was employed in 25 children 8-to-12 years with ASD (N = 14) or typical development (TD, N = 11). A low dose of hydrocortisone and placebo were administered via liquid suspension. Analysis of variance (ANOVA) was used to examine the within-subject factor "Condition" (hydrocortisone/placebo) and "Time" (pre and post) and the between-subject factor "Group" (ASD vs. TD). Pearson correlations examined the relationship between hormone levels and clinical profile. There was a significant Time × Condition × Group interaction F (1.23) = 4.18, p = 0.05 showing a rise in OT during the experimental condition (hydrocortisone) and a drop during the placebo condition for the TD group but not the ASD group. There were no group differences for AVP. Hormone levels were associated with social profiles. For the TD group, an inverse relationship was observed. OT increased during physiological challenge suggesting that OT played a stress-buffering role during cortisol administration. In contrast for the ASD group, OT remained unchanged or decreased during both the physiological challenge and the placebo condition, suggesting that OT failed to serve as a stress buffer under conditions of physiological stress. While OT has been tied to the social ability of children with ASD, the diminished moderating effect of OT on cortisol may also play a contributory role in the heightened stress often observed in children with ASD. These results contribute to our understanding of the growing complexity of the effects of OT on social behavior as well as the functional interplay and differential regulation OT may have on stress modulation.

A Comparative Review of microRNA Expression Patterns in Autism Spectrum Disorder.

PubMed

Hicks, Steven D; Middleton, Frank A

2016-01-01

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by a wide spectrum of deficits in social interaction, communication, and behavior. There is a significant genetic component to ASD, yet no single gene variant accounts for >1% of incidence. Posttranscriptional mechanisms such as microRNAs (miRNAs) regulate gene expression without altering the genetic code. They are abundant in the developing brain and are dysregulated in children with ASD. Patterns of miRNA expression are altered in the brain, blood, saliva, and olfactory precursor cells of ASD subjects. The ability of miRNAs to regulate broad molecular pathways in response to environmental stimuli makes them an intriguing player in ASD, a disorder characterized by genetic predisposition with ill-defined environmental triggers. In addition, the availability and extracellular stability of miRNAs make them an ideal candidate for biomarker discovery. Here, we discuss 27 miRNAs with overlap across ASD studies, including 3 miRNAs identified in 3 or more studies (miR-23a, miR-146a, and miR-106b). Together, these 27 miRNAs have 1245 high-confidence mRNA targets, a significant number of which are expressed in the brain. Furthermore, these mRNA targets demonstrate over-representation of autism-related genes with enrichment of neurotrophic signaling molecules. Brain-derived neurotrophic factor, a molecule involved in hippocampal neurogenesis and altered in ASD, is targeted by 6 of the 27 miRNAs of interest. This neurotrophic pathway represents one intriguing mechanism by which perturbations in miRNA signaling might influence central nervous system development in children with ASD.

How doing a dynamical analysis of gait movement may provide information about Autism

NASA Astrophysics Data System (ADS)

Wu, D.; Torres, E.; Nguyen, J.; Mistry, S.; Whyatt, C.; Kalampratsidou, V.; Kolevzon, A.; Jose, J.

Individuals with Autism Spectrum Disorder (ASD) are known to have deficits in language and social skills. They also have deficits on how they move. Why individuals get ASD? It is not generally known. There is, however, one particular group of children with a SHANK3 gene deficiency (Phelan-McDermid Syndrome (PMDS)) that present symptoms similar to ASD. We have been searching for universal mechanism in ASD going beyond the usual heterogeneous ASD symptoms. We studied motions in gaits for both PMDS patients and idiopathic ASD. We have examined their motions continuously at milliseconds time scale, away from naked eye detection. Gait is a complex process, requiring a complex integration and coordination of different joints' motions. Significant information about the development and/or deficits in the sensory system is hidden in our gaits. We discovered that the speed smoothness in feet motion during gaits is a critical feature that provides a significant distinction between subjects with ASD and typical controls. The differences in appearance of the speed fluctuations suggested a different coordination mechanism in subjects with disorders. Our work provides a very important feature in gait motion that has significant physiological information.

Active and observational reward learning in adults with autism spectrum disorder: relationship with empathy in an atypical sample.

PubMed

Bellebaum, Christian; Brodmann, Katja; Thoma, Patrizia

2014-01-01

Autism spectrum disorders (ASDs) are characterised by disturbances in social behaviour. A prevailing hypothesis suggests that these problems are related to deficits in assigning rewarding value to social stimuli. The present study aimed to examine monetary reward processing in adults with ASDs by means of event-related potentials (ERPs). Ten individuals with mild ASDs (Asperger's syndrome and high-functioning autism) and 12 healthy control subjects performed an active and an observational probabilistic reward-learning task. Both groups showed similar overall learning performance. With respect to reward processing, subjects with ASDs exhibited a general reduction in feedback-related negativity (FRN) amplitude, irrespective of feedback valence and type of learning (active or observational). Individuals with ASDs showed lower scores for cognitive empathy, while affective empathy did not differ between groups. Correlation analyses revealed that higher empathy (both cognitive and affective) negatively affected performance in observational learning in controls and in active learning in ASDs (only cognitive empathy). No relationships were seen between empathy and ERPs. Reduced FRN amplitudes are discussed in terms of a deficit in fast reward processing in ASDs, which may indicate altered reward system functioning.

Resting-State Neurophysiological Activity Patterns in Young People with ASD, ADHD, and ASD + ADHD.

PubMed

Shephard, Elizabeth; Tye, Charlotte; Ashwood, Karen L; Azadi, Bahar; Asherson, Philip; Bolton, Patrick F; McLoughlin, Grainne

2018-01-01

Altered power of resting-state neurophysiological activity has been associated with autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), which commonly co-occur. We compared resting-state neurophysiological power in children with ASD, ADHD, co-occurring ASD + ADHD, and typically developing controls. Children with ASD (ASD/ASD + ADHD) showed reduced theta and alpha power compared to children without ASD (controls/ADHD). Children with ADHD (ADHD/ASD + ADHD) displayed decreased delta power compared to children without ADHD (ASD/controls). Children with ASD + ADHD largely presented as an additive co-occurrence with deficits of both disorders, although reduced theta compared to ADHD-only and reduced delta compared to controls suggested some unique markers. Identifying specific neurophysiological profiles in ASD and ADHD may assist in characterising more homogeneous subgroups to inform treatment approaches and aetiological investigations.

Subtyping of Toddlers with ASD Based on Patterns of Social Attention Deficits

DTIC Science & Technology

2014-10-01

AWARD NUMBER: W81XWH-13-1-0179 TITLE: Subtyping of Toddlers with ASD Based on Patterns of Social Attention Deficits PRINCIPAL INVESTIGATOR...TITLE AND SUBTITLE Subtyping of Toddlers with ASD Based on Patterns of Social Attention Deficits 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-13-1-0179...tracking data. 15. SUBJECT TERMS ASD, subgrouping, toddlers , heterogeneity, eye-tracking, visual attention, dyadic orienting, hierarchical

Serum Antibody Biomarkers for ASD

DTIC Science & Technology

2015-10-01

autism blood biomarker. In addition, we have identified two new proteins that are linked to ASD. 15. SUBJECT TERMS ASD, autism spectrum disorders . TD...4 8. Appendices…………………………………………………………. 5 3 Introduction: Autism spectrum disorder (ASD) is a neurodevelopmental disorder ...immune responses in young children with autism spectrum disorders : their relationship to gastrointestinal symptoms and dietary intervention

Autonomic responses to social and nonsocial pictures in adolescents with autism spectrum disorder.

PubMed

Louwerse, Anneke; Tulen, Joke H M; van der Geest, Jos N; van der Ende, Jan; Verhulst, Frank C; Greaves-Lord, Kirstin

2014-02-01

It remains unclear why individuals with autism spectrum disorder (ASD) tend to respond in an atypical manner in social situations. Investigating autonomic and subjective responses to social vs. nonsocial stimuli may help to reveal underlying mechanisms of these atypical responses. This study examined autonomic responses (skin conductance level and heart rate) and subjective responses to social vs. nonsocial pictures in 37 adolescents with an ASD and 36 typically developing (TD) adolescents. Thirty-six pictures from the International Affective Picture System were presented, divided into six categories based on social content (social vs. nonsocial) and pleasantness (pleasant, neutral, and unpleasant). Both in adolescents with ASD as well as TD adolescents, pictures with a social content resulted in higher skin conductance responses (SCRs) for pleasant and unpleasant pictures than for neutral pictures. No differences in SCRs were found for the three nonsocial picture categories. Unpleasant pictures, both with and without a social content, showed more heart rate deceleration than neutral pictures. Self-reported arousal ratings were influenced by the social and affective content of a picture. No differences were found between individuals with ASD and TD individuals in their autonomic and subjective responses to the picture categories. These results suggest that adolescents with ASD do not show atypical autonomic or subjective responses to pictures with and without a social content. These findings make it less likely that impairments in social information processing in individuals with ASD can be explained by atypical autonomic responses to social stimuli. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.

Recognizing Biological Motion and Emotions from Point-Light Displays in Autism Spectrum Disorders

PubMed Central

Nackaerts, Evelien; Wagemans, Johan; Helsen, Werner; Swinnen, Stephan P.; Wenderoth, Nicole; Alaerts, Kaat

2012-01-01

One of the main characteristics of Autism Spectrum Disorder (ASD) are problems with social interaction and communication. Here, we explored ASD-related alterations in ‘reading’ body language of other humans. Accuracy and reaction times were assessed from two observational tasks involving the recognition of ‘biological motion’ and ‘emotions’ from point-light displays (PLDs). Eye movements were recorded during the completion of the tests. Results indicated that typically developed-participants were more accurate than ASD-subjects in recognizing biological motion or emotions from PLDs. No accuracy differences were revealed on two control-tasks (involving the indication of color-changes in the moving point-lights). Group differences in reaction times existed on all tasks, but effect sizes were higher for the biological and emotion recognition tasks. Biological motion recognition abilities were related to a person’s ability to recognize emotions from PLDs. However, ASD-related atypicalities in emotion recognition could not entirely be attributed to more basic deficits in biological motion recognition, suggesting an additional ASD-specific deficit in recognizing the emotional dimension of the point light displays. Eye movements were assessed during the completion of tasks and results indicated that ASD-participants generally produced more saccades and shorter fixation-durations compared to the control-group. However, especially for emotion recognition, these altered eye movements were associated with reductions in task-performance. PMID:22970227

Recognizing biological motion and emotions from point-light displays in autism spectrum disorders.

PubMed

Nackaerts, Evelien; Wagemans, Johan; Helsen, Werner; Swinnen, Stephan P; Wenderoth, Nicole; Alaerts, Kaat

2012-01-01

One of the main characteristics of Autism Spectrum Disorder (ASD) are problems with social interaction and communication. Here, we explored ASD-related alterations in 'reading' body language of other humans. Accuracy and reaction times were assessed from two observational tasks involving the recognition of 'biological motion' and 'emotions' from point-light displays (PLDs). Eye movements were recorded during the completion of the tests. Results indicated that typically developed-participants were more accurate than ASD-subjects in recognizing biological motion or emotions from PLDs. No accuracy differences were revealed on two control-tasks (involving the indication of color-changes in the moving point-lights). Group differences in reaction times existed on all tasks, but effect sizes were higher for the biological and emotion recognition tasks. Biological motion recognition abilities were related to a person's ability to recognize emotions from PLDs. However, ASD-related atypicalities in emotion recognition could not entirely be attributed to more basic deficits in biological motion recognition, suggesting an additional ASD-specific deficit in recognizing the emotional dimension of the point light displays. Eye movements were assessed during the completion of tasks and results indicated that ASD-participants generally produced more saccades and shorter fixation-durations compared to the control-group. However, especially for emotion recognition, these altered eye movements were associated with reductions in task-performance.

Autism spectrum disorders according to DSM-IV-TR and comparison with DSM-5 draft criteria: an epidemiological study.

PubMed

Mattila, Marja-Leena; Kielinen, Marko; Linna, Sirkka-Liisa; Jussila, Katja; Ebeling, Hanna; Bloigu, Risto; Joseph, Robert M; Moilanen, Irma

2011-06-01

The latest definitions of autism spectrum disorders (ASDs) were specified in DSM-IV-TR in 2000. DSM-5 criteria are planned for 2013. Here, we estimated the prevalence of ASDs and autism according to DSM-IV-TR, clarified confusion concerning diagnostic criteria, and evaluated DSM-5 draft criteria for ASD posted by the American Psychiatry Association (APA) in February 2010. This was an epidemiological study of 5,484 eight-year-old children in Finland, 4,422 (81%) of them rated via the Autism Spectrum Screening Questionnaire by parents and/or teachers, and 110 examined by using a structured interview, semi-structured observation, IQ measurement, school-day observation, and patient records. Diagnoses were assigned according to DSM-IV-TR criteria and DSM-5 draft criteria in children with a full-scale IQ (FSIQ) ≥50. Patient records were evaluated in children with an FSIQ <50 to discover diagnoses of ASDs. The prevalence of ASDs was 8.4 in 1,000 and that of autism 4.1 in 1,000 according to DSM-IV-TR. Of the subjects with ASDs and autism, 65% and 61% were high-functioning (FSIQ ≥70), respectively. The prevalence of pervasive developmental disorder not otherwise specified was not estimated because of inconsistency in DSM-IV-TR criteria. DSM-5 draft criteria were shown to be less sensitive in regard to identification of subjects with ASDs, particularly those with Asperger's syndrome and some high-functioning subjects with autism. DSM-IV-TR helps with the definition of ASDs only up to a point. We suggest modifications to five details of DSM-5 draft criteria posted by the APA in February 2010. Completing revision of DSM criteria for ASDs is a challenging task. Copyright © 2011 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Divide and Conquer: Sub-Grouping of ASD Improves ASD Detection Based on Brain Morphometry.

PubMed

Katuwal, Gajendra J; Baum, Stefi A; Cahill, Nathan D; Michael, Andrew M

2016-01-01

Low success (<60%) in autism spectrum disorder (ASD) classification using brain morphometry from the large multi-site ABIDE dataset and inconsistent findings on brain morphometric abnormalities in ASD can be attributed to the ASD heterogeneity. In this study, we show that ASD brain morphometry is highly heterogeneous, and demonstrate that the heterogeneity can be mitigated and classification improved if autism severity (AS), verbal IQ (VIQ) and age are used with morphometric features. Morphometric features from structural MRIs (sMRIs) of 734 males (ASD: 361, controls: 373) of ABIDE were derived using FreeSurfer. Applying the Random Forest classifier, an AUC of 0.61 was achieved. Adding VIQ and age to morphometric features, AUC improved to 0.68. Sub-grouping the subjects by AS, VIQ and age improved the classification with the highest AUC of 0.8 in the moderate-AS sub-group (AS = 7-8). Matching subjects on age and/or VIQ in each sub-group further improved the classification with the highest AUC of 0.92 in the low AS sub-group (AS = 4-5). AUC decreased with AS and VIQ, and was the lowest in the mid-age sub-group (13-18 years). The important features were mainly from the frontal, temporal, ventricular, right hippocampal and left amygdala regions. However, they highly varied with AS, VIQ and age. The curvature and folding index features from frontal, temporal, lingual and insular regions were dominant in younger subjects suggesting their importance for early detection. When the experiments were repeated using the Gradient Boosting classifier similar results were obtained. Our findings suggest that identifying brain biomarkers in sub-groups of ASD can yield more robust and insightful results than searching across the whole spectrum. Further, it may allow identification of sub-group specific brain biomarkers that are optimized for early detection and monitoring, increasing the utility of sMRI as an important tool for early detection of ASD.

Divide and Conquer: Sub-Grouping of ASD Improves ASD Detection Based on Brain Morphometry

PubMed Central

Baum, Stefi A.; Cahill, Nathan D.; Michael, Andrew M.

2016-01-01

Low success (<60%) in autism spectrum disorder (ASD) classification using brain morphometry from the large multi-site ABIDE dataset and inconsistent findings on brain morphometric abnormalities in ASD can be attributed to the ASD heterogeneity. In this study, we show that ASD brain morphometry is highly heterogeneous, and demonstrate that the heterogeneity can be mitigated and classification improved if autism severity (AS), verbal IQ (VIQ) and age are used with morphometric features. Morphometric features from structural MRIs (sMRIs) of 734 males (ASD: 361, controls: 373) of ABIDE were derived using FreeSurfer. Applying the Random Forest classifier, an AUC of 0.61 was achieved. Adding VIQ and age to morphometric features, AUC improved to 0.68. Sub-grouping the subjects by AS, VIQ and age improved the classification with the highest AUC of 0.8 in the moderate-AS sub-group (AS = 7–8). Matching subjects on age and/or VIQ in each sub-group further improved the classification with the highest AUC of 0.92 in the low AS sub-group (AS = 4–5). AUC decreased with AS and VIQ, and was the lowest in the mid-age sub-group (13–18 years). The important features were mainly from the frontal, temporal, ventricular, right hippocampal and left amygdala regions. However, they highly varied with AS, VIQ and age. The curvature and folding index features from frontal, temporal, lingual and insular regions were dominant in younger subjects suggesting their importance for early detection. When the experiments were repeated using the Gradient Boosting classifier similar results were obtained. Our findings suggest that identifying brain biomarkers in sub-groups of ASD can yield more robust and insightful results than searching across the whole spectrum. Further, it may allow identification of sub-group specific brain biomarkers that are optimized for early detection and monitoring, increasing the utility of sMRI as an important tool for early detection of ASD. PMID:27065101

A Comparison of Ambulatory Care Sensitive Hospitalizations Among Children With and Without Autism Spectrum Disorder.

PubMed

Carbone, Paul S; Young, Paul C; Stoddard, Gregory J; Wilkes, Jacob; Trasande, Leonardo

2015-01-01

To compare the prevalence of hospitalizations for ambulatory care sensitive conditions (ACSC) in children with and without autism spectrum disorder (ASD) and to compare inpatient health care utilization (total charges and length of stay) for the same conditions in children with and without ASD. The 2009 Kids' Inpatient Database was used to examine hospitalizations for ACSC in children within 3 cohorts: those with ASD, those with chronic conditions (CC) without ASD, and those with no CC. The proportion of hospitalizations for ACSC in the ASD cohort was 55.9%, compared with 28.2% in the CC cohort and 22.9% in the no-CC cohort (P < .001). Hospitalized children with ASD were more likely to be admitted for a mental health condition, epilepsy, constipation, pneumonia, dehydration, vaccine-preventable diseases, underweight, and nutritional deficiencies compared with the no-CC cohort. Compared with the CC cohort, the ASD cohort was more likely to be admitted for mental health conditions, epilepsy, constipation, dehydration, and underweight. Hospitalized children with ASD admitted for mental health conditions had significantly higher total charges and longer LOS compared with the other 2 cohorts. The proportion of potentially preventable hospitalizations is higher in hospitalized children with ASD compared with children without ASD. These data underscore the need to improve outpatient care of children with ASD, especially in the areas of mental health care and seizure management. Future research should focus on understanding the reasons for increased inpatient health care utilization in children with ASD admitted for mental health conditions. Copyright © 2015 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

Acute stress symptoms during the second Lebanon war in a random sample of Israeli citizens.

PubMed

Cohen, Miri; Yahav, Rivka

2008-02-01

The aims of this study were to assess prevalence of acute stress disorder (ASD) and acute stress symptoms (ASS) in Israel during the second Lebanon war. A telephone survey was conducted in July 2006 of a random sample of 235 residents of northern Israel, who were subjected to missile attacks, and of central Israel, who were not subjected to missile attacks. Results indicate that ASS scores were higher in the northern respondents; 6.8% of the northern sample and 3.9% of the central sample met ASD criteria. Appearance of each symptom ranged from 15.4% for dissociative to 88.4% for reexperiencing, with significant differences between northern and central respondents only for reexperiencing and arousal. A low ASD rate and a moderate difference between areas subjected and not subjected to attack were found.

The Impact of Autism Spectrum Disorder and Alexithymia on Judgments of Moral Acceptability

PubMed Central

2015-01-01

One’s own emotional response toward a hypothetical action can influence judgments of its moral acceptability. Some individuals with autism spectrum disorder (ASD) exhibit atypical emotional processing, and moral judgments. Research suggests, however, that emotional deficits in ASD are due to co-occurring alexithymia, meaning atypical moral judgments in ASD may be due to alexithymia also. Individuals with and without ASD (matched for alexithymia) judged the moral acceptability of emotion-evoking statements and identified the emotion evoked. Moral acceptability judgments were predicted by alexithymia. Crucially, however, this relationship held only for individuals without ASD. While ASD diagnostic status did not directly predict either judgment, those with ASD did not base their moral acceptability judgments on emotional information. Findings are consistent with evidence demonstrating that decision-making is less subject to emotional biases in those with ASD. PMID:26375827

Contribution of SHANK3 Mutations to Autism Spectrum Disorder

PubMed Central

Moessner, Rainald ; Marshall, Christian R. ; Sutcliffe, James S. ; Skaug, Jennifer ; Pinto, Dalila ; Vincent, John ; Zwaigenbaum, Lonnie ; Fernandez, Bridget ; Roberts, Wendy ; Szatmari, Peter ; Scherer, Stephen W. 

2007-01-01

Mutations in SHANK3, which encodes a synaptic scaffolding protein, have been described in subjects with an autism spectrum disorder (ASD). To assess the quantitative contribution of SHANK3 to the pathogenesis of autism, we determined the frequency of DNA sequence and copy-number variants in this gene in 400 ASD-affected subjects ascertained in Canada. One de novo mutation and two gene deletions were discovered, indicating a contribution of 0.75% in this cohort. One additional SHANK3 deletion was characterized in two ASD-affected siblings from another collection, which brings the total number of published mutations in unrelated ASD-affected families to seven. The combined data provide support that haploinsufficiency of SHANK3 can cause a monogenic form of autism in sufficient frequency to warrant consideration in clinical diagnostic testing. PMID:17999366

The first 1000 days of the autistic brain: a systematic review of diffusion imaging studies.

PubMed

Conti, Eugenia; Calderoni, Sara; Marchi, Viviana; Muratori, Filippo; Cioni, Giovanni; Guzzetta, Andrea

2015-01-01

There is overwhelming evidence that autism spectrum disorder (ASD) is related to altered brain connectivity. While these alterations are starting to be well characterized in subjects where the clinical picture is fully expressed, less is known on their earlier developmental course. In the present study we systematically reviewed current knowledge on structural connectivity in ASD infants and toddlers. We searched PubMed and Medline databases for all English language papers, published from year 2000, exploring structural connectivity in populations of infants and toddlers whose mean age was below 30 months. Of the 264 papers extracted, four were found to be eligible and were reviewed. Three of the four selected studies reported higher fractional anisotropy values in subjects with ASD compared to controls within commissural fibers, projections fibers, and association fibers, suggesting brain hyper-connectivity in the earliest phases of the disorder. Similar conclusions emerged from the other diffusion parameters assessed. These findings are reversed to what is generally found in studies exploring older patient groups and suggest a developmental course characterized by a shift toward hypo-connectivity starting at a time between two and four years of age.

Robot-mediated Imitation Skill Training for Children with Autism

PubMed Central

Zheng, Zhi; Young, Eric M.; Swanson, Amy R.; Weitlauf, Amy S.; Warren, Zachary E.; Sarkar, Nilanjan

2016-01-01

Autism spectrum disorder (ASD) impacts 1 in 68 children in the US, with tremendous individual and societal costs. Technology-aided intervention, more specifically robotic intervention, has gained momentum in recent years due to the inherent affinity of many children with ASD towards technology. In this paper we present a novel robot-mediated intervention system for imitation skill learning, which is considered a core deficit area for children with ASD. The Robot-mediated Imitation Skill Training Architecture (RISTA) is designed in such a manner that it can operate either completely autonomously or in coordination with a human therapist depending on the intervention need. Experimental results are presented from small user studies validating system functionality, assessing user tolerance, and documenting subject performance. Preliminary results show that this novel robotic system draws more attention from the children with ASD and teaches gestures more effectively as compared to a human therapist. While no broad generalized conclusions can be made about the effectiveness of RISTA based on our small user studies, initial results are encouraging and justify further exploration in the future. PMID:26353376

Abnormal Cortical Plasticity in Youth with Autism Spectrum Disorder: A Transcranial Magnetic Stimulation Case–Control Pilot Study

PubMed Central

Gilbert, Donald L.; Erickson, Craig A.; Horn, Paul S.; Shaffer, Rebecca C.; Wink, Logan K.; Laue, Cameron S.; Wu, Steve W.

2016-01-01

Abstract Objective: This case–control study investigated the use of a low-intensity repetitive transcranial magnetic stimulation (rTMS) protocol to measure motor cortex (M1) plasticity in youth with autism spectrum disorder (ASD) compared with typically developing children (TDC). We hypothesized that impairments in long-term potentiation-like properties represent a neurophysiological biomarker of abnormal cortical function in ASD. Methods: We studied youth with ASD aged 11–18 years and matched controls (TDC). Intermittent theta burst stimulation (iTBS) was delivered to the dominant M1 at an intensity of 70% of resting motor threshold. Suprathreshold single-pulse TMS was performed to compare amplitudes of motor-evoked potentials (MEP) measured from surface electromyography electrodes on a target muscle before (20 pulses) and after (10 pulses/time point) iTBS at predefined timepoints (up to 30 minutes) to measure any potentiation effects. A linear mixed model was used to examine group differences in MEP amplitudes over time following iTBS. Results: Nine youth with ASD (mean age 15.6; 7 males; 6 right-hand dominant) and 9 TDC (mean age 14.5; 5 males; 9 right-hand dominant) participated. All subjects tolerated the procedure well. Both groups had a mean increase in excitability after iTBS for 30 minutes; however, the time course of excitability changes differed (F9,144 = 2.05; p = 0.038). Post-hoc testing identified a significant decrease in amplitude of the ASD group at 20 minutes following iTBS compared with the TDC after correcting for multiple comparisons. Conclusion: In this study, we demonstrate early evidence for a potential physiological biomarker of cortical plasticity in youth with ASD using a rapid low-intensity rTMS protocol with a discriminate measure at 20 minutes following stimulation. The procedure was well tolerated by all 18 participants. Future work will include modification of the protocol to improve the ability to distinguish subtypes of ASD based on behavioral and cognitive testing. PMID:27007257

32 CFR 56.9 - Ensuring compliance with this part in Federal financial assistance programs and activities.

Code of Federal Regulations, 2012 CFR

2012-07-01

... approval of these supplementary guidelines from the ASD(MRA&L), or designee, before issuing them. Prior to their issuance, the ASD(MRA&L), or designee, shall submit supplementary guidelines prepared pursuant to... Components deal with the employment of civilians in programs and activities subject to this part the ASD(MRA...

32 CFR 56.9 - Ensuring compliance with this part in Federal financial assistance programs and activities.

Code of Federal Regulations, 2013 CFR

2013-07-01

... approval of these supplementary guidelines from the ASD(MRA&L), or designee, before issuing them. Prior to their issuance, the ASD(MRA&L), or designee, shall submit supplementary guidelines prepared pursuant to... Components deal with the employment of civilians in programs and activities subject to this part the ASD(MRA...

32 CFR 56.9 - Ensuring compliance with this part in Federal financial assistance programs and activities.

Code of Federal Regulations, 2014 CFR

2014-07-01

... approval of these supplementary guidelines from the ASD(MRA&L), or designee, before issuing them. Prior to their issuance, the ASD(MRA&L), or designee, shall submit supplementary guidelines prepared pursuant to... Components deal with the employment of civilians in programs and activities subject to this part the ASD(MRA...

Interventions to Support Social Interaction in Children with Autism Spectrum Disorders: A Systematic Review of Single Case Studies

ERIC Educational Resources Information Center

Ozuna, Jennifer; Mavridis, Alexis; Hott, Brittany L.

2015-01-01

Social interaction is a core deficit in individuals with autism spectrum disorder (ASD). Therefore, parents and teachers need effective interventions to support students with ASD. This synthesis provides a quantitative analysis of single-subject studies that examine interventions to support social interactions in children with ASD. Results suggest…

Sleep Disturbances and Correlates of Children with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Liu, Xianchen; Hubbard, Julie A.; Fabes, Richard A.; Adam, James B.

2006-01-01

This study examined sleep patterns, sleep problems, and their correlates in children with autism spectrum disorders (ASD). Subjects consisted of 167 ASD children, including 108 with autistic disorder, 27 with Asperger's syndrome, and 32 with other diagnoses of ASD. Mean age was 8.8 years (SD = 4.2), 86% were boys. Parents completed a…

European studies on prevalence and risk of autism spectrum disorders according to immigrant status-a review.

PubMed

Kawa, Rafal; Saemundsen, Evald; Lóa Jónsdóttir, Sigrídur; Hellendoorn, Annika; Lemcke, Sanne; Canal-Bedia, Ricardo; García-Primo, Patricia; Moilanen, Irma

2017-02-01

Autism spectrum disorders (ASDs), once considered to be rare, are now reaching prevalence estimates of 1% and higher. Studies conducted in North America indicate large racial/ethnic disparities in the diagnosis of ASDs. Others show, that immigrant children have similar prevalence rates of ASDs as native children, although they are diagnosed later compared with native children. In relation to a EU funded network action, Enhancing the Scientific Study of Early Autism, it was considered important to review the literature on this subject. A comprehensive literature search was undertaken for original articles reporting on prevalence and risk for ASD in Europe among immigrants and ethnic minorities and data across studies were compared. Seventeen studies conducted in Europe concerning immigrants and ethnic minorities were found. Fifteen studies suggest a higher prevalence rate of ASDs among children of immigrants in comparison to native children (RR = 1.02-1.74; OR = 0.6-10.5). One study revealed higher prevalence of autism (OR = 2.2; 95% CI 1.6-3.1) and lower prevalence of Asperger syndrome in immigrants (OR = 0.6; 95% CI 0.3-0.97). One study showed a lower prevalence of Asperger syndrome in immigrants (aOR = 0.1, 95% CI 0.01-0.5). The majority of those analyses involved immigrants from outside Europe, e.g. from Africa and South America. After analysing the results of studies conducted in Europe, it is unclear if higher prevalence estimates of ASDs among immigrants in this region reflect true differences, especially considering many potential confounding factors, e.g. genetic, biological, environmental and cultural. Considering the number of people migrating within Europe there is a substantial need to study further the prevalence of ASDs in immigrant groups. © The Author 2016. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

Abnormal social reward processing in autism as indexed by pupillary responses to happy faces

PubMed Central

2012-01-01

Background Individuals with Autism Spectrum Disorders (ASD) typically show impaired eye contact during social interactions. From a young age, they look less at faces than typically developing (TD) children and tend to avoid direct gaze. However, the reason for this behavior remains controversial; ASD children might avoid eye contact because they perceive the eyes as aversive or because they do not find social engagement through mutual gaze rewarding. Methods We monitored pupillary diameter as a measure of autonomic response in children with ASD (n = 20, mean age = 12.4) and TD controls (n = 18, mean age = 13.7) while they looked at faces displaying different emotions. Each face displayed happy, fearful, angry or neutral emotions with the gaze either directed to or averted from the subjects. Results Overall, children with ASD and TD controls showed similar pupillary responses; however, they differed significantly in their sensitivity to gaze direction for happy faces. Specifically, pupillary diameter increased among TD children when viewing happy faces with direct gaze as compared to those with averted gaze, whereas children with ASD did not show such sensitivity to gaze direction. We found no group differences in fixation that could explain the differential pupillary responses. There was no effect of gaze direction on pupil diameter for negative affect or neutral faces among either the TD or ASD group. Conclusions We interpret the increased pupillary diameter to happy faces with direct gaze in TD children to reflect the intrinsic reward value of a smiling face looking directly at an individual. The lack of this effect in children with ASD is consistent with the hypothesis that individuals with ASD may have reduced sensitivity to the reward value of social stimuli. PMID:22958650

Prefrontal activation during inhibitory control measured by near-infrared spectroscopy for differentiating between autism spectrum disorders and attention deficit hyperactivity disorder in adults.

PubMed

Ishii-Takahashi, Ayaka; Takizawa, Ryu; Nishimura, Yukika; Kawakubo, Yuki; Kuwabara, Hitoshi; Matsubayashi, Junko; Hamada, Kasumi; Okuhata, Shiho; Yahata, Noriaki; Igarashi, Takashi; Kawasaki, Shingo; Yamasue, Hidenori; Kato, Nobumasa; Kasai, Kiyoto; Kano, Yukiko

2014-01-01

The differential diagnosis of autism spectrum disorders (ASDs) and attention deficit hyperactivity disorder (ADHD) based solely on symptomatic and behavioral assessments can be difficult, even for experts. Thus, the development of a neuroimaging marker that differentiates ASDs from ADHD would be an important contribution to this field. We assessed the differences in prefrontal activation between adults with ASDs and ADHD using an entirely non-invasive and portable neuroimaging tool, near-infrared spectroscopy. This study included 21 drug-naïve adults with ASDs, 19 drug-naïve adults with ADHD, and 21 healthy subjects matched for age, sex, and IQ. Oxygenated hemoglobin concentration changes in the prefrontal cortex were assessed during a stop signal task and a verbal fluency task. During the stop signal task, compared to the control group, the ASDs group exhibited lower activation in a broad prefrontal area, whereas the ADHD group showed underactivation of the right premotor area, right presupplementary motor area, and bilateral dorsolateral prefrontal cortices. Significant differences were observed in the left ventrolateral prefrontal cortex between the ASDs and ADHD groups during the stop signal task. The leave-one-out cross-validation method using mean oxygenated hemoglobin changes yielded a classification accuracy of 81.4% during inhibitory control. These results were task specific, as the brain activation pattern observed during the verbal fluency task did not differentiate the ASDs and ADHD groups significantly. This study therefore provides evidence of a difference in left ventrolateral prefrontal activation during inhibitory control between adults with ASDs and ADHD. Thus, near-infrared spectroscopy may be useful as an auxiliary tool for the differential diagnosis of such developmental disorders.

Disturbed holistic processing in autism spectrum disorders verified by two cognitive tasks requiring perception of complex visual stimuli.

PubMed

Nakahachi, Takayuki; Yamashita, Ko; Iwase, Masao; Ishigami, Wataru; Tanaka, Chitaru; Toyonaga, Koji; Maeda, Shizuyo; Hirotsune, Hideto; Tei, Yosyo; Yokoi, Koichi; Okajima, Shoji; Shimizu, Akira; Takeda, Masatoshi

2008-06-30

Central coherence is a key concept in research on autism spectrum disorders (ASD). It refers to the process in which diverse information is integrated and higher meaning is constructed in context. A malfunction in this process could result in abnormal attention to partial information in preference to the whole. To verify this hypothesis, we studied the performance of two visual tasks by 10 patients with autistic disorder or Asperger's disorder and by 26 (experiment 1) or 25 (experiment 2) normal subjects. In experiment 1, the subjects memorized pictures, some pictures with a change related to the main theme (D1) and others with a change not related to the main theme (D2); then the same pictures were randomly presented to the subjects who were asked to find the change. In experiment 2, the subjects were presented pictures of a normal (N) or a Thatcherized (T) face arranged side by side inversely (I) or uprightly (U) and to judge them as the same or different. In experiment 1, ASD subjects exhibited significantly lower rates of correct responses in D1 but not in D2. In experiment 2, ASD subjects exhibited significantly longer response times in NT-U but not in TN-I. These results showed a deficit in holistic processing, which is consistent with weak central coherence in ASD.

The impact of autism spectrum disorder and alexithymia on judgments of moral acceptability.

PubMed

Brewer, Rebecca; Marsh, Abigail A; Catmur, Caroline; Cardinale, Elise M; Stoycos, Sarah; Cook, Richard; Bird, Geoffrey

2015-08-01

One's own emotional response toward a hypothetical action can influence judgments of its moral acceptability. Some individuals with autism spectrum disorder (ASD) exhibit atypical emotional processing, and moral judgments. Research suggests, however, that emotional deficits in ASD are due to co-occurring alexithymia, meaning atypical moral judgments in ASD may be due to alexithymia also. Individuals with and without ASD (matched for alexithymia) judged the moral acceptability of emotion-evoking statements and identified the emotion evoked. Moral acceptability judgments were predicted by alexithymia. Crucially, however, this relationship held only for individuals without ASD. While ASD diagnostic status did not directly predict either judgment, those with ASD did not base their moral acceptability judgments on emotional information. Findings are consistent with evidence demonstrating that decision-making is less subject to emotional biases in those with ASD. (c) 2015 APA, all rights reserved).

Valence Scaling of Dynamic Facial Expressions Is Altered in High-Functioning Subjects with Autism Spectrum Disorders: An FMRI Study

ERIC Educational Resources Information Center

Rahko, Jukka S.; Paakki, Jyri-Johan; Starck, Tuomo H.; Nikkinen, Juha; Pauls, David L.; Katsyri, Jari V.; Jansson-Verkasalo, Eira M.; Carter, Alice S.; Hurtig, Tuula M.; Mattila, Marja-Leena; Jussila, Katja K.; Remes, Jukka J.; Kuusikko-Gauffin, Sanna A.; Sams, Mikko E.; Bolte, Sven; Ebeling, Hanna E.; Moilanen, Irma K.; Tervonen, Osmo; Kiviniemi, Vesa

2012-01-01

FMRI was performed with the dynamic facial expressions fear and happiness. This was done to detect differences in valence processing between 25 subjects with autism spectrum disorders (ASDs) and 27 typically developing controls. Valence scaling was abnormal in ASDs. Positive valence induces lower deactivation and abnormally strong activity in ASD…

Caregiver Strain and Sensory Features in Children with Autism Spectrum Disorder and other Developmental Disabilities

PubMed Central

Kirby, Anne V.; White, Tamira J.; Baranek, Grace T.

2015-01-01

Caring for children with disabilities contributes to increased levels of parent stress, or caregiver strain. However, the potential relationship of sensory features to strain among caregivers of children with autism spectrum disorder (ASD) and other developmental disabilities (DD) is unknown. Sensory features include over-reactions, under-reactions, and unusual interests in sensations, which may negatively impact family functioning. This descriptive study confirmed three caregiver strain types (i.e., objective, subjective internalized, subjective externalized) and explored differences among ASD (n=71) and DD (n=36) groups, with the ASD group reporting higher levels. Furthermore, this study explored the contribution of sensory features to caregiver strain, finding differential contributions to strain in the ASD group and covariate contributions (i.e., child cognition, mother’s education) in the DD group. PMID:25551265

Effects of two Asian sand dusts transported from the dust source regions of Inner Mongolia and northeast China on murine lung eosinophilia

DOE Office of Scientific and Technical Information (OSTI.GOV)

He, Miao, E-mail: hemiao.cmu@gmail.com; Department of Health Sciences, Oita University of Nursing and Health Sciences, 870-1201 Oita; Ichinose, Takamichi, E-mail: ichinose@oita-nhs.ac.jp

The quality and quantity of toxic materials adsorbed onto Asian sand dust (ASD) are different based on dust source regions and passage routes. The aggravating effects of two ASDs (ASD1 and ASD2) transported from the source regions of Inner Mongolia and northeast China on lung eosinophilia were compared to clarify the role of toxic materials in ASD. The ASDs contained different amounts of lipopolysaccharides (LPS) and β-glucan (ASD1 < ASD2) and SiO{sub 2} (ASD1 > ASD2). CD-1 mice were instilled intratracheally with ASD1, ASD2 and/or ovalbumin (OVA) four times at 2-week intervals. ASD1 and ASD2 enhanced eosinophil recruitment induced bymore » OVA in the submucosa of the airway, with goblet cell proliferation in the bronchial epithelium. ASD1 and ASD2 synergistically increased OVA-induced eosinophil-relevant cytokines interleukin-5 (IL-5), IL-13 (ASD1 < ASD2) and chemokine eotaxin (ASD1 > ASD2) in bronchoalveolar lavage fluid. ASD2 aggravating effects on lung eosinophilia were greater than ASD1. The role of LPS and β-glucan in ASD2 on the production of pro-inflammatory mediators was assessed using in vitro bone marrow-derived macrophages (BMDMs) from wild type, Toll-like receptor 2-deficient (TLR2 −/−), TLR4 −/−, and MyD88 −/− mice (on Balb/c background). ASD2-stimulated TLR2 −/− BMDMs enhanced IL-6, IL-12, TNF-α, MCP-1 and MIP-1α secretion compared with ASD2-stimulated TLR4 −/− BMDMs. Protein expression from ASD2-stimulated MyD88 −/− BMDM were very low or undetectable. The in vitro results indicate that lung eosinophilia caused by ASD is TLR4 dependent. Therefore, the aggravation of OVA-related lung eosinophilia by ASD may be dependent on toxic substances derived from microbes, such as LPS, rather than SiO{sub 2}. - Highlights: • Asian sand dust (ASD) from the deserts of China causes serious respiratory problems. • The aggravating effects of two ASDs on lung eosinophilia were compared. • The ASDs contained different LPS and β-glucan (ASD1 < ASD2) and SiO{sub 2} (ASD1 > ASD2). • The ASD2 aggravating effects on lung eosinophilia were greater than ASD1. • The aggravation of lung eosinophilia may be dependent on LPS in ASD, rather than SiO{sub 2}.« less

Altered proliferation and networks in neural cells derived from idiopathic autistic individuals.

PubMed

Marchetto, Maria C; Belinson, Haim; Tian, Yuan; Freitas, Beatriz C; Fu, Chen; Vadodaria, Krishna; Beltrao-Braga, Patricia; Trujillo, Cleber A; Mendes, Ana P D; Padmanabhan, Krishnan; Nunez, Yanelli; Ou, Jing; Ghosh, Himanish; Wright, Rebecca; Brennand, Kristen; Pierce, Karen; Eichenfield, Lawrence; Pramparo, Tiziano; Eyler, Lisa; Barnes, Cynthia C; Courchesne, Eric; Geschwind, Daniel H; Gage, Fred H; Wynshaw-Boris, Anthony; Muotri, Alysson R

2017-06-01

Autism spectrum disorders (ASD) are common, complex and heterogeneous neurodevelopmental disorders. Cellular and molecular mechanisms responsible for ASD pathogenesis have been proposed based on genetic studies, brain pathology and imaging, but a major impediment to testing ASD hypotheses is the lack of human cell models. Here, we reprogrammed fibroblasts to generate induced pluripotent stem cells, neural progenitor cells (NPCs) and neurons from ASD individuals with early brain overgrowth and non-ASD controls with normal brain size. ASD-derived NPCs display increased cell proliferation because of dysregulation of a β-catenin/BRN2 transcriptional cascade. ASD-derived neurons display abnormal neurogenesis and reduced synaptogenesis leading to functional defects in neuronal networks. Interestingly, defects in neuronal networks could be rescued by insulin growth factor 1 (IGF-1), a drug that is currently in clinical trials for ASD. This work demonstrates that selection of ASD subjects based on endophenotypes unraveled biologically relevant pathway disruption and revealed a potential cellular mechanism for the therapeutic effect of IGF-1.

Additive effect of congenital heart disease and early developmental disorders on attention-deficit/hyperactivity disorder and autism spectrum disorder: a nationwide population-based longitudinal study.

PubMed

Tsao, Pei-Chen; Lee, Yu-Sheng; Jeng, Mei-Jy; Hsu, Ju-Wei; Huang, Kai-Lin; Tsai, Shih-Jen; Chen, Mu-Hong; Soong, Wen-Jue; Kou, Yu Ru

2017-11-01

In this retrospective nationwide population-based case-control study, we investigated the impact of congenital heart disease (CHD) on the development of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), which remains unclear. Children aged <18 years that were diagnosed with CHD (n = 3552) between January 1, 1997 and December 31, 2009 were identified from the National Health Insurance Research Database in Taiwan. Non-CHD controls (n = 14,208) matched for age and sex (1:4) were selected from the same dataset. All subjects were observed until December 31, 2011 or their death. Comorbid perinatal conditions and early developmental disorders (EDD) that were diagnosed before ADHD and ASD diagnosis were also analyzed. The incidence rates of perinatal comorbidities, EDD, ADHD, and ASD were higher in the CHD group than in the control group. Multivariate Cox regression analysis revealed that the CHD group had an increased risk of developing ADHD (adjusted hazard ratio [aHR] 2.52, 95% confidence interval CI 1.96-3.25) and ASD (aHR 1.97, 95% CI 1.11-3.52) after adjusting for confounding comorbidities. EDD, but not perinatal comorbidities were also independent risk factors for ADHD and ASD after adjustment. Subgroup analysis indicated that the risk for ADHD (HR 16.59, 95% CI 12.17-22.60) and ASD (HR 80.68, 95% CI 39.96-176.12) was greatly increased in CHD subjects with EDD than in non-CHD subjects without EDD. These findings suggested that CHD at birth and EDD during early childhood were two independent risk factors for ADHD and ASD and that concurrent CHD and EDD might additively increase these risks.

Three-column osteotomy surgery versus standard surgical management for the correction of adult spinal deformity: a cohort study.

PubMed

Ji, Xinran; Chen, Hua; Zhang, Yiling; Zhang, Lihai; Zhang, Wei; Berven, Sigurd; Tang, Peifu

2015-02-03

The aim of this study was to analyze and compare the surgical data, clinical outcomes, and complications between three-column osteotomy (3-COS) and standard surgical management (SSM) for the treatment of adult spine deformity (ASD). A total of 112 patients who underwent consecutive 3-COS (n = 48) and SSM (n = 64) procedures for ASD correction at a single institution from 2001 to 2011 were reviewed in this study. The outcomes were assessed using the Scoliosis Research Society (SRS)-22 scores. The complications of patients with 3-COS and SSM were also compared. No significant differences were found in patient characteristics between SSM and 3-COS groups. Surgical data and radiographic parameters showed that the patients of the 3-COS group suffered more severe ASD than those of the SSM group. The distribution of surgical complications revealed that SSM group underwent more complications than 3-COS groups with no significant differences. At final follow-up, the total SRS-22 score of SSM was not significant between pre-operation and post-operation. However, the total SRS-22 score of 3-COS at final follow-up was significantly higher than pre-operation. For severe ASD patients with high grade pelvic incidence (PI), pelvic tilt (PT), and PI/lumbar lordosis (LL) mismatch and who have subjected to spine surgeries more than twice before, 3-COS might be more effective than SSM in improving the clinical outcomes. However, due to the higher reoperation rate of 3-COS, SSM may be more appropriate than SSM for correcting the not serious ASD patients.

What do home videos tell us about early motor and socio-communicative behaviours in children with autistic features during the second year of life – an exploratory study

PubMed Central

Zappella, Michele; Einspieler, Christa; Bartl-Pokorny, Katrin D.; Krieber, Magdalena; Coleman, Mary; Bölte, Sven; Marschik, Peter B.

2018-01-01

Background Little is known about the first half year of life of individuals later diagnosed with autism spectrum disorders (ASD). There is even a complete lack of observations on the first 6 months of life of individuals with transient autistic behaviours who improved in their socio-communicative functions in the pre-school age. Aim To compare early development of individuals with transient autistic behaviours and those later diagnosed with ASD. Study design Exploratory study; retrospective home video analysis. Subjects 18 males, videoed between birth and the age of 6 months (ten individuals later diagnosed with ASD; eight individuals who lost their autistic behaviours after the age of 3 and achieved age-adequate communicative abilities, albeit often accompanied by tics and attention deficit). Method The detailed video analysis focused on general movements (GMs), the concurrent motor repertoire, eye contact, responsive smiling, and pre-speech vocalisations. Results Abnormal GMs were observed more frequently in infants later diagnosed with ASD, whereas all but one infant with transient autistic behaviours had normal GMs (p < 0.05). Eye contact and responsive smiling were inconspicuous for all individuals. Cooing was not observable in six individuals across both groups. Conclusions GMs might be one of the markers which could assist the earlier identification of ASD. We recommend to implement the GM assessment in prospective studies on ASD. PMID:26246137

Cognitive inflexibility in Japanese adolescents and adults with autism spectrum disorders

PubMed Central

Yasuda, Yuka; Hashimoto, Ryota; Ohi, Kazutaka; Yamamori, Hidenaga; Fujimoto, Michiko; Umeda-Yano, Satomi; Fujino, Haruo; Takeda, Masatoshi

2014-01-01

AIM: To investigate executive function in Japanese adolescents and adults with autism spectrum disorders (ASD) compared to Japanese controls. METHODS: Thirty-three individuals with ASD and 33 controls participated. The ASD and control groups’ demographic variables were matched for gender (male/female: 20/13 vs 20/13), age (26.1 ± 11.5 vs 26.8 ± 9.6), years of education (13.2 ± 2.9 vs 14.2 ± 1.9), full-scale intelligence quotient (IQ) (103.0 ± 16.7 vs 103.7 ± 14.7), performance IQ (96.2 ± 16.1 vs 97.8 ± 15.0), and verbal IQ (107.9 ± 16.3 vs 107.7 ± 14.4). Participants performed the Wisconsin Card Sorting Test (WCST), which assesses the executive processes involved in problem solving and cognitive flexibility, and the Continuous Performance Test (CPT), which assesses attention and impulsivity. Symptoms were assessed by the Autism-Spectrum Quotient Japanese version (AQ-J). First, we compared the scores of the WCST between the groups using a Mann-Whitney U-test and conducted an analysis of covariance for the variables with the scores of category archives and CPT scores as covariates. Second, we analyzed the correlation between the scores of the WCST and the AQ-J in the ASD group using Pearson’s r. RESULTS: The total errors (TE) and the percentages of perseverative errors of the Milner type (%PEM) and Nelson type (%PEN) among the TE in the ASD group were significantly worse compared with the control group (ASD vs Control, respectively: TE: 16.0 ± 6.2 vs 12.6 ± 3.5, P = 0.012; %PEM: 11.7 ± 10.7 vs 6.6 ± 8.9, P = 0.037; %PEN: 20.1 ± 14.5 vs 8.7 ± 10.4, P = 0.0011). In contrast, no significant difference was observed between the two groups in the scores of categories achieved on the WCST or the CPT. An analysis of covariance revealed significant differences between the groups in the %PEN scores (P = 0.0062) but not in the TE or the %PEM scores. These results suggest that Japanese adolescents and adults with ASD have cognitive inflexibility. Furthermore, our results suggest that Japanese adolescents and adults with ASD may have difficulties using negative feedback because perseverative errors of the Nelson type indicate persistence in choosing the incorrect reaction. By contrast, there was no significant correlation between the WCST and AQ-J scores. CONCLUSION: We confirmed the presence of cognitive inflexibility in Japanese adolescents and adults with ASD. Our results also indicated that subjects with ASD may not use negative feedback effectively. PMID:25019056

Corticosteroid therapy in regressive autism: a retrospective study of effects on the Frequency Modulated Auditory Evoked Response (FMAER), language, and behavior

PubMed Central

2014-01-01

Background Up to a third of children with Autism Spectrum Disorder (ASD) manifest regressive autism (R-ASD).They show normal early development followed by loss of language and social skills. Absent evidence-based therapies, anecdotal evidence suggests improvement following use of corticosteroids. This study examined the effects of corticosteroids for R-ASD children upon the 4 Hz frequency modulated evoked response (FMAER) arising from language cortex of the superior temporal gyrus (STG) and upon EEG background activity, language, and behavior. An untreated clinical convenience sample of ASD children served as control sample. Methods Twenty steroid-treated R-ASD (STAR) and 24 not-treated ASD patients (NSA), aged 3 - 5 years, were retrospectively identified from a large database. All study participants had two sequential FMAER and EEG studies;Landau-Kleffner syndrome diagnosis was excluded. All subjects’ records contained clinical receptive and expressive language ratings based upon a priori developed metrics. The STAR group additionally was scored behaviorally regarding symptom severity as based on the Diagnostic and Statistical Manual IV (DSM-IV) ASD criteria list. EEGs were visually scored for abnormalities. FMAER responses were assessed quantitatively by spectral analysis. Treated and untreated group means and standard deviations for the FMAER, EEG, language, and behavior, were compared by paired t-test and Fisher’s exact tests. Results The STAR group showed a significant increase in the 4 Hz FMAER spectral response and a significant reduction in response distortion compared to the NSA group. Star group subjects’ language ratings were significantly improved and more STAR than NSA group subjects showed significant language improvement. Most STAR group children showed significant behavioral improvement after treatment. STAR group language and behavior improvement was retained one year after treatment. Groups did not differ in terms of minor EEG abnormalities. Steroid treatment produced no lasting morbidity. Conclusions 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. Please see related article http://www.biomedcentral.com/1741-7015/12/79 PMID:24885033

Usefulness of near-infrared spectroscopy to detect brain dysfunction in children with autism spectrum disorder when inferring the mental state of others.

PubMed

Iwanaga, Ryoichiro; Tanaka, Goro; Nakane, Hideyuki; Honda, Sumihisa; Imamura, Akira; Ozawa, Hiroki

2013-05-01

The purpose of this study was to examine the usefulness of near-infrared spectroscopy (NIRS) for identifying abnormalities in prefrontal brain activity in children with autism spectrum disorders (ASD) as they inferred the mental states of others. The subjects were 16 children with ASD aged between 8 and 14 years and 16 age-matched healthy control children. Oxygenated hemoglobin concentration was measured in the subject's prefrontal brain region on NIRS during tasks expressing a person's mental state (MS task) and expressing an object's characteristics (OC task). There was a significant main effect of group (ASD vs control), with the control group having more activity than the ASD group. But there was no significant main effect of task (MS task vs OC task) or hemisphere (right vs left). Significant interactions of task and group were found, with the control group showing more activity than the ASD group during the MS task relative to the OC task. NIRS showed that there was lower activity in the prefrontal brain area when children with ASD performed MS tasks. Therefore, clinicians might be able to use NIRS and these tasks for conveniently detecting brain dysfunction in children with ASD related to inferring mental states, in the clinical setting. © 2013 The Authors. Psychiatry and Clinical Neurosciences © 2013 Japanese Society of Psychiatry and Neurology.

Diagnosing ASD in Adults without ID: Accuracy of the ADOS-2 and the ADI-R

ERIC Educational Resources Information Center

Fusar-Poli, Laura; Brondino, Natascia; Rocchetti, Matteo; Panisi, Cristina; Provenzani, Umberto; Damiani, Stefano; Politi, Pierluigi

2017-01-01

Diagnosing autism spectrum disorder (ASD) in adulthood often represents a challenge in clinical practice. The aim of the present study was to evaluate the sensitivity and specificity of the ADOS and ADI-R in diagnosing ASD in adults. 113 subjects with an IQ of 70 or above were assessed through an extensive clinical evaluation. The ADOS-2 Module 4…

Imaging Depression in Adults With ASD

DTIC Science & Technology

2015-10-30

immunologic bias in autism spectrum disorder (ASD) confers greater risk for co-occurring depression than severity of ASD. If depression severity is associated...other healthcare professionals or caregivers with an interest in autism spectrum disorders , open to the public. No subject has consented to and enrolled...nationally known researchers in two areas: sign language linguistics and the study of social communication among individuals with autism spectrum disorders

The association between familial ASD diagnosis, autism symptomatology and developmental functioning in young children.

PubMed

Estabillo, Jasper A; Matson, Johnny L; Jiang, Xinrui

2016-10-01

Few studies have directly compared individuals with and without a relative diagnosed with ASD on various domains. The present study aimed to examine the relationship between familial ASD diagnosis and the exhibition of ASD symptoms in young children with and without ASD diagnoses. Participants included 8353 children aged 17-37 months old and their families. They were divided into four groups based on individual and family diagnosis, then compared on autism symptomatology and developmental domains. No differences were found between ASD groups on overall scores and each of the factor domains, indicating no association between family ASD diagnosis and ASD symptomatology or developmental functioning. Disparate results were found for atypically developing groups with and without relatives diagnosed with ASD. Implications of these results are discussed.

Children with autism spectrum disorders show abnormal conditioned response timing on delay, but not trace, eyeblink conditioning

PubMed Central

Oristaglio, Jeff; West, Susan Hyman; Ghaffari, Manely; Lech, Melissa S.; Verma, Beeta R.; Harvey, John A.; Welsh, John P.; Malone, Richard P.

2013-01-01

Children with autism spectrum disorder (ASD) and age-matched typically-developing (TD) peers were tested on two forms of eyeblink conditioning (EBC), a Pavlovian associative learning paradigm where subjects learn to execute an appropriately-timed eyeblink in response to a previously neutral conditioning stimulus (CS). One version of the task, trace EBC, interposes a stimulus-free interval between the presentation of the CS and the unconditioned stimulus (US), a puff of air to the eye which causes subjects to blink. In delay EBC, the CS overlaps in time with the delivery of the US, usually with both stimuli terminating simultaneously. ASD children performed normally during trace EBC, exhibiting no differences from typically-developing (TD) subjects with regard to learning rate or the timing of the CR. However, when subsequently tested on delay EBC, subjects with ASD displayed abnormally-timed conditioned eye blinks that began earlier and peaked sooner than those of TD subjects, consistent with previous findings. The results suggest an impaired ability of children with ASD to properly time conditioned eye blinks which appears to be specific to delay EBC. We suggest that this deficit may reflect a dysfunction of cerebellar cortex in which increases in the intensity or duration of sensory input can temporarily disrupt the accuracy of motor timing over short temporal intervals. PMID:23769889

Response time intra-subject variability: commonalities between children with autism spectrum disorders and children with ADHD

PubMed Central

Adamo, Nicoletta; Huo, Lan; Adelsberg, Samantha; Petkova, Eva; Castellanos, F. Xavier

2013-01-01

Despite the common co-occurrence of symptoms of attention deficit hyperactivity disorder (ADHD) in individuals with autism spectrum disorders (ASD), the underlying mechanisms are under-explored. A potential candidate for investigation is response time intra-subject variability (RT-ISV), a hypothesized marker of attentional lapses. Direct comparisons of RT-ISV in ASD versus ADHD are limited and contradictory. We aimed to examine whether distinct fluctuations in RT-ISV characterize children with ASD and with ADHD relative to typically developing children (TDC). We applied both a priori-based and data-driven strategies to RT performance of 46 children with ASD, 46 with ADHD, and 36 TDC (aged 7–11.9 years). Specifically, we contrasted groups relative to the amplitude of four preselected frequency bands as well as to 400 frequency bins from 0.006 to 0.345 Hz. In secondary analyses, we divided the ASD group into children with and without substantial ADHD symptoms (ASD+ and ASD−, respectively). Regardless of the strategy employed, RT-ISV fluctuations at frequencies between 0.20 and 0.345 Hz distinguished children with ADHD, but not children with ASD, from TDC. Children with ASD+ and those with ADHD shared elevated amplitudes of RT-ISV fluctuations in frequencies between 0.18 and 0.345 Hz relative to TDC. In contrast, the ASD− subgroup did not differ from TDC in RT-ISV frequency fluctuations. RT-ISV fluctuations in frequencies 0.18–0.345 Hz (i.e., periods between 3 and 5 s) are associated with ADHD symptoms regardless of categorical diagnosis and may represent a biomarker. These results suggest that children with ADHD and those with ASD+ share common underlying pathophysiological mechanisms of RT-ISV. PMID:23716135

Sparse brain network using penalized linear regression

NASA Astrophysics Data System (ADS)

Lee, Hyekyoung; Lee, Dong Soo; Kang, Hyejin; Kim, Boong-Nyun; Chung, Moo K.

2011-03-01

Sparse partial correlation is a useful connectivity measure for brain networks when it is difficult to compute the exact partial correlation in the small-n large-p setting. In this paper, we formulate the problem of estimating partial correlation as a sparse linear regression with a l1-norm penalty. The method is applied to brain network consisting of parcellated regions of interest (ROIs), which are obtained from FDG-PET images of the autism spectrum disorder (ASD) children and the pediatric control (PedCon) subjects. To validate the results, we check their reproducibilities of the obtained brain networks by the leave-one-out cross validation and compare the clustered structures derived from the brain networks of ASD and PedCon.

Human movement stochastic variability leads to diagnostic biomarkers In Autism Spectrum Disorders (ASD)

NASA Astrophysics Data System (ADS)

Wu, Di; Torres, Elizabeth B.; Jose, Jorge V.

2015-03-01

ASD is a spectrum of neurodevelopmental disorders. The high heterogeneity of the symptoms associated with the disorder impedes efficient diagnoses based on human observations. Recent advances with high-resolution MEM wearable sensors enable accurate movement measurements that may escape the naked eye. It calls for objective metrics to extract physiological relevant information from the rapidly accumulating data. In this talk we'll discuss the statistical analysis of movement data continuously collected with high-resolution sensors at 240Hz. We calculated statistical properties of speed fluctuations within the millisecond time range that closely correlate with the subjects' cognitive abilities. We computed the periodicity and synchronicity of the speed fluctuations' from their power spectrum and ensemble averaged two-point cross-correlation function. We built a two-parameter phase space from the temporal statistical analyses of the nearest neighbor fluctuations that provided a quantitative biomarker for ASD and adult normal subjects and further classified ASD severity. We also found age related developmental statistical signatures and potential ASD parental links in our movement dynamical studies. Our results may have direct clinical applications.

Late Positive Potential ERP Responses to Social and Nonsocial Stimuli in Youth with Autism Spectrum Disorder

PubMed Central

Benning, Stephen D.; Kovac, Megan; Campbell, Alana; Miller, Stephanie; Hanna, Eleanor K.; Damiano, Cara R.; Sabatino-DiCriscio, Antoinette; Turner-Brown, Lauren; Sasson, Noah J.; Aaron, Rachel V.; Kinard, Jessica; Dichter, Gabriel S.

2016-01-01

We examined the late positive potential (LPP) event related potential in response to social and nonsocial stimuli from 9-19 years old youth with (n = 35) and without (n = 34) ASD. Social stimuli were faces with positive expressions and nonsocial stimuli were related to common restricted interests in ASD (e.g., electronics, vehicles, etc.). The ASD group demonstrated relatively smaller LPP amplitude to social stimuli and relatively larger LPP amplitude to nonsocial stimuli. There were no group differences in subjective ratings of images, and there were no significant correlations between LPP amplitude and ASD symptom severity within the ASD group. LPP results suggest blunted motivational responses to social stimuli and heightened motivational responses to nonsocial stimuli in youth with ASD. PMID:27344337

Risky decisions and their consequences: neural processing by boys with Antisocial Substance Disorder.

PubMed

Crowley, Thomas J; Dalwani, Manish S; Mikulich-Gilbertson, Susan K; Du, Yiping P; Lejuez, Carl W; Raymond, Kristen M; Banich, Marie T

2010-09-22

Adolescents with conduct and substance problems ("Antisocial Substance Disorder" (ASD)) repeatedly engage in risky antisocial and drug-using behaviors. We hypothesized that, during processing of risky decisions and resulting rewards and punishments, brain activation would differ between abstinent ASD boys and comparison boys. We compared 20 abstinent adolescent male patients in treatment for ASD with 20 community controls, examining rapid event-related blood-oxygen-level-dependent (BOLD) responses during functional magnetic resonance imaging. In 90 decision trials participants chose to make either a cautious response that earned one cent, or a risky response that would either gain 5 cents or lose 10 cents; odds of losing increased as the game progressed. We also examined those times when subjects experienced wins, or separately losses, from their risky choices. We contrasted decision trials against very similar comparison trials requiring no decisions, using whole-brain BOLD-response analyses of group differences, corrected for multiple comparisons. During decision-making ASD boys showed hypoactivation in numerous brain regions robustly activated by controls, including orbitofrontal and dorsolateral prefrontal cortices, anterior cingulate, basal ganglia, insula, amygdala, hippocampus, and cerebellum. While experiencing wins, ASD boys had significantly less activity than controls in anterior cingulate, temporal regions, and cerebellum, with more activity nowhere. During losses ASD boys had significantly more activity than controls in orbitofrontal cortex, dorsolateral prefrontal cortex, brain stem, and cerebellum, with less activity nowhere. Adolescent boys with ASD had extensive neural hypoactivity during risky decision-making, coupled with decreased activity during reward and increased activity during loss. These neural patterns may underlie the dangerous, excessive, sustained risk-taking of such boys. The findings suggest that the dysphoria, reward insensitivity, and suppressed neural activity observed among older addicted persons also characterize youths early in the development of substance use disorders.

A Dopamine Hypothesis of Autism Spectrum Disorder.

PubMed

Pavăl, Denis

2017-01-01

Autism spectrum disorder (ASD) comprises a group of neurodevelopmental disorders characterized by social deficits and stereotyped behaviors. While several theories have emerged, the pathogenesis of ASD remains unknown. Although studies report dopamine signaling abnormalities in autistic patients, a coherent dopamine hypothesis which could link neurobiology to behavior in ASD is currently lacking. In this paper, we present such a hypothesis by proposing that autistic behavior arises from dysfunctions in the midbrain dopaminergic system. We hypothesize that a dysfunction of the mesocorticolimbic circuit leads to social deficits, while a dysfunction of the nigrostriatal circuit leads to stereotyped behaviors. Furthermore, we discuss 2 key predictions of our hypothesis, with emphasis on clinical and therapeutic aspects. First, we argue that dopaminergic dysfunctions in the same circuits should associate with autistic-like behavior in nonautistic subjects. Concerning this, we discuss the case of PANDAS (pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections) which displays behaviors similar to those of ASD, presumed to arise from dopaminergic dysfunctions. Second, we argue that providing dopamine modulators to autistic subjects should lead to a behavioral improvement. Regarding this, we present clinical studies of dopamine antagonists which seem to have improving effects on autistic behavior. Furthermore, we explore the means of testing our hypothesis by using neuroreceptor imaging, which could provide comprehensive evidence for dopamine signaling dysfunctions in autistic subjects. Lastly, we discuss the limitations of our hypothesis. Along these lines, we aim to provide a dopaminergic model of ASD which might lead to a better understanding of the ASD pathogenesis. © 2017 S. Karger AG, Basel.

Excessive Cap-dependent Translation as a Molecular Mechanism Underlying ASD

DTIC Science & Technology

2012-08-01

SUPPLEMENTARY NOTES 14. ABSTRACT We hypothesize that excessive cap-dependent translation is a causative factor in autism spectrum disorder...compounds to therapeutically target eIF4E-eIF4G interactions and eIF4A for treating patients with ASD. 15. SUBJECT TERMS autism spectrum...Introduction We hypothesize that excessive cap-dependent translation is a causative factor in autism spectrum disorder (ASD). To test this

Effects of propranolol on conversational reciprocity in autism spectrum disorder: a pilot, double-blind, single-dose psychopharmacological challenge study.

PubMed

Zamzow, Rachel M; Ferguson, Bradley J; Stichter, Janine P; Porges, Eric C; Ragsdale, Alexandra S; Lewis, Morgan L; Beversdorf, David Q

2016-04-01

Pharmacological intervention for autism spectrum disorder (ASD) is an important addition to treatment, yet currently available agents target co-morbid psychiatric concerns, such as aggression and irritability. Propranolol, a beta-adrenergic antagonist with anxiolytic effects, has been shown to improve verbal fluency and working memory in adults and adolescents with ASD in single-dose challenges. The present pilot study explores the acute effects of propranolol on a measure of conversational reciprocity in this population. We also examined whether autonomic activity and anxiety moderate or mediate response to the drug, given relationships between these variables and ASD, as well as the drug's effects. In a within-subject crossover design, 20 individuals with ASD received a single dose of propranolol or placebo during two sessions in a double-blinded, counterbalanced manner. After drug administration, participants performed a conversational reciprocity task by engaging in a short conversation with the researcher. Measurements of autonomic activity and anxiety were obtained before and after drug administration. Propranolol significantly improved performance on the conversational reciprocity task total [d = 0.40] and nonverbal communication domain scores when compared to the placebo condition. However, neither autonomic activity nor anxiety was significantly associated with drug response. Acute propranolol administration improved conversational reciprocity in ASD. Further exploration of these preliminary findings, as well as other potential treatment response predictors, with serial doses is warranted.

Robotic set-up to quantify hand-eye behavior in motor execution and learning of children with autism spectrum disorder.

PubMed

Casellato, Claudia; Gandolla, Marta; Crippa, Alessandro; Pedrocchi, Alessandra

2017-07-01

Autism spectrum disorder (ASD) is a multifaceted neurodevelopmental disorder characterized by a persistence of social and communication impairment, and restricted and repetitive behaviors. However, motor disorders have also been described, but not objectively assessed. Most studies showed inefficient eye-hand coordination and motor learning in children with ASD; in other experiments, mechanisms of acquisition of internal models in self-generated movements appeared to be normal in autism. In this framework, we have developed a robotic protocol, recording gaze and hand data during upper limb tasks, in which a haptic pen-like handle is moved along specific trajectories displayed on the screen. The protocol includes trials of reaching under a perturbing force field and catching moving targets, with or without visual availability of the whole path. We acquired 16 typically-developing scholar-age children and one child with ASD as a case study. Speed-accuracy tradeoff, motor performance, and gaze-hand spatial coordination have been evaluated. Compared to typically developing peers, in the force field sequence, the child with ASD showed an intact but delayed learning, and more variable gazehand patterns. In the catching trials, he showed less efficient movements, but an intact capability of exploiting the available a-priori plan. The proposed protocol represents a powerful tool, easily tunable, for quantitative (longitudinal) assessment, and for subject-tailored training in ASD.

High rates of parkinsonism in adults with autism.

PubMed

Starkstein, Sergio; Gellar, Scott; Parlier, Morgan; Payne, Leslie; Piven, Joseph

2015-01-01

While it is now recognized that autism spectrum disorder (ASD) is typically a life-long condition, there exist only a handful of systematic studies on middle-aged and older adults with this condition. We first performed a structured examination of parkinsonian motor signs in a hypothesis-generating, pilot study (study I) of 19 adults with ASD over 49 years of age. Observing high rates of parkinsonism in those off atypical neuroleptics (2/12, 17 %) in comparison to published population rates for Parkinson's disease and parkinsonism, we examined a second sample of 37 adults with ASD, over 39 years of age, using a structured neurological assessment for parkinsonism. Twelve of the 37 subjects (32 %) met the diagnostic criteria for parkinsonism; however, of these, 29 subjects were on atypical neuroleptics, complicating interpretation of the findings. Two of eight (25 %) subjects not taking atypical neuroleptic medications met the criteria for parkinsonism. Combining subjects who were not currently taking atypical neuroleptic medications, across both studies, we conservatively classified 4/20 (20 %) with parkinsonism. We find a high frequency of parkinsonism among ASD individuals older than 39 years. If high rates of parkinsonism and potentially Parkinson's disease are confirmed in subsequent studies of ASD, this observation has important implications for understanding the neurobiology of autism and treatment of manifestations in older adults. Given the prevalence of autism in school-age children, the recognition of its life-long natural history, and the recognition of the aging of western societies, these findings also support the importance of further systematic study of other aspects of older adults with autism.

Effects of two Asian sand dusts transported from the dust source regions of Inner Mongolia and northeast China on murine lung eosinophilia.

PubMed

He, Miao; Ichinose, Takamichi; Song, Yuan; Yoshida, Yasuhiro; Arashidani, Keiichi; Yoshida, Seiichi; Liu, Boying; Nishikawa, Masataka; Takano, Hirohisa; Sun, Guifan

2013-11-01

The quality and quantity of toxic materials adsorbed onto Asian sand dust (ASD) are different based on dust source regions and passage routes. The aggravating effects of two ASDs (ASD1 and ASD2) transported from the source regions of Inner Mongolia and northeast China on lung eosinophilia were compared to clarify the role of toxic materials in ASD. The ASDs contained different amounts of lipopolysaccharides (LPS) and β-glucan (ASD1ASD2). CD-1 mice were instilled intratracheally with ASD1, ASD2 and/or ovalbumin (OVA) four times at 2-week intervals. ASD1 and ASD2 enhanced eosinophil recruitment induced by OVA in the submucosa of the airway, with goblet cell proliferation in the bronchial epithelium. ASD1 and ASD2 synergistically increased OVA-induced eosinophil-relevant cytokines interleukin-5 (IL-5), IL-13 (ASD1ASD2) in bronchoalveolar lavage fluid. ASD2 aggravating effects on lung eosinophilia were greater than ASD1. The role of LPS and β-glucan in ASD2 on the production of pro-inflammatory mediators was assessed using in vitro bone marrow-derived macrophages (BMDMs) from wild type, Toll-like receptor 2-deficient (TLR2-/-), TLR4-/-, and MyD88-/- mice (on Balb/c background). ASD2-stimulated TLR2-/- BMDMs enhanced IL-6, IL-12, TNF-α, MCP-1 and MIP-1α secretion compared with ASD2-stimulated TLR4-/- BMDMs. Protein expression from ASD2-stimulated MyD88-/- BMDM were very low or undetectable. The in vitro results indicate that lung eosinophilia caused by ASD is TLR4 dependent. Therefore, the aggravation of OVA-related lung eosinophilia by ASD may be dependent on toxic substances derived from microbes, such as LPS, rather than SiO2. © 2013. Published by Elsevier Inc. All rights reserved.

The Broader Cognitive Phenotype of Autism in Parents: How Specific Is the Tendency for Local Processing and Executive Dysfunction?

ERIC Educational Resources Information Center

Bolte, Sven; Poustka, Fritz

2006-01-01

Background: The objective of this study was to investigate the tendency for local processing style ("weak central coherence") and executive dysfunction in parents of subjects with an autism spectrum disorder (ASD) compared with parents of individuals with early onset schizophrenia (EOS) and mental retardation (MR). Method: Sixty-two…

Production of Syllable Stress in Speakers with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Paul, Rhea; Bianchi, Nancy; Augustyn, Amy; Klin, Ami; Volkmar, Fred R.

2008-01-01

This paper reports a study of the ability to reproduce stress in a nonsense syllable imitation task by adolescent speakers with autism spectrum disorders (ASD), as compared to typically developing (TD) age-mates. Results are reported for both raters' judgments of the subjects' stress production, as well as acoustic measures of pitch range and…

Variant in OXTR gene and functional connectivity of the hypothalamus in normal subjects.

PubMed

Wang, Junping; Qin, Wen; Liu, Bing; Wang, Dawei; Zhang, Yunting; Jiang, Tianzi; Yu, Chunshui

2013-11-01

The oxytocin receptor gene (OXTR) rs53576A has been associated with autism spectrum disorders (ASDs). A smaller hypothalamic volume has been reported in healthy male A-allele carriers than in male GG homozygotes and in patients with ASDs than in healthy controls. These findings prompt the hypothesis that male AA homozygotes may have weaker hypothalamic functional connectivity when compared to male G-allele carriers. We calculated local functional connectivity density (FCD) using a voxel-wise data-driven approach based on resting-state functional MRI data in 270 young healthy subjects. Both the main effect of genotype and the gender-by-genotype interaction were considered. Of the whole brain, only the local FCD of the hypothalamus exhibited the main effect of genotype. Post-hoc testing revealed significantly lower local FCD in male AA homozygotes compared to male G-allele carriers although there was only a trend of significance in the gender-by-genotype interaction. We further analyzed the resting-state functional connectivity (rsFC) of the hypothalamic region that demonstrating significant genotype differences in local FCD. We found a significant gender-by-genotype interaction in rsFC between the hypothalamic region and the left dorsolateral prefrontal cortex, but no significant main effect of genotype was found. Post-hoc testing revealed that this rsFC was significantly weaker in male AA homozygotes compared to male G-allele carriers. Our findings identify gender-dependent mechanisms of OXTR rs53576 gene variation impacting the functional connectivity of the hypothalamus in healthy individuals and suggest that these mechanisms are important for understanding ASDs. Copyright © 2013 Elsevier Inc. All rights reserved.

Designing and recruiting to UK autism spectrum disorder research databases: do they include representative children with valid ASD diagnoses?

PubMed Central

Warnell, F; George, B; McConachie, H; Johnson, M; Hardy, R; Parr, J R

2015-01-01

Objectives (1) Describe how the Autism Spectrum Database-UK (ASD-UK) was established; (2) investigate the representativeness of the first 1000 children and families who participated, compared to those who chose not to; (3) investigate the reliability of the parent-reported Autism Spectrum Disorder (ASD) diagnoses, and present evidence about the validity of diagnoses, that is, whether children recruited actually have an ASD; (4) present evidence about the representativeness of the ASD-UK children and families, by comparing their characteristics with the first 1000 children and families from the regional Database of children with ASD living in the North East (Daslne), and children and families identified from epidemiological studies. Setting Recruitment through a network of 50 UK child health teams and self-referral. Patients Parents/carers with a child with ASD, aged 2–16 years, completed questionnaires about ASD and some gave professionals’ reports about their children. Results 1000 families registered with ASD-UK in 30 months. Children of families who participated, and of the 208 who chose not to, were found to be very similar on: gender ratio, year of birth, ASD diagnosis and social deprivation score. The reliability of parent-reported ASD diagnoses of children was very high when compared with clinical reports (over 96%); no database child without ASD was identified. A comparison of gender, ASD diagnosis, age at diagnosis, school placement, learning disability, and deprivation score of children and families from ASD-UK with 1084 children and families from Daslne, and families from population studies, showed that ASD-UK families are representative of families of children with ASD overall. Conclusions ASD-UK includes families providing parent-reported data about their child and family, who appear to be broadly representative of UK children with ASD. Families continue to join the databases and more than 3000 families can now be contacted by researchers about UK autism research. PMID:26341584

Chromosomal microarray analysis of consecutive individuals with autism spectrum disorders or learning disability presenting for genetic services.

PubMed

Roberts, Jennifer L; Hovanes, Karine; Dasouki, Majed; Manzardo, Ann M; Butler, Merlin G

2014-02-01

Chromosomal microarray analysis is now commonly used in clinical practice to identify copy number variants (CNVs) in the human genome. We report our experience with the use of the 105 K and 180K oligonucleotide microarrays in 215 consecutive patients referred with either autism or autism spectrum disorders (ASD) or developmental delay/learning disability for genetic services at the University of Kansas Medical Center during the past 4 years (2009-2012). Of the 215 patients [140 males and 75 females (male/female ratio=1.87); 65 with ASD and 150 with learning disability], abnormal microarray results were seen in 45 individuals (21%) with a total of 49 CNVs. Of these findings, 32 represented a known diagnostic CNV contributing to the clinical presentation and 17 represented non-diagnostic CNVs (variants of unknown significance). Thirteen patients with ASD had a total of 14 CNVs, 6 CNVs recognized as diagnostic and 8 as non-diagnostic. The most common chromosome involved in the ASD group was chromosome 15. For those with a learning disability, 32 patients had a total of 35 CNVs. Twenty-six of the 35 CNVs were classified as a known diagnostic CNV, usually a deletion (n=20). Nine CNVs were classified as an unknown non-diagnostic CNV, usually a duplication (n=8). For the learning disability subgroup, chromosomes 2 and 22 were most involved. Thirteen out of 65 patients (20%) with ASD had a CNV compared with 32 out of 150 patients (21%) with a learning disability. The frequency of chromosomal microarray abnormalities compared by subject group or gender was not statistically different. A higher percentage of individuals with a learning disability had clinical findings of seizures, dysmorphic features and microcephaly, but not statistically significant. While both groups contained more males than females, a significantly higher percentage of males were present in the ASD group. © 2013 Elsevier B.V. All rights reserved.

Investigation of iterative image reconstruction in low-dose breast CT

NASA Astrophysics Data System (ADS)

Bian, Junguo; Yang, Kai; Boone, John M.; Han, Xiao; Sidky, Emil Y.; Pan, Xiaochuan

2014-06-01

There is interest in developing computed tomography (CT) dedicated to breast-cancer imaging. Because breast tissues are radiation-sensitive, the total radiation exposure in a breast-CT scan is kept low, often comparable to a typical two-view mammography exam, thus resulting in a challenging low-dose-data-reconstruction problem. In recent years, evidence has been found that suggests that iterative reconstruction may yield images of improved quality from low-dose data. In this work, based upon the constrained image total-variation minimization program and its numerical solver, i.e., the adaptive steepest descent-projection onto the convex set (ASD-POCS), we investigate and evaluate iterative image reconstructions from low-dose breast-CT data of patients, with a focus on identifying and determining key reconstruction parameters, devising surrogate utility metrics for characterizing reconstruction quality, and tailoring the program and ASD-POCS to the specific reconstruction task under consideration. The ASD-POCS reconstructions appear to outperform the corresponding clinical FDK reconstructions, in terms of subjective visualization and surrogate utility metrics.

Increased gray-matter volume in medication-naive high-functioning children with autism spectrum disorder.

PubMed

Palmen, Saskia J M C; Hulshoff Pol, Hilleke E; Kemner, Chantal; Schnack, Hugo G; Durston, Sarah; Lahuis, Bertine E; Kahn, René S; Van Engeland, Herman

2005-04-01

To establish whether high-functioning children with autism spectrum disorder (ASD) have enlarged brains in later childhood, and if so, whether this enlargement is confined to the gray and/or to the white matter and whether it is global or more prominent in specific brain regions. Brain MRI scans were acquired from 21 medication-naive, high-functioning children with ASD between 7 and 15 years of age and 21 comparison subjects matched for gender, age, IQ, height, weight, handedness, and parental education, but not pubertal status. Patients showed a significant increase of 6% in intracranium, total brain, cerebral gray matter, cerebellum, and of more than 40% in lateral and third ventricles compared to controls. The cortical gray-matter volume was evenly affected in all lobes. After correction for brain volume, ventricular volumes remained significantly larger in patients. High-functioning children with ASD showed a global increase in gray-matter, but not white-matter and cerebellar volume, proportional to the increase in brain volume, and a disproportional increase in ventricular volumes, still present after correction for brain volume. Advanced pubertal development in the patients compared to the age-matched controls may have contributed to the findings reported in the present study.

The Swedish version of the Ritvo autism and asperger diagnostic scale: revised (RAADS-R). A validation study of a rating scale for adults.

PubMed

Andersen, Lisa M J; Näswall, Katharina; Manouilenko, Irina; Nylander, Lena; Edgar, Johan; Ritvo, Riva Ariella; Ritvo, Edward; Bejerot, Susanne

2011-12-01

There is a paucity of diagnostic instruments for adults with autism spectrum disorder (ASD). This study evaluates the psychometric properties of the Swedish version of the Ritvo Autism and Asperger Diagnostic Scale-Revised (RAADS-R), an 80-item self-rating scale designed to assist clinicians diagnosing ASD in adults. It was administered to 75 adults with ASD and 197 comparison cases. Also, a subset completed the Autism Spectrum Quotient (AQ). Three out of four subscales had high internal consistency. Sensitivity was 91% and specificity was 93%. The ASD subjects had significantly higher mean scores on all subscales. ASD females had higher scores than ASD males on the sensory motor subscale, a dimension not included in the AQ. RAADS-R showed promising test re-test reliability.

Proton magnetic resonance spectroscopy as a probe into the pathophysiology of autism spectrum disorders (ASD): a review.

PubMed

Baruth, Joshua M; Wall, Christopher A; Patterson, Marc C; Port, John D

2013-04-01

Proton magnetic resonance spectroscopy ((1) H-MRS) is a safe, noninvasive way of quantifying in vivo biochemical and metabolite concentration levels in individuals with Autism Spectrum Disorders (ASD). Findings to date suggest ASD is associated with widespread reduction in N-acetylaspartate (NAA), creatine plus phosphocreatine (Cr), choline-containing compounds (Cho), myo-inositol (mI), and glutamate plus glutamine plus gamma-Aminobutyric Acid (Glx); however, variable findings, and even substantial increases, are not uncommon depending on the study and/or region-of-interest. Widespread reduction of NAA, Cr, Cho, mI, and Glx in ASD likely reflects impaired neuronal function and/or metabolism related to abnormal neurodevelopmental processes. Future studies should attempt to relate (1) H-MRS findings to histological findings and control for variability in subject age and functioning level; this would assist in evaluating the relationship between (1) H-MRS metabolic levels and neuronal and glial cell densities, as well as neurodevelopmental process associated with ASD. Furthermore, more longitudinal (1) H-MRS studies are needed in both control and ASD subjects to attempt to standardize metabolite levels across different developmental periods in well-defined endophenotypes. This will provide for a standard rubric for which metabolic aberrations (as well as treatment responses) can be measured. With higher magnetic field strengths and spectral-editing techniques capable of quantifying less-concentrated metabolites, (1) H-MRS will continue to be an important tool in ASD research. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.

Development and validation of an item response theory-based Social Responsiveness Scale short form.

PubMed

Sturm, Alexandra; Kuhfeld, Megan; Kasari, Connie; McCracken, James T

2017-09-01

Research and practice in autism spectrum disorder (ASD) rely on quantitative measures, such as the Social Responsiveness Scale (SRS), for characterization and diagnosis. Like many ASD diagnostic measures, SRS scores are influenced by factors unrelated to ASD core features. This study further interrogates the psychometric properties of the SRS using item response theory (IRT), and demonstrates a strategy to create a psychometrically sound short form by applying IRT results. Social Responsiveness Scale analyses were conducted on a large sample (N = 21,426) of youth from four ASD databases. Items were subjected to item factor analyses and evaluation of item bias by gender, age, expressive language level, behavior problems, and nonverbal IQ. Item selection based on item psychometric properties, DIF analyses, and substantive validity produced a reduced item SRS short form that was unidimensional in structure, highly reliable (α = .96), and free of gender, age, expressive language, behavior problems, and nonverbal IQ influence. The short form also showed strong relationships with established measures of autism symptom severity (ADOS, ADI-R, Vineland). Degree of association between all measures varied as a function of expressive language. Results identified specific SRS items that are more vulnerable to non-ASD-related traits. The resultant 16-item SRS short form may possess superior psychometric properties compared to the original scale and emerge as a more precise measure of ASD core symptom severity, facilitating research and practice. Future research using IRT is needed to further refine existing measures of autism symptomatology. © 2017 Association for Child and Adolescent Mental Health.

Psycho-Cognitive Intervention for ASD from Cross-Species Behavioral Analyses of Infants, Chicks and Common Marmosets.

PubMed

Koshiba, Mamiko; Karino, Genta; Mimura, Koki; Nakamura, Shun; Yui, Kunio; Kunikata, Tetsuya; Yamanouchi, Hideo

2016-01-01

Educational treatment to support social development of children with autism spectrum disorder (ASD) is an important topic in developmental psychiatry. However, it remains difficult to objectively quantify the socio-emotional development of ASD children. To address this problem, we developed a novel analytical method that assesses subjects' complex behaviors using multivariate analysis, 'Behavior Output analysis for Quantitative Emotional State Translation' (BOUQUET). Here, we examine the potential for psycho-cognitive ASD therapy based on comparative evaluations of clinical (human) and experimental (animal) models. Our observations of ASD children (vs. their normally developing siblings) and the domestic chick in socio-sensory deprivation models show the importance of unimodal sensory stimulation, particularly important for tactile- and auditory-biased socialization. Identifying psycho-cognitive elements in early neural development, human newborn infants in neonatal intensive care unit as well as a New World monkey, the common marmoset, also prompted us to focus on the development of voluntary movement against gravity. In summary, striking behavioral similarities between children with ASD and domestic chicks' socio-sensory deprivation models support the role of multimodal sensory-motor integration as a prerequisite step for normal development of socio-emotional and psycho-cognitive functions. Data obtained in the common marmoset model also suggest that switching from primitive anti-gravity reflexes to complex voluntary movement may be a critical milestone for psycho-cognitive development. Combining clinical findings with these animal models, and using multivariate integrative analyses may facilitate the development of effective interventions to improve social functions in infants and in children with neurodevelopmental disorders.

Spatiotemporal characteristics of gaze of children with autism spectrum disorders while looking at classroom scenes

PubMed Central

Higuchi, Takahiro; Noritake, Atsushi; Yanagimoto, Yoshitoki; Kobayashi, Hodaka; Nakamura, Kae; Kaneko, Kazunari

2017-01-01

Children with autism spectrum disorders (ASD) who have neurodevelopmental impairments in social communication often refuse to go to school because of difficulties in learning in class. The exact cause of maladaptation to school in such children is unknown. We hypothesized that these children have difficulty in paying attention to objects at which teachers are pointing. We performed gaze behavior analysis of children with ASD to understand their difficulties in the classroom. The subjects were 26 children with ASD (19 boys and 7 girls; mean age, 8.6 years) and 27 age-matched children with typical development (TD) (14 boys and 13 girls; mean age, 8.2 years). We measured eye movements of the children while they performed free viewing of two movies depicting actual classes: a Japanese class in which a teacher pointed at cartoon characters and an arithmetic class in which the teacher pointed at geometric figures. In the analysis, we defined the regions of interest (ROIs) as the teacher’s face and finger, the cartoon characters and geometric figures at which the teacher pointed, and the classroom wall that contained no objects. We then compared total gaze time for each ROI between the children with ASD and TD by two-way ANOVA. Children with ASD spent less gaze time on the cartoon characters pointed at by the teacher; they spent more gaze time on the wall in both classroom scenes. We could differentiate children with ASD from those with TD almost perfectly by the proportion of total gaze time that children with ASD spent looking at the wall. These results suggest that children with ASD do not follow the teacher’s instructions in class and persist in gazing at inappropriate visual areas such as walls. Thus, they may have difficulties in understanding content in class, leading to maladaptation to school. PMID:28472111

Intra-individual cognitive imbalance in ASD between perceptual reasoning and ambiguity-solving related to tool use: Comparison among children exhibiting ASD, AD/HD, and typical development.

PubMed

Wakusawa, Keisuke; Nara, Chieko; Kubota, Yuki; Tomizawa, Yayoi; Taki, Yasuyuki; Sassa, Yuko; Kobayashi, Satoru; Suzuki-Muromoto, Sato; Hirose, Mieko; Yokoyama, Hiroyuki; Nara, Takahiro; Kure, Shigeo; Mori, Norio; Takei, Noriyoshi; Kawashima, Ryuta

2018-01-01

Several studies have suggested that objective deficits in the processing of abstract information in conjunction with an enhanced ability to process concrete information is a definitive characteristic of autism spectrum disorder (ASD). However, this cognitive imbalance is not necessarily clear in high-functioning autistic individuals who do not display absolute differences relative to typically developing (TD) populations. Thus, the purpose of this study was to identify this cognitive tendency in high-functioning autistic individuals using intra-individual cognitive comparisons. The reaction times (RTs) of TD children, children with ASD, and children with attention deficit hyperactivity disorder (AD/HD) (n=17 in each group, mean age=11.9years, age range=9.8-15.8years) were compared using the Which/How-to-Apply Tools (W/HAT) test, which consists of tasks requiring the adaptive use of novel tools and familiar tools in atypical and typical situations. Differences in RTs between the atypical and typical trials ([A-T]) were used to assess intra-individual cognitive imbalances. As predicted, the [A-T] scores of the ASD group were significantly higher than those of the TD group even though the RTs in the atypical and typical trials did not differ. Additionally, the [A-T] values were significantly higher in the ASD group than in the AD/HD group, which indicates that the cognitive imbalance was specific to ASD individuals. No significant interaction was detected between the trial and subject group. The findings of this study demonstrate that a cognitive imbalance in ASD individuals may enhance the current understanding of the pathophysiology of this disorder, which is found in a range of individuals, including those with obvious cortical dysfunction to those with only intra-individual imbalances. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Spatiotemporal characteristics of gaze of children with autism spectrum disorders while looking at classroom scenes.

PubMed

Higuchi, Takahiro; Ishizaki, Yuko; Noritake, Atsushi; Yanagimoto, Yoshitoki; Kobayashi, Hodaka; Nakamura, Kae; Kaneko, Kazunari

2017-01-01

Children with autism spectrum disorders (ASD) who have neurodevelopmental impairments in social communication often refuse to go to school because of difficulties in learning in class. The exact cause of maladaptation to school in such children is unknown. We hypothesized that these children have difficulty in paying attention to objects at which teachers are pointing. We performed gaze behavior analysis of children with ASD to understand their difficulties in the classroom. The subjects were 26 children with ASD (19 boys and 7 girls; mean age, 8.6 years) and 27 age-matched children with typical development (TD) (14 boys and 13 girls; mean age, 8.2 years). We measured eye movements of the children while they performed free viewing of two movies depicting actual classes: a Japanese class in which a teacher pointed at cartoon characters and an arithmetic class in which the teacher pointed at geometric figures. In the analysis, we defined the regions of interest (ROIs) as the teacher's face and finger, the cartoon characters and geometric figures at which the teacher pointed, and the classroom wall that contained no objects. We then compared total gaze time for each ROI between the children with ASD and TD by two-way ANOVA. Children with ASD spent less gaze time on the cartoon characters pointed at by the teacher; they spent more gaze time on the wall in both classroom scenes. We could differentiate children with ASD from those with TD almost perfectly by the proportion of total gaze time that children with ASD spent looking at the wall. These results suggest that children with ASD do not follow the teacher's instructions in class and persist in gazing at inappropriate visual areas such as walls. Thus, they may have difficulties in understanding content in class, leading to maladaptation to school.

Frequency of Dendritic Cells and Their Expression of Costimulatory Molecules in Children with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Saad, Khaled; Zahran, Asmaa M.; Elsayh, Khalid I.; Abdel-Rahman, Ahmed A.; Al-Atram, Abdulrahman A.; Hussein, Almontaser; El-Gendy, Yasmin G.

2017-01-01

The aim of our study was to evaluate the frequencies of myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs) in children with ASD. Subjects were 32 children with ASD and 30 healthy children as controls. The numbers of mDCs and pDCs and the expression of CD86 and CD80 on the entire DCs were detected by flow cytometry. ASD children…

Predictive Factors for Patients Undergoing ASD Device Occlusion Who "Crossover" to Surgery.

PubMed

Mulukutla, Venkatachalam; Qureshi, Athar M; Pignatelli, Ricardo; Ing, Frank F

2018-03-01

The aim of this study was to define characteristics of those patients who are referred for device closure of an Atrial septal defect (ASD), but identified to "crossover" surgery. All patients who underwent surgical and device (Amplatzer or Helex occluder) closures of secundum ASDs from 2001 to 2010 were reviewed and organized into three groups: surgical closure, device closure, and "crossover" group. 369 patients underwent ASD closure (265 device, 104 surgical). 42 of the 265 patients referred for device closure "crossed over" to the surgical group at various stages of the catheterization procedure. The device group had defect size measuring 14.2 mm (mean) and an ASD index (Defect Size (mm)/BSA) of 14.0 compared to the corresponding values in the surgical group (20.1 mm, ASD index 25.9) (P < 0.001) and in the "crossover" group (20.7 mm, 22.6 ASD index) (P < 0.001). 79 patients in the device group had a deficient rim, and 86% were located in the retroaortic region. 33 patients in the "crossover" group had deficient rims with 70% deficiency in the posterior/inferior rim. The device group with deficient rims had an ASD index of 14.7 compared with the crossover group ASD index of 23.8 (P < 0.001). Comparing the device and "crossover" groups, an ASD index greater than 23.7 had a 90% specificity in "crossing over" to surgery. The crossover and surgical groups had statistically larger ASD defect size indexes compared with the device group. Deficient rim in the posterior/inferior rim is associated with a large ASD size index which is a predictive factor for crossing over to surgery. Catheterization did not negatively impact surgical results in the "crossover" group.

Previous Exposure to Anesthesia and Autism Spectrum Disorder (ASD): A Puerto Rican Population-Based Sibling Cohort Study.

PubMed

Creagh, O; Torres, H; Rivera, K; Morales-Franqui, M; Altieri-Acevedo, G; Warner, D

2016-01-01

Autism Spectrum Disorder (ASD) is characterized by impaired social interaction and communication, and by restricted and repetitive behavior, that begins usually before a child is three years old.(1) Researchers have shown that prevalence rates in the U.S. may be as high as 1 in 68.(52) A number of studies have examined the effects of early exposure to anesthesia on brain development and subsequent impairment in neurocognitive function; yet, little is known about the possible effects of anesthetic agents on social-behavioral functioning. The association between exposure to anesthesia either in uterus, during the first years of life, or later and development of Autistic Spectrum Disorder (ASD) or its severity was determined in a retrospective population based cohort study. Identify if children who had previous exposure to anesthesia either in uterus, first years of life during their developing brain years, or later, are at risk of developing ASD and its severe form of the disease. Data was obtained from structured interviews administered to a sample of 515 parents/guardians distributed in two groups: ASD = 262 children diagnosed with this condition and Non-ASD: 253 children (siblings of ASD group) without diagnosis (95% confidence interval) that freely decided to participate and agreed to a consent form. Variables studied include: demographics, diagnosis and severity of ASD, exposure to anesthesia, method of childbirth, and age of exposure Children less than 2 years of age were considered into have developing brain period. Data was analyzed using Chi-square or Fisher exact test. In contrast to non-ASD group, most of the children within ASD group were male, 76% (p=0.0001). With regards to methods of childbirth, 64% of the ASD population were vaginal delivery (VD; Non-anesthesia exposure group) and 36% cesarean delivery (CD) compared to non-autistic population with 71% VD and 29% CD, which demonstrates no statistical difference between both groups (p=0.1113). Out of the 36% of ASD population that underwent CD, 7% were performed using general anesthesia and 93% regional anesthesia, while the 29% of the CD of non-ASD, 5% were performed using general anesthesia and 95% regional anesthesia. This reveals no statistical significance (p=0.7569) with the development of ASD and the type of anesthesia used when comparing ASD with non-ASD patients. In view of severity of autism, in VD, 56% of ASD population had mild form of the disorder, 34% moderate, and 10% severe; while CD had a 54% mild form of the disorder, 33% moderate, and 13% severe. This shows no statistical association (p=0.8069) when comparing exposure to anesthesia in uterus to subsequent severe form of ASD. Of the 262 ASD patients, 99 had exposure to anesthetics before their diagnosis, while in Non-ASD population, 110 had exposure to anesthesia, demonstrating no statistically significant association between both groups (p=0.2091). Out of 99 ASD patients exposed to anesthesia prior to their diagnosis, 72 were exposed before age 2. When compared to the 110 Non-ASD patients exposed to anesthesia, 86 had exposure during this developing brain period, which indicates no statistically significant association (p=0.4207). In addition, most of the ASD children exposed to anesthesia during developing brain were diagnosed with mild degree of the disorder when compared to ASD children without any previous exposure to anesthesia (p=0.9700) during the same period. When the exposure occurred after age 2, ASD children developed mild form of the disorder as compared with ASD children without any previous exposure to anesthesia (p=0.1699) in that period. Children under early exposure to anesthesia in uterus, first 2 years of life, or later are not more likely to develop neither ASD nor severe form of the disorder.

Previous Exposure to Anesthesia and Autism Spectrum Disorder (ASD): A Puerto Rican Population-Based Sibling Cohort Study.

PubMed

Creagh, O; Torres, H; Rivera, K; Morales-Franqui, M; Altieri-Acevedo, G; Warner, D

2015-01-01

Autism Spectrum Disorder (ASD) is characterized by impaired social interaction and communication, and by restricted and repetitive behavior, that begins usually before a child is three years old.1 Researchers have shown that prevalence rates in the U.S. may be as high as 1 in 68.52 A number of studies have examined the effects of early exposure to anesthesia on brain development and subsequent impairment in neurocognitive function; yet, little is known about the possible effects of anesthetic agents on social-behavioral functioning. The association between exposure to anesthesia either in uterus, during the first years of life, or later and development of Autistic Spectrum Disorder (ASD) or its severity was determined in a retrospective population based cohort study. Identify if children who had previous exposure to anesthesia either in uterus, first years of life during their developing brain years, or later, are at risk of developing ASD and its severe form of the disease. Data was obtained from structured interviews administered to a sample of 515 parents/guardians distributed in two groups: ASD = 262 children diagnosed with this condition and Non-ASD: 253 children (siblings of ASD group) without diagnosis (p = 0.8069) when comparing exposure to anesthesia in uterus to subsequent severe form of ASD. Of the 262 ASD patients, 99 had exposure to anesthetics before their diagnosis, while in Non-ASD population, 110 had exposure to anesthesia, demonstrating no statistically significant association between both groups (p = 0.2091). Out of 99 ASD patients exposed to anesthesia prior to their diagnosis, 72 were exposed before age 2. When compared to the 110 Non-ASD patients exposed to anesthesia, 86 had exposure during this developing brain period, which indicates no statistically significant association (p = 0.4207). In addition, most of the ASD children exposed to anesthesia during developing brain were diagnosed with mild degree of the disorder when compared to ASD children without any previous exposure to anesthesia (p = 0.9700) during the same period. When the exposure occurred after age 2, ASD children developed mild form of the disorder as compared with ASD children without any previous exposure to anesthesia (p = 0.1699) in that period. Children under early exposure to anesthesia in uterus, first 2 years of life, or later are not more likely to develop neither ASD nor severe form of the disorder. INDEX WORDS: Anesthesia, Autism Spectrum Disorder, Puerto Rico. (95% confidence interval) that freely decided to participate and agreed to a consent form. Variables studied, include: demographics, diagnosis and severity of ASD, exposure to anesthesia, method of childbirth, and age of exposure. Children less than 2 years of age were considered into have developing brain period. Data was analyzed using Chi-square or Fisher exact test. In contrast to non-ASD group, most of the children within ASD group were male, 76% (p = 0.0001). With regards to methods of childbirth, 64% of the ASD population were vaginal delivery (VD; Non-anesthesia exposure group) and 36% cesarean delivery (CD) compared to non-autistic population with 71% VD and 29% CD, which demonstrates no statistical difference between both groups (p = 0.1113). Out of the 36% of ASD population that underwent CD, 7% were performed using general anesthesia and 93% regional anesthesia, while the 29% of the CD of non-ASD, 5% were performed using general anesthesia and 95% regional anesthesia. This reveals no statistical significance (p = 0.7569) with the development of ASD and the type of anesthesia used when comparing ASD with non-ASD patients. In view of severity of autism, in VD, 56% of ASD population had mild form of the disorder, 34% moderate, and 10% severe; while CD had a 54% mild form of the disorder, 33% moderate, and 13% severe. This shows no statistical association.

INDUCED EEG GAMMA OSCILLATION ALIGNMENT IMPROVES DIFFERENTIATION BETWEEN AUTISM AND ADHD GROUP RESPONSES IN A FACIAL CATEGORIZATION TASK

PubMed Central

Gross, Eric; El-Baz, Ayman S.; Sokhadze, Guela E.; Sears, Lonnie; Casanova, Manuel F.; Sokhadze, Estate M.

2012-01-01

Introduction Children diagnosed with an autism spectrum disorder (ASD) often lack the ability to recognize and properly respond to emotional stimuli. Emotional deficits also characterize children with attention deficit/hyperactivity disorder (ADHD), in addition to exhibiting limited attention span. These abnormalities may effect a difference in the induced EEG gamma wave burst (35–45 Hz) peaked approximately 300–400 milliseconds following an emotional stimulus. Because induced gamma oscillations are not fixed at a definite point in time post-stimulus, analysis of averaged EEG data with traditional methods may result in an attenuated gamma burst power. Methods We used a data alignment technique to improve the averaged data, making it a better representation of the individual induced EEG gamma oscillations. A study was designed to test the response of a subject to emotional stimuli, presented in the form of emotional facial expression images. In a four part experiment, the subjects were instructed to identify gender in the first two blocks of the test, followed by differentiating between basic emotions in the final two blocks (i.e. anger vs. disgust). EEG data was collected from ASD (n=10), ADHD (n=9), and control (n=11) subjects via a 128 channel EGI system, and processed through a continuous wavelet transform and bandpass filter to isolate the gamma frequencies. A custom MATLAB code was used to align the data from individual trials between 200–600 ms post-stimulus, EEG site, and condition by maximizing the Pearson product-moment correlation coefficient between trials. The gamma power for the 400 ms window of maximum induced gamma burst was then calculated and compared between subject groups. Results and Conclusion Condition (anger/disgust recognition, gender recognition) × Alignment × Group (ADHD, ASD, Controls) interaction was significant at most of parietal topographies (e.g., P3–P4, P7–P8). These interactions were better manifested in the aligned data set. Our results show that alignment of the induced gamma oscillations improves sensitivity of this measure in differentiation of EEG responses to emotional facial stimuli in ADHD and ASD. PMID:22754277

INDUCED EEG GAMMA OSCILLATION ALIGNMENT IMPROVES DIFFERENTIATION BETWEEN AUTISM AND ADHD GROUP RESPONSES IN A FACIAL CATEGORIZATION TASK.

PubMed

Gross, Eric; El-Baz, Ayman S; Sokhadze, Guela E; Sears, Lonnie; Casanova, Manuel F; Sokhadze, Estate M

2012-01-01

INTRODUCTION: Children diagnosed with an autism spectrum disorder (ASD) often lack the ability to recognize and properly respond to emotional stimuli. Emotional deficits also characterize children with attention deficit/hyperactivity disorder (ADHD), in addition to exhibiting limited attention span. These abnormalities may effect a difference in the induced EEG gamma wave burst (35-45 Hz) peaked approximately 300-400 milliseconds following an emotional stimulus. Because induced gamma oscillations are not fixed at a definite point in time post-stimulus, analysis of averaged EEG data with traditional methods may result in an attenuated gamma burst power. METHODS: We used a data alignment technique to improve the averaged data, making it a better representation of the individual induced EEG gamma oscillations. A study was designed to test the response of a subject to emotional stimuli, presented in the form of emotional facial expression images. In a four part experiment, the subjects were instructed to identify gender in the first two blocks of the test, followed by differentiating between basic emotions in the final two blocks (i.e. anger vs. disgust). EEG data was collected from ASD (n=10), ADHD (n=9), and control (n=11) subjects via a 128 channel EGI system, and processed through a continuous wavelet transform and bandpass filter to isolate the gamma frequencies. A custom MATLAB code was used to align the data from individual trials between 200-600 ms post-stimulus, EEG site, and condition by maximizing the Pearson product-moment correlation coefficient between trials. The gamma power for the 400 ms window of maximum induced gamma burst was then calculated and compared between subject groups. RESULTS AND CONCLUSION: Condition (anger/disgust recognition, gender recognition) × Alignment × Group (ADHD, ASD, Controls) interaction was significant at most of parietal topographies (e.g., P3-P4, P7-P8). These interactions were better manifested in the aligned data set. Our results show that alignment of the induced gamma oscillations improves sensitivity of this measure in differentiation of EEG responses to emotional facial stimuli in ADHD and ASD.

Atypical Processing of Gaze Cues and Faces Explains Comorbidity between Autism Spectrum Disorder (ASD) and Attention Deficit/Hyperactivity Disorder (ADHD).

PubMed

Groom, Madeleine J; Kochhar, Puja; Hamilton, Antonia; Liddle, Elizabeth B; Simeou, Marina; Hollis, Chris

2017-05-01

This study investigated the neurobiological basis of comorbidity between autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD). We compared children with ASD, ADHD or ADHD+ASD and typically developing controls (CTRL) on behavioural and electrophysiological correlates of gaze cue and face processing. We measured effects of ASD, ADHD and their interaction on the EDAN, an ERP marker of orienting visual attention towards a spatially cued location and the N170, a right-hemisphere lateralised ERP linked to face processing. We identified atypical gaze cue and face processing in children with ASD and ADHD+ASD compared with the ADHD and CTRL groups. The findings indicate a neurobiological basis for the presence of comorbid ASD symptoms in ADHD. Further research using larger samples is needed.

Umbilical cord blood androgen levels and ASD-related phenotypes at 12 and 36 months in an enriched risk cohort study.

PubMed

Park, Bo Y; Lee, Brian K; Burstyn, Igor; Tabb, Loni P; Keelan, Jeff A; Whitehouse, Andrew J O; Croen, Lisa A; Fallin, Margaret D; Hertz-Picciotto, Irva; Montgomery, Owen; Newschaffer, Craig J

2017-01-01

Autism spectrum disorder (ASD) affects more than 1% of children in the USA. The male-to-female prevalence ratio of roughly 4:1 in ASD is a well-recognized but poorly understood phenomenon. An explicit focus on potential etiologic pathways consistent with this sex difference, such as those involving prenatal androgen exposure, may help elucidate causes of ASD. Furthermore, the multi-threshold liability model suggests that the genetic mechanisms in females with ASD may be distinct and may modulate ASD risk in families with female ASD in the pedigree. We examined umbilical cord blood from 137 children in the Early Autism Risk Longitudinal Investigation (EARLI) cohort. EARLI is an ASD-enriched risk cohort with all children having an older sibling already diagnosed with ASD. Fetal testosterone (T), androstenedione (A4), and dehyroepiandrosterone (DHEA) levels were measured in cord blood using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Robust linear regression models were used to determine associations between cord blood androgen levels and 12-month Autism Observation Scales for Infants (AOSI) scores and 36-month Social Responsiveness Scale (SRS) scores adjusting for potential confounders. Increasing androgens were not associated with increasing 12-month AOSI score or 36-month total SRS score in either boys or girls. However, the association between T and autistic traits among subjects with a female older affected sibling was greater at 12 months (test of interaction, P  = 0.008) and deficits in reciprocal social behavior at 36 months were also greater (test of interaction, P  = 0.006) than in subjects whose older affected sibling was male. While increased prenatal testosterone levels were not associated with autistic traits at 12 or 36 months, our findings of a positive association in infants whose older ASD-affected siblings were female suggests an androgen-related mechanism that may be dependent on, or related to, genetic liability factors present more often in families containing female ASD cases. However, this initial finding, based on a small subgroup of our sample, should be interpreted with considerable caution.

Explaining Enhanced Logical Consistency during Decision Making in Autism

PubMed Central

De Martino, Benedetto; Harrison, Neil A.; Knafo, Steven; Bird, Geoff; Dolan, Raymond J.

2009-01-01

The emotional responses elicited by the way options are framed often results in lack of logical consistency in human decision making. In this study, we investigated subjects with autism spectrum disorder (ASD) using a financial task in which the monetary prospects were presented as either loss or gain. We report both behavioral evidence that ASD subjects show a reduced susceptibility to the framing effect and psycho-physiological evidence that they fail to incorporate emotional context into the decision-making process. On this basis, we suggest that this insensitivity to contextual frame, although enhancing choice consistency in ASD, may also underpin core deficits in this disorder. These data highlight both benefits and costs arising from multiple decision processes in human cognition. PMID:18923049

Explaining enhanced logical consistency during decision making in autism.

PubMed

De Martino, Benedetto; Harrison, Neil A; Knafo, Steven; Bird, Geoff; Dolan, Raymond J

2008-10-15

The emotional responses elicited by the way options are framed often results in lack of logical consistency in human decision making. In this study, we investigated subjects with autism spectrum disorder (ASD) using a financial task in which the monetary prospects were presented as either loss or gain. We report both behavioral evidence that ASD subjects show a reduced susceptibility to the framing effect and psycho-physiological evidence that they fail to incorporate emotional context into the decision-making process. On this basis, we suggest that this insensitivity to contextual frame, although enhancing choice consistency in ASD, may also underpin core deficits in this disorder. These data highlight both benefits and costs arising from multiple decision processes in human cognition.

Driving Behaviors in Adults with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Daly, Brian P.; Nicholls, Elizabeth G.; Patrick, Kristina E.; Brinckman, Danielle D.; Schultheis, Maria T.

2014-01-01

This pilot study investigated driving history and driving behaviors between adults diagnosed with autism spectrum disorders (ASD) as compared to non-ASD adult drivers. Seventy-eight licensed drivers with ASD and 94 non-ASD comparison participants completed the Driver Behavior Questionnaire. Drivers with ASD endorsed significantly lower ratings of…

Elevated amygdala response to faces and gaze aversion in autism spectrum disorder.

PubMed

Tottenham, Nim; Hertzig, Margaret E; Gillespie-Lynch, Kristen; Gilhooly, Tara; Millner, Alexander J; Casey, B J

2014-01-01

Autism spectrum disorders (ASD) are often associated with impairments in judgment of facial expressions. This impairment is often accompanied by diminished eye contact and atypical amygdala responses to face stimuli. The current study used a within-subjects design to examine the effects of natural viewing and an experimental eye-gaze manipulation on amygdala responses to faces. Individuals with ASD showed less gaze toward the eye region of faces relative to a control group. Among individuals with ASD, reduced eye gaze was associated with higher threat ratings of neutral faces. Amygdala signal was elevated in the ASD group relative to controls. This elevated response was further potentiated by experimentally manipulating gaze to the eye region. Potentiation by the gaze manipulation was largest for those individuals who exhibited the least amount of naturally occurring gaze toward the eye region and was associated with their subjective threat ratings. Effects were largest for neutral faces, highlighting the importance of examining neutral faces in the pathophysiology of autism and questioning their use as control stimuli with this population. Overall, our findings provide support for the notion that gaze direction modulates affective response to faces in ASD.

A prospective study of prenatal mercury exposure from maternal dental amalgams and autism severity.

PubMed

Geier, David A; Kern, Janet K; Geier, Mark R

2009-01-01

Dental amalgams containing 50% mercury (Hg) have been used in dentistry for the last 150 years, and Hg exposure during key developmental periods was associated with autism spectrum disorders (ASDs). This study examined increased Hg exposure from maternal dental amalgams during pregnancy among 100 qualifying participants born between 1990-1999 and diagnosed with DSM-IV autism (severe) or ASD (mild). Logistic regression analysis (age, gender, race, and region of residency adjusted) by quintile of maternal dental amalgams during pregnancy revealed the ratio of autism:ASD (severe:mild) were about 1 (no effect) for < or =5 amalgams and increased for > or =6 amalgams. Subjects with > or =6 amalgams were 3.2-fold significantly more likely to be diagnosed with autism (severe) in comparison to ASD (mild) than subjects with < or =5 amalgams. Dental amalgam policies should consider Hg exposure in women before and during the child-bearing age and the possibility of subsequent fetal exposure and adverse outcomes.

EEG evidence for mirror neuron dysfunction in autism spectrum disorders.

PubMed

Oberman, Lindsay M; Hubbard, Edward M; McCleery, Joseph P; Altschuler, Eric L; Ramachandran, Vilayanur S; Pineda, Jaime A

2005-07-01

Autism spectrum disorders (ASD) are largely characterized by deficits in imitation, pragmatic language, theory of mind, and empathy. Previous research has suggested that a dysfunctional mirror neuron system may explain the pathology observed in ASD. Because EEG oscillations in the mu frequency (8-13 Hz) over sensorimotor cortex are thought to reflect mirror neuron activity, one method for testing the integrity of this system is to measure mu responsiveness to actual and observed movement. It has been established that mu power is reduced (mu suppression) in typically developing individuals both when they perform actions and when they observe others performing actions, reflecting an observation/execution system which may play a critical role in the ability to understand and imitate others' behaviors. This study investigated whether individuals with ASD show a dysfunction in this system, given their behavioral impairments in understanding and responding appropriately to others' behaviors. Mu wave suppression was measured in ten high-functioning individuals with ASD and ten age- and gender-matched control subjects while watching videos of (1) a moving hand, (2) a bouncing ball, and (3) visual noise, or (4) moving their own hand. Control subjects showed significant mu suppression to both self and observed hand movement. The ASD group showed significant mu suppression to self-performed hand movements but not to observed hand movements. These results support the hypothesis of a dysfunctional mirror neuron system in high-functioning individuals with ASD.

Shared and Disorder-Specific Neurocomputational Mechanisms of Decision-Making in Autism Spectrum Disorder and Obsessive-Compulsive Disorder.

PubMed

Carlisi, Christina O; Norman, Luke; Murphy, Clodagh M; Christakou, Anastasia; Chantiluke, Kaylita; Giampietro, Vincent; Simmons, Andrew; Brammer, Michael; Murphy, Declan G; Mataix-Cols, David; Rubia, Katya

2017-12-01

Autism spectrum disorder (ASD) and obsessive-compulsive disorder (OCD) often share phenotypes of repetitive behaviors, possibly underpinned by abnormal decision-making. To compare neural correlates underlying decision-making between these disorders, brain activation of boys with ASD (N = 24), OCD (N = 20) and typically developing controls (N = 20) during gambling was compared, and computational modeling compared performance. Patients were unimpaired on number of risky decisions, but modeling showed that both patient groups had lower choice consistency and relied less on reinforcement learning compared to controls. ASD individuals had disorder-specific choice perseverance abnormalities compared to OCD individuals. Neurofunctionally, ASD and OCD boys shared dorsolateral/inferior frontal underactivation compared to controls during decision-making. During outcome anticipation, patients shared underactivation compared to controls in lateral inferior/orbitofrontal cortex and ventral striatum. During reward receipt, ASD boys had disorder-specific enhanced activation in inferior frontal/insular regions relative to OCD boys and controls. Results showed that ASD and OCD individuals shared decision-making strategies that differed from controls to achieve comparable performance to controls. Patients showed shared abnormalities in lateral-(orbito)fronto-striatal reward circuitry, but ASD boys had disorder-specific lateral inferior frontal/insular overactivation, suggesting that shared and disorder-specific mechanisms underpin decision-making in these disorders. Findings provide evidence for shared neurobiological substrates that could serve as possible future biomarkers. © The Author 2017. Published by Oxford University Press.

Designing and recruiting to UK autism spectrum disorder research databases: do they include representative children with valid ASD diagnoses?

PubMed

Warnell, F; George, B; McConachie, H; Johnson, M; Hardy, R; Parr, J R

2015-09-04

(1) Describe how the Autism Spectrum Database-UK (ASD-UK) was established; (2) investigate the representativeness of the first 1000 children and families who participated, compared to those who chose not to; (3) investigate the reliability of the parent-reported Autism Spectrum Disorder (ASD) diagnoses, and present evidence about the validity of diagnoses, that is, whether children recruited actually have an ASD; (4) present evidence about the representativeness of the ASD-UK children and families, by comparing their characteristics with the first 1000 children and families from the regional Database of children with ASD living in the North East (Dasl(n)e), and children and families identified from epidemiological studies. Recruitment through a network of 50 UK child health teams and self-referral. Parents/carers with a child with ASD, aged 2-16 years, completed questionnaires about ASD and some gave professionals' reports about their children. 1000 families registered with ASD-UK in 30 months. Children of families who participated, and of the 208 who chose not to, were found to be very similar on: gender ratio, year of birth, ASD diagnosis and social deprivation score. The reliability of parent-reported ASD diagnoses of children was very high when compared with clinical reports (over 96%); no database child without ASD was identified. A comparison of gender, ASD diagnosis, age at diagnosis, school placement, learning disability, and deprivation score of children and families from ASD-UK with 1084 children and families from Dasl(n)e, and families from population studies, showed that ASD-UK families are representative of families of children with ASD overall. ASD-UK includes families providing parent-reported data about their child and family, who appear to be broadly representative of UK children with ASD. Families continue to join the databases and more than 3000 families can now be contacted by researchers about UK autism research. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Relating ASD symptoms to well-being: moving across different construct levels.

PubMed

Deserno, M K; Borsboom, D; Begeer, S; Geurts, H M

2018-05-01

Little is known about the specific factors that contribute to the well-being (WB) of individuals with autism spectrum disorder (ASD). A plausible hypothesis is that ASD symptomatology has a direct negative effect on WB. In the current study, the emerging tools of network analysis allow to explore the functional interdependencies between specific symptoms of ASD and domains of WB in a multivariate framework. We illustrate how studying both higher-order (total score) and lower-order (subscale) representations of ASD symptomatology can clarify the interrelations of factors relevant for domains of WB. We estimated network structures on three different construct levels for ASD symptomatology, as assessed with the Adult Social Behavior Questionnaire (item, subscale, total score), relating them to daily functioning (DF) and subjective WB in 323 adult individuals with clinically identified ASD (aged 17-70 years). For these networks, we assessed the importance of specific factors in the network structure. When focusing on the highest representation level of ASD symptomatology (i.e. a total score), we found a negative connection between ASD symptom severity and domains of WB. However, zooming in on lower representation levels of ASD symptomatology revealed that this connection was mainly funnelled by ASD symptoms related to insistence on sameness and experiencing reduced contact and that those symptom scales, in turn, impact different domains of WB. Zooming in across construct levels of ASD symptom severity into subscales of ASD symptoms can provide us with important insights into how specific domains of ASD symptoms relate to specific domains of DF and WB.

The Prevalence and Psychopathological Correlates of Sibling Bullying in Children with and without Autism Spectrum Disorder.

PubMed

Toseeb, Umar; McChesney, Gillian; Wolke, Dieter

2018-07-01

Using data from a prospective population based study, the prevalence and psychopathological correlates of sibling bullying in children with and without autism spectrum disorder (ASD) were estimated. There were 475 children with ASD and 13,702 children without ASD aged 11 years. Children with ASD were more likely to be bullied by their siblings compared to those without ASD. They were also more likely than those without ASD to both bully and be bullied by their siblings, which was associated with lower prosocial skills as well as more internalizing and externalizing problems compared to those not involved in any sibling bullying. Interventions to improve social and emotional outcomes in children with ASD should focus on both the affected and the unaffected sibling.

Brief Report: Sexual Attraction and Relationships in Adolescents with Autism.

PubMed

May, Tamara; Pang, Ken C; Williams, Katrina

2017-06-01

Past research suggests more variation in sexual attraction in Autism Spectrum Disorder (ASD) using clinical samples. This study utilised a population representative group of 14/15 year olds from the Longitudinal Study of Australian Children. Ninety-four adolescents (73 males, 21 females) with ASD and 3454 (1685 males, 1675 females) without self-reported on sexual attraction and past sexual relationships. Females with ASD reported lower rates of heterosexual preference (adjusted odds ratio: 0.14, p < .001), higher rates of bisexuality (adjusted odds ratio: 6.05, p < .001) and uncertainty in attraction (adjusted odds ratio: 10.44, p < .001) compared with non-ASD females. ASD males reported fewer prior boyfriends/girlfriends. Findings confirm female adolescents with ASD have differences in sexual attraction compared with non-ASD females.

Resting-State Neurophysiological Activity Patterns in Young People with ASD, ADHD, and ASD + ADHD

ERIC Educational Resources Information Center

Shephard, Elizabeth; Tye, Charlotte; Ashwood, Karen L.; Azadi, Bahar; Asherson, Philip; Bolton, Patrick F.; McLoughlin, Grainne

2018-01-01

Altered power of resting-state neurophysiological activity has been associated with autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), which commonly co-occur. We compared resting-state neurophysiological power in children with ASD, ADHD, co-occurring ASD + ADHD, and typically developing controls. Children with ASD…

Dental Homes for Children With Autism: A Longitudinal Analysis of Iowa Medicaid's I-Smile Program.

PubMed

Chi, Donald L; Momany, Elizabeth T; Mancl, Lloyd A; Lindgren, Scott D; Zinner, Samuel H; Steinman, Kyle J

2016-05-01

Medicaid-enrolled children with autism spectrum disorder (ASD) encounter significant barriers to dental care. Iowa's I-Smile Program was implemented in 2006 to improve dental use for all children in Medicaid. This study compared dental home and preventive dental utilization rates for Medicaid-enrolled children by ASD status and within three time periods (pre-implementation, initial implementation, maturation) and determined I-Smile's longitudinal influence on ASD-related dental use disparities. Data from 2002-2011 were analyzed for newly Medicaid-enrolled children aged 3-17 years (N=30,059); identified each child's ASD status; and assessed whether the child had a dental home or utilized preventive dental care. Log-linear regression models were used to generate rate ratios. Analyses were conducted in 2015. In 2003-2011, 9.8% of children with ASD had dental homes compared with 8% of children without ASD; 36.3% of children with ASD utilized preventive care compared to 45.7% of children without ASD. There were no significant differences in dental home rates by ASD status during pre-implementation, initial implementation, or maturation. There were no significant differences in preventive dental utilization by ASD status during pre-implementation or initial implementation, but children with ASD were significantly less likely to utilize preventive care during maturation (rate ratio=0.79, p<0.001). Longitudinal trends in dental home and preventive dental utilization rates were not significant (p=0.54 and p=0.71, respectively). Among newly Medicaid-enrolled children in Iowa's I-Smile Program, those with ASDs were not less likely than those without ASD to have dental homes but were significantly less likely to utilize preventive dental care. Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Dental Homes for Children With Autism

PubMed Central

Chi, Donald L.; Momany, Elizabeth T.; Mancl, Lloyd A.; Lindgren, Scott D.; Zinner, Samuel H.; Steinman, Kyle J.

2015-01-01

Introduction Medicaid-enrolled children with autism spectrum disorder (ASD) encounter significant barriers to dental care. Iowa’s I-Smile Program was implemented in 2006 to improve dental use for all children in Medicaid. This study compared dental home and preventive dental utilization rates for Medicaid-enrolled children by ASD status and within three time periods (pre-implementation, initial implementation, maturation) and determined I-Smile’s longitudinal influence on ASD-related dental use disparities. Methods Data from 2002–2011 were analyzed for newly Medicaid-enrolled children aged 3–17 years (N=30,059), identified each child’s ASD status, and assessed whether the child had a dental home or utilized preventive dental care. Log-linear regression models were used to generate rate ratios. Analyses were conducted in 2015. Results In 2003–2011, 9.8% of children with ASD had dental homes compared with 8% of children without ASD; 36.3% of children with ASD utilized preventive care compared to 45.7% of children without ASD. There were no significant differences in dental home rates by ASD status during pre-implementation, initial implementation, or maturation. There were no significant differences in preventive dental utilization by ASD status during pre-implementation or initial implementation, but children with ASD were significantly less likely to utilize preventive care during maturation (rate ratio=0.79, p<0.001). Longitudinal trends in dental home and preventive dental utilization rates were not significant (p=0.54 and p=0.71, respectively). Conclusions Among newly Medicaid-enrolled children in Iowa’s I-Smile Program, those with ASDs were not less likely than those without ASD to have dental homes but were significantly less likely to utilize preventive dental care. PMID:26514624

Postural Control and Emotion in Children with Autism Spectrum Disorders

PubMed Central

Gouleme, Nathalie; Scheid, Isabelle; Peyre, Hugo; Seassau, Magali; Maruani, Anna; Clarke, Julia; Delorme, Richard; Bucci, Maria Pia

2017-01-01

Abstract Autism Spectrum Disorders subjects (ASD) are well known to have deficits in social interaction. We recorded simultaneously eye movements and postural sway during exploration of emotional faces in children with ASD and typically developing children (TD). We analyzed several postural and ocular parameters. The results showed that all postural parameters were significantly greater in children with ASD; ASD made significantly fewer saccades and had shorter fixation time than TD, particularly in the eyes, and especially for unpleasant emotions. These results suggest that poor postural control of ASD and their impaired visual strategies could be due to a lack of interest in social cognition, causing a delay in the development of the cortical areas, and thus could have an effect on their postural control. PMID:29177103

Validating a Culturally-sensitive Social Competence Training Programme for Adolescents with ASD in a Chinese Context: An Initial Investigation.

PubMed

Chan, Raymond Won Shing; Leung, Cecilia Nga Wing; Ng, Denise Ching Yiu; Yau, Sania Sau Wai

2018-02-01

Previous studies on social skills training on ASD were done almost exclusively in the West with children as the main subjects. Demonstrations of the applicability of social interventions in different cultures and age groups are warranted. The current study outlined the development and preliminary evaluation of a CBT-context-based social competence training for ASD (CBT-CSCA) developed in Hong Kong for Chinese adolescents with ASD. Twenty-five adolescents (aged 12-17 years, with a FSIQ above 80) were recruited. Significant improvements in social competence, autistic symptoms and general psychopathology at post-training and 3-month follow-up were reported by the parents. The study provided initial evidence support to the applicability of social competence training for adolescents with ASD in a different culture.

Predictive models for subtypes of autism spectrum disorder based on single-nucleotide polymorphisms and magnetic resonance imaging.

PubMed

Jiao, Y; Chen, R; Ke, X; Cheng, L; Chu, K; Lu, Z; Herskovits, E H

2011-01-01

Autism spectrum disorder (ASD) is a neurodevelopmental disorder, of which Asperger syndrome and high-functioning autism are subtypes. Our goal is: 1) to determine whether a diagnostic model based on single-nucleotide polymorphisms (SNPs), brain regional thickness measurements, or brain regional volume measurements can distinguish Asperger syndrome from high-functioning autism; and 2) to compare the SNP, thickness, and volume-based diagnostic models. Our study included 18 children with ASD: 13 subjects with high-functioning autism and 5 subjects with Asperger syndrome. For each child, we obtained 25 SNPs for 8 ASD-related genes; we also computed regional cortical thicknesses and volumes for 66 brain structures, based on structural magnetic resonance (MR) examination. To generate diagnostic models, we employed five machine-learning techniques: decision stump, alternating decision trees, multi-class alternating decision trees, logistic model trees, and support vector machines. For SNP-based classification, three decision-tree-based models performed better than the other two machine-learning models. The performance metrics for three decision-tree-based models were similar: decision stump was modestly better than the other two methods, with accuracy = 90%, sensitivity = 0.95 and specificity = 0.75. All thickness and volume-based diagnostic models performed poorly. The SNP-based diagnostic models were superior to those based on thickness and volume. For SNP-based classification, rs878960 in GABRB3 (gamma-aminobutyric acid A receptor, beta 3) was selected by all tree-based models. Our analysis demonstrated that SNP-based classification was more accurate than morphometry-based classification in ASD subtype classification. Also, we found that one SNP--rs878960 in GABRB3--distinguishes Asperger syndrome from high-functioning autism.

Detection of intracardiac shunt flow in atrial septal defect using a real-time two-dimensional color-coded Doppler flow imaging system and comparison with contrast two-dimensional echocardiography.

PubMed

Suzuki, Y; Kambara, H; Kadota, K; Tamaki, S; Yamazato, A; Nohara, R; Osakada, G; Kawai, C

1985-08-01

To evaluate the noninvasive detection of shunt flow using a newly developed real-time 2-dimensional color-coded Doppler flow imaging system (D-2DE), 20 patients were examined, including 10 with secundum atrial septal defect (ASD) and 10 control subjects. These results were compared with contrast 2-dimensional echocardiography (C-2DE). Doppler 2DE displayed the blood flow toward the transducer as red and the blood flow away from the transducer as blue in 8 shades, each shade adding green according to the degree of variance in Doppler frequency. In the patients with ASD, D-2DE clearly visualized left-to-right shunt flow in 7 of 10 patients. In 5 of these 7 patients, C-2DE showed a negative contrast effect in the same area of the right atrium. Thus, D-2DE increased the sensitivity over C-2DE for detecting left-to-right shunt flow (from 50% to 70%). However, the specificity was slightly less in D-2DE (90%) than C-2DE (100%). Doppler 2DE could not visualize right-to-left shunt flow in all patients with ASD, though C-2DE showed a positive contrast effect in the left-sided heart in 9 of 10 patients with ASD. Thus, D-2DE is clinically useful for detecting left-to-right shunt flow in patients with ASD.

Evaluation of the validity of the Autism Spectrum Quotient (AQ) in differentiating high-functioning autistic spectrum disorder from schizophrenia.

PubMed

Naito, Kenichi; Matsui, Yusuke; Maeda, Kiyoshi; Tanaka, Kiwamu

2010-09-30

The aim of this study is to examine the validity of the Autism Spectrum Quotient (AQ) to differentiate high-functioning autistic spectrum disorder (ASD) from schizophrenia (SCH). The AQ was developed by Baron-Cohen et al. to measure autistic traits. In addition to the original AQ items, we created self-administered questions about psychotic symptoms (S-scale). We administered the modified AQ to 51 ASD patients and 46 SCH patients, and we compared these two groups in terms of total AQ score, AQ subscale scores and S-scale score. We applied receiver operating characteristic (ROC) curves to examine the discriminating power of the AQ. The mean total AQ score of the ASD group (32.6; SD=6.8; range: 8-48) was significantly higher than that of the SCH group (21.8; SD=7.4; range: 10-39) (p<0.001). All AQ subscale scores of the ASD group were significantly higher than those of the SCH group. By using a cut-off score of 29 for the AQ total score, we were able to correctly classify 80% of the subjects. At this cut-off, the positive and negative predictive values were 0.83 and 0.78, respectively. Inclusion of additional questions of the S-scale did not increase the power of differentiation. These results indicate that the usefulness of the AQ in differentiating high-functioning ASD from SCH is limited.

Effects of acute beta-adrenergic antagonism on verbal problem solving in autism spectrum disorder and exploration of treatment response markers.

PubMed

Zamzow, Rachel M; Ferguson, Bradley J; Ragsdale, Alexandra S; Lewis, Morgan L; Beversdorf, David Q

2017-08-01

Autism spectrum disorder (ASD) is characterized by impairments in social communication as well as restricted, repetitive behaviors. Evidence suggests that some individuals with ASD have cognitive impairments related to weak central coherence and hyperrestricted processing. Reducing noradrenergic activity may improve aspects of network processing and thus improve cognitive abilities, such as verbal problem solving, in individuals with ASD. The present pilot study explores the effects of acute administration of the beta-adrenergic antagonist propranolol on verbal problem solving in adults and adolescents with ASD. In a within-subject crossover-design, 20 participants with ASD received a single dose of propranolol or placebo on one of two sessions in a double-blinded, counterbalanced manner. Verbal problem solving was assessed via an anagram task. Baseline measurements of autonomic nervous system functioning were obtained, and anxiety was assessed at baseline and following drug administration. Participants solved the anagrams more quickly in the propranolol condition, as compared to the placebo condition, suggesting a potential cognitive benefit of this agent. Additionally, we observed a negative linear relationship between response to propranolol on the anagram task and two measures of baseline autonomic activity, as well as a positive linear relationship between drug response and baseline anxiety. These relationships propose potential markers for treatment response, as propranolol influences both autonomic functioning and anxiety. Further investigation is needed to expand on the present single-dose psychopharmacological challenge and explore the observed effects of propranolol in a serial-dose setting.

Comparison of Fecal Microbiota in Children with Autism Spectrum Disorders and Neurotypical Siblings in the Simons Simplex Collection.

PubMed

Son, Joshua S; Zheng, Ling J; Rowehl, Leahana M; Tian, Xinyu; Zhang, Yuanhao; Zhu, Wei; Litcher-Kelly, Leighann; Gadow, Kenneth D; Gathungu, Grace; Robertson, Charles E; Ir, Diana; Frank, Daniel N; Li, Ellen

2015-01-01

In order to assess potential associations between autism spectrum disorder (ASD) phenotype, functional GI disorders and fecal microbiota, we recruited simplex families, which had only a single ASD proband and neurotypical (NT) siblings, through the Simons Simplex Community at the Interactive Autism Network (SSC@IAN). Fecal samples and metadata related to functional GI disorders and diet were collected from ASD probands and NT siblings of ASD probands (age 7-14). Functional gastrointestinal disorders (FGID) were assessed using the parent-completed ROME III questionnaire for pediatric FGIDs, and problem behaviors were assessed using the Child Behavior Check List (CBCL). Targeted quantitative polymerase chain reaction (qPCR) assays were conducted on selected taxa implicated in ASD, including Sutterella spp., Bacteroidetes spp. and Prevotella spp. Illumina sequencing of the V1V2 and the V1V3 regions of the bacterial 16S rRNA genes from fecal DNA was performed to an average depth of 208,000 and 107,000 high-quality reads respectively. Twenty-five of 59 ASD children and 13 of 44 NT siblings met ROME III criteria for at least one FGID. Functional constipation was more prevalent in ASD (17 of 59) compared to NT siblings (6 of 44, P = 0.035). The mean CBCL scores in NT siblings with FGID, ASD children with FGID and ASD without FGID were comparably higher (58-62 vs. 44, P < 0.0001) when compared to NT children without FGID. There was no significant difference in macronutrient intake between ASD and NT siblings. There was no significant difference in ASD severity scores between ASD children with and without FGID. No significant difference in diversity or overall microbial composition was detected between ASD children with NT siblings. Exploratory analysis of the 16S rRNA sequencing data, however, identified several low abundance taxa binned at the genus level that were associated with ASD and/or first order ASD*FGID interactions (FDR <0.1).

Comparison of Fecal Microbiota in Children with Autism Spectrum Disorders and Neurotypical Siblings in the Simons Simplex Collection

PubMed Central

Son, Joshua S.; Zheng, Ling J.; Rowehl, Leahana M.; Tian, Xinyu; Zhang, Yuanhao; Zhu, Wei; Litcher-Kelly, Leighann; Gadow, Kenneth D.; Gathungu, Grace; Robertson, Charles E.; Ir, Diana; Frank, Daniel N.; Li, Ellen

2015-01-01

In order to assess potential associations between autism spectrum disorder (ASD) phenotype, functional GI disorders and fecal microbiota, we recruited simplex families, which had only a single ASD proband and neurotypical (NT) siblings, through the Simons Simplex Community at the Interactive Autism Network (SSC@IAN). Fecal samples and metadata related to functional GI disorders and diet were collected from ASD probands and NT siblings of ASD probands (age 7–14). Functional gastrointestinal disorders (FGID) were assessed using the parent-completed ROME III questionnaire for pediatric FGIDs, and problem behaviors were assessed using the Child Behavior Check List (CBCL). Targeted quantitative polymerase chain reaction (qPCR) assays were conducted on selected taxa implicated in ASD, including Sutterella spp., Bacteroidetes spp. and Prevotella spp. Illumina sequencing of the V1V2 and the V1V3 regions of the bacterial 16S rRNA genes from fecal DNA was performed to an average depth of 208,000 and 107,000 high-quality reads respectively. Twenty-five of 59 ASD children and 13 of 44 NT siblings met ROME III criteria for at least one FGID. Functional constipation was more prevalent in ASD (17 of 59) compared to NT siblings (6 of 44, P = 0.035). The mean CBCL scores in NT siblings with FGID, ASD children with FGID and ASD without FGID were comparably higher (58–62 vs. 44, P < 0.0001) when compared to NT children without FGID. There was no significant difference in macronutrient intake between ASD and NT siblings. There was no significant difference in ASD severity scores between ASD children with and without FGID. No significant difference in diversity or overall microbial composition was detected between ASD children with NT siblings. Exploratory analysis of the 16S rRNA sequencing data, however, identified several low abundance taxa binned at the genus level that were associated with ASD and/or first order ASD*FGID interactions (FDR <0.1). PMID:26427004

Vaccination Patterns in Children After Autism Spectrum Disorder Diagnosis and in Their Younger Siblings.

PubMed

Zerbo, Ousseny; Modaressi, Sharareh; Goddard, Kristin; Lewis, Edwin; Fireman, Bruce H; Daley, Matthew F; Irving, Stephanie A; Jackson, Lisa A; Donahue, James G; Qian, Lei; Getahun, Darios; DeStefano, Frank; McNeil, Michael M; Klein, Nicola P

2018-05-01

In recent years, rates of vaccination have been declining. Whether this phenomenon disproportionately affects children with autism spectrum disorder (ASD) or their younger siblings is unknown. To investigate if children after receiving an ASD diagnosis obtain their remaining scheduled vaccines according to the Advisory Committee on Immunization Practices (ACIP) recommendations and to compare the vaccination patterns of younger siblings of children with ASD with the vaccination patterns of younger siblings of children without ASD. This investigation was a retrospective matched cohort study. The setting was 6 integrated health care delivery systems across the United States within the Vaccine Safety Datalink. Participants were children born between January 1, 1995, and September 30, 2010, and their younger siblings born between January 1, 1997, and September 30, 2014. The end of follow-up was September 30, 2015. Recommended childhood vaccines between ages 1 month and 12 years. The proportion of children who received all of their vaccine doses according to ACIP recommendations. The study included 3729 children with ASD (676 [18.1%] female), 592 907 children without ASD, and their respective younger siblings. Among children without ASD, 250 193 (42.2%) were female. For vaccines recommended between ages 4 and 6 years, children with ASD were significantly less likely to be fully vaccinated compared with children without ASD (adjusted rate ratio, 0.87; 95% CI, 0.85-0.88). Within each age category, vaccination rates were significantly lower among younger siblings of children with ASD compared with younger siblings of children without ASD. The adjusted rate ratios varied from 0.86 for siblings younger than 1 year to 0.96 for those 11 to 12 years old. Parents who had a child with ASD were more likely to refuse at least 1 recommended vaccine for that child's younger sibling and to limit the number of vaccines administered during the younger sibling's first year of life. Children with ASD and their younger siblings were undervaccinated compared with the general population. The results of this study suggest that children with ASD and their younger siblings are at increased risk of vaccine-preventable diseases.

Psychosis in autism: comparison of the features of both conditions in a dually affected cohort†

PubMed Central

Larson, Felicity V.; Wagner, Adam P.; Jones, Peter B.; Tantam, Digby; Lai, Meng-Chuan; Baron-Cohen, Simon; Holland, Anthony J.

2017-01-01

Background There is limited information on the presentation and characteristics of psychotic illness experienced by people with autism spectrum disorder (ASD). Aims To describe autistic and psychotic phenomenology in a group of individuals with comorbid ASD and psychosis (ASD–P) and compare this group with populations affected by either, alone. Method We studied 116 individuals with ASD–P. We compared features of their ASD with people with ASD and no comorbid psychosis (ASD–NP), and clinical characteristics of psychosis in ASD–P with people with psychosis only. Results Individuals with ASD–P had more diagnoses of atypical psychosis and fewer of schizophrenia compared with individuals with psychosis only. People with ASD–P had fewer stereotyped interests/behaviours compared with those with ASD–NP. Conclusions Our data show there may be a specific subtype of ASD linked to comorbid psychosis. The results support findings that psychosis in people with ASD is often atypical, particularly regarding affective disturbance. PMID:27979819

Driving Behaviour Profile of Drivers with Autism Spectrum Disorder (ASD)

ERIC Educational Resources Information Center

Chee, Derserri Y.; Lee, Hoe C.; Patomella, Ann-Helen; Falkmer, Torbjörn

2017-01-01

The symptomatology of autism spectrum disorder (ASD) can make driving risky, but little is known about the on-road driving behaviour of individuals with ASD. This study assessed and compared the on-road driving performance of drivers with and without ASD, and explored how the symptomatology of ASD hinders or facilitates on-road driving…

Randomized Trial of Hyperbaric Oxygen Therapy for Children with Autism

ERIC Educational Resources Information Center

Granpeesheh, Doreen; Tarbox, Jonathan; Dixon, Dennis R.; Wilke, Arthur E.; Allen, Michael S.; Bradstreet, James Jeffrey

2010-01-01

Autism Spectrum Disorders (ASDs) are characterized by the presence of impaired development in social interaction and communication and the presence of a restricted repertoire of activity and interests. While numerous treatments for ASDs have been proposed, very few have been subjected to rigorous scientific investigation. Hyperbaric oxygen therapy…

Nutritional deficiencies and overweight prevalence among children with autism spectrum disorder.

PubMed

Shmaya, Yael; Eilat-Adar, Sigal; Leitner, Yael; Reif, Shimon; Gabis, Lidia

2015-03-01

Children with autism spectrum disorder (ASD) are at risk of developing nutritional deviations. Three to six year old children with ASD were compared to their typically developing siblings and to a typically developing age and gender matched control group, in order to evaluate their intake and body mass index. Nutrient intake was compared to the Dietary Reference Intake using three-day diet diaries completed by the parents. The sum percentage of nutritional deficiencies in the ASD group compared to the typical development group was 342.5% (±122.9%) vs. 275.9% (±106.8%), respectively (P=0.026). A trend toward higher deficiency in the ASD group was observed as compared to the sibling group 363% (±122.9%) vs. 283.2% (±94.7%) (P=0.071). A higher body mass index was found in the ASD group compared to their counterparts, despite their nutritional deficiencies. In conclusion, children with ASD are more likely to suffer from nutritional deficiencies despite higher body mass index. Copyright © 2014 Elsevier Ltd. All rights reserved.

Sticking with it: Psychotherapy outcomes for adults with autism spectrum disorder in a university counseling center setting.

PubMed

Anderberg, Emily; Cox, Jonathan C; Neeley Tass, E Shannon; Erekson, David M; Gabrielsen, Terisa P; Warren, Jared S; Cline, Jared; Petersen, Devin; South, Mikle

2017-12-01

Young adults with autism spectrum disorders (ASD) experience high rates of comorbid mental health concerns in addition to distress arising from the core symptoms of autism. Many adults with ASD seek psychological treatment in outpatient facilities in their communities that are not specifically geared toward individuals with ASD. However, few studies have looked at the effectiveness of standard psychotherapeutic care in adults with ASD. This study aimed to discover how individuals with ASD fare in psychotherapy within a college counseling setting, compared to their neurotypical peers. Clients with ASD (n = 76) or possible ASD (n = 91) were retrospectively identified from counseling center case notes. Data from the Outcome Questionnaire-45 (OQ) were retrieved for each therapy session as a measure of client distress. Clients with ASD showed no difference in level of distress at intake compared to their neurotypical peers (n = 21,546), and improved about the same amount from pre- to post-treatment. However, students with ASD stayed in treatment for significantly more sessions than neurotypical clients, and took significantly longer to achieve maximum improvement on OQ reports. Results are discussed with implications for university and other community based treatment settings. Autism Res 2017, 10: 2048-2055. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. This study aimed to discover how individuals with autism spectrum disorders (ASD) fare in psychotherapy within a university counseling setting, compared to their neurotypical peers. Clients with ASD showed no difference in level of distress at intake compared to their neurotypical peers, and improved about the same amount from pre- to post-treatment. However, students with ASD stayed in treatment for significantly more sessions than neurotypical clients, and took significantly longer to achieve maximum improvement on Outcome Questionnaire-45 reports. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

Parental concerns, provider response, and timeliness of autism spectrum disorder diagnosis.

PubMed

Zuckerman, Katharine Elizabeth; Lindly, Olivia Jasmine; Sinche, Brianna Kathleen

2015-06-01

To assess differences between child age at first parental concern and age at first parental discussion of concerns with a health care provider among children with autism spectrum disorder (ASD) vs those with intellectual disability/developmental delay (ID/DD), and to assess whether provider response to parental concerns is associated with delays in ASD diagnosis. Using nationally representative data from the 2011 Survey of Pathways to Diagnosis and Treatment, we compared child age at parent's first developmental concern with age at first discussion of concerns with a provider, and categorized provider response as proactive or reassuring/passive, among 1420 children with ASD and 2098 children with ID/DD. In the children with ASD, we tested the association between provider response type and years of diagnostic delay. Compared with children with ID/DD, children with ASD were younger when parents first had concerns and first discussed those concerns with a provider. Compared with parents of children with ID/DD, parents of children with ASD were less likely to receive proactive responses to their concerns and more likely to receive reassuring/passive responses. Among children with ASD, those with more proactive provider responses to concerns had shorter delays in ASD diagnosis compared with those with passive/reassuring provider responses. Although parents of children with ASD have early concerns, delays in diagnosis are common, particularly when providers' responses are reassuring or passive, highlighting the need for targeted improvements in primary care. Copyright © 2015 Elsevier Inc. All rights reserved.

DSM-5 ASD moves forward into the past.

PubMed

Tsai, Luke Y; Ghaziuddin, Mohammad

2014-02-01

The fifth edition of the diagnostic and statistical manual of mental disorders (DSM-5) (APA in diagnostic and statistical manual of mental disorders, Author, Washington, 2013) has decided to merge the subtypes of pervasive developmental disorders into a single category of autism spectrum disorder (ASD) on the assumption that they cannot be reliably differentiated from one another. The purpose of this review is to analyze the basis of this assumption by examining the comparative studies between Asperger's disorder (AsD) and autistic disorder (AD), and between pervasive developmental disorder not otherwise specified (PDDNOS) and AD. In all, 125 studies compared AsD with AD. Of these, 30 studies concluded that AsD and AD were similar conditions while 95 studies found quantitative and qualitative differences between them. Likewise, 37 studies compared PDDNOS with AD. Nine of these concluded that PDDNOS did not differ significantly from AD while 28 reported quantitative and qualitative differences between them. Taken together, these findings do not support the conceptualization of AD, AsD and PDDNOS as a single category of ASD. Irrespective of the changes proposed by the DSM-5, future research and clinical practice will continue to find ways to meaningfully subtype the ASD.

Symptom Profile of ADHD in Youth With High-Functioning Autism Spectrum Disorder: A Comparative Study in Psychiatrically Referred Populations.

PubMed

Joshi, Gagan; Faraone, Stephen V; Wozniak, Janet; Tarko, Laura; Fried, Ronna; Galdo, Maribel; Furtak, Stephannie L; Biederman, Joseph

2017-08-01

To compare the clinical presentation of ADHD between youth with autism spectrum disorder (ASD) and ADHD and a sample of youth with ADHD only. A psychiatrically referred sample of autism spectrum disorder (ASD) youth with ADHD attending a specialized ambulatory program for ASD ( n = 107) and a sample of youth with ADHD attending a general child psychiatry ambulatory clinic ( n = 74) were compared. Seventy-six percent of youth with ASD met Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) criteria for ADHD. The clinical presentation of ADHD in youth with ASD was predominantly similar to its typical presentation including age at onset (3.5 ± 1.7 vs. 4.0 ± 1.9; p = .12), distribution of diagnostic subtypes, the qualitative and quantitative symptom profile, and symptom severity. Combined subtype was the most frequent presentation of ADHD in ASD youth. Despite the robust presentation of ADHD, a significant majority of ASD youth with ADHD failed to receive appropriate ADHD treatment (41% vs. 24%; p = .02). A high rate of comorbidity with ADHD was observed in psychiatrically referred youth with ASD, with a clinical presentation typical of the disorder.

Parenting a Child with ASD: Comparison of Parenting Style Between ASD, Anxiety, and Typical Development.

PubMed

Ventola, Pamela; Lei, Jiedi; Paisley, Courtney; Lebowitz, Eli; Silverman, Wendy

2017-09-01

Parenting children with ASD has a complex history. Given parents' increasingly pivotal role in children's treatment, it is critical to consider parental style and behaviours. This study (1) compares parenting style of parents of children with ASD, parents of children with anxiety disorders, and parents of typically developing (TD) children and (2) investigates contributors to parenting style within and between groups. Parents of children with anxiety had a distinct parenting style compared to ASD and TD parents. Unique relationships between child symptoms and parenting behaviours emerged across the three groups. Understanding factors that impact parenting between and within clinical groups can guide the development of interventions better tailored to support the needs of parents, particularly parents of children with ASD.

Comparing Diagnostic Outcomes of Autism Spectrum Disorder Using "DSM-IV-TR" and "DSM-5" Criteria

ERIC Educational Resources Information Center

Harstad, Elizabeth B.; Fogler, Jason; Sideridis, Georgios; Weas, Sarah; Mauras, Carrie; Barbaresi, William J.

2015-01-01

Controversy exists regarding the "DSM-5" criteria for ASD. This study tested the psychometric properties of the "DSM-5" model and determined how well it performed across different gender, IQ, and "DSM-IV-TR" sub-type, using clinically collected data on 227 subjects (median age = 3.95 years, majority had IQ > 70).…

The Relationship between Theory of Mind and Executive Function in a Sample of Children from Mainland China

ERIC Educational Resources Information Center

Yang, Juan; Zhou, Shijie; Yao, Shuqiao; Su, Linyan; McWhinnie, Chad

2009-01-01

To explore the relationship between theory of mind (ToM) and executive function (EF) in a sample of individuals from mainland China, 20 children with autism spectrum disorders (ASD), 26 children with Attention Deficit Hyperactivity Disorder (ADHD), and 30 normal control subjects were compared on two batteries of ToM tasks and EF tasks. Children…

Examining the Clinical Correlates of Autism Spectrum Disorder in Youth by Ascertainment Source

ERIC Educational Resources Information Center

Joshi, Gagan; Faraone, Stephen V.; Wozniak, Janet; Petty, Carter; Fried, Ronna; Galdo, Maribel; Furtak, Stephannie L.; McDermott, Katie; Epstien, Cecily; Walker, Rosemary; Caron, Ashley; Feinberg, Leah; Biederman, Joseph

2014-01-01

To examine whether presentation of autism spectrum disorder (ASD) and associated patterns of psychiatric comorbidity and dysfunction vary by referral source. ASD youth referred to a specialized ambulatory program for ASD (N = 143) were compared to ASD youth referred to a general child psychiatry clinic (N = 217). More ASD clinic youth met criteria…

Fmr1 and Nlgn3 knockout rats: novel tools for investigating autism spectrum disorders.

PubMed

Hamilton, Shannon M; Green, Jennie R; Veeraragavan, Surabi; Yuva, Lisa; McCoy, Aaron; Wu, Yumei; Warren, Joe; Little, Lara; Ji, Diana; Cui, Xiaoxia; Weinstein, Edward; Paylor, Richard

2014-04-01

Animal models are critical for gaining insights into autism spectrum disorder (ASD). Despite their apparent advantages to mice for neural studies, rats have not been widely used for disorders of the human CNS, such as ASD, for the lack of convenient genome manipulation tools. Here we describe two of the first transgenic rat models for ASD, developed using zinc-finger nuclease (ZFN) methodologies, and their initial behavioral assessment using a rapid juvenile test battery. A syndromic and nonsyndromic rat model for ASD were created as two separate knockout rat lines with heritable disruptions in the genes encoding Fragile X mental retardation protein (FMRP) and Neuroligin3 (NLGN3). FMRP, a protein with numerous proposed functions including regulation of mRNA and synaptic protein synthesis, and NLGN3, a member of the neuroligin synaptic cell-adhesion protein family, have been implicated in human ASD. Juvenile subjects from both knockout rat lines exhibited abnormalities in ASD-relevant phenotypes including juvenile play, perseverative behaviors, and sensorimotor gating. These data provide important first evidence regarding the utility of rats as genetic models for investigating ASD-relevant genes.

Autism and social robotics: A systematic review.

PubMed

Pennisi, Paola; Tonacci, Alessandro; Tartarisco, Gennaro; Billeci, Lucia; Ruta, Liliana; Gangemi, Sebastiano; Pioggia, Giovanni

2016-02-01

Social robotics could be a promising method for Autism Spectrum Disorders (ASD) treatment. The aim of this article is to carry out a systematic literature review of the studies on this topic that were published in the last 10 years. We tried to address the following questions: can social robots be a useful tool in autism therapy? We followed the PRISMA guidelines, and the protocol was registered within PROSPERO database (CRD42015016158). We found many positive implications in the use of social robots in therapy as for example: ASD subjects often performed better with a robot partner rather than a human partner; sometimes, ASD patients had, toward robots, behaviors that TD patients had toward human agents; ASDs had a lot of social behaviors toward robots; during robotic sessions, ASDs showed reduced repetitive and stereotyped behaviors and, social robots manage to improve spontaneous language during therapy sessions. Therefore, robots provide therapists and researchers a means to connect with autistic subjects in an easier way, but studies in this area are still insufficient. It is necessary to clarify whether sex, intelligence quotient, and age of participants affect the outcome of therapy and whether any beneficial effects only occur during the robotic session or if they are still observable outside the clinical/experimental context. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

Overlap Between Autism Spectrum Disorders and Attention Deficit Hyperactivity Disorder: Searching for Distinctive/Common Clinical Features.

PubMed

Craig, Francesco; Lamanna, Anna Linda; Margari, Francesco; Matera, Emilia; Simone, Marta; Margari, Lucia

2015-06-01

Recent studies support several overlapping traits between autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD), assuming the existence of a combined phenotype. The aim of our study was to evaluate the common or distinctive clinical features between ASD and ADHD in order to identify possible different phenotypes that could have a clinical value. We enrolled 181 subjects divided into four diagnostic groups: ADHD group, ASD group, ASD+ADHD group (that met diagnostic criteria for both ASD and ADHD), and control group. Intelligent quotient (IQ), emotional and behavior problems, ADHD symptoms, ASD symptoms, and adaptive behaviors were investigated through the following test: Wechsler Intelligence Scale for Children, Wechsler Preschool and Primary Scale of Intelligence or Leiter International Performances Scale Revised, Child Behavior Checklist, Conners' Rating Scales-Revised, SNAP-IV Rating Scale, the Social Communication Questionnaire, Vineland Adaptive Behavior Scales. The ASD+ADHD group differs from ADHD or ASD in some domains such as lower IQ mean level and a higher autistic symptoms severity. However, the ASD+ADHD group shares inattention and hyperactivity deficit and some emotional and behavior problems with the ADHD group, while it shares adaptive behavior impairment with ASD group. These findings provide a new understanding of clinical manifestation of ASD+ADHD phenotype, they may also inform a novel treatment target. © 2015 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research.

A Meta-Analysis of the Impact of Anaerobic Soil Disinfestation on Pest Suppression and Yield of Horticultural Crops

PubMed Central

Shrestha, Utsala; Augé, Robert M.; Butler, David M.

2016-01-01

Anaerobic soil disinfestation (ASD) is a proven but relatively new strategy to control soil borne pests of horticultural crops through anaerobic decomposition of organic soil amendments. The ASD technique has primarily been used to control soil borne pathogens; however, this technique has also shown potential to control plant parasitic nematodes and weeds. ASD can utilize a broad range of carbon (C) amendments and optimization may improve efficacy across environments. In this context, a meta-analysis using a random-effects model was conducted to determine effect sizes of the ASD effect on soil borne pathogens (533 studies), plant parasitic nematodes (91 studies), and weeds (88 studies) compared with unamended controls. Yield response to ASD was evaluated (123 studies) compared to unamended and fumigated controls. We also examined moderator variables for environmental conditions and amendments to explore the impact of these moderators on ASD effectiveness on pests and yield. Across all pathogen types with the exception of Sclerotinia spp., ASD studies show suppression of bacterial, oomycete and fungal pathogens (59 to 94%). Pathogen suppression was effective under all environmental conditions (50 to 94%) and amendment types (53 to 97%), except when amendments were applied at rates less than 0.3 kg m-2. The ASD effect ranged from 15 to 56% for nematode suppression and 32 to 81% for weed suppression, but these differences were not significant. Significant nematode moderators included study type, soil type, sampling depth, incubation period, and use of mixed amendments. Weed suppression due to ASD showed significant heterogeneity for all environmental conditions, confirming that these studies do not share a common effect size. Total crop yield was not reduced by ASD when compared to a fumigant control and yield was significantly higher (30%) compared to an unamended control, suggesting ASD as a feasible option to maintain yield without chemical soil fumigants. We conclude ASD is effective against soil borne pathogens and while not conclusive due to a limited number of studies, we expect the same for nematodes and weeds given observed effect sizes. Findings should assist researchers in exploring ASD efficacy in particular environmental conditions and allow for development of standard treatment protocols. PMID:27617017

A New Interactive Screening Test for Autism Spectrum Disorders in Toddlers.

PubMed

Choueiri, Roula; Wagner, Sheldon

2015-08-01

To develop a clinically valid interactive level 2 screening assessment for autism spectrum disorders (ASD) in toddlers that is brief, easily administered, and scored by clinicians. We describe the development, training, standardization, and validation of the Rapid Interactive Screening Test for Autism in Toddlers (RITA-T) with ASD-specific diagnostic instruments. The RITA-T can be administered and scored in 10 minutes. We studied the validity of the RITA-T to distinguish between toddlers with ASD from toddlers with developmental delay (DD)/non-ASD in an early childhood clinic. We also evaluated the test's performance in toddlers with no developmental concerns. We identified a cutoff score based on sensitivity, specificity, and positive predictive value of the RITA-T that best differentiates between ASD and DD/non-ASD. A total of 61 toddlers were enrolled. RITA-T scores were correlated with ASD-specific diagnostic tools (r = 0.79; P < .01) and ASD clinical diagnoses (r = 0.77; P < .01). Mean scores were significantly different in subjects with ASD, those with DD/non-ASD, and those with no developmental concerns (20.8 vs 13 vs 10.6, respectively; P < .0001). At a cutoff score of >14 , the RITA-T had a sensitivity of 1.00, specificity of 0.84, and positive predictive value of 0.88 for identifying ASD risk in a high-risk group. The RITA-T is a promising new level 2 interactive screening tool for improving the early identification of ASD in toddlers in general pediatric and early intervention settings and allowing access to treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

Clinical and autoimmune features of a patient with autism spectrum disorder seropositive for anti-NMDA-receptor autoantibody.

PubMed

Gréa, Hélène; Scheid, Isabelle; Gaman, Alexandru; Rogemond, Véronique; Gillet, Sandy; Honnorat, Jérôme; Bolognani, Federico; Czech, Christian; Bouquet, Céline; Toledano, Elie; Bouvard, Manuel; Delorme, Richard; Groc, Laurent; Leboyer, Marion

2017-03-01

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by dysfunctions in social interactions resulting from a complex interplay between immunogenetic and environmental risk factors. Autoimmunity has been proposed as a major etiological component of ASD. Whether specific autoantibodies directed against brain targets are involved in ASD remains an open question. Here, we identified within a cohort an ASD patient with multiple circulating autoantibodies, including the well-characterized one against glutamate NMDA receptor (NMDAR-Ab). The patient exhibited alexithymia and previously suffered from two major depressive episodes without psychotic symptoms. Using a single molecule-based imaging approach, we demonstrate that neither NMDAR-Ab type G immunoglobulin purified from the ASD patient serum, nor that from a seropositive healthy subject, disorganize membrane NMDAR complexes at synapses. These findings suggest that the autistic patient NMDAR-Abs do not play a direct role in the etiology of ASD and that other autoantibodies directed against neuronal targets should be investigated.

Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder

PubMed Central

Yuen, Ryan KC; Merico, Daniele; Bookman, Matt; Howe, Jennifer L; Thiruvahindrapuram, Bhooma; Patel, Rohan V; Whitney, Joe; Deflaux, Nicole; Bingham, Jonathan; Wang, Zhuozhi; Pellecchia, Giovanna; Buchanan, Janet A; Walker, Susan; Marshall, Christian R; Uddin, Mohammed; Zarrei, Mehdi; Deneault, Eric; D’Abate, Lia; Chan, Ada JS; Koyanagi, Stephanie; Paton, Tara; Pereira, Sergio L; Hoang, Ny; Engchuan, Worrawat; Higginbotham, Edward J; Ho, Karen; Lamoureux, Sylvia; Li, Weili; MacDonald, Jeffrey R; Nalpathamkalam, Thomas; Sung, Wilson WL; Tsoi, Fiona J; Wei, John; Xu, Lizhen; Tasse, Anne-Marie; Kirby, Emily; Van Etten, William; Twigger, Simon; Roberts, Wendy; Drmic, Irene; Jilderda, Sanne; Modi, Bonnie MacKinnon; Kellam, Barbara; Szego, Michael; Cytrynbaum, Cheryl; Weksberg, Rosanna; Zwaigenbaum, Lonnie; Woodbury-Smith, Marc; Brian, Jessica; Senman, Lili; Iaboni, Alana; Doyle-Thomas, Krissy; Thompson, Ann; Chrysler, Christina; Leef, Jonathan; Savion-Lemieux, Tal; Smith, Isabel M; Liu, Xudong; Nicolson, Rob; Seifer, Vicki; Fedele, Angie; Cook, Edwin H; Dager, Stephen; Estes, Annette; Gallagher, Louise; Malow, Beth A; Parr, Jeremy R; Spence, Sarah J; Vorstman, Jacob; Frey, Brendan J; Robinson, James T; Strug, Lisa J; Fernandez, Bridget A; Elsabbagh, Mayada; Carter, Melissa T; Hallmayer, Joachim; Knoppers, Bartha M; Anagnostou, Evdokia; Szatmari, Peter; Ring, Robert H; Glazer, David; Pletcher, Mathew T; Scherer, Stephen W

2017-01-01

We are performing whole genome sequencing (WGS) of families with Autism Spectrum Disorder (ASD) to build a resource, named MSSNG, to enable the sub-categorization of phenotypes and underlying genetic factors involved. Here, we report WGS of 5,205 samples from families with ASD, accompanied by clinical information, creating a database accessible in a cloud platform, and through an internet portal with controlled access. We found an average of 73.8 de novo single nucleotide variants and 12.6 de novo insertion/deletions (indels) or copy number variations (CNVs) per ASD subject. We identified 18 new candidate ASD-risk genes such as MED13 and PHF3, and found that participants bearing mutations in susceptibility genes had significantly lower adaptive ability (p=6×10−4). In 294/2,620 (11.2%) of ASD cases, a molecular basis could be determined and 7.2% of these carried CNV/chromosomal abnormalities, emphasizing the importance of detecting all forms of genetic variation as diagnostic and therapeutic targets in ASD. PMID:28263302

"Decoding versus comprehension": Brain responses underlying reading comprehension in children with autism.

PubMed

Bednarz, Haley M; Maximo, Jose O; Murdaugh, Donna L; O'Kelley, Sarah; Kana, Rajesh K

2017-06-01

Despite intact decoding ability, deficits in reading comprehension are relatively common in children with autism spectrum disorders (ASD). However, few neuroimaging studies have tested the neural bases of this specific profile of reading deficit in ASD. This fMRI study examined activation and synchronization of the brain's reading network in children with ASD with specific reading comprehension deficits during a word similarities task. Thirteen typically developing children and 18 children with ASD performed the task in the MRI scanner. No statistically significant group differences in functional activation were observed; however, children with ASD showed decreased functional connectivity between the left inferior frontal gyrus (LIFG) and the left inferior occipital gyrus (LIOG). In addition, reading comprehension ability significantly positively predicted functional connectivity between the LIFG and left thalamus (LTHAL) among all subjects. The results of this study provide evidence for altered recruitment of reading-related neural resources in ASD children and suggest specific weaknesses in top-down modulation of semantic processing. Copyright © 2017 Elsevier Inc. All rights reserved.

Newborn screening for autism: in search of candidate biomarkers

PubMed Central

Mizejewski, Gerald J; Lindau-Shepard, Barbara; Pass, Kenneth A

2013-01-01

Background Autism spectrum disorder (ASD) represents a wide range of neurodevelopmental disorders characterized by impairments in social interaction, language, communication and range of interests. Autism is usually diagnosed in children 3–5 years of age using behavioral characteristics; thus, diagnosis shortly after birth would be beneficial for early initiation of treatment. Aim This retrospective study sought to identify newborns at risk for ASD utilizing bloodspot specimens in an immunoassay. Materials & methods The present study utilized stored frozen specimens from ASD children already diagnosed at 15–36 months of age. The newborn specimens and controls were analyzed by immunoassay in a multiplex system that included 90 serum biomarkers and subjected to statisical analysis. Results Three sets of five biomarkers associated with ASD were found that differed from control groups. The 15 candidate biomarkers were then discussed regarding their association with ASD. Conclusion This study determined that a statistically selected panel of 15 biomarkers successfully discriminated presumptive newborns at risk for ASD from those of nonaffected controls. PMID:23547820

DNA Methylation Analysis of HTR2A Regulatory Region in Leukocytes of Autistic Subjects.

PubMed

Hranilovic, Dubravka; Blazevic, Sofia; Stefulj, Jasminka; Zill, Peter

2016-02-01

Disturbed brain and peripheral serotonin homeostasis is often found in subjects with autism spectrum disorder (ASD). The role of the serotonin receptor 2A (HTR2A) in the regulation of central and peripheral serotonin homeostasis, as well as its altered expression in autistic subjects, have implicated the HTR2A gene as a major candidate for the serotonin disturbance seen in autism. Several studies, yielding so far inconclusive results, have attempted to associate autism with a functional SNP -1438 G/A (rs6311) in the HTR2A promoter region, while possible contribution of epigenetic mechanisms, such as DNA methylation, to HTR2A dysregulation in autism has not yet been investigated. In this study, we compared the mean DNA methylation within the regulatory region of the HTR2A gene between autistic and control subjects. DNA methylation was analysed in peripheral blood leukocytes using bisulfite conversion and sequencing of the HTR2A region containing rs6311 polymorphism. Autistic subjects of rs6311 AG genotype displayed higher mean methylation levels within the analysed region than the corresponding controls (P < 0.05), while there was no statistically significant difference for AA and GG carriers. Our study provides preliminary evidence for increased HTR2A promoter methylation in leukocytes of a portion of adult autistic subjects, indicating that epigenetic mechanisms might contribute to HTR2A dysregulation observed in individuals with ASD. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

Comparing growth in linguistic comprehension and reading comprehension in school-aged children with autism versus typically developing children.

PubMed

Grimm, Ryan P; Solari, Emily J; McIntyre, Nancy S; Zajic, Matthew; Mundy, Peter C

2018-04-01

Many children with autism spectrum disorders (ASD) struggle with reading comprehension. Linguistic comprehension is an important predictor of reading comprehension, especially as children progress through elementary school and later grades. Yet, there is a dearth of research examining longitudinal relations between linguistic comprehensions in school-age children with ASD compared to typically-developing peers (TD). This study compared the developmental trajectories of linguistic and reading comprehension in samples of children with ASD and age-matched TD peers. Both groups were administered measures of linguistic and reading comprehension multiple times over a 30-month period. Latent growth curve modeling demonstrated children with ASD performed at significantly lower levels on both measures at the first timepoint and these deficits persisted across time. Children with ASD exhibited growth in both skills comparable to their TD peers, but this was not sufficient to enable them to eventually achieve at a level similar to the TD group. Due to the wide age range of the sample, age was controlled and displayed significant effects. Findings suggest linguistic comprehension skills are related to reading comprehension in children with ASD, similar to TD peers. Further, intervention in linguistic comprehension skills for children with ASD should begin early and there may be a finite window in which these skills are malleable, in terms of improving reading comprehension skills. Autism Res 2018, 11: 624-635. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. There is relatively little research concerning reading comprehension development in children with ASD and how they compare to TD peers. This study found children with ASD began at lower achievement levels of linguistic comprehension and reading comprehension than TD peers, but the skills developed at a similar rate. Intervening early and raising initial levels of linguistic and reading comprehension may enable children with ASD to perform similarly to TD peers over time. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

A Meta-Analysis of School-Based Social Skills Interventions for Children With Autism Spectrum Disorders

ERIC Educational Resources Information Center

Bellini, Scott; Peters, Jessica K.; Benner, Lauren; Hopf, Andrea

2007-01-01

Social skills deficits are a central feature of autism spectrum disorders (ASD). This meta-analysis of 55 single-subject design studies examined the effectiveness of school-based social skills interventions for children and adolescents with ASD. Intervention, maintenance, and generalization effects were measured by computing the percentage of…

On the Application of Quantitative EEG for Characterizing Autistic Brain: A Systematic Review

PubMed Central

Billeci, Lucia; Sicca, Federico; Maharatna, Koushik; Apicella, Fabio; Narzisi, Antonio; Campatelli, Giulia; Calderoni, Sara; Pioggia, Giovanni; Muratori, Filippo

2013-01-01

Autism-Spectrum Disorders (ASD) are thought to be associated with abnormalities in neural connectivity at both the global and local levels. Quantitative electroencephalography (QEEG) is a non-invasive technique that allows a highly precise measurement of brain function and connectivity. This review encompasses the key findings of QEEG application in subjects with ASD, in order to assess the relevance of this approach in characterizing brain function and clustering phenotypes. QEEG studies evaluating both the spontaneous brain activity and brain signals under controlled experimental stimuli were examined. Despite conflicting results, literature analysis suggests that QEEG features are sensitive to modification in neuronal regulation dysfunction which characterize autistic brain. QEEG may therefore help in detecting regions of altered brain function and connectivity abnormalities, in linking behavior with brain activity, and subgrouping affected individuals within the wide heterogeneity of ASD. The use of advanced techniques for the increase of the specificity and of spatial localization could allow finding distinctive patterns of QEEG abnormalities in ASD subjects, paving the way for the development of tailored intervention strategies. PMID:23935579

Patterns of Joint Improvisation in Adults with Autism Spectrum Disorder.

PubMed

Brezis, Rachel-Shlomit; Noy, Lior; Alony, Tali; Gotlieb, Rachel; Cohen, Rachel; Golland, Yulia; Levit-Binnun, Nava

2017-01-01

Recent research on autism spectrum disorders (ASDs) suggests that individuals with autism may have a basic deficit in synchronizing with others, and that this difficulty may lead to more complex social and communicative deficits. Here, we examined synchronization during an open-ended joint improvisation (JI) paradigm, called the mirror game (MG). In the MG, two players take turns leading, following, and jointly improvising motion using two handles set on parallel tracks, while their motion tracks are recorded with high temporal and spatial resolution. A series of previous studies have shown that players in the MG attain moments of highly synchronized co-confident (CC) motion, in which there is no typical kinematic pattern of leader and reactive follower. It has been suggested that during these moments players act as a coupled unit and feel high levels of connectedness. Here, we aimed to assess whether participants with ASD are capable of attaining CC, and whether their MG performance relates to broader motor and social skills. We found that participants with ASD ( n = 34) can indeed attain CC moments when playing with an expert improviser, though their performance was attenuated in several ways, compared to typically developing (TD) participants ( n = 35). Specifically, ASD participants had lower rates of CC, compared with TD participants, which was most pronounced during the following rounds. In addition, the duration of their CC segments was shorter, across all rounds. When controlling for participants' motor skills (both on the MG console, and more broadly) some of the variability in MG performance was explained, but group differences remained. ASD participants' alexithymia further correlated with their difficulty following another's lead; though other social skills did not relate to MG performance. Participants' subjective reports of the game suggest that other cognitive and emotional factors, such as attention, motivation, and reward-processing, which were not directly measured in the experiment, may impact their performance. Together, these results show that ASD participants can attain moments of high motor synchronization with an expert improviser, even during an open-ended task. Future studies should examine the ways in which these skills may be further harnessed in clinical settings.

Patterns of Joint Improvisation in Adults with Autism Spectrum Disorder

PubMed Central

Brezis, Rachel-Shlomit; Noy, Lior; Alony, Tali; Gotlieb, Rachel; Cohen, Rachel; Golland, Yulia; Levit-Binnun, Nava

2017-01-01

Recent research on autism spectrum disorders (ASDs) suggests that individuals with autism may have a basic deficit in synchronizing with others, and that this difficulty may lead to more complex social and communicative deficits. Here, we examined synchronization during an open-ended joint improvisation (JI) paradigm, called the mirror game (MG). In the MG, two players take turns leading, following, and jointly improvising motion using two handles set on parallel tracks, while their motion tracks are recorded with high temporal and spatial resolution. A series of previous studies have shown that players in the MG attain moments of highly synchronized co-confident (CC) motion, in which there is no typical kinematic pattern of leader and reactive follower. It has been suggested that during these moments players act as a coupled unit and feel high levels of connectedness. Here, we aimed to assess whether participants with ASD are capable of attaining CC, and whether their MG performance relates to broader motor and social skills. We found that participants with ASD (n = 34) can indeed attain CC moments when playing with an expert improviser, though their performance was attenuated in several ways, compared to typically developing (TD) participants (n = 35). Specifically, ASD participants had lower rates of CC, compared with TD participants, which was most pronounced during the following rounds. In addition, the duration of their CC segments was shorter, across all rounds. When controlling for participants’ motor skills (both on the MG console, and more broadly) some of the variability in MG performance was explained, but group differences remained. ASD participants’ alexithymia further correlated with their difficulty following another’s lead; though other social skills did not relate to MG performance. Participants’ subjective reports of the game suggest that other cognitive and emotional factors, such as attention, motivation, and reward-processing, which were not directly measured in the experiment, may impact their performance. Together, these results show that ASD participants can attain moments of high motor synchronization with an expert improviser, even during an open-ended task. Future studies should examine the ways in which these skills may be further harnessed in clinical settings. PMID:29114236

Developmental Trajectories in Children With and Without Autism Spectrum Disorders: The First 3 Years

PubMed Central

Landa, Rebecca J.; Stuart, Elizabeth A.; Gross, Alden L.; Faherty, Ashley

2014-01-01

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 identified after 14 months, and no ASD. Despite groups’ initial similar developmental level at 6 months, ASD groups exhibited atypical trajectories thereafter. Impairment from 14 to 24 months was greater in the Early-ASD than the Later-ASD group, but comparable at 36 months. Developmental plateau and regression occurred in some children with ASD, regardless of timing of ASD diagnosis. Findings indicate a preclinical phase of varying duration for ASD. PMID:23110514

Examining the Clinical Correlates of Autism Spectrum Disorder in Youth by Ascertainment Source

PubMed Central

Joshi, Gagan; Faraone, Stephen V; Wozniak, Janet; Petty, Carter; Fried, Ronna; Galdo, Maribel; Furtak, Stephannie L.; McDermott, Katie; Epstien, Cecily; Walker, Rosemary; Caron, Ashley; Feinberg, Leah; Biederman, Joseph

2014-01-01

Objective To examine whether presentation of autism spectrum disorder (ASD) and associated patterns of psychiatric comorbidity and dysfunction vary by referral source. Methods ASD youth referred to a specialized ambulatory program for ASD (N=143) were compared to ASD youth referred to a general child psychiatry clinic (N=217). Results More ASD clinic youth met criteria for a more robust form of ASD (autistic disorder); more youth referred to the psychiatry clinic met criteria for broader spectrum ASD (PDD-NOS). General psychiatry clinic youth with ASD suffered from a greater burden of psychopathologies and higher levels of dysfunction. Conclusion The presentation of ASD in psychiatrically referred youth differs between general and ASD-specialized clinics, though both referral populations have high levels of comorbidity and dysfunction. PMID:24566937

Age at Autism Spectrum Disorder (ASD) Diagnosis by Race, Ethnicity, and Primary Household Language Among Children with Special Health Care Needs, United States, 2009-2010.

PubMed

Jo, Heejoo; Schieve, Laura A; Rice, Catherine E; Yeargin-Allsopp, Marshalyn; Tian, Lin H; Blumberg, Stephen J; Kogan, Michael D; Boyle, Coleen A

2015-08-01

We examined prevalence of diagnosed autism spectrum disorder (ASD) and age at diagnosis according to child's race/ethnicity and primary household language. From the 2009-2010 National Survey of Children with Special Health Care Needs, we identified 2729 3-17-year-old US children whose parent reported a current ASD diagnosis. We compared ASD prevalence, mean diagnosis age, and percentage with later diagnoses (≥5 years) across racial/ethnic/primary household language groups: non-Hispanic-white, any language (NHW); non-Hispanic-black, any language (NHB); Hispanic-any-race, English (Hispanic-English); and Hispanic-any-race, other language (Hispanic-Other). We assessed findings by parent-reported ASD severity level and adjusted for family sociodemographics. ASD prevalence estimates were 15.3 (NHW), 10.4 (NHB), 14.1 (Hispanic-English), and 5.2 (Hispanic-Other) per 1000 children. Mean diagnosis age was comparable across racial/ethnic/language groups for 3-4-year-olds. For 5-17-year-olds, diagnosis age varied by race/ethnicity/language and also by ASD severity. In this group, NHW children with mild/moderate ASD had a significantly higher proportion (50.8 %) of later diagnoses than NHB (33.5 %) or Hispanic-Other children (18.0 %). However, NHW children with severe ASD had a comparable or lower (albeit non-significant) proportion (16.4 %) of later diagnoses than NHB (37.8 %), Hispanic-English (30.8 %), and Hispanic-Other children (12.0 %). While NHW children have comparable ASD prevalence and diagnosis age distributions as Hispanic-English children, they have both higher prevalence and proportion of later diagnoses than NHB and Hispanic-Other children. The diagnosis age findings were limited to mild/moderate cases only. Thus, the prevalence disparity might be primarily driven by under-representation (potentially under-identification) of older children with mild/moderate ASD in the two minority groups.

Oscillatory rhythm of reward: anticipation and processing of rewards in children with and without autism.

PubMed

Stavropoulos, Katherine Kuhl-Meltzoff; Carver, Leslie J

2018-01-01

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition, and multiple theories have emerged concerning core social deficits. While the social motivation hypothesis proposes that deficits in the social reward system cause individuals with ASD to engage less in social interaction, the overly intense world hypothesis (sensory over-responsivity) proposes that individuals with ASD find stimuli to be too intense and may have hypersensitivity to social interaction, leading them to avoid these interactions. EEG was recorded during reward anticipation and reward processing. Reward anticipation was measured using alpha asymmetry, and post-feedback theta was utilized to measure reward processing. Additionally, we calculated post-feedback alpha suppression to measure attention and salience. Participants were 6- to 8-year-olds with ( N  = 20) and without ( N  = 23) ASD. Children with ASD showed more left-dominant alpha suppression when anticipating rewards accompanied by nonsocial stimuli compared to social stimuli. During reward processing, children with ASD had less theta activity than typically developing (TD) children. Alpha activity after feedback showed the opposite pattern: children with ASD had greater alpha suppression than TD children. Significant correlations were observed between behavioral measures of autism severity and EEG activity in both the reward anticipation and reward processing time periods. The findings provide evidence that children with ASD have greater approach motivation prior to nonsocial (compared to social) stimuli. Results after feedback suggest that children with ASD evidence less robust activity thought to reflect evaluation and processing of rewards (e.g., theta) compared to TD children. However, children with ASD evidence greater alpha suppression after feedback compared to TD children. We hypothesize that post-feedback alpha suppression reflects general cognitive engagement-which suggests that children with ASD may experience feedback as overly intense. Taken together, these results suggest that aspects of both the social motivation hypothesis and the overly intense world hypothesis may be occurring simultaneously.

The familial co-aggregation of ASD and ADHD: a register-based cohort study.

PubMed

Ghirardi, L; Brikell, I; Kuja-Halkola, R; Freitag, C M; Franke, B; Asherson, P; Lichtenstein, P; Larsson, H

2018-02-01

Autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD) frequently co-occur. The presence of a genetic link between ASD and ADHD symptoms is supported by twin studies, but the genetic overlap between clinically ascertained ASD and ADHD remains largely unclear. We therefore investigated how ASD and ADHD co-aggregate in individuals and in families to test for the presence of a shared genetic liability and examined potential differences between low- and high-functioning ASD in the link with ADHD. We studied 1 899 654 individuals born in Sweden between 1987 and 2006. Logistic regression was used to estimate the association between clinically ascertained ASD and ADHD in individuals and in families. Stratified estimates were obtained for ASD with (low-functioning) and without (high-functioning) intellectual disability. Individuals with ASD were at higher risk of having ADHD compared with individuals who did not have ASD (odds ratio (OR)=22.33, 95% confidence interval (CI): 21.77-22.92). The association was stronger for high-functioning than for low-functioning ASD. Relatives of individuals with ASD were at higher risk of ADHD compared with relatives of individuals without ASD. The association was stronger in monozygotic twins (OR=17.77, 95% CI: 9.80-32.22) than in dizygotic twins (OR=4.33, 95% CI: 3.21-5.85) and full siblings (OR=4.59, 95% CI: 4.39-4.80). Individuals with ASD and their relatives are at increased risk of ADHD. The pattern of association across different types of relatives supports the existence of genetic overlap between clinically ascertained ASD and ADHD, suggesting that genomic studies might have underestimated this overlap.

Executive functioning and local-global visual processing: candidate endophenotypes for autism spectrum disorder?

PubMed

Van Eylen, Lien; Boets, Bart; Cosemans, Nele; Peeters, Hilde; Steyaert, Jean; Wagemans, Johan; Noens, Ilse

2017-03-01

Heterogeneity within autism spectrum disorder (ASD) hampers insight in the etiology and stimulates the search for endophenotypes. Endophenotypes should meet several criteria, the most important being the association with ASD and the higher occurrence rate in unaffected ASD relatives than in the general population. We evaluated these criteria for executive functioning (EF) and local-global (L-G) visual processing. By administering an extensive cognitive battery which increases the validity of the measures, we examined which of the cognitive anomalies shown by ASD probands also occur in their unaffected relatives (n = 113) compared to typically developing (TD) controls (n = 100). Microarrays were performed, so we could exclude relatives from probands with a de novo mutation in a known ASD susceptibility copy number variant, thus increasing the probability that genetic risk variants are shared by the ASD relatives. An overview of studies investigating EF and L-G processing in ASD relatives was also provided. For EF, ASD relatives - like ASD probands - showed impairments in response inhibition, cognitive flexibility and generativity (specifically, ideational fluency), and EF impairments in daily life. For L-G visual processing, the ASD relatives showed no anomalies on the tasks, but they reported more attention to detail in daily life. Group differences were similar for siblings and for parents of ASD probands, and yielded larger effect sizes in a multiplex subsample. The group effect sizes for the comparison between ASD probands and TD individuals were generally larger than those of the ASD relatives compared to TD individuals. Impaired cognitive flexibility, ideational fluency and response inhibition are strong candidate endophenotypes for ASD. They could help to delineate etiologically more homogeneous subgroups, which is clinically important to allow assigning ASD probands to different, more targeted, interventions. © 2016 Association for Child and Adolescent Mental Health.

Mid-childhood outcomes of infant siblings at familial high-risk of autism spectrum disorder.

PubMed

Shephard, Elizabeth; Milosavljevic, Bosiljka; Pasco, Greg; Jones, Emily J H; Gliga, Teodora; Happé, Francesca; Johnson, Mark H; Charman, Tony

2017-03-01

Almost 20% of infants with an older sibling with autism spectrum disorder (ASD) exhibit ASD themselves by age 3 years. The longer-term outcomes of high-risk infants are less clear. We examined symptoms of ASD, attention-deficit/hyperactivity disorder (ADHD) and anxiety, language, IQ, and adaptive behaviour at age 7 years in high- and low-risk children prospectively studied since the first year of life. Clinical outcomes were compared between high-risk children who met diagnostic criteria for ASD at age 7 (HR-ASD-7 group, n = 15), high-risk children without ASD (HR-Non-ASD-7 group, n = 24), and low-risk control children (LR group, n = 37). Diagnostic stability between age 3 and 7 years was moderate, with five children who did not meet diagnostic criteria for ASD at age 3 years being assigned the diagnosis at age 7, and three children showing the opposite pattern. The HR-ASD-7 group showed elevated ADHD and anxiety symptoms and had lower adaptive behaviour scores than LR controls. The HR-Non-ASD-7 group had higher repetitive behaviour, lower adaptive functioning and elevated scores on one anxiety subscale (Separation Anxiety) compared to LR controls, but evidence for subclinical ASD symptoms (the broader autism phenotype, BAP) was limited in the group as a whole, although we identified a subgroup with elevated ASD traits. The difficulties experienced by high-risk siblings at school-age extend beyond ASD symptoms. The pattern of difficulties exhibited by the HR-ASD-7 group may inform our understanding of developmental trajectories of co-occurring psychopathology in ASD. Autism Res 2017, 10: 546-557. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

Psychiatric Comorbidity and Functioning in a Clinically Referred Population of Adults with Autism Spectrum Disorders: A Comparative Study

ERIC Educational Resources Information Center

Joshi, Gagan; Wozniak, Janet; Petty, Carter; Martelon, Mary Kate; Fried, Ronna; Bolfek, Anela; Kotte, Amelia; Stevens, Jonathan; Furtak, Stephannie L.; Bourgeois, Michelle; Caruso, Janet; Caron, Ashley; Biederman, Joseph

2013-01-01

To systematically examine the patterns of psychiatric comorbidity and functioning in clinically referred adults with autism spectrum disorders (ASD). Psychiatrically referred adults with and without ASD were compared on measures assessing for psychiatric comorbidity and psychosocial functioning. Sixty-three adults with ASD participated in the…

Corpus Callosum Morphometrics in Young Children with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Boger-Megiddo, Inbal; Shaw, Dennis W. W.; Friedman, Seth D.; Sparks, Bobbi F.; Artru, Alan A.; Giedd, Jay N.; Dawson, Geraldine; Dager, Stephen R.

2006-01-01

This study assessed digital corpus callosum cross sectional areas in 3-4 year olds with autism spectrum disorder (ASD) compared to typically developing (TD) and developmentally delayed (DD) children. Though not different in absolute size compared to TD, ASD callosums were disproportionately small adjusted for increased ASD cerebral volume. ASD…

[Correlation between serum 25-hydroxyvitamin D level and core symptoms of autism spectrum disorder in children].

PubMed

Dong, H Y; Wang, B; Li, H H; Shan, L; Jia, F Y

2017-12-02

Objective: To explore the relationship between serum 25-hydroxyvitamin D levels and core symptoms of autism spectrum disorder (ASD) in children. Method: In this cross-sectional study, ASD children 4 to 6 years of age who were diagnosed in Department of Developmental and Behavioral Pediatrics, First Hospital of Jilin university from January to May 2017 were assigned to ASD group, and children for routine growth and development assessment in Jilin province were assigned to control group. The two groups were well matched for age and sex, and none of them had received vitamin D supplementation. Serum 25-hydroxyvitamin D levels were measured by HPLC-MS/MS method. The patients of the ASD group were assessed with autism behavior checklist (ABC), childhood autism rating scale (CARS), social response scale (SRS), and autism treatment evaluation checklist (ATEC). The levels of vitamin D were divided into normal(>0.03 ng/L), insufficient (0.01-0.03 ng/L) and deficient (<0.01 ng/L). Levels of serum vitamin D between the two groups were compared by two independent sample t -test, and the difference in the percentages of normal, insufficient and deficient levels of vitamin D was tested by chi-square test, and correlations between vitamin D levels and the total scores or subscales of ABC, CARS, SRS and ATEC were analyzed by Pearson correlation analysis. Result: The 87 subjects in the ASD group included 75 males and 12 females, with a mean (±SD) age of (4.7±0.7) years. The 301 subjects in the control group included 249 males and 52 females, with a mean (±SD) age of (4.8±0.8) years. Serum vitamin D level in ASD children was significantly lower than that of the control group ( (0.021±0.008) vs . (0.036±0.016) ng/L, t= -8.17, P< 0.01), and the between-group percentage difference of normal, insufficient and deficient levels of vitamin D was statistically significant (12 (14%) vs . 186 (62%) , 67 (77%) vs . 113 (37%) , 8 (9%) vs . 2 (1%) , χ(2)=72.1, P< 0.01). There were negative correlations between serum vitamin D level in ASD children and total ABC score or ABC subscale scores (body behavior, self-care, language and social interaction)( r=- 0.531, - 0.397,-0.283,-0.248,-0.262, P= 0.000, 0.000, 0.007, 0.020, 0.014). There were negative correlations between serum vitamin D level in ASD children and total CARS score and CARS subscale scores (imitation, nonverbal communication and general impression) ( r=- 0.352, - 0.216, - 0.248, - 0.216, P= 0.001, 0.046, 0.021, 0.046). There were negative correlations between serum vitamin D level in ASD children and SRS behavior subscale or ATEC social interaction subscale ( r=- 0.536, P= 0.005, r=- 0.400, P= 0.014). Conclusion: Serum 25-hydroxyvitamin D level in children with ASD is obviously lower than that in the healthy control group, and there are negative correlations between vitamin D levels and core symptoms of ASD. Trial registration Chinese Clinical Trial Registry, ChiCTR-CCC-13004498.

[Pre- and perinatal risk factors in autism spectrum disorder and attention deficit/hyperactivity disorder].

PubMed

Schmitz, Johanna C; Cholemkery, Hannah; Medda, Juliane; Freitag, Christine M

2017-01-01

Epidemiological studies indicate the relevance of pre- and perinatal risk factors for the genesis of attention deficit/hyperactivity disorder and autism spectrum disorder. This study compares potential risk factors in a clinical sample of children with ADHD, ASD, the combination of both diseases, ADHD and oppositional defiant or conduct disorder (ADHD & ODD/CD) and examined whether the existence of additional risk factors promotes the occurrence of combined diseases. We compared the pre- and perinatal risk factors of 341 patients (299 boys, 42 girls) from a clinical population, differentiating between children with ADHD (n=80), ASD (n=122), ADHD & ASD (n=55), or ADHD & ODD/CD (n=84). We observed a higher rate of maternal smoking, a higher rate of migration, and lower parental education among the children with ADHD & ODD/CD compared to those with ASD or ADHD. The rate of migration background was higher among the children with ASD compared to children with ADHD. Miscarriage was a specific risk factor for ADHD & ASD. Numerous risk factors described in epidemiological studies occurred only rarely in our clinical sample. The distribution of most risk factors was comparable between the examined diseases.

Symptom Profile of Attention-Deficit/Hyperactivity Disorder in Youth with High-functioning Autism Spectrum Disorder: A Comparative Study in Psychiatrically Referred Populations

PubMed Central

Joshi, Gagan; Faraone, Stephen V.; Wozniak, Janet; Tarko, Laura; Fried, Ronna; Galdo, Maribel; Furtak, Stephannie L.; Biederman, Joseph

2014-01-01

Objective To compare the clinical presentation of ADHD between youth with autism spectrum disorder (ASD) and ADHD and a sample of youth with ADHD only. Method A psychiatrically referred sample of autism spectrum disorder (ASD) youth with ADHD attending a specialized ambulatory program for ASD (n = 107) and a sample of youth with ADHD attending a general child psychiatry ambulatory clinic (n = 74) were compared. Results Seventy-six percent of youth with ASD met Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) criteria for ADHD. The clinical presentation of ADHD in youth with ASD was predominantly similar to its typical presentation including age at onset (3.5 ± 1.7 vs. 4.0 ± 1.9; p = .12), distribution of diagnostic subtypes, the qualitative and quantitative symptom profile, and symptom severity. Combined subtype was the most frequent presentation of ADHD in ASD youth. Conclusion Despite the robust presentation of ADHD, a significant majority of ASD youth with ADHD failed to receive appropriate ADHD treatment (41% vs. 24%; p = .02). A high rate of comorbidity with ADHD was observed in psychiatrically referred youth with ASD, with a clinical presentation typical of the disorder. PMID:25085653

Mitochondrial dysfunction in the gastrointestinal mucosa of children with autism: A blinded case-control study

PubMed Central

Rose, Shannon; Bennuri, Sirish C.; Murray, Katherine F.; Buie, Timothy; Winter, Harland

2017-01-01

Gastrointestinal (GI) symptoms are prevalent in autism spectrum disorder (ASD) but the pathophysiology is poorly understood. Imbalances in the enteric microbiome have been associated with ASD and can cause GI dysfunction potentially through disruption of mitochondrial function as microbiome metabolites modulate mitochondrial function and mitochondrial dysfunction is highly associated with GI symptoms. In this study, we compared mitochondrial function in rectal and cecum biopsies under the assumption that certain microbiome metabolites, such as butyrate and propionic acid, are more abundant in the cecum as compared to the rectum. Rectal and cecum mucosal biopsies were collected during elective diagnostic colonoscopy. Using a single-blind case-control design, complex I and IV and citrate synthase activities and complex I-V protein quantity from 10 children with ASD, 10 children with Crohn’s disease and 10 neurotypical children with nonspecific GI complaints were measured. The protein for all complexes, except complex II, in the cecum as compared to the rectum was significantly higher in ASD samples as compared to other groups. For both rectal and cecum biopsies, ASD samples demonstrated higher complex I activity, but not complex IV or citrate synthase activity, compared to other groups. Mitochondrial function in the gut mucosa from children with ASD was found to be significantly different than other groups who manifested similar GI symptomatology suggesting a unique pathophysiology for GI symptoms in children with ASD. Abnormalities localized to the cecum suggest a role for imbalances in the microbiome, potentially in the production of butyrate, in children with ASD. PMID:29028817

Increased prevalence of seizures in boys who were probands with the FMR1 premutation and co-morbid autism spectrum disorder

PubMed Central

Chonchaiya, Weerasak; Au, Jacky; Schneider, Andrea; Hessl, David; Harris, Susan W.; Laird, Meredith; Mu, Yi; Tassone, Flora; Nguyen, Danh V.

2014-01-01

Seizures are a common co-occurring condition in those with fragile X syndrome (FXS), and in those with idiopathic autism spectrum disorder (ASD). Seizures are also associated with ASD in those with FXS. However, little is known about the rate of seizures and how commonly these problems co-occur with ASD in boys with the FMR1 premutation. We, therefore, determined the prevalence of seizures and ASD in boys with the FMR1 permutation compared with their sibling counterparts and population prevalence estimates. Fifty premutation boys who presented as clinical probands (N = 25), or non-probands (identified by cascade testing after the proband was found) (N = 25), and 32 non-carrier controls were enrolled. History of seizures was documented and ASD was diagnosed by standardized measures followed by a team consensus of ASD diagnosis. Seizures (28%) and ASD (68%) were more prevalent in probands compared with non-probands (0 and 28%), controls (0 and 0%), and population estimates (1 and 1.7%). Seizures occurred more frequently in those with the premutation and co-morbid ASD particularly in probands compared with those with the premutation alone (25 vs. 3.85%, p = 0.045). Although cognitive and adaptive functioning in non-probands were similar to controls, non-probands were more likely to meet the diagnosis of ASD than controls (28 vs. 0%, p < 0.0001). In conclusion, seizures were relatively more common in premutation carriers who presented clinically as probands of the family and seizures were commonly associated with ASD in these boys. Therefore, boys with the premutation, particularly if they are probands should be assessed carefully for both ASD and seizures. PMID:22001913

Clinical phenotype of ASD-associated DYRK1A haploinsufficiency.

PubMed

Earl, Rachel K; Turner, Tychele N; Mefford, Heather C; Hudac, Caitlin M; Gerdts, Jennifer; Eichler, Evan E; Bernier, Raphael A

2017-01-01

DYRK1A is a gene recurrently disrupted in 0.1-0.5% of the ASD population. A growing number of case reports with DYRK1A haploinsufficiency exhibit common phenotypic features including microcephaly, intellectual disability, speech delay, and facial dysmorphisms. Phenotypic information from previously published DYRK1A cases ( n  = 51) and participants in an ongoing study at the University of Washington (UW, n  = 10) were compiled. Frequencies of recurrent phenotypic features in this population were compared to features observed in a large sample with idiopathic ASD from the Simons Simplex Collection ( n  = 1981). UW DYRK1A cases were further characterized quantitatively and compared to a randomly subsampled set of idiopathic ASD cases matched on age and gender ( n  = 10) and to cases with an ASD-associated disruptive mutation to CHD8 ( n  = 12). Contribution of familial genetic background to clinical heterogeneity was assessed by comparing head circumference, IQ, and ASD-related symptoms of UW DYRK1A cases to their unaffected parents. DYRK1A haploinsufficiency results in a common phenotypic profile including intellectual disability, speech and motor difficulties, microcephaly, feeding difficulties, and vision abnormalities. Eighty-nine percent of DYRK1A cases ascertained for ASD presented with a constellation of five or more of these symptoms. When compared quantitatively, DYRK1A cases presented with significantly lower IQ and adaptive functioning compared to idiopathic cases and significantly smaller head size compared to both idiopathic and CHD8 cases. Phenotypic variability in parental head circumference, IQ, and ASD-related symptoms corresponded to observed variability in affected child phenotype. Results confirm a core clinical phenotype for DYRK1A disruptions, with a combination of features that is distinct from idiopathic ASD. Cases with DYRK1A mutations are also distinguishable from disruptive mutations to CHD8 by head size. Measurable, quantitative characterization of DYRK1A haploinsufficiency illuminates clinical variability, which may be, in part, due to familial genetic background.

Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis

PubMed Central

Rossignol, D A; Frye, R E

2012-01-01

A comprehensive literature search was performed to collate evidence of mitochondrial dysfunction in autism spectrum disorders (ASDs) with two primary objectives. First, features of mitochondrial dysfunction in the general population of children with ASD were identified. Second, characteristics of mitochondrial dysfunction in children with ASD and concomitant mitochondrial disease (MD) were compared with published literature of two general populations: ASD children without MD, and non-ASD children with MD. The prevalence of MD in the general population of ASD was 5.0% (95% confidence interval 3.2, 6.9%), much higher than found in the general population (∼0.01%). The prevalence of abnormal biomarker values of mitochondrial dysfunction was high in ASD, much higher than the prevalence of MD. Variances and mean values of many mitochondrial biomarkers (lactate, pyruvate, carnitine and ubiquinone) were significantly different between ASD and controls. Some markers correlated with ASD severity. Neuroimaging, in vitro and post-mortem brain studies were consistent with an elevated prevalence of mitochondrial dysfunction in ASD. Taken together, these findings suggest children with ASD have a spectrum of mitochondrial dysfunction of differing severity. Eighteen publications representing a total of 112 children with ASD and MD (ASD/MD) were identified. The prevalence of developmental regression (52%), seizures (41%), motor delay (51%), gastrointestinal abnormalities (74%), female gender (39%), and elevated lactate (78%) and pyruvate (45%) was significantly higher in ASD/MD compared with the general ASD population. The prevalence of many of these abnormalities was similar to the general population of children with MD, suggesting that ASD/MD represents a distinct subgroup of children with MD. Most ASD/MD cases (79%) were not associated with genetic abnormalities, raising the possibility of secondary mitochondrial dysfunction. Treatment studies for ASD/MD were limited, although improvements were noted in some studies with carnitine, co-enzyme Q10 and B-vitamins. Many studies suffered from limitations, including small sample sizes, referral or publication biases, and variability in protocols for selecting children for MD workup, collecting mitochondrial biomarkers and defining MD. Overall, this evidence supports the notion that mitochondrial dysfunction is associated with ASD. Additional studies are needed to further define the role of mitochondrial dysfunction in ASD. PMID:21263444

Prevalence of Creatine Deficiency Syndromes in Children With Nonsyndromic Autism.

PubMed

Schulze, Andreas; Bauman, Margaret; Tsai, Anne Chun-Hui; Reynolds, Ann; Roberts, Wendy; Anagnostou, Evdokia; Cameron, Jessie; Nozzolillo, Alixandra A; Chen, Shiyi; Kyriakopoulou, Lianna; Scherer, Stephen W; Loh, Alvin

2016-01-01

Creatine deficiency may play a role in the neurobiology of autism and may represent a treatable cause of autism. The goal of the study was to ascertain the prevalence of creatine deficiency syndromes (CDSs) in children with autism spectrum disorder (ASD). In a prospective multicenter study, 443 children were investigated after a confirmed diagnosis of ASD. Random spot urine screening for creatine metabolites (creatine, guanidinoacetate, creatinine, and arginine) with liquid chromatography-tandem mass spectrometry and second-tier testing with high-performance liquid chromatography methodology was followed by recall testing in 24-hour urines and confirmatory testing by Sanger-based DNA sequencing of GAMT, GATM, and SLC6A8 genes. Additional diagnostic tests included plasma creatine metabolites and in vivo brain proton magnetic resonance spectroscopy. The creatine metabolites in spot urine in the autism group were compared with 128 healthy controls controlled for age. In 443 subjects with ASD investigated for CDS, we had 0 events (event: 0, 95% confidence interval 0-0.0068), therefore with 95% confidence the prevalence of CDS is <7 in 1000 children with ASD. The autism and control groups did not vary in terms of creatine metabolites (P > .0125) in urine. Our study revealed a very low prevalence of CDS in children with nonsyndromic ASD and no obvious association between creatine metabolites and autism. Unlike our study population, we expect more frequent CDS among children with severe developmental delay, speech impairment, seizures, and movement disorders in addition to impairments in social communication, restricted interests, and repetitive behaviors. Copyright © 2016 by the American Academy of Pediatrics.

From High Intellectual Potential to Asperger Syndrome: Evidence for Differences and a Fundamental Overlap-A Systematic Review.

PubMed

Boschi, Aurélie; Planche, Pascale; Hemimou, Cherhazad; Demily, Caroline; Vaivre-Douret, Laurence

2016-01-01

Background: An increasing number of clinicians point to similar clinical features between some children with High Intellectual Potential (HIP or "Giftedness" = Total IQ > 2 SD ), and children with Autism Spectrum Disorder (ASD) without intellectual or language delay, formerly diagnosed with Asperger Syndrome. Some of these common features are social interaction impairments, special interests, and in some cases high-verbal abilities. The aim of this article is to determine whether these similarities exist at more fundamental levels, other than clinical, and to explore the literature in order to provide empirical support for an overlap between ASD and HIP. Method: First, comparative studies between ASD and HIP children were sought. Because of a lack of data, the respective characteristics of ASD and HIP subjects were explored by a cross-sectional review of different areas of research. Emphasis was placed on psychometric and cognitive evaluations, experimental and developmental assessments, and neurobiological research, following a "bottom-up" procedure. Results: This review highlights the existence of similarities in the neurocognitive, developmental and neurobiological domains between these profiles, which require further study. In addition, the conclusions of several studies show that there are differences between HIP children with a homogeneous Intellectual Quotient profile and children with a heterogeneous Intellectual Quotient profile. Conclusion: HIP seems to cover different developmental profiles, one of which might share features with ASD. A new line of investigation providing a possible starting-point for future research is proposed. Its implications, interesting from both clinical and research perspectives, are discussed.

From High Intellectual Potential to Asperger Syndrome: Evidence for Differences and a Fundamental Overlap—A Systematic Review

PubMed Central

Boschi, Aurélie; Planche, Pascale; Hemimou, Cherhazad; Demily, Caroline; Vaivre-Douret, Laurence

2016-01-01

Background: An increasing number of clinicians point to similar clinical features between some children with High Intellectual Potential (HIP or “Giftedness” = Total IQ > 2 SD), and children with Autism Spectrum Disorder (ASD) without intellectual or language delay, formerly diagnosed with Asperger Syndrome. Some of these common features are social interaction impairments, special interests, and in some cases high-verbal abilities. The aim of this article is to determine whether these similarities exist at more fundamental levels, other than clinical, and to explore the literature in order to provide empirical support for an overlap between ASD and HIP. Method: First, comparative studies between ASD and HIP children were sought. Because of a lack of data, the respective characteristics of ASD and HIP subjects were explored by a cross-sectional review of different areas of research. Emphasis was placed on psychometric and cognitive evaluations, experimental and developmental assessments, and neurobiological research, following a “bottom-up” procedure. Results: This review highlights the existence of similarities in the neurocognitive, developmental and neurobiological domains between these profiles, which require further study. In addition, the conclusions of several studies show that there are differences between HIP children with a homogeneous Intellectual Quotient profile and children with a heterogeneous Intellectual Quotient profile. Conclusion: HIP seems to cover different developmental profiles, one of which might share features with ASD. A new line of investigation providing a possible starting-point for future research is proposed. Its implications, interesting from both clinical and research perspectives, are discussed. PMID:27812341

Investigating autism spectrum disorder and autistic traits in early onset eating disorder.

PubMed

Pooni, Jyoti; Ninteman, Aafke; Bryant-Waugh, Rachel; Nicholls, Dasha; Mandy, William

2012-05-01

To investigate whether young people (8-16 years) with an eating disorder have a higher prevalence of autism spectrum disorder (ASDs) and elevated autistic traits compared to typically developing (TD) peers. Twenty-two participants with early onset eating disorder (EOED) were assessed using standardized ASD measures and compared to IQ matched TD (n = 24) and ASD (n = 20) controls. An ASD diagnosis was no more common in EOED than in TD controls. However, repetitive and stereotyped behavior was more often observed in the EOED group and, compared to TD controls, there was a trend (p = .07) toward greater autistic social impairment in EOED. Whilst participants with EOED did not show increased ASD prevalence, they did have elevated autistic traits of clinical significance, particularly repetitive and stereotyped behavior. Further work is required to determine whether inflexibility and social difficulties in EOED have identical phenomenology and etiology to those seen in ASD. Copyright © 2012 Wiley Periodicals, Inc.

Social and monetary reward processing in autism spectrum disorders

PubMed Central

2012-01-01

Background Social motivation theory suggests that deficits in social reward processing underlie social impairments in autism spectrum disorders (ASD). However, the extent to which abnormalities in reward processing generalize to other classes of stimuli remains unresolved. The aim of the current study was to examine if reward processing abnormalities in ASD are specific to social stimuli or can be generalized to other classes of reward. Additionally, we sought to examine the results in the light of behavioral impairments in ASD. Methods Participants performed adapted versions of the social and monetary incentive delay tasks. Data from 21 unmedicated right-handed male participants with ASD and 21 age- and IQ-matched controls were analyzed using a factorial design to examine the blood-oxygen-level-dependent (BOLD) response during the anticipation and receipt of both reward types. Results Behaviorally, the ASD group showed less of a reduction in reaction time (RT) for rewarded compared to unrewarded trials than the control group. In terms of the fMRI results, there were no significant group differences in reward circuitry during reward anticipation. During the receipt of rewards, there was a significant interaction between group and reward type in the left dorsal striatum (DS). The ASD group showed reduced activity in the DS compared to controls for social rewards but not monetary rewards and decreased activation for social rewards compared to monetary rewards. Controls showed no significant difference between the two reward types. Increased activation in the DS during social reward processing was associated with faster response times for rewarded trials, compared to unrewarded trials, in both groups. This is in line with behavioral results indicating that the ASD group showed less of a reduction in RT for rewarded compared to unrewarded trials. Additionally, de-activation to social rewards was associated with increased repetitive behavior in ASD. Conclusions In line with social motivation theory, the ASD group showed reduced activation, compared to controls, during the receipt of social rewards in the DS. Groups did not differ significantly during the processing of monetary rewards. BOLD activation in the DS, during social reward processing, was associated with behavioral impairments in ASD. PMID:23014171

Social and monetary reward processing in autism spectrum disorders.

PubMed

Delmonte, Sonja; Balsters, Joshua H; McGrath, Jane; Fitzgerald, Jacqueline; Brennan, Sean; Fagan, Andrew J; Gallagher, Louise

2012-09-26

Social motivation theory suggests that deficits in social reward processing underlie social impairments in autism spectrum disorders (ASD). However, the extent to which abnormalities in reward processing generalize to other classes of stimuli remains unresolved. The aim of the current study was to examine if reward processing abnormalities in ASD are specific to social stimuli or can be generalized to other classes of reward. Additionally, we sought to examine the results in the light of behavioral impairments in ASD. Participants performed adapted versions of the social and monetary incentive delay tasks. Data from 21 unmedicated right-handed male participants with ASD and 21 age- and IQ-matched controls were analyzed using a factorial design to examine the blood-oxygen-level-dependent (BOLD) response during the anticipation and receipt of both reward types. Behaviorally, the ASD group showed less of a reduction in reaction time (RT) for rewarded compared to unrewarded trials than the control group. In terms of the fMRI results, there were no significant group differences in reward circuitry during reward anticipation. During the receipt of rewards, there was a significant interaction between group and reward type in the left dorsal striatum (DS). The ASD group showed reduced activity in the DS compared to controls for social rewards but not monetary rewards and decreased activation for social rewards compared to monetary rewards. Controls showed no significant difference between the two reward types. Increased activation in the DS during social reward processing was associated with faster response times for rewarded trials, compared to unrewarded trials, in both groups. This is in line with behavioral results indicating that the ASD group showed less of a reduction in RT for rewarded compared to unrewarded trials. Additionally, de-activation to social rewards was associated with increased repetitive behavior in ASD. In line with social motivation theory, the ASD group showed reduced activation, compared to controls, during the receipt of social rewards in the DS. Groups did not differ significantly during the processing of monetary rewards. BOLD activation in the DS, during social reward processing, was associated with behavioral impairments in ASD.

Sex differences in autism: a resting-state fMRI investigation of functional brain connectivity in males and females

PubMed Central

Swinnen, Stephan P.; Wenderoth, Nicole

2016-01-01

Autism spectrum disorders (ASD) are far more prevalent in males than in females. Little is known however about the differential neural expression of ASD in males and females. We used a resting-state fMRI-dataset comprising 42 males/42 females with ASD and 75 male/75 female typical-controls to examine whether autism-related alterations in intrinsic functional connectivity are similar or different in males and females, and particularly whether alterations reflect ‘neural masculinization’, as predicted by the Extreme Male Brain theory. Males and females showed a differential neural expression of ASD, characterized by highly consistent patterns of hypo-connectivity in males with ASD (compared to typical males), and hyper-connectivity in females with ASD (compared to typical females). Interestingly, patterns of hyper-connectivity in females with ASD reflected a shift towards the (high) connectivity levels seen in typical males (neural masculinization), whereas patterns of hypo-connectivity observed in males with ASD reflected a shift towards the (low) typical feminine connectivity patterns (neural feminization). Our data support the notion that ASD is a disorder of sexual differentiation rather than a disorder characterized by masculinization in both genders. Future work is needed to identify underlying factors such as sex hormonal alterations that drive these sex-specific neural expressions of ASD. PMID:26989195

The Immune System, Cytokines, and Biomarkers in Autism Spectrum Disorder.

PubMed

Masi, Anne; Glozier, Nicholas; Dale, Russell; Guastella, Adam J

2017-04-01

Autism Spectrum Disorder (ASD) is a pervasive neurodevelopmental condition characterized by variable impairments in communication and social interaction as well as restricted interests and repetitive behaviors. Heterogeneity of presentation is a hallmark. Investigations of immune system problems in ASD, including aberrations in cytokine profiles and signaling, have been increasing in recent times and are the subject of ongoing interest. With the aim of establishing whether cytokines have utility as potential biomarkers that may define a subgroup of ASD, or function as an objective measure of response to treatment, this review summarizes the role of the immune system, discusses the relationship between the immune system, the brain, and behavior, and presents previously-identified immune system abnormalities in ASD, specifically addressing the role of cytokines in these aberrations. The roles and identification of biomarkers are also addressed, particularly with respect to cytokine profiles in ASD.

Atypical activation of the mirror neuron system during perception of hand motion in autism.

PubMed

Martineau, Joëlle; Andersson, Frédéric; Barthélémy, Catherine; Cottier, Jean-Philippe; Destrieux, Christophe

2010-03-12

Disorders in the autism spectrum are characterized by deficits in social and communication skills such as imitation, pragmatic language, theory of mind, and empathy. The discovery of the "mirror neuron system" (MNS) in macaque monkeys may provide a basis from which to explain some of the behavioral dysfunctions seen in individuals with autism spectrum disorders (ASD).We studied seven right-handed high-functioning male autistic and eight normal subjects (TD group) using functional magnetic resonance imaging during observation and execution of hand movements compared to a control condition (rest). The between group comparison of the contrast [observation versus rest] provided evidence of a bilateral greater activation of inferior frontal gyrus during observation of human motion than during rest for the ASD group than for the TD group. This hyperactivation of the pars opercularis (belonging to the MNS) during observation of human motion in autistic subjects provides strong support for the hypothesis of atypical activity of the MNS that may be at the core of the social deficits in autism. Copyright 2010 Elsevier B.V. All rights reserved.

Eye-tracking Reveals Abnormal Visual Preference for Geometric Images as an Early Biomarker of an ASD Subtype Associated with Increased Symptom Severity

PubMed Central

Pierce, Karen; Marinero, Steven; Hazin, Roxana; McKenna, Benjamin; Barnes, Cynthia Carter; Malige, Ajith

2015-01-01

Background Clinically and biologically, ASD is heterogeneous. Unusual patterns of visual preference as indexed by eye-tracking are hallmarks, yet whether they can be used to define an early biomarker of ASD as a whole, or leveraged to define a subtype is unclear. To begin to examine this issue, large cohorts are required. Methods A sample of 334 toddlers from 6 distinct groups (115 ASD, 20 ASD-Features, 57 DD, 53 Other, 64 TD, and 25 Typ SIB) participated. Toddlers watched a movie containing both geometric and social images. Fixation duration and number of saccades within each AOI and validation statistics for this independent sample computed. Next, to maximize power, data from our previous study (N=110) was added totaling 444 subjects. A subset of toddlers repeated the eye-tracking procedure. Results As in the original study, a subset of toddlers with ASD fixated on geometric images greater than 69%. Using this cutoff, sensitivity for ASD was 21%, specificity 98%, and PPV 86%. Toddlers with ASD who strongly preferred geometric images had (a) worse cognitive, language, and social skills relative to toddlers with ASD who strongly preferred social images and (b) fewer saccades when viewing geometric images. Unaffected siblings of ASD probands did not show evidence of heightened preference for geometric images. Test-retest reliability was good. Examination of age effects suggest that this test may not be appropriate with children > 4 years. Conclusions Enhanced visual preference for geometric repetition may be an early developmental biomarker of an ASD subtype with more severe symptoms. PMID:25981170

High Functioning Autism Spectrum Disorders in Adults: Consequences for Primary Caregivers Compared to Schizophrenia and Depression

ERIC Educational Resources Information Center

Grootscholten, Inge A. C.; van Wijngaarden, Bob; Kan, Cornelis C.

2018-01-01

Primary caregivers experience consequences from being in close contact to a person with autism spectrum disorder (ASD). This study used the Involvement Evaluation Questionnaire to explore the level of consequences of 104 caregivers involved with adults with High Functioning ASD (HF-ASD) and compared these with the consequences reported by…

Anxiety and Quality of Life: Clinically Anxious Children with and without Autism Spectrum Disorders Compared

ERIC Educational Resources Information Center

van Steensel, Francisca J. A.; Bogels, Susan M.; Dirksen, Carmen D.

2012-01-01

Comorbid anxiety disorders are common in children with autism spectrum disorders (ASD). However, studies comparing children with ASD to clinically anxious children are rare. This study investigated anxiety problems and health-related quality of life in children with high-functioning ASD and comorbid anxiety disorders (referred to as the ASD…

How to deal with atrial septal defect closure from right internal jugular vein: Role of venous-arterial circuit for sizing and over-the-wire device implantation.

PubMed

Butera, Gianfranco; Lovin, Nicusor; Basile, Domenica Paola

2017-01-01

Secundum atrial septum defect (ASD) is the most common congenital heart disease. It is usually treated by a transcatheter approach using a femoral venous access. In case of bilateral femoral vein occlusion, the internal jugular venous approach for ASD closure is an option, in particular in cases where ASD balloon occlusion test and sizing is needed. Here, we report on a new technique for ASD closure using a venous-arterial circuit from the right internal jugular vein to the femoral artery. Two patients (females, 4 and 10 years of age) had occlusion of both femoral veins because of a previous history of pulmonary atresia and intact ventricular septum, for which they underwent percutaneous radiofrequency perforation and balloon angioplasty. These subjects needed balloon occlusion test of a residual ASD to size the hole and to check for hemodynamic suitability to ASD closure. After performing a venous-arterial circuit, a 24 mm St Jude ASD sizing balloon catheter was advanced over the circuit and the defect closed for 15 min to check hemodynamics and size the defect. ASD was closed is hemodinamically suitable. This technique was safe and reliable. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Characteristics of Autism Spectrum Disorder in Cornelia de Lange Syndrome

ERIC Educational Resources Information Center

Moss, Jo; Howlin, Patricia; Magiati, Iliana; Oliver, Chris

2012-01-01

Background: The prevalence of autism spectrum disorder (ASD) symptomatology is comparatively high in Cornelia de Lange syndrome (CdLS). However, the profile and developmental trajectories of these ASD characteristics are potentially different to those observed in individuals with idiopathic ASD. In this study we examine the ASD profile in CdLS in…

Communication difficulties perceived by parents of children with developmental disorders.

PubMed

Sun, Ingrid Ya I; Fernandes, Fernanda Dreux Miranda

2014-01-01

The child's inclusion in his/her social-cultural context is very important to his/her adaptation and well-being. The family has a major role as a facilitator of this process. Therefore the difficulties of these families in communicating with children with communication disorders are an important issue to be assessed in order to support orientations to families. The present study aimed to identify and compare communication difficulties perceived by parents of children with Down Syndrome (DS), Autism Spectrum Disorders (ASD) and Specific Language Impairment (SLI). Information was gathered with the use of a questionnaire with 24 questions regarding the perception of parents about their child communication disorders and the difficulties they identify. The questions were divided into four domains: 1 - Parents' personal difficulties; 2 - Parents' impression about themselves regarding their child; 3 - Parents' impressions about other persons' reactions to their child and 4 - Parents' impression about their child. Sixty parents were the subjects of this study: 20 had children with DS, 20 with SLI and 20 with ASD. All children had ages between 6 and 12 years. It was possible to observe that there was significant difference between the parents of ASD children with those of DS and SLI on the second, third and fourth domains. The questionnaire is effective to the identification of the communication disorders of ASD children based on their parents' reports but not to other developmental disorders.

The Neural Substrates of Cognitive Control Deficits in Autism Spectrum Disorders

PubMed Central

Solomon, Marjorie; Ozonoff, Sally; Ursu, Stefan; Ravizza, Susan; Cummings, Neil; Ly, Stanford; Carter, Cameron

2009-01-01

Executive functions deficits are among the most frequently reported symptoms of autism spectrum disorders (ASDs), however, there have been few functional magnetic resonance imaging (fMRI) studies that investigate the neural substrates of executive functions deficits in ASDs, and only one in adolescents. The current study examined cognitive control –the ability to maintain task context online to support adaptive functioning in the face of response competition—in 22 adolescents aged 12–18 with autism spectrum disorders and 23 age, gender, and IQ matched typically developing subjects. During the cue phase of the task, where subjects must maintain information online to overcome a prepotent response tendency, typically developing subjects recruited significantly more anterior frontal (BA 10), parietal (BA 7, 40), and occipital regions (BA 18) for high control trials (25% of trials) versus low control trials (75% of trials). Both groups showed similar activation for low control cues, however the ASD group exhibited significantly less activation for high control cues. Functional connectivity analysis using time series correlation, factor analysis, and beta series correlation methods provided convergent evidence that the ASD group exhibited lower levels of functional connectivity and less network integration between frontal, parietal, and occipital regions. In the typically developing group, fronto-parietal connectivity was related to lower error rates on high control trials. In the autism group, reduced fronto-parietal connectivity was related to attention deficit hyperactivity disorder symptoms. PMID:19410583

Comparing Children with ASD and Their Peers' Growth in Print Knowledge.

PubMed

Dynia, Jaclyn M; Brock, Matthew E; Logan, Jessica A R; Justice, Laura M; Kaderavek, Joan N

2016-07-01

Many children with autism spectrum disorder (ASD) struggle with reading. An increased focus on emergent literacy skills-particularly print knowledge-might improve later reading outcomes. We analyzed longitudinal measures of print knowledge (i.e., alphabet knowledge and print-concept knowledge) for 35 preschoolers with ASD relative to a sample of 35 typically developing peers. Through multilevel growth curve analysis, we found that relative to their peers, children with ASD had comparable alphabet knowledge, lower print-concept knowledge, and acquired both skills at a similar rate. These findings suggest that children with ASD are unlikely to acquire print-concept knowledge commensurate to their peers without an increased emphasis on high-quality instruction that targets this skill.

Persuasive Writing and Self-Regulation Training for Writers with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Asaro-Saddler, Kristie; Bak, Nicole

2014-01-01

In this single-subject study, we examined the effects of a persuasive writing and self-regulation strategy on the writing of children with autism spectrum disorders (ASD). Six children with ASD worked in pairs to learn a mnemonic-based strategy for planning and writing a persuasive essay using the self-regulated strategy development (SRSD)…

Teaching Children with High-Functioning Autism Spectrum Disorders to Write Persuasive Essays

ERIC Educational Resources Information Center

Asaro-Saddler, Kristie; Bak, Nicole

2012-01-01

In this single-subject design study, we examined the effects of an intervention targeting planning and self-regulation strategy use on the persuasive writing of children with high-functioning autism spectrum disorders (ASD). Three 8- to 9-year-old children with ASD in third and fourth grades learned a mnemonic-based strategy for planning and…

Remediation of Deficits in Recognition of Facial Emotions in Children with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Weinger, Paige M.; Depue, Richard A.

2011-01-01

This study evaluated the efficacy of the Mind Reading interactive computer software to remediate emotion recognition deficits in children with autism spectrum disorders (ASD). Six unmedicated children with ASD and 11 unmedicated non-clinical control subjects participated in the study. The clinical sample used the software for five sessions. The…

Pros and Cons of Character Portrayals of Autism on TV and Film

ERIC Educational Resources Information Center

Nordahl-Hansen, Anders; Øien, Roald A.; Fletcher-Watson, Sue

2018-01-01

Portrayals of characters with autism spectrum disorder (ASD) and/or with autistic traits on film and in TV-series are increasing. Such portrayals may contribute in increasing awareness of the condition but can also increase stereotypes. Thus, these character portrayals are subject to heated debate within the ASD-community, but also in the general…

Emotion Recognition in Children and Adolescents with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Kuusikko, Sanna; Haapsamo, Helena; Jansson-Verkasalo, Eira; Hurtig, Tuula; Mattila, Marja-Leena; Ebeling, Hanna; Jussila, Katja; Bolte, Sven; Moilanen, Irma

2009-01-01

We examined upper facial basic emotion recognition in 57 subjects with autism spectrum disorders (ASD) (M = 13.5 years) and 33 typically developing controls (M = 14.3 years) by using a standardized computer-aided measure (The Frankfurt Test and Training of Facial Affect Recognition, FEFA). The ASD group scored lower than controls on the total…

State-Dependent Changes of Connectivity Patterns and Functional Brain Network Topology in Autism Spectrum Disorder

ERIC Educational Resources Information Center

Barttfeld, Pablo; Wicker, Bruno; Cukier, Sebastian; Navarta, Silvana; Lew, Sergio; Leiguarda, Ramon; Sigman, Mariano

2012-01-01

Anatomical and functional brain studies have converged to the hypothesis that autism spectrum disorders (ASD) are associated with atypical connectivity. Using a modified resting-state paradigm to drive subjects' attention, we provide evidence of a very marked interaction between ASD brain functional connectivity and cognitive state. We show that…

Uneven Expressive Language Development in Mandarin-Exposed Preschool Children with ASD: Comparing Vocabulary, Grammar, and the Decontextualized Use of Language via the PCDI-Toddler Form.

PubMed

Su, Yi Esther; Naigles, Letitia R; Su, Lin-Yan

2018-05-21

Data from children with ASD who are learning Indo-European languages indicate that (a) they vary hugely in their expressive language skills and (b) their pragmatic/socially-based language is more impaired than their structural language. We investigate whether similar patterns of language development exist for Mandarin-exposed children with ASD. Parent report data of the Putonghua Communicative Development Inventory-Toddler Form were collected from 160 17-83-month-old children with ASD. These children with ASD demonstrated similar levels of variability as Western children with ASD. In particular, they could be divided into three distinct subgroups (high verbal, middle verbal, low verbal), all of which manifested relative strengths in lexical and grammatical language compared to pragmatic usage of decontextualized language.

Driving Behaviour Profile of Drivers with Autism Spectrum Disorder (ASD).

PubMed

Chee, Derserri Y; Lee, Hoe C; Patomella, Ann-Helen; Falkmer, Torbjörn

2017-09-01

The symptomatology of autism spectrum disorder (ASD) can make driving risky, but little is known about the on-road driving behaviour of individuals with ASD. This study assessed and compared the on-road driving performance of drivers with and without ASD, and explored how the symptomatology of ASD hinders or facilitates on-road driving performance. Sixteen drivers with ASD and 21 typically-developed drivers participated in the study. Drivers with ASD underperformed in vehicle manoeuvring, especially at left-turns, right-turns and pedestrian crossings. However, drivers with ASD outperformed the TD group in aspects related to rule-following such as using the indicator at roundabouts and checking for cross-traffic when approaching intersections. Drivers with ASD in the current study presented with a range of capabilities and weaknesses during driving.

Attention deficit hyperactivity disorder symptoms in adults with autism spectrum disorders.

PubMed

Johnston, Kate; Dittner, Antonia; Bramham, Jessica; Murphy, Clodagh; Knight, Anya; Russell, Ailsa

2013-08-01

Features of attention deficit hyperactivity disorder (ADHD) and impairments on neuropsychological, tests of attention have been documented in children with autism spectrum disorders (ASDs). To date, there has been a lack of research comparing attention in adults with ASD and adults with ADHD. In study 1, 31 adults with ASD and average intellectual function completed self-report measures of ADHD symptoms. These were compared with self-report measures of ADHD symptoms in 38 adults with ADHD and 29 general population controls. In study 2, 28 adults with a diagnosis of ASD were compared with an age- and intelligence quotient-matched sample of 28 adults with ADHD across a range of measures of attention. Study 1 showed that 36.7% of adults with ASD met Diagnostic and Statistical Manual-IV criteria for current ADHD "caseness" (Barkley Current self-report scores questionnaire). Those with a diagnosis of pervasive developmental disorder-not otherwise specified were most likely to describe ADHD symptoms. The ASD group differed significantly from both the ADHD and control groups on total and individual symptom self-report scores. On neuropsychological testing, adults with ASD and ADHD showed comparable performance on tests of selective attention. Significant group differences were seen on measures of attentional switching; adults with ADHD were significantly faster and more inaccurate, and individuals with Asperger's syndrome showed a significantly slower and more accurate response style. Self-reported rates of ADHD among adults with ASD are significantly higher than in the general adult population and may be underdiagnosed. Adults with ASD have attentional difficulties on some neuropsychological measures. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.

Functional and dysfunctional brain circuits underlying emotional processing of music in autism spectrum disorders.

PubMed

Caria, Andrea; Venuti, Paola; de Falco, Simona

2011-12-01

Despite intersubject variability, dramatic impairments of socio-communicative skills are core features of autistic spectrum disorder (ASD). A deficit in the ability to express and understand emotions has often been hypothesized to be an important correlate of such impairments. Little is known about individuals with ASD's ability to sense emotions conveyed by nonsocial stimuli such as music. Music has been found to be capable of evoking and conveying strong and consistent positive and negative emotions in healthy subjects. The ability to process perceptual and emotional aspects of music seems to be maintained in ASD. Individuals with ASD and neurotypical (NT) controls underwent a single functional magnetic resonance imaging (fMRI) session while processing happy and sad music excerpts. Overall, fMRI results indicated that while listening to both happy and sad music, individuals with ASD activated cortical and subcortical brain regions known to be involved in emotion processing and reward. A comparison of ASD participants with NT individuals demonstrated decreased brain activity in the premotor area and in the left anterior insula, especially in response to happy music excerpts. Our findings shed new light on the neurobiological correlates of preserved and altered emotional processing in ASD.

[Randomised controlled study of inter-hemispheric electroencephalographic coherence following assisted therapy with dolphins in children with autism spectrum disorders].

PubMed

Ortiz-Sanchez, P; Mulas, F; Abad-Mas, L; Roca, P; Gandia-Beneto, R

2018-03-01

Autism spectrum disorder (ASD) is a neurodevelopmental disorder associated with impairments in executive function, language, emotional function, and social function. Its anatomofunctional substrate is related to a disorganization of the brain's functional connections. The aim is to investigate the cerebral connections in subjects with ASD through the analysis of the interhemispheric coherence (IHC) of the quantified electroencephalogram and its changes after dolphin assisted therapy (DAT) versus therapeutical intervention without dolphins (TIWD). The IHC was determined in 44 subjects with ASD before randomly assigning them to two therapeutic groups: DAT (n = 22) and TIWD (n = 22). The results were statistically analyzed through the multi-measure ANOVA test for within-subject (time) and between-subject (DAT vs TIWD) factors. The IHC showed a significant reduction (p < 0.05) for both groups in the delta, theta, beta, and alpha frequencies (p < 0.001) in the anterior frontal region (F3-F4), alpha in the central region (C3-C4) (p < 0.05), and alpha (p < 0.05) and beta (p < 0.001) in the temporal region (T3-T4). In the intersection with the specific treatment (DAT), the coherence in the alpha band increased in Fp1-Fp2 (p < 0.05), and the delta did not decline in F3-F4 (p < 0.05). In 5-year-old children with ASD, DAT increases the IHC in the anterior frontal region and stabilizes the tendency to reduce the delta band in the posterior frontal region.

Brief Report: Syndromes in Autistic Children in a Finnish Birth Cohort.

PubMed

Timonen-Soivio, Laura; Vanhala, Raija; Malm, Heli; Hinkka-Yli-Salomäki, Susanna; Gissler, Mika; Brown, Alan; Sourander, Andre

2016-08-01

We studied the association between specific congenital syndromes and autism spectrum disorders (ASD) in the large Finnish Register material. Our data include all children diagnosed with ASD (n = 4441) according to Finnish Hospital Discharge Register in 1987-2000. Four controls per each case were matched to sex, birthplace, date of birth (±30 days) and residence in Finland (n = 17,695). The prevalence of specific congenital syndromes in the Finnish Register of Congenital Malformations was evaluated among the ASD group and the controls by sex. The results of this study suggest that there is an association between several etiologically different syndromes and ASD when compared to controls without ASD. Statistically significant associations were observed with 47,XYY, Sotos syndrome, neurofibromatosis I, and syndrome not otherwise specified. Syndromes were more common among males with ASD compared to controls. These results support the previous studies of etiological heterogeneity of ASD and have importance in clinical examination, management and rehabilitation.

Behavior problems at 5 years of age and maternal mental health in autism and intellectual disability.

PubMed

Totsika, Vasiliki; Hastings, Richard P; Emerson, Eric; Berridge, Damon M; Lancaster, Gillian A

2011-11-01

We examined child behavior problems and maternal mental health in a British population-representative sample of 5 year-old children with an autism spectrum disorder (ASD), controlling for the presence of an intellectual disability (ID). Behavior problems were significantly higher in children with ASD with/out ID compared to typically developing children, but compared to children with ID only hyperactivity was significantly higher in children with ASD/ID. After controlling for ID and maternal mental health, the presence of ASD significantly increased the odds for hyperactivity, conduct problems and emotional symptoms. Negative maternal outcomes (serious mental illness, psychological distress, and physical health limitations) were not consistently elevated in ASD. The findings highlight the early age at which behavior problems emerge in ASD, and suggest that at this age , there may not be a clear disadvantage for maternal mental health associated with having a child with ASD in the family, over and above that conferred by child behavior problems.

On characterizing population commonalities and subject variations in brain networks.

PubMed

Ghanbari, Yasser; Bloy, Luke; Tunc, Birkan; Shankar, Varsha; Roberts, Timothy P L; Edgar, J Christopher; Schultz, Robert T; Verma, Ragini

2017-05-01

Brain networks based on resting state connectivity as well as inter-regional anatomical pathways obtained using diffusion imaging have provided insight into pathology and development. Such work has underscored the need for methods that can extract sub-networks that can accurately capture the connectivity patterns of the underlying population while simultaneously describing the variation of sub-networks at the subject level. We have designed a multi-layer graph clustering method that extracts clusters of nodes, called 'network hubs', which display higher levels of connectivity within the cluster than to the rest of the brain. The method determines an atlas of network hubs that describes the population, as well as weights that characterize subject-wise variation in terms of within- and between-hub connectivity. This lowers the dimensionality of brain networks, thereby providing a representation amenable to statistical analyses. The applicability of the proposed technique is demonstrated by extracting an atlas of network hubs for a population of typically developing controls (TDCs) as well as children with autism spectrum disorder (ASD), and using the structural and functional networks of a population to determine the subject-level variation of these hubs and their inter-connectivity. These hubs are then used to compare ASD and TDCs. Our method is generalizable to any population whose connectivity (structural or functional) can be captured via non-negative network graphs. Copyright © 2015 Elsevier B.V. All rights reserved.

Bone Density in Adolescents and Young Adults with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Ekhlaspour, Laya; Baskaran, Charumathi; Campoverde, Karen Joanie; Sokoloff, Natalia Cano; Neumeyer, Ann M.; Misra, Madhusmita

2016-01-01

Patients with autism spectrum disorder (ASD) are at increased risk for fracture, and peri-pubertal boys with ASD have lower bone mineral density (BMD) than controls. Data are lacking regarding BMD in older adolescents with ASD. We compared BMD using dual-energy X-ray absorptiometry in 9 adolescents/young adults with ASD against 9 typically…

Brief Report: Autism Symptoms in Infants with Fragile X Syndrome

ERIC Educational Resources Information Center

Roberts, Jane E.; Tonnsen, Bridgette L.; McCary, Lindsay M.; Caravella, Kelly E.; Shinkareva, Svetlana V.

2016-01-01

Fragile X syndrome (FXS) is the most common known genetic cause of autism spectrum disorder (ASD). Although 50-75% of children with FXS meet ASD criteria, no studies have compared ASD symptoms in infants with FXS versus other high risk groups, such as siblings of children with ASD (ASIBs). Using the Autism Observation Scale for Infants, our…

Atypical Processing of Gaze Cues and Faces Explains Comorbidity between Autism Spectrum Disorder (ASD) and Attention Deficit/Hyperactivity Disorder (ADHD)

ERIC Educational Resources Information Center

Groom, Madeleine J.; Kochhar, Puja; Hamilton, Antonia; Liddle, Elizabeth B.; Simeou, Marina; Hollis, Chris

2017-01-01

This study investigated the neurobiological basis of comorbidity between autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD). We compared children with ASD, ADHD or ADHD+ASD and typically developing controls (CTRL) on behavioural and electrophysiological correlates of gaze cue and face processing. We measured effects…

Dual Cognitive and Biological Correlates of Anxiety in Autism Spectrum Disorders

ERIC Educational Resources Information Center

Hollocks, Matthew J.; Pickles, Andrew; Howlin, Patricia; Simonoff, Emily

2016-01-01

Young people with autism spectrum disorder (ASD) have a high prevalence (~40 %) of anxiety disorders compared to their non-ASD peers. It is unclear whether cognitive and biological processes associated with anxiety in ASD are analogous to anxiety in typically developing (TD) populations. In this study 55 boys with ASD (34 with a co-occurring…

Dysfunctional information processing in individuals with acute exposure to sexual abuse: An ERP study.

PubMed

Han, Changwoo; Park, Minkyung; Lee, Jun-Young; Jung, Hee Yeon; Park, Su Mi; Choi, Jung-Seok

2018-06-01

Acute stress disorder (ASD) and posttraumatic stress disorder (PTSD) may occur after traumatic event and also cause significant life time impairment. P300 event-related potential (ERP) is a potential biological marker for PTSD and can reflect cognitive impairment in information processing and attention. Despite the usefulness of ERP, there are few attempts to reveal relationships between ASD and P300. In the present study, we aimed to determine if the P300 of the patients who were the victims of sexual abuse reflected the quantitative trait of ASD or if P300 is applicable as a state marker for predicting the risk of PTSD.Fifteen female victims of sexual abuse diagnosed with ASD and 18 healthy controls (HCs) without trauma exposure participated in this study. We investigated the P300 ERPs in patients with ASD to compare them with those of HCs. ERPs were acquired from female adults during an auditory oddball task. Between-group differences in amplitudes or latencies of P300 were investigated using repeated-measures analysis of variance.The ASD groups showed reduced P300 amplitudes at the midline centroparietal site as well as reduced accuracy rates during an auditory oddball task compared with the HCs.These results indicate that ASD have abnormalities in the P300 compared to those in HCs. Moreover, the reduction in P300 could be considered a candidate neurophysiological marker for ASD.

Personality and self-insight in individuals with autism spectrum disorder.

PubMed

Schriber, Roberta A; Robins, Richard W; Solomon, Marjorie

2014-01-01

Autism spectrum disorder (ASD) involves widespread difficulties in social interaction, communication, and behavioral flexibility. Consequently, individuals with ASD are believed to exhibit a number of unique personality tendencies, including a lack of insight into those tendencies. However, surprisingly little research has examined these issues. Study 1 compared self-reports of Big Five personality traits in adults with ASD (n = 37) to those of typically developing (TD) adults (n = 42). Study 2 examined whether any observed personality differences replicated in children/adolescents with ASD (n = 50) and TD controls (n = 50) according to self- and parent reports of personality. Study 2 also assessed level of self-insight in individuals with ASD relative to TD individuals by examining the degree to which self-reports converged with parent reports in terms of self-other agreement and self-enhancement (vs. self-diminishment) biases. Individuals with ASD were more Neurotic and less Extraverted, Agreeable, Conscientious, and Open to Experience. These personality differences replicated for (a) children, adolescents, and adults; (b) self- and parent reports; and (c) males and females. However, personality traits were far from perfect predictors of ASD vs. TD group membership, did not predict within-group variability in ASD symptom severity, and had differential links to maladjustment in the ASD and TD groups, suggesting that ASD represents more than just an extreme standing on trait dimensions. Finally, individuals with ASD had a tendency to self-enhance and TD individuals, to self-diminish, but both groups showed comparable self-other agreement. Thus, individuals with ASD exhibit distinct personalities relative to TD individuals but may have a similar level of insight into them.

Personality and Self-Insight in Individuals with Autism Spectrum Disorder

PubMed Central

Schriber, Roberta A.; Robins, Richard W.; Solomon, Marjorie

2014-01-01

Autism spectrum disorder (ASD) involves widespread difficulties in social interaction, communication, and behavioral flexibility. Consequently, individuals with ASD are believed to exhibit a number of unique personality tendencies, including a lack of insight into them. However, surprisingly little research has examined these issues. Study 1 compared self-reports of Big Five personality traits in adults with ASD (N=37) to those of typically developing (TD) adults (N=42). Study 2 examined whether any observed personality differences replicated in children/adolescents with ASD (N=50) and TD controls (N=50) according to self- and parent reports. Study 2 also assessed level of self-insight in individuals with ASD relative to TD individuals by examining the degree to which self-reports converged with parent reports in terms of self-other agreement and self-enhancement (vs. self-diminishment) biases. Individuals with ASD were more Neurotic and less Extraverted, Agreeable, Conscientious, and Open to Experience. These personality differences replicated for (a) children, adolescents, and adults, (b) self- and parent reports, and (c) males and females. However, personality traits were far from perfect predictors of ASD vs. TD group membership, did not predict within-group variability in ASD symptom severity, and had differential links to maladjustment in the ASD and TD groups, suggesting that ASD represents more than just an extreme standing on trait dimensions. Finally, individuals with ASD had a tendency to self-enhance, and TD individuals, to self-diminish, but both groups showed comparable self-other agreement. Thus, individuals with ASD exhibit distinct personalities relative to TD individuals but may have a similar level of insight into them. PMID:24377361

Financial and employment impact of intellectual disability on families of children with autism.

PubMed

Saunders, Barbara S; Tilford, J Mick; Fussell, Jill J; Schulz, Eldon G; Casey, Patrick H; Kuo, Dennis Z

2015-03-01

Families of children with autism spectrum disorder (ASD) endure significant financial and employment burden because of their children's numerous needed services. The study objective is to describe additional impact on families of children with intellectual disability (ID) in addition to ASD. The study is a secondary data analysis of the 2009-2010 National Survey of Children with Special Health Care Needs. Children whose parents answered "yes" when asked whether their child had ASD or ID were classified as having ASD alone (unweighted n = 2,406), ID alone (unweighted n = 1,363), or both ASD/ID (unweighted n = 620). Bivariate and multivariate analyses compared study outcomes of family financial and caregiver burden using ASD as the reference group. All analyses were weighted using person-level estimates. Of children with ASD, 24% also had ID. More than half of caregivers of children with ASD/ID reported financial difficulty (52%) and having to stop work to care for their child (51%). Compared with ASD alone, caregivers of children with both ASD/ID were more likely to report financial difficulty (aOR 1.65, 95% CI 1.10-2.46), cutting work hours (aOR 1.43, 95% CI .98-2.08), and stop working (aOR 2.32, 95% CI 1.57-3.43). No differences were found between caregivers of children with ASD only and ID only. We conclude that having ID in addition to ASD may be associated with greater negative impact on family financial and employment burden. Recognition of ID in addition to ASD is important to tailor the clinical approach and sufficiently support families. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

Prevalence of the Wish to be of the Opposite Gender in Adolescents and Adults with Autism Spectrum Disorder.

PubMed

van der Miesen, Anna I R; Hurley, Hannah; Bal, Anneloes M; de Vries, Annelou L C

2018-05-07

Several studies have suggested an overrepresentation of (symptoms of) autism spectrum disorder (ASD) among individuals with gender dysphoria. Three studies have taken the inverse approach in children with ASD and showed increased parent report of the wish to be of the opposite gender in this group. This study compared the self-reported wish to be of the opposite gender (one item of the Youth Self-Report [YSR] and the Adult Self-Report [ASR]) of 573 adolescents (469 assigned boys and 104 assigned girls) and 807 adults (616 assigned males and 191 assigned females) with ASD to 1016 adolescents and 846 adults from the general population. Emotional and behavioral problems were measured by the DSM-oriented scales of the YSR and ASR. In addition, the Children's Social Behavior Questionnaire and the Adult Social Behavior Questionnaire were used to measure specific subdomains of the ASD spectrum to test whether specific subdomains of ASD were particularly involved. Significantly more adolescents (6.5%) and adults (11.4%) with ASD endorsed this item as compared to the general population (3-5%). In adolescents, assigned girls endorsed this item more than assigned boys. No significant gender differences were found in the adults with ASD. In addition, on all DSM-oriented scales of both the YSR and ASR, adolescents and adults with ASD who endorsed the gender item had significantly higher scores compared to those without. There were no significant associations between endorsement of the gender item and any specific subdomain of ASD, providing no evidence for a sole role of one of the ASD subdomains and endorsement of the wish to be the opposite gender.

Lower Hospital Charges and Societal Costs for Catheter Device Closure of Atrial Septal Defects.

PubMed

Sanchez, Jessica N; Seckeler, Michael D

2017-10-01

Atrial septal defects (ASD) are among the most common congenital heart defects. As more ASDs are corrected by interventional catheterization instead of surgery, it is critical to understand the associated clinical and societal costs. The goal of this study was to use a national U.S. database to describe hospital charges and societal costs for surgical and catheter-based (ASD) closure. Retrospective review of hospital discharge data from the Kids' Inpatient Database from January 2010 to December 2012. The database was queried for admissions for <21 years old with ICD-9 procedure codes for surgical (35.51 or 35.61) or catheter (35.52) ASD closure; those with other cardiac conditions and/or additional cardiac procedures were excluded. Age, length of stay (LOS), and hospital charges and lost parental wages (societal costs) were compared between groups using t test or Mann-Whitney U test, as appropriate. Four hundred and eighty-six surgical and 305 catheter ASD closures were identified. LOS, hospital charges, and total societal costs were higher in surgical ASD compared to catheter ASD admissions (3.6 vs. 1.3 days, p < 0.001, $87,465 vs. $64,109, p < 0.001, and $90,000 vs. $64,966, p < 0.001, respectively). In this review of a large national inpatient database, we found that hospital and societal costs for surgical ASD closure are significantly higher than catheter ASD closure in the United States in the current era. Factors that likely contribute to this include longer LOS and longer post-operative recovery. Using "real-world" data, this study demonstrates a substantial cost advantage for catheter ASD closure compared to surgical.

External Validation of the Adult Spinal Deformity (ASD) Frailty Index (ASD-FI) in the Scoli-RISK-1 Patient Database.

PubMed

Miller, Emily K; Lenke, Lawrence G; Neuman, Brian J; Sciubba, Daniel M; Kebaish, Khaled M; Smith, Justin S; Qiu, Yong; Dahl, Benny T; Pellisé, Ferran; Matsuyama, Yukihiro; Carreon, Leah Y; Fehlings, Michael G; Cheung, Kenneth M; Lewis, Stephen; Dekutoski, Mark B; Schwab, Frank J; Boachie-Adjei, Oheneba; Mehdian, Hossein; Bess, Shay; Shaffrey, Christopher I; Ames, Christopher P

2018-05-14

Analysis of a prospective multicenter database. To assess the ability of the recently created Adult Spinal Deformity (ASD) Frailty Index (ASD-FI) to predict odds of major complications and length of hospital stay for patients who had more severe preoperative deformity and underwent more invasive ASD surgery compared with patients in the database used to create the index. Accurate preoperative estimates of risk are necessary given the high complication rates currently associated with ASD surgery. Patients were enrolled by participating institutions in Europe, Asia, and North America from 2009 to 2011. ASD-FI scores were used to classify 267 patients as not frail (NF) (<0.3), frail (0.3-0. 5), or severely frail (SF) (>0.5). Multivariable logistic regression, adjusted for preoperative and surgical covariates such as operative time and blood loss, was performed to determine the relationship between ASD-FI category and incidence of major complications, overall incidence of complications, and length of hospital stay. The mean ASD-FI score was 0.3 (range, 0-0.7). We categorized 105 patients as NF, 103 as frail, and 59 as SF. The adjusted odds of developing a major complication were higher for SF patients (odds ratio = 4.4; 95% CI 2.0, 9.9) compared with NF patients. After adjusting for covariates, length of hospital stay for SF patients increased by 19% (95% CI 1.4%, 39%) compared with NF patients. The odds of developing a major complication or having increased length of stay were similar between frail and NF patients. Greater patient frailty, as measured by the ASD-FI, is associated with a longer hospital stay and greater risk of major complications among patients who have severe preoperative deformity and undergo invasive surgical procedures. 2.

Long-term memory in older children/adolescents and adults with autism spectrum disorder.

PubMed

Williams, Diane L; Minshew, Nancy J; Goldstein, Gerald; Mazefsky, Carla A

2017-09-01

This study extends prior memory reports in autism spectrum disorders (ASD) by investigating memory for narratives after longer recall periods and by examining developmental aspects of narrative memory using a cross-sectional design. Forty-seven older children/adolescents with ASD and 31 youth with typical development (TD) and 39 adults with ASD and 45 TD adults were compared on memory for stories from standardized measures appropriate for each age group at three intervals (immediate, 30 min, and 2 day). Both the youth with and without ASD had difficulty with memory for story details with increasing time intervals. More of the youths with ASD performed in the range of impairment when recalling the stories 2 days later as compared to the TD group. The adults with ASD had more difficulty on memory for story details with increasing delay and were poorer at recall of thematic information (needed to create a gist) across the three delay conditions as compared to the TD group. Analyses of the individual results suggested that memory for details of most of the adults with ASD was not impaired when applying a clinical standard; however, a significant percentage of the adults with ASD did not make use of thematic information to organize the narrative information, which would have helped them to remember the stories. The youth with and without ASD performed similarly when both were at a stage of development when memory for details is the primary strategy. The adults with ASD had difficulty with use organizational strategies to support episodic memory. Autism Res 2017, 10: 1523-1532. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

Effects of Parent-Implemented Early Start Denver Model Intervention on Chinese Toddlers with Autism Spectrum Disorder: A Non-Randomized Controlled Trial.

PubMed

Zhou, Bingrui; Xu, Qiong; Li, Huiping; Zhang, Ying; Wang, Yi; Rogers, Sally J; Xu, Xiu

2018-04-01

To evaluate the effects of a 26-week, high-intensity, parent-implemented Early Start Denver Model (P-ESDM) intervention on developmental outcomes, severity of autism spectrum disorder (ASD), and parental stress of ASD toddlers in China. Subjects in P-ESDM group (n = 23) were recruited from 1.5- to 2.5-year-old toddlers who were screened positive in Xuhui and Minhang Districts and were diagnosed with ASD. A community (comparison) group of age-matched toddlers with ASD (n = 20) was recruited from other areas. Subjects of the P-ESDM group attended 1.5-hr parent coaching per week for 26 weeks, and those in the community group received interventions available from communities. Assessments were conducted at baseline (T1) and 26 weeks later (T2). After adjusting for baseline differences between the two groups, P-ESDM group demonstrated greater improvement than the community group in general development, especially in Language domain. Neither group demonstrated significant change in ASD severity, but the P-ESDM group showed greater improvement in social affect, parent-reported social communication and symbolic play than community group did. Finally, parents in P-ESDM group experienced decreased parenting stress while those in community group showed an opposite trend, though the differences did not reach significant association with the P-ESDM intervention. Chinese toddlers with ASD receiving 26 weeks of P-ESDM via regular coaching sessions showed significant greater improvement than those receiving community interventions in multiple aspects of development including social communications. These findings add support to the importance of providing early screening, diagnosis, and immediate referral for evidence-based interventions to improve outcome of young children with ASD. Autism Res 2018, 11: 654-666. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. The development of early screening and diagnosis of autism spectrum disorder (ASD) in China has highlighted the importance of early intervention for young children with ASD. Our current study demonstrated that parent-implemented Early Start Denver Model (P-ESDM) via coaching from professionals improved developmental outcomes, especially in the language domain, and social communicational behaviors of Chinese toddlers with ASD. P-ESDM may help parents in China provide effective early intervention to their children with ASD via improving their skills when they are still at a waiting list for services or lack access to intervention, and has the potential to alleviate their parenting stress. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

Sex differences in autism: a resting-state fMRI investigation of functional brain connectivity in males and females.

PubMed

Alaerts, Kaat; Swinnen, Stephan P; Wenderoth, Nicole

2016-06-01

Autism spectrum disorders (ASD) are far more prevalent in males than in females. Little is known however about the differential neural expression of ASD in males and females. We used a resting-state fMRI-dataset comprising 42 males/42 females with ASD and 75 male/75 female typical-controls to examine whether autism-related alterations in intrinsic functional connectivity are similar or different in males and females, and particularly whether alterations reflect 'neural masculinization', as predicted by the Extreme Male Brain theory. Males and females showed a differential neural expression of ASD, characterized by highly consistent patterns of hypo-connectivity in males with ASD (compared to typical males), and hyper-connectivity in females with ASD (compared to typical females). Interestingly, patterns of hyper-connectivity in females with ASD reflected a shift towards the (high) connectivity levels seen in typical males (neural masculinization), whereas patterns of hypo-connectivity observed in males with ASD reflected a shift towards the (low) typical feminine connectivity patterns (neural feminization). Our data support the notion that ASD is a disorder of sexual differentiation rather than a disorder characterized by masculinization in both genders. Future work is needed to identify underlying factors such as sex hormonal alterations that drive these sex-specific neural expressions of ASD. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Altered urinary porphyrins and mercury exposure as biomarkers for autism severity in Egyptian children with autism spectrum disorder.

PubMed

Khaled, Eman M; Meguid, Nagwa A; Bjørklund, Geir; Gouda, Amr; Bahary, Mohamed H; Hashish, Adel; Sallam, Nermin M; Chirumbolo, Salvatore; El-Bana, Mona A

2016-12-01

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that affects social, communication, and behavioral development. Recent evidence supported but also questioned the hypothetical role of compounds containing mercury (Hg) as contributors to the development of ASD. Specific alterations in the urinary excretion of porphyrin-containing ring catabolites have been associated with exposure to Hg in ASD patients. In the present study, the level of urinary porphyrins, as biomarkers of Hg toxicity in children with ASD, was evaluated, and its correlation with severity of the autistic behavior further explored. A total of 100 children was enrolled in the present study. They were classified into three groups: children with ASD (40), healthy controls (40), and healthy siblings of the ASD children (20). Children with ASD were diagnosed using DSM-IV-TR, ADI-R, and CARS tests. Urinary porphyrins were evaluated within the three groups using high-performance liquid chromatography (HPLC), after plasma evaluation of mercury (Hg) and lead (Pb) in the same groups. Results showed that children with ASD had significantly higher levels of Hg, Pb, and the porphyrins pentacarboxyporphyrin, coproporphyrin, precoproporphyrin, uroporphyrins, and hexacarboxyporphyrin compared to healthy controls and healthy siblings of the ASD children. However, there was no significant statistical difference in the level of heptacarboxyporphyrin among the three groups, while a significant positive correlation between the levels of coproporphyrin and precoproporphyrin and autism severity was observed. Mothers of ASD children showed a higher percentage of dental amalgam restorations compared to the mothers of healthy controls suggesting that high Hg levels in children with ASD may relate to the increased exposure to Hg from maternal dental amalgam during pregnancy and lactation. The results showed that the ASD children in the present study had increased blood Hg and Pb levels compared with healthy control children indicating that disordered porphyrin metabolism might interfere with the pathology associated with the autistic neurologic phenotype. The present study indicates that coproporphyrin and precoproporhyrin may be utilized as possible biomarkers for heavy metal exposure and autism severity in children with ASD.

Maternal stress and perinatal features in autism and attention deficit/hyperactivity disorder.

PubMed

Say, Gökçe Nur; Karabekiroğlu, Koray; Babadağı, Zehra; Yüce, Murat

2016-04-01

We investigated the shared and non-shared perinatal risk factors for autism spectrum disorders (ASD) and attention deficit/hyperactivity disorder (ADHD) in a clinical sample. Additionally, we compared these groups regarding pre/postpartum maternal stress and the duration of breastfeeding. Children aged 3-18 years old with ASD (n = 100) were compared with age- and gender-matched children with ADHD (n = 100) and with age- and gender-matched healthy controls (n = 80). Prematurity of the neonate and maternal stress/depressive mood in pregnancy were common risk factors shared by ASD and ADHD. Postpartum maternal depressive mood may be more specific to ASD, while shorter duration of breastfeeding may be related to ADHD. ASD and ADHD may have some perinatal features in common. Identification of perinatal factors for ASD and ADHD carries clinical implications in terms of primary prevention. © 2015 Japan Pediatric Society.

Response time variability under slow and fast-incentive conditions in children with ASD, ADHD and ASD+ADHD.

PubMed

Tye, Charlotte; Johnson, Katherine A; Kelly, Simon P; Asherson, Philip; Kuntsi, Jonna; Ashwood, Karen L; Azadi, Bahare; Bolton, Patrick; McLoughlin, Gráinne

2016-12-01

Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) show significant behavioural and genetic overlap. Both ADHD and ASD are characterised by poor performance on a range of cognitive tasks. In particular, increased response time variability (RTV) is a promising indicator of risk for both ADHD and ASD. However, it is not clear whether different indices of RTV and changes to RTV according to task conditions are able to discriminate between the two disorders. Children with ASD (n = 19), ADHD (n = 18), ASD + ADHD (n = 29) and typically developing controls (TDC; n = 26) performed a four-choice RT task with slow-baseline and fast-incentive conditions. Performance was characterised by mean RT (MRT), standard deviation of RT (SD-RT), coefficient of variation (CV) and ex-Gaussian distribution measures of Mu, Sigma and Tau. In the slow-baseline condition, categorical diagnoses and trait measures converged to indicate that children with ADHD-only and ASD + ADHD demonstrated increased MRT, SD-RT, CV and Tau compared to TDC and ASD-only. Importantly, greater improvement in MRT, SD-RT and Tau was demonstrated in ADHD and ASD + ADHD from slow-baseline to fast-incentive conditions compared to TDC and ASD-only. Slower and more variable RTs are markers of ADHD compared to ASD and typically developing controls during slow and less rewarding conditions. Energetic factors and rewards improve task performance to a greater extent in children with ADHD compared to children with ASD. These findings suggest that RTV can be distinguished in ASD, ADHD and ASD + ADHD based on the indices of variability used and the conditions in which they are elicited. Further work identifying neural processes underlying increased RTV is warranted, in order to elucidate disorder-specific and disorder-convergent aetiological pathways. © 2016 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.

Common and distinct neural features of social and non-social reward processing in autism and social anxiety disorder.

PubMed

Richey, John A; Rittenberg, Alison; Hughes, Lauren; Damiano, Cara R; Sabatino, Antoinette; Miller, Stephanie; Hanna, Eleanor; Bodfish, James W; Dichter, Gabriel S

2014-03-01

Autism spectrum disorders (ASDs) and social anxiety disorder (SAD) are both characterized by social dysfunction, but no study to date has compared neural responses to social rewards in ASDs and SAD. Neural responses during social and non-social reward anticipation and outcomes were examined in individuals with ASD (n = 16), SAD (n = 15) and a control group (n = 19) via functional magnetic resonance imaging. Analyses modeling all three groups revealed increased nucleus accumbens (NAc) activation in SAD relative to ASD during monetary reward anticipation, whereas both the SAD and ASD group demonstrated decreased bilateral NAc activation relative to the control group during social reward anticipation. During reward outcomes, the SAD group did not differ significantly from the other two groups in ventromedial prefrontal cortex activation to either reward type. Analyses comparing only the ASD and SAD groups revealed greater bilateral amygdala activation to social rewards in SAD relative to ASD during both anticipation and outcome phases, and the magnitude of left amygdala hyperactivation in the SAD group during social reward anticipation was significantly correlated with the severity of trait anxiety symptoms. Results suggest reward network dysfunction to both monetary and social rewards in SAD and ASD during reward anticipation and outcomes, but that NAc hypoactivation during monetary reward anticipation differentiates ASD from SAD.

Altered Gene Expression and Function of Peripheral Blood Natural Killer Cells in Children with Autism

PubMed Central

Enstrom, A M; Lit, L; Onore, C E; Gregg, J P; Hansen, R; Pessah, I N; Hertz-Picciotto, I; Van de Water, J A; Sharp, F R; Ashwood, P

2009-01-01

Immune related abnormalities have repeatedly been reported in autism spectrum disorders (ASD), including evidence of immune dysregulation and autoimmune phenomena. NK cells may play an important role in neurodevelopmental disorders such as ASD. Here we performed a gene expression screen and cellular functional analysis on peripheral blood obtained from 52 children with ASD and 27 typically developing control children enrolled in the case-control CHARGE study. RNA expression of NK cell receptors and effector molecules were significantly upregulated in ASD. Flow cytometric analysis of NK cells demonstrated increased production of perforin, granzyme B, and interferon gamma (IFNγ) under resting conditions in children with ASD (p<0.01). Following NK cell stimulation in the presence of K562 target cells, the cytotoxicity of NK cells was significantly reduced in ASD compared with controls (p<0.02). Furthermore, under similar stimulation conditions the presence of perforin, granzyme B, and IFNγ in NK cells from ASD children was significantly lower compared with controls (p<0.001). These findings suggest possible dysfunction of NK cells in children with ASD. Abnormalities in NK cells may represent a susceptibility factor in ASD and may predispose to the development of autoimmunity and/or adverse neuroimmune interactions during critical periods of development. PMID:18762240

Longitudinal Analyses of Expressive Language Development Reveal Two Distinct Language Profiles among Young Children with Autism Spectrum Disorders

PubMed Central

Tek, Saime; Mesite, Laura; Fein, Deborah; Naigles, Letitia

2013-01-01

Although children with ASD show significant variation in language skills, research on what type(s) of language profiles they demonstrate has been limited. Using growth-curve analyses, we investigated how different groups of young children with ASD show increases in the size of their lexicon, morpho-syntactic production as measured by Brown’s 14 grammatical morphemes, and wh-question complexity, compared to TD children, across six time points. Children with ASD who had higher verbal skills were comparable to TD children on most language measures, whereas the children with ASD who had low verbal skills had flatter trajectories in most language measures. Thus, two distinct language profiles emerged for children with ASD. PMID:23719855

Comparing the functional performance of children and youths with autism, developmental disabilities, and no disability using the revised pediatric evaluation of disability inventory item banks.

PubMed

Kao, Ying-Chia; Kramer, Jessica M; Liljenquist, Kendra; Tian, Feng; Coster, Wendy J

2012-01-01

OBJECTIVE. We compared the functional performance of children with autism spectrum disorders (ASD), intellectual and developmental disabilities (IDD), and without disabilities using the revised Pediatric Evaluation of Disability Inventory-Computer Adaptive Test (PEDI-CAT) Social/Cognitive, Daily Activities, and Responsibility domains. METHOD. A nationally representative sample of parents of children ages 0-21 without disabilities (n = 2,205), with ASD (n = 108), or with IDD (n = 150) completed an online survey. We obtained predicted PEDI-CAT scaled scores for three reference ages (5, 10, 15) from a modified analysis of covariance model and compared each group's scores using contrasts of the regression parameters. RESULTS. We found no significant differences between the ASD and IDD groups. The group with ASD demonstrated significantly lower performance than the group without disabilities across the three domains at ages 10 and 15. CONCLUSION. Scores on the PEDI-CAT differentiated the group with ASD from the group without disabilities. Children with ASD and IDD did not demonstrate different performance profiles. Copyright © 2012 by the American Occupational Therapy Association, Inc.

Imaging Depression in Adults with ASD

DTIC Science & Technology

2016-10-01

DISTRIBUTION UNLIMITED 13. SUPPLEMENTARY NOTES 14.ABSTRACT Aim A: To determine if the immunologic bias in autism spectrum disorder (ASD) confers greater...with no results to report to date. 1S. SUBJECT TERMS AUTISM , BRAIN IMAGING, DEPRESSION, SOCIAL REJECTION 16. SECURITY CLASSIFICATION OF: 17...which will be followed by an exploratory hedonic reward task, Monitory Incentive Delay. 2. KEYWORDS: autism , brain imaging, depression, social

Increasing Social Interactions Using Prompts and Rewards for Adolescents with ASD in an Ice Hockey Practice Context

ERIC Educational Resources Information Center

Beiers, Kevin; Derby, K. Mark; McLaughlin, T. F.

2016-01-01

We evaluated the effects of using prompts and reinforcement procedures to increase the social interaction of two children with autism (ASD). This study took place during the context of a hockey practice. Two adolescent participants were evaluated using an ABAB single subject reversal design. Baseline data were collected prior to and after the…

Effects of the Picture Exchange Communication System (PECS) on Maladaptive Behavior in Children with Autism Spectrum Disorders (ASD): A Review of the Literature

ERIC Educational Resources Information Center

Battaglia, Dana; McDonald, Mary E.

2015-01-01

This paper provides an overview of the literature investigating the functional relationship between the use of the Picture Exchange Communication System (PECS) and maladaptive behavior (i.e., aggression, tantrums) in individuals with autism spectrum disorders (ASD). Digital searches were conducted to identify single subject design studies…

Validating a Culturally-Sensitive Social Competence Training Programme for Adolescents with ASD in a Chinese Context: An Initial Investigation

ERIC Educational Resources Information Center

Chan, Raymond Won Shing; Leung, Cecilia Nga Wing; Ng, Denise Ching Yiu; Yau, Sania Sau Wai

2018-01-01

Previous studies on social skills training on ASD were done almost exclusively in the West with children as the main subjects. Demonstrations of the applicability of social interventions in different cultures and age groups are warranted. The current study outlined the development and preliminary evaluation of a CBT-context-based social competence…

Epigenetic regulation of RELN and GAD1 in the frontal cortex (FC) of autism spectrum disorder (ASD) subjects.

PubMed

Zhubi, Adrian; Chen, Ying; Guidotti, Alessandro; Grayson, Dennis R

2017-11-01

Both Reelin (RELN) and glutamate decarboxylase 67 (GAD1) have been implicated in the pathophysiology of Autism Spectrum Disorders (ASD). We have previously shown that both mRNAs are reduced in the cerebella (CB) of ASD subjects through a mechanism that involves increases in the amounts of MECP2 binding to the corresponding promoters. In the current study, we examined the expression of RELN, GAD1, GAD2, and several other mRNAs implicated in this disorder in the frontal cortices (FC) of ASD and CON subjects. We also focused on the role that epigenetic processes play in the regulation of these genes in ASD brain. Our goal is to better understand the molecular basis for the down-regulation of genes expressed in GABAergic neurons in ASD brains. We measured mRNA levels corresponding to selected GABAergic genes using qRT-PCR in RNA isolated from both ASD and CON groups. We determined the extent of binding of MECP2 and DNMT1 repressor proteins by chromatin immunoprecipitation (ChIP) assays. The amount of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) present in the promoters of the target genes was quantified by methyl DNA immunoprecipitation (MeDIP) and hydroxyl MeDIP (hMeDIP). We detected significant reductions in the mRNAs associated with RELN and GAD1 and significant increases in mRNAs encoding the Ten-eleven Translocation (TET) enzymes 1, 2, and 3. We also detected increased MECP2 and DNMT1 binding to the corresponding promoter regions of GAD1, RELN, and GAD2. Interestingly, there were decreased amounts of 5mC at both promoters and little change in 5hmC content in these same DNA fragments. Our data demonstrate that RELN, GAD1, and several other genes selectively expressed in GABAergic neurons, are down-regulated in post-mortem ASD FC. In addition, we observed increased DNMT1 and MECP2 binding at the corresponding promoters of these genes. The finding of increased MECP2 binding to the RELN, GAD1 and GAD2 promoters, with reduced amounts of 5mC and unchanged amounts of 5hmC present in these regions, suggests the possibility that DNMT1 interacts with and alters MECP2 binding properties to selected promoters. Comparisons between data obtained from the FC with CB studies showed some common themes between brain regions which are discussed. Copyright © 2017 ISDN. Published by Elsevier Ltd. All rights reserved.

Sources of group differences in functional connectivity: an investigation applied to autism spectrum disorder.

PubMed

Jones, Tyler B; Bandettini, Peter A; Kenworthy, Lauren; Case, Laura K; Milleville, Shawn C; Martin, Alex; Birn, Rasmus M

2010-01-01

An increasing number of fMRI studies are using the correlation of low-frequency fluctuations between brain regions, believed to reflect synchronized variations in neuronal activity, to infer "functional connectivity". In studies of autism spectrum disorder (ASD), decreases in this measure of connectivity have been found by focusing on the response to task modulation, by using only the rest periods, or by analyzing purely resting-state data. This difference in connectivity, however, could result from a number of different mechanisms--differences in noise, task-related fluctuations, task performance, or spontaneous neuronal activity. In this study, we investigate the difference in functional connectivity between adolescents with high-functioning ASD and typically developing control subjects by examining the residual fluctuations occurring on top of the fMRI response to an overt verbal fluency task. We find decreased correlations of these residuals (a decreased "connectivity") in ASD subjects. Furthermore, we find that this decrease was not due to task-related effects, block-to-block variations in task performance, or increased noise, and the difference was greatest when primarily rest periods are considered. These findings suggest that the estimate of disrupted functional connectivity in ASD is likely driven by differences in task-unrelated neuronal fluctuations.

Abnormalities of Intrinsic Functional Connectivity in Autism Spectrum Disorders

PubMed Central

Monk, Christopher S.; Peltier, Scott J.; Wiggins, Jillian Lee; Weng, Shih-Jen; Carrasco, Melisa; Risi, Susan; Lord, Catherine

2009-01-01

Autism spectrum disorders (ASD) impact social functioning and communication, and individuals with these disorders often have restrictive and repetitive behaviors. Accumulating data indicate that ASD is associated with alterations of neural circuitry. Functional MRI (FMRI) studies have focused on connectivity in the context of psychological tasks. However, even in the absence of a task, the brain exhibits a high degree of functional connectivity, known as intrinsic or resting connectivity. Notably, the default network, which includes the posterior cingulate cortex, retro-splenial, lateral parietal cortex/angular gyrus, medial prefrontal cortex, superior frontal gyrus, temporal lobe, and parahippocampal gyrus, is strongly active when there is no task. Altered intrinsic connectivity within the default network may underlie offline processing that may actuate ASD impairments. Using FMRI, we sought to evaluate intrinsic connectivity within the default network in ASD. Relative to controls, the ASD group showed weaker connectivity between the posterior cingulate cortex and superior frontal gyrus and stronger connectivity between the posterior cingulate cortex and both the right temporal lobe and right parahippocampal gyrus. Moreover, poorer social functioning in the ASD group was correlated with weaker connectivity between the posterior cingulate cortex and the superior frontal gyrus. In addition, more severe restricted and repetitive behaviors in ASD were correlated with stronger connectivity between the posterior cingulate cortex and right parahippocampal gyrus. These findings indicate that ASD subjects show altered intrinsic connectivity within the default network, and connectivity between these structures is associated with specific ASD symptoms. PMID:19409498

Comparison of Perinatal Risk Factors Associated with Autism Spectrum Disorder (ASD), Intellectual Disability (ID), and Co-Occurring ASD and ID

ERIC Educational Resources Information Center

Schieve, Laura A.; Clayton, Heather B.; Durkin, Maureen S.; Wingate, Martha S.; Drews-Botsch, Carolyn

2015-01-01

While studies report associations between perinatal outcomes and both autism spectrum disorder (ASD) and intellectual disability (ID), there has been little study of ASD with versus without co-occurring ID. We compared perinatal risk factors among 7547 children in the 2006-2010 Autism and Developmental Disability Monitoring Network classified as…

Brief Report: Adaptive Functioning in Children with ASD, ADHD and ASD + ADHD

ERIC Educational Resources Information Center

Ashwood, Karen L.; Tye, Charlotte; Azadi, Bahare; Cartwright, Sally; Asherson, Philip; Bolton, Patrick

2015-01-01

Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) often co-occur. Children with ASD and ADHD demonstrate deficits in adaptive functioning, yet pure and comorbid groups have not been directly compared. Vineland Adaptive Behaviour Scales (VABS-II) data were examined in boys with ASD (n = 17), ADHD (n = 31) and…

Parenting a Child with ASD: Comparison of Parenting Style between ASD, Anxiety, and Typical Development

ERIC Educational Resources Information Center

Ventola, Pamela; Lei, Jiedi; Paisley, Courtney; Lebowitz, Eli; Silverman, Wendy

2017-01-01

Parenting children with ASD has a complex history. Given parents' increasingly pivotal role in children's treatment, it is critical to consider parental style and behaviours. This study (1) compares parenting style of parents of children with ASD, parents of children with anxiety disorders, and parents of typically developing (TD) children and (2)…

A Group-Administered Social Skills Training for 8- to 12-Year-Old, High-Functioning Children with Autism Spectrum Disorders: An Evaluation of Its Effectiveness in a Naturalistic Outpatient Treatment Setting

ERIC Educational Resources Information Center

Deckers, Anne; Muris, Peter; Roelofs, Jeffrey; Arntz, Arnoud

2016-01-01

A social skills training (SST) for high-functioning children with autism spectrum disorders (ASD) was evaluated in an outpatient setting using a combined between- and within-subject design in which SST and a waiting list condition were compared. According to parents and teachers, the SST produced greater improvement of social skills than the…

Emotional prosody processing in autism spectrum disorder

PubMed Central

Kliemann, Dorit; Dziobek, Isabel; Heekeren, Hauke R.

2017-01-01

Abstract Individuals with Autism Spectrum Disorder (ASD) are characterized by severe deficits in social communication, whereby the nature of their impairments in emotional prosody processing have yet to be specified. Here, we investigated emotional prosody processing in individuals with ASD and controls with novel, lifelike behavioral and neuroimaging paradigms. Compared to controls, individuals with ASD showed reduced emotional prosody recognition accuracy on a behavioral task. On the neural level, individuals with ASD displayed reduced activity of the STS, insula and amygdala for complex vs basic emotions compared to controls. Moreover, the coupling between the STS and amygdala for complex vs basic emotions was reduced in the ASD group. Finally, groups differed with respect to the relationship between brain activity and behavioral performance. Brain activity during emotional prosody processing was more strongly related to prosody recognition accuracy in ASD participants. In contrast, the coupling between STS and anterior cingulate cortex (ACC) activity predicted behavioral task performance more strongly in the control group. These results provide evidence for aberrant emotional prosody processing of individuals with ASD. They suggest that the differences in the relationship between the neural and behavioral level of individuals with ASD may account for their observed deficits in social communication. PMID:27531389

[Personality traits in adults with autism spectrum disorders measured by means of the Temperament and Character Inventory].

PubMed

Vuijk, R; de Nijs, P F A; Vitale, S G; Simons-Sprong, M; Hengeveld, M W

2012-01-01

There is growing interest in autism spectrum disorders (asd) in adulthood. Someone can be diagnosed with ASD, but the diagnosis tells us very little about the patient’s temperament, character and personality. Comparatively little is known about the personality traits of persons with ASD. To map personality traits of persons with asd. The Temperament and Character Inventory (tci) was administered to a group of 68 men diagnosed with asd at the Lucertis Sarr expertise centre for Autism and at the Department of Psychiatry, Erasmus mc, Rotterdam, the Netherlands. The control group, specified in the instructions for the tci, consisted of a group of 447 men from the general population. Compared to the control group, men with asd scored higher on the scale Harm Avoidance, but lower on Sociability, Novelty Seeking, Reward Dependence, Self-directedness, and Cooperativeness. The score pattern found in men with asd is consistent with the clinical picture of asd and corresponds to earlier results of research done in Sweden. In our study we argue that negatively interpreted temperament and character traits can often be interpreted in a positive way.

Gross Motor Profile and Its Association with Socialization Skills in Children with Autism Spectrum Disorders.

PubMed

Pusponegoro, Hardiono D; Efar, Pustika; Soedjatmiko; Soebadi, Amanda; Firmansyah, Agus; Chen, Hui-Ju; Hung, Kun-Long

2016-12-01

While social impairment is considered to be the core deficit in children with autism spectrum disorder (ASD), a large proportion of these children have poor gross motor ability, and gross motor deficits may influence socialization skills in children with ASD. The objectives of this study were to compare gross motor skills in children with ASD to typically developing children, to describe gross motor problems in children with ASD, and to investigate associations between gross motor and socialization skills in children with ASD. This was a cross-sectional study including 40 ASD children aged from 18 months to 6 years and 40 age-matched typically developing controls. Gross motor and socialization skills were scored using the Vineland Adaptive Behavior Scales, 2 nd edition (Vineland-II). Below average gross motor function was found in eight of 40 (20%) ASD children. The mean gross motor v-scale score in the ASD group was 15.1 [standard deviation (SD) 3.12], significantly lower than in the control group [18.7, SD 2.09, p = 0.0001; 95% confidence intervals (CI) from -4.725 to -2.525]. The differences were most prominent in ball throwing and catching, using stairs, jumping, and bicycling. The ASD children with gross motor impairments had a mean socialization domain score of 66.6 (SD 6.50) compared to 85.7 (SD 10.90) in those without gross motor impairments (p = 0.0001, 95% CI from -25.327 to -12.736). Children with ASD had lower gross motor skills compared to typically developing children. Gross motor impairments were found in 20% of the ASD children, and these children also had lower socialization skills than those without gross motor impairments. Copyright © 2016. Published by Elsevier B.V.

Parent-child agreement regarding children's acute stress: the role of parent acute stress reactions.

PubMed

Kassam-Adams, Nancy; García-España, J Felipe; Miller, Victoria A; Winston, Flaura

2006-12-01

We examined parent-child agreement regarding child acute stress disorder (ASD) and the relationship between parent ASD symptoms and parent ratings of child ASD. Parent-child dyads (N = 219; child age 8-17 years) were assessed within 1 month of child injury. Parent-child agreement was examined regarding child ASD presence, severity, and specific symptoms. Relationships among parent ASD and parent- and child-reported child ASD were examined using regression analysis and generalized estimating equations (GEE). Parent-child agreement was low for presence of child ASD (kappa = 0.22) and for individual symptoms. Parent and child ratings of child ASD severity were moderately correlated (r = 0.35). Parent ASD was independently associated with parent-rated child ASD, after accounting for child self-rating (beta =.65). Generalized estimating equations indicated that parents with ASD overestimated child ASD and parents without ASD underestimated child ASD, compared to the child's self-rating. Parents' own responses to a potentially traumatic event appear to influence their assessment of child symptoms. Clinicians should obtain child self-report of ASD whenever possible and take parent symptoms into account when interpreting parent reports. Helping parents to assess a child's needs following a potentially traumatic event may be a relevant target for clinical attention.

Dental caries experience and periodontal treatment needs of children with autistic spectrum disorder.

PubMed

Fakroon, S; Arheiam, A; Omar, S

2015-04-01

To assess dental caries experience and periodontal treatment needs among Libyan children diagnosed with autistic spectrum disorder (ASD). A cross-sectional, comparative case-control study was used, in which dental caries experience of 50 children with ASD was compared with that of 50 controls. The children with ASD were recruited from Benghazi Centre of Children with ASD, Libya. Controls were recruited from school children and matched for age, gender and socioeconomic status. DMFT, dmft for dental caries experience and CPITN for periodontal treatment needs were calculated according to WHO criteria by a calibrated examiner. Scores for DMFT as well as CPITN indices were compared using bivariate analysis. The data analysed for this study comprised observations from a group of children (cases = 50) diagnosed with ASD matched with healthy children (controls = 50). Consequently, each group consisted of 40 males and 10 females aged between 3 and 14 years (mean 7.29 ± 3.11). The ASD children showed significantly lower means for DMFT and dmft teeth as well as higher periodontal treatment needs (p > 0.05). Children with ASD were found to be more likely caries-free and have lower DMFT scores and higher unmet periodontal treatment needs than did the unaffected control children.

Attention profiles in autism spectrum disorder and subtypes of attention-deficit/hyperactivity disorder.

PubMed

Boxhoorn, Sara; Lopez, Eva; Schmidt, Catharina; Schulze, Diana; Hänig, Susann; Freitag, Christine M

2018-03-06

Attention problems are observed in attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Most neuropsychological studies that compared both disorders focused on complex executive functions (EF), but missed to contrast basic attention functions, as well as ASD- and ADHD subtypes. The present study compared EF as well as basic attention functioning of children with the combined subtype (ADHD-C), the predominantly inattentive subtype (ADHD-I), and autism spectrum disorder without ADHD (ASD-) with typically developing controls (TD). Basic attention functions and EF profiles were analysed by testing the comprehensive attention function model of van Zomeren and Brouwer using profile analysis. Additionally, neurocognitive impairments in ASD- and ADHD were regressed on dimensional measures of attention- and hyperactive-impulsive symptoms across and within groups. ADHD-C revealed a strong impairment across measures of EF compared to ASD- and TD. The ADHD-C profile furthermore showed disorder specific impairments in interference control, whereas the ASD- profile showed a disorder specific impairment in basic attention component divided attention. Attention- and hyperactive-impulsive symptom severity did not predict neurocognitive impairments across- or within groups. Study findings thus support disorder and subtype specific attention/EF profiles, which refute the idea of a continuum of ADHD-I, ADHD-C, and ASD with increasing neurocognitive impairments.

The visual rooting reflex in individuals with autism spectrum disorders and co-occurring intellectual disability.

PubMed

de Bildt, Annelies; Mulder, Erik J; Van Lang, Natasja D J; de With, S A Jytte; Minderaa, Ruud B; Stahl, Sherin S; Anderson, George M

2012-02-01

The rooting reflex has long been studied by neurologists and developmentalists and is defined as an orientation toward tactile stimulation in the perioral region or visual stimulation near the face. Nearly, all previous reports of the visual rooting reflex (VRR) concern its presence in adults with neurological dysfunction. Previously, the VRR was reported to be present in a majority of individuals with autism and absent in control subjects. In the present larger study, we examined the presence of the VRR in 155 individuals with ASD and co-occurring Intellectual Disability (ASD + ID: autism, N = 60; Pervasive Developmental Disorder-Not Otherwise Specified (PDD_NOS), N = 95) and in a contrast group of 65 individuals with ID only. The VRR was present significantly more often in the ASD + ID (43.9%) group than in the ID-only group (24.6%; χ(1)(2)= 7.19; P = 0.007). Individuals with autism displayed a VRR more often (55.0%) than individuals with PDD-NOS (36.8%; χ(1)(2)= 4.92; P = 0.026) and individuals with ID only (24.6%; χ(1)(2)= 12.09; P = 0.001). A positive VRR was associated with lower IQ and adaptive functioning; in the ASD + ID group, ADI-R/ADOS domain scores were significantly higher in the VRR-positive subgroup. The results replicate and extend the finding of an increased occurrence of the VRR in autism. Although some association with IQ was observed, the VRR occurred substantially more often in the autism group compared with an intellectually disabled group, indicating some degree of specificity. Additional studies of infants and children with typical development, ASD and ID are needed to determine the utility of the VRR in ASD risk assessment and to elucidate possible specific behavioral associations. Copyright © 2011, International Society for Autism Research, Wiley-Liss, Inc.

Effects of intranasal oxytocin on the neural basis of face processing in autism spectrum disorder.

PubMed

Domes, Gregor; Heinrichs, Markus; Kumbier, Ekkehardt; Grossmann, Annette; Hauenstein, Karlheinz; Herpertz, Sabine C

2013-08-01

Autism spectrum disorder (ASD) is associated with altered face processing and decreased activity in brain regions involved in face processing. The neuropeptide oxytocin has been shown to promote face processing and modulate brain activity in healthy adults. The present study examined the effects of oxytocin on the neural basis of face processing in adults with Asperger syndrome (AS). A group of 14 individuals with AS and a group of 14 neurotypical control participants performed a face-matching and a house-matching task during functional magnetic resonance imaging. The effects of a single dose of 24 IU intranasally administered oxytocin were tested in a randomized, placebo-controlled, within-subject, cross-over design. Under placebo, the AS group showed decreased activity in the right amygdala, fusiform gyrus, and inferior occipital gyrus compared with the control group during face processing. After oxytocin treatment, right amygdala activity to facial stimuli increased in the AS group. These findings indicate that oxytocin increases the saliency of social stimuli and in ASD and suggest that oxytocin might promote face processing and eye contact in individuals with ASD as prerequisites for neurotypical social interaction. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Schizophrenia and autism as contrasting minds: neural evidence for the hypo-hyper-intentionality hypothesis.

PubMed

Ciaramidaro, Angela; Bölte, Sven; Schlitt, Sabine; Hainz, Daniela; Poustka, Fritz; Weber, Bernhard; Bara, Bruno G; Freitag, Christine; Walter, Henrik

2015-01-01

Both schizophrenia (SCZ) and autism spectrum disorder (ASD) are characterized by mentalizing problems and associated neural dysfunction of the social brain. However, the deficits in mental state attribution are somehow opposed: Whereas patients with SCZ tend to over-attribute intentions to agents and physical events ("hyper-intentionality"), patients with autism treat people as devoid of intentions ("hypo-intentionality"). Here we aimed to investigate whether this hypo-hyper-intentionality hypothesis can be supported by neural evidence during a mentalizing task. Using functional magnetic resonance imaging (fMRI), we investigated the neural responses and functional connectivity during reading others intention. Scanning was performed in 23 individuals with ASD, 18 with paranoid SCZ and 23 gender and IQ matched control subjects. Both clinical groups showed reduced brain activation compared to controls for the contrast intentional vs physical information processing in left posterior superior temporal sulcus (pSTS) and ventral medial prefrontal cortex (vMPFC) for SCZ, and right pSTS in ASD. As predicted, these effects were caused in a group specific way: Relative increased activation for physical information processing in SCZ that was also correlated with positive PANNS score and relative decreased activation for intentional information processing in ASD. Additionally, we could demonstrate opposed connectivity patterns between the right pSTS and vMPFC in the clinical groups, ie, increased for SCZ, decreased for ASD. These findings represent opposed neural signatures in key regions of the social brain as predicted by the hyper-hypo-intentionality hypothesis. © The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

A novel Brain Computer Interface for classification of social joint attention in autism and comparison of 3 experimental setups: A feasibility study.

PubMed

Amaral, Carlos P; Simões, Marco A; Mouga, Susana; Andrade, João; Castelo-Branco, Miguel

2017-10-01

We present a novel virtual-reality P300-based Brain Computer Interface (BCI) paradigm using social cues to direct the focus of attention. We combined interactive immersive virtual-reality (VR) technology with the properties of P300 signals in a training tool which can be used in social attention disorders such as autism spectrum disorder (ASD). We tested the novel social attention training paradigm (P300-based BCI paradigm for rehabilitation of joint-attention skills) in 13 healthy participants, in 3 EEG systems. The more suitable setup was tested online with 4 ASD subjects. Statistical accuracy was assessed based on the detection of P300, using spatial filtering and a Naïve-Bayes classifier. We compared: 1 - g.Mobilab+ (active dry-electrodes, wireless transmission); 2 - g.Nautilus (active electrodes, wireless transmission); 3 - V-Amp with actiCAP Xpress dry-electrodes. Significant statistical classification was achieved in all systems. g.Nautilus proved to be the best performing system in terms of accuracy in the detection of P300, preparation time, speed and reported comfort. Proof of concept tests in ASD participants proved that this setup is feasible for training joint attention skills in ASD. This work provides a unique combination of 'easy-to-use' BCI systems with new technologies such as VR to train joint-attention skills in autism. Our P300 BCI paradigm is feasible for future Phase I/II clinical trials to train joint-attention skills, with successful classification within few trials, online in ASD participants. The g.Nautilus system is the best performing one to use with the developed BCI setup. Copyright © 2017 Elsevier B.V. All rights reserved.

EEG-based Affect and Workload Recognition in a Virtual Driving Environment for ASD Intervention

PubMed Central

Wade, Joshua W.; Key, Alexandra P.; Warren, Zachary E.; Sarkar, Nilanjan

2017-01-01

objective To build group-level classification models capable of recognizing affective states and mental workload of individuals with autism spectrum disorder (ASD) during driving skill training. Methods Twenty adolescents with ASD participated in a six-session virtual reality driving simulator based experiment, during which their electroencephalogram (EEG) data were recorded alongside driving events and a therapist’s rating of their affective states and mental workload. Five feature generation approaches including statistical features, fractal dimension features, higher order crossings (HOC)-based features, power features from frequency bands, and power features from bins (Δf = 2 Hz) were applied to extract relevant features. Individual differences were removed with a two-step feature calibration method. Finally, binary classification results based on the k-nearest neighbors algorithm and univariate feature selection method were evaluated by leave-one-subject-out nested cross-validation to compare feature types and identify discriminative features. Results The best classification results were achieved using power features from bins for engagement (0.95) and boredom (0.78), and HOC-based features for enjoyment (0.90), frustration (0.88), and workload (0.86). Conclusion Offline EEG-based group-level classification models are feasible for recognizing binary low and high intensity of affect and workload of individuals with ASD in the context of driving. However, while promising the applicability of the models in an online adaptive driving task requires further development. Significance The developed models provide a basis for an EEG-based passive brain computer interface system that has the potential to benefit individuals with ASD with an affect- and workload-based individualized driving skill training intervention. PMID:28422647

Truncating mutations of MAGEL2 cause Prader-Willi phenotypes and autism.

PubMed

Schaaf, Christian P; Gonzalez-Garay, Manuel L; Xia, Fan; Potocki, Lorraine; Gripp, Karen W; Zhang, Baili; Peters, Brock A; McElwain, Mark A; Drmanac, Radoje; Beaudet, Arthur L; Caskey, C Thomas; Yang, Yaping

2013-11-01

Prader-Willi syndrome (PWS) is caused by the absence of paternally expressed, maternally silenced genes at 15q11-q13. We report four individuals with truncating mutations on the paternal allele of MAGEL2, a gene within the PWS domain. The first subject was ascertained by whole-genome sequencing analysis for PWS features. Three additional subjects were identified by reviewing the results of exome sequencing of 1,248 cases in a clinical laboratory. All four subjects had autism spectrum disorder (ASD), intellectual disability and a varying degree of clinical and behavioral features of PWS. These findings suggest that MAGEL2 is a new gene causing complex ASD and that MAGEL2 loss of function can contribute to several aspects of the PWS phenotype.

A novel ventricular restraint device (ASD) repetitively deliver Salvia miltiorrhiza to epicardium have good curative effects in heart failure management.

PubMed

Naveed, Muhammad; Wenhua, Li; Gang, Wang; Mohammad, Imran Shair; Abbas, Muhammad; Liao, Xiaoqian; Yang, Mengqi; Zhang, Li; Liu, Xiaolin; Qi, Xiaoming; Chen, Yineng; Jiadi, Lv; Ye, Linlan; Zhijie, Wang; Ding, Chen Ding; Feng, Yu; Xiaohui, Zhou

2017-11-01

A novel ventricular restraint is the non-transplant surgical option for the management of an end-stage dilated heart failure (HF). To expand the therapeutic techniques we design a novel ventricular restraint device (ASD) which has the ability to deliver a therapeutic drug directly to the heart. We deliver a Traditional Chinese Medicine (TCM) Salvia miltiorrhiza (Danshen Zhusheye) through active hydraulic ventricular support drug delivery system (ASD) and we hypothesize that it will show better results in HF management than the restraint device and drug alone. SD rats were selected and divided into five groups (n=6), Normal, HF, HF+SM (IV), HF+ASD, HF+ASD+SM groups respectively. Post myocardial infarction (MI), electrocardiography (ECG) showed abnormal heart function in all groups and HF+ASD+SM group showed a significant therapeutic improvement with respect to other treatment HF, HF+ASD, and HF+SM (IV) groups on day 30. The mechanical functions of the heart such as heart rate, LVEDP, and LVSP were brought to normal when treated with ASD+SM and show significant (P value<0.01) compared to other groups. BNP significantly declines in HF+ASD+SM group animals compared with other treatment groups. Masson's Trichrome staining was used to study histopathology of cardiac myocytes and quantification of fibrosis was assessed. The large blue fibrotic area was observed in HF, HF+ASD, and HF+SM (IV) groups while HF+ASD+SM showed negligible fibrotic myocyte at the end of study period (30days). This study proves that novel ASD device augments the therapeutic effect of the drug and delivers Salvia miltiorrhiza to the cardiomyocytes significantly as well as provides additional support to the dilated ventricle by the heart failure. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Subtyping cognitive profiles in Autism Spectrum Disorder using a Functional Random Forest algorithm.

PubMed

Feczko, E; Balba, N M; Miranda-Dominguez, O; Cordova, M; Karalunas, S L; Irwin, L; Demeter, D V; Hill, A P; Langhorst, B H; Grieser Painter, J; Van Santen, J; Fombonne, E J; Nigg, J T; Fair, D A

2018-05-15

DSM-5 Autism Spectrum Disorder (ASD) comprises a set of neurodevelopmental disorders characterized by deficits in social communication and interaction and repetitive behaviors or restricted interests, and may both affect and be affected by multiple cognitive mechanisms. This study attempts to identify and characterize cognitive subtypes within the ASD population using our Functional Random Forest (FRF) machine learning classification model. This model trained a traditional random forest model on measures from seven tasks that reflect multiple levels of information processing. 47 ASD diagnosed and 58 typically developing (TD) children between the ages of 9 and 13 participated in this study. Our RF model was 72.7% accurate, with 80.7% specificity and 63.1% sensitivity. Using the random forest model, the FRF then measures the proximity of each subject to every other subject, generating a distance matrix between participants. This matrix is then used in a community detection algorithm to identify subgroups within the ASD and TD groups, and revealed 3 ASD and 4 TD putative subgroups with unique behavioral profiles. We then examined differences in functional brain systems between diagnostic groups and putative subgroups using resting-state functional connectivity magnetic resonance imaging (rsfcMRI). Chi-square tests revealed a significantly greater number of between group differences (p < .05) within the cingulo-opercular, visual, and default systems as well as differences in inter-system connections in the somato-motor, dorsal attention, and subcortical systems. Many of these differences were primarily driven by specific subgroups suggesting that our method could potentially parse the variation in brain mechanisms affected by ASD. Copyright © 2017. Published by Elsevier Inc.

Challenging behavior and co-morbid psychopathology in adults with intellectual disability and autism spectrum disorders.

PubMed

McCarthy, Jane; Hemmings, Colin; Kravariti, Eugenia; Dworzynski, Katharina; Holt, Geraldine; Bouras, Nick; Tsakanikos, Elias

2010-01-01

We investigated the relationship between challenging behavior and co-morbid psychopathology in adults with intellectual disability (ID) and autism spectrum disorders (ASDs) (N=124) as compared to adults with ID only (N=562). All participants were first time referrals to specialist mental health services and were living in community settings. Clinical diagnoses were based on ICD-10 criteria and presence of challenging behavior was assessed with the Disability Assessment Schedule (DAS-B). The analyses showed that ASD diagnosis was significantly associated with male gender, younger age and lower level of ID. Challenging behavior was about four times more likely in adults with ASD as compared to non-ASD adults. In those with challenging behavior, there were significant differences in co-morbid psychopathology between ASD and non-ASD adults. However, after controlling for level of ID, gender and age, there was no association between co-morbid psychopathology and presence of challenging behavior. Overall, the results suggest that presence of challenging behavior is independent from co-morbid psychopathology in adults with ID and ASD. Copyright 2009 Elsevier Ltd. All rights reserved.

Prevalence of parent-reported ASD and ADHD in the UK: findings from the Millennium Cohort Study.

PubMed

Russell, Ginny; Rodgers, Lauren R; Ukoumunne, Obioha C; Ford, Tamsin

2014-01-01

The UK prevalence of parent-reported autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD) were estimated from the Millennium Cohort Study. Case definition was if a doctor or health care professional had ever told parents that their child had ASD and/or ADHD. Data were collected in 2008/2009 for 14,043 children. 1.7 % of children were reported as having ASD (95 % CI 1.4-2.0) at mean age 7.2 years (SD = 0.2; range = 6.3-8.2). 1.4 % reportedly had ADHD (95 % CI 1.2-1.7), and 0.3 % had both ASD and ADHD (95 % CI 0.2-0.5). After adjusting for socio-economic disadvantage, only male sex (p < 0.001 for both conditions) and cognitive ability, p = 0.004 (ASD); p = 0.01 (ADHD) remained strongly associated. The observed prevalence of parent-reported ASD is high compared to earlier UK and US estimates. Parent-reported ADHD is low compared to US estimates using the same measure.

Multi-scale radiomic analysis of sub-cortical regions in MRI related to autism, gender and age

NASA Astrophysics Data System (ADS)

Chaddad, Ahmad; Desrosiers, Christian; Toews, Matthew

2017-03-01

We propose using multi-scale image textures to investigate links between neuroanatomical regions and clinical variables in MRI. Texture features are derived at multiple scales of resolution based on the Laplacian-of-Gaussian (LoG) filter. Three quantifier functions (Average, Standard Deviation and Entropy) are used to summarize texture statistics within standard, automatically segmented neuroanatomical regions. Significance tests are performed to identify regional texture differences between ASD vs. TDC and male vs. female groups, as well as correlations with age (corrected p < 0.05). The open-access brain imaging data exchange (ABIDE) brain MRI dataset is used to evaluate texture features derived from 31 brain regions from 1112 subjects including 573 typically developing control (TDC, 99 females, 474 males) and 539 Autism spectrum disorder (ASD, 65 female and 474 male) subjects. Statistically significant texture differences between ASD vs. TDC groups are identified asymmetrically in the right hippocampus, left choroid-plexus and corpus callosum (CC), and symmetrically in the cerebellar white matter. Sex-related texture differences in TDC subjects are found in primarily in the left amygdala, left cerebellar white matter, and brain stem. Correlations between age and texture in TDC subjects are found in the thalamus-proper, caudate and pallidum, most exhibiting bilateral symmetry.

Deficit in visual temporal integration in autism spectrum disorders.

PubMed

Nakano, Tamami; Ota, Haruhisa; Kato, Nobumasa; Kitazawa, Shigeru

2010-04-07

Individuals with autism spectrum disorders (ASD) are superior in processing local features. Frith and Happe conceptualize this cognitive bias as 'weak central coherence', implying that a local enhancement derives from a weakness in integrating local elements into a coherent whole. The suggested deficit has been challenged, however, because individuals with ASD were not found to be inferior to normal controls in holistic perception. In these opposing studies, however, subjects were encouraged to ignore local features and attend to the whole. Therefore, no one has directly tested whether individuals with ASD are able to integrate local elements over time into a whole image. Here, we report a weakness of individuals with ASD in naming familiar objects moved behind a narrow slit, which was worsened by the absence of local salient features. The results indicate that individuals with ASD have a clear deficit in integrating local visual information over time into a global whole, providing direct evidence for the weak central coherence hypothesis.

Association of Autism with Maternal Infections, Perinatal and Other Risk Factors: A Case-Control Study.

PubMed

Guisso, Dikran Richard; Saadeh, Fadi S; Saab, Dahlia; El Deek, Joud; Chamseddine, Sarah; El Hassan, Hadi Abou; Majari, Ghidaa; Boustany, Rose-Mary

2018-06-01

This case-control study explores the association between pregnancy/birth complications and other factors with Autism Spectrum Disorder (ASD) in Lebanese subjects aged 2-18 years. Researchers interviewed 136 ASD cases from the American University of Beirut Medical Center Special Kids Clinic, and 178 controls selected by systematic digit dialing in the Greater-Beirut area. Male gender (Adjusted Odds Ratio [95% CI]: 3.9 [2.2-7.0]); postpartum feeding difficulties (2.5 [1.2-5.4]); maternal infections/complications during pregnancy (2.9 [1.5-5.5], 2.1 [1.1-3.9]); consanguinity (2.5 [1.0-6.0]); family history of psychiatric disorders (2.2 [1.1-4.4]) were risk factors for ASD. Being born first/second (0.52 [0.28-0.95]) and maternal psychological support during pregnancy (0.49 [0.27-0.89]) were negatively associated with ASD. Identifying ASD correlates is crucial for instigating timely screening and subsequent early intervention.

Idiom Comprehension Deficits in High-Functioning Autism Spectrum Disorder Using a Korean Autism Social Language Task.

PubMed

Lee, Seul Bee; Song, Seung Ha; Ham, Ju Hyun; Song, Dong Ho; Cheon, Keun-Ah

2015-11-01

High-functioning autism spectrum disorder (ASD) involves pragmatic impairment of language skills. Among numerous tasks for assessing pragmatic linguistic skills, idioms are important to evaluating high-functioning ASD. Nevertheless, no assessment tool has been developed with specific consideration of Korean culture. Therefore, we designed the Korean Autism Social Language Task (KASLAT) to test idiom comprehension in ASD. The aim of the current study was to introduce this novel psychological tool and evaluate idiom comprehension deficits in high-functioning ASD. The participants included 42 children, ages 6-11 years, who visited our child psychiatric clinic between April 2014 and May 2015. The ASD group comprised 16 children; the attention deficit hyperactivity disorder (ADHD) group consisted of 16 children. An additional 10 normal control children who had not been diagnosed with either disorder participated in this study. Idiom comprehension ability was assessed in these three groups using the KASLAT. Both ASD and ADHD groups had significantly lower scores on the matched and mismatched tasks, compared to the normal control children (matched tasks mean score: ASD 11.56, ADHD 11.56, normal control 14.30; mismatched tasks mean score: ASD 6.50, ADHD 4.31, normal control 11.30). However, no significant differences were found in scores of KASLAT between the ADHD and ASD groups. These findings suggest that children with ASD exhibit greater impairment in idiom comprehension, compared to normal control children. The KASLAT may be useful in evaluating idiom comprehension ability.

Sexual Orientation, Gender Identity, and Romantic Relationships in Adolescents and Adults with Autism Spectrum Disorder.

PubMed

Dewinter, J; De Graaf, H; Begeer, S

2017-09-01

This study compared sexual orientation and romantic relationship experience in a large sample of adolescents and adults with autism spectrum disorder (ASD) (n = 675) and general population peers (n = 8064). Gender identity was explored in the ASD group in relation to assigned gender at birth. Compared to general population peers, more people with ASD, especially women, reported sexual attraction to both same- and opposite-sex partners. About half of the participants with ASD was in a relationship (heterosexual in most cases) and most of them lived with their partner. A notable number of autistic participants, again more women than men, reported gender non-conforming feelings. Attention to gender identity and sexual diversity in education and clinical work with people with ASD is advised.

Simple Mindreading Abilities Predict Complex Theory of Mind: Developmental Delay in Autism Spectrum Disorders.

PubMed

Pino, Maria Chiara; Mazza, Monica; Mariano, Melania; Peretti, Sara; Dimitriou, Dagmara; Masedu, Francesco; Valenti, Marco; Franco, Fabia

2017-09-01

Theory of mind (ToM) is impaired in individuals with autism spectrum disorders (ASD). The aims of this study were to: (i) examine the developmental trajectories of ToM abilities in two different mentalizing tasks in children with ASD compared to TD children; and (ii) to assess if a ToM simple test known as eyes-test could predict performance on the more advanced ToM task, i.e. comic strip test. Based on a sample of 37 children with ASD and 55 TD children, our results revealed slower development at varying rates in all ToM measures in children with ASD, with delayed onset compared to TD children. These results could stimulate new treatments for social abilities, which would lessen the social deficit in ASD.

The Stability of Self-Reported Anxiety in Youth with Autism Versus ADHD or Typical Development.

PubMed

Schiltz, Hillary; McIntyre, Nancy; Swain-Lerro, Lindsay; Zajic, Matthew; Mundy, Peter

2017-12-01

Children with autism spectrum disorder (ASD) are at risk for anxiety symptoms. Few anxiety measures are validated for individuals with ASD, and the nature of ASD raises questions about reliability of self-reported anxiety. This study examined longitudinal stability and change of self-reported anxiety in higher functioning youth with ASD (HFASD) compared to youth with symptoms of attention deficit hyperactivity disorder and typical development (TD) using the Multidimensional Anxiety Scale for Children (March, 2012; March et al. J Am Acad Child Adolesc Psychiatry 36(4):554-565, 1997). Diagnostic groups demonstrated comparable evidence of stability for most dimensions of anxiety. The HFASD group displayed higher anxiety than both comparison groups, especially physical symptoms. These findings have implications for identification and measurement of anxiety in ASD.

Television, video game and social media use among children with ASD and typically developing siblings.

PubMed

Mazurek, Micah O; Wenstrup, Colleen

2013-06-01

This study examined the nature of television, video game, and social media use in children (ages 8-18) with autism spectrum disorders (ASD, n = 202) compared to typically developing siblings (TD, n = 179), and relative to other activities. Parents completed measures assessing children's screen-based and other extracurricular activities. Children with ASD spent approximately 62% more time watching television and playing video games than in all non-screen activities combined. Compared with TD siblings, children with ASD spent more hours per day playing video games (2.4 vs. 1.6 for boys, and 1.8 vs. 0.8 for girls), and had higher levels of problematic video game use. In contrast, children with ASD spent little time using social media or socially interactive video games.

Assessment of the Relationship between Diagnoses of ASD and Caregiver Symptom Endorsement in Adults Diagnosed with Intellectual Disability

ERIC Educational Resources Information Center

Matson, Johnny L.; Hess, Julie A.; Mahan, Sara; Fodstad, Jill C.; Neal, Daniene

2013-01-01

Individuals diagnosed with an intellectual disability (ID) share overlapping traits with those diagnosed with both ID and an Autism Spectrum Disorder (ASD). Therefore, the purpose of this study was to determine if caregivers' reports of symptoms of ASD are of value (i.e., when comparing them to clinical diagnoses of ASD) and to determine which…

A Comparison of Motor Delays in Young Children: Autism Spectrum Disorder, Developmental Delay, and Developmental Concerns

ERIC Educational Resources Information Center

Provost, Beth; Lopez, Brian R.; Heimerl, Sandra

2007-01-01

This study assessed motor delay in young children 21-41 months of age with autism spectrum disorder (ASD), and compared motor scores in children with ASD to those of children without ASD. Fifty-six children (42 boys, 14 girls) were in three groups: children with ASD, children with developmental delay (DD), and children with developmental concerns…

Increased Clinical and Neurocognitive Impairment in Children with Autism Spectrum Disorders and Comorbid Bipolar Disorder

ERIC Educational Resources Information Center

Weissman, Adam S.; Bates, Marsha E.

2010-01-01

Bipolar (BD) symptomatology is prevalent in children with autism spectrum disorders (ASD) and may lead to increased impairment. The current study compared clinical and neurocognitive impairment in children (7-13 years) diagnosed with ASD (n=55), BD (n=34), ASD + BD (n=23), and a non-clinical control group (n=27). Relative to the ASD group, the ASD…

Amniotic fluid inflammatory cytokines: potential markers of immunologic dysfunction in autism spectrum disorders.

PubMed

Abdallah, Morsi W; Larsen, Nanna; Grove, Jakob; Nørgaard-Pedersen, Bent; Thorsen, Poul; Mortensen, Erik L; Hougaard, David M

2013-09-01

The aim of the study was to analyze cytokine profiles in amniotic fluid (AF) samples of children developing autism spectrum disorders (ASD) and controls, adjusting for maternal autoimmune disorders and maternal infections during pregnancy. AF samples of 331 ASD cases and 698 controls were analyzed for inflammatory cytokines using Luminex xMAP technology utilizing a historic birth cohort. Clinical data were retrieved from nationwide registers, and case-control differences in AF cytokine levels were assessed using chi-square tests, logistic and tobit regression models. Overall, individuals with ASD had significantly elevated AF levels of TNF-α and TNF-β compared to controls. Analyzing individuals diagnosed only with ICD-10 codes yielded significantly elevated levels of IL-4, IL-10, TNF-α and TNF-β in ASD patients. Restricting analysis to infantile autism cases showed significantly elevated levels of IL-4, TNF-α and TNF-β compared to controls with no psychiatric comorbidities. Elevated levels of IL-6 and IL-5 were found in individuals with other childhood psychiatric disorders (OCPD) when compared to controls with no psychiatric comorbidities. AF samples of individuals with ASD or OCPD showed differential cytokine profiles compared to frequency-matched controls. Further studies to examine the specificity of the reported cytokine profiles in ASD and OCPD are required.

Visual local and global processing in low-functioning deaf individuals with and without autism spectrum disorder.

PubMed

Maljaars, J P W; Noens, I L J; Scholte, E M; Verpoorten, R A W; van Berckelaer-Onnes, I A

2011-01-01

The ComFor study has indicated that individuals with intellectual disability (ID) and autism spectrum disorder (ASD) show enhanced visual local processing compared with individuals with ID only. Items of the ComFor with meaningless materials provided the best discrimination between the two samples. These results can be explained by the weak central coherence account. The main focus of the present study is to examine whether enhanced visual perception is also present in low-functioning deaf individuals with and without ASD compared with individuals with ID, and to evaluate the underlying cognitive style in deaf and hearing individuals with ASD. Different sorting tasks (selected from the ComFor) were administered from four subsamples: (1) individuals with ID (n = 68); (2) individuals with ID and ASD (n = 72); (3) individuals with ID and deafness (n = 22); and (4) individuals with ID, ASD and deafness (n = 15). Differences in performance on sorting tasks with meaningful and meaningless materials between the four subgroups were analysed. Age and level of functioning were taken into account. Analyses of covariance revealed that results of deaf individuals with ID and ASD are in line with the results of hearing individuals with ID and ASD. Both groups showed enhanced visual perception, especially on meaningless sorting tasks, when compared with hearing individuals with ID, but not compared with deaf individuals with ID. In ASD either with or without deafness, enhanced visual perception for meaningless information can be understood within the framework of the central coherence theory, whereas in deafness, enhancement in visual perception might be due to a more generally enhanced visual perception as a result of auditory deprivation. © 2010 The Authors. Journal of Intellectual Disability Research © 2010 Blackwell Publishing Ltd.

Novel Probiotic Therapies for Autism

DTIC Science & Technology

2012-08-01

1 AD_________________ Award Number: W81XWH-11-1-0515 TITLE: Novel Probiotic Therapies for Autism PRINCIPAL...2011 -21 August 2012 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Novel Probiotic Therapies for Autism 5b. GRANT NUMBER W81XWH-11-0515 5c...suggest a gut-microbiome-brain connection in autism, and identify a potential probiotic therapy for ASD. 15. SUBJECT TERMS autism, ASD, probiotic

Fundamental Visual Representations of Social Cognition in ASD

DTIC Science & Technology

2016-12-01

visual adaptation functions in Autism , again pointing to basic sensory processing anomalies in this population. Our research team is developing...challenging-to-test ASD pediatric population. 15. SUBJECT TERMS Autism , Visual Adaptation, Retinotopy, Social Communication, Eye-movements, fMRI, EEG, ERP...social interaction are a hallmark symptom of Autism , and the lack of appropriate eye- contact during interpersonal interactions is an oft-noted feature

Instructional Practice for Students with Autism Spectrum and Related Disorders: Exploring the Teaching of Writing in Two Self-Contained Classrooms

ERIC Educational Resources Information Center

Asaro-Saddler, Kristie; Arcidiacono, Mary Beth; Morris Deyoe, Meghan

2017-01-01

Writing is an important skill that pervades all subjects and is required for postschool success. Many students with autism spectrum disorders (ASD) struggle with writing, yet it has been an underresearched area. To determine what writing practices are being implemented with students with ASD, we observed the practices of two teachers who instruct…

Heart Rate Profiles of Children with and without Autism Spectrum Disorder in Response to Physical Play: A Preliminary Investigation

ERIC Educational Resources Information Center

Breslin, Casey M.; Rudisill, Mary E.; Wadsworth, Danielle W.

2015-01-01

In this study, the heart rate response of children with and without autism spectrum disorder (ASD) exposed to outdoor free play sessions during preschool was examined. Participants (n = 7; four children with ASD and three children who show typical development) wore Actiheart heart rate monitors during 6 school days. Using a single-subject design,…

Using Technology to Support Students with Autism Spectrum Disorders in the Writing Process: A Pilot Study

ERIC Educational Resources Information Center

Asaro-Saddler, Kristie; Knox, Haley Muir; Meredith, Holly; Akhmedjanova, Diana

2015-01-01

Writing is an important content area that pervades all subject areas and is required for post-school success, yet many students with autism spectrum disorders (ASD) often struggle in written expression. In this article we discuss the characteristics of students with ASD that make writing difficult, and the strengths, such as the use of technology,…

Comparing motor performance, praxis, coordination, and interpersonal synchrony between children with and without Autism Spectrum Disorder (ASD).

PubMed

Kaur, Maninderjit; M Srinivasan, Sudha; N Bhat, Anjana

2018-01-01

Children with Autism Spectrum Disorder (ASD) have basic motor impairments in balance, gait, and coordination as well as autism-specific impairments in praxis/motor planning and interpersonal synchrony. Majority of the current literature focuses on isolated motor behaviors or domains. Additionally, the relationship between cognition, symptom severity, and motor performance in ASD is unclear. We used a comprehensive set of measures to compare gross and fine motor, praxis/imitation, motor coordination, and interpersonal synchrony skills across three groups of children between 5 and 12 years of age: children with ASD with high IQ (HASD), children with ASD with low IQ (LASD), and typically developing (TD) children. We used the Bruininks-Oseretsky Test of Motor Proficiency and the Bilateral Motor Coordination subtest of the Sensory Integration and Praxis Tests to assess motor performance and praxis skills respectively. Children were also examined while performing simple and complex rhythmic upper and lower limb actions on their own (solo context) and with a social partner (social context). Both ASD groups had lower gross and fine motor scores, greater praxis errors in total and within various error types, lower movement rates, greater movement variability, and weaker interpersonal synchrony compared to the TD group. In addition, the LASD group had lower gross motor scores and greater mirroring errors compared to the HASD group. Overall, a variety of motor impairments are present across the entire spectrum of children with ASD, regardless of their IQ scores. Both, fine and gross motor performance significantly correlated with IQ but not with autism severity; however, praxis errors (mainly, total, overflow, and rhythmicity) strongly correlated with autism severity and not IQ. Our study findings highlight the need for clinicians and therapists to include motor evaluations and interventions in the standard-of-care of children with ASD and for the broader autism community to recognize dyspraxia as an integral part of the definition of ASD. Copyright © 2017 Elsevier Ltd. All rights reserved.

Prevalence of non-febrile seizures in children with idiopathic autism spectrum disorder and their unaffected siblings: a retrospective cohort study.

PubMed

McCue, Lena M; Flick, Louise H; Twyman, Kimberly A; Xian, Hong; Conturo, Thomas E

2016-11-28

Autism spectrum disorder (ASD) is a heterogeneous disorder characterized not only by deficits in communication and social interactions but also a high rate of co-occurring disorders, including metabolic abnormalities, gastrointestinal and sleep disorders, and seizures. Seizures, when present, interfere with cognitive development and are associated with a higher mortality rate in the ASD population. To determine the relative prevalence of non-febrile seizures in children with idiopathic ASD from multiplex and simplex families compared with the unaffected siblings in a cohort of 610 children with idiopathic ASD and their 160 unaffected siblings, participating in the Autism Genetic Resource Exchange project, the secondary analysis was performed comparing the life-time prevalence of non-febrile seizures. Statistical models to account for non-independence of observations, inherent with the data from multiplex families, were used in assessing potential confounding effects of age, gender, and history of febrile seizures on odds of having non-febrile seizures. The life-time prevalence of non-febrile seizures was 8.2% among children with ASD and 2.5% among their unaffected siblings. In a logistic regression analysis that adjusted for familial clustering, children with ASD had 5.27 (95%CI: 1.51-18.35) times higher odds of having non-febrile seizures compared to their unaffected siblings. In this comparison, age, presence of gastrointestinal dysfunction, and history of febrile seizures were significantly associated with the prevalence of non-febrile seizures. Children with idiopathic ASD are significantly more likely to have non-febrile seizures than their unaffected siblings, suggesting that non-febrile seizures may be ASD-specific. Further studies are needed to determine modifiable risk factors for non-febrile seizures in ASD.

Therapeutic Horseback Riding Outcomes of Parent-Identified Goals for Children with Autism Spectrum Disorder: An ABA′ Multiple Case Design Examining Dosing and Generalization to the Home and Community

PubMed Central

Baird, Joanne M.; Kim, Young Joo; Rajora, Kuwar B.; D’Silva, Delma; Podolinsky, Lin; Mazefsky, Carla; Minshew, Nancy

2014-01-01

We examined whether different doses of therapeutic riding influenced parent-nominated target behaviors of children with autism spectrum disorder (ASD) (a) during the session (b) at home, and (c) in the community. We used a single subject multiple Baseline, multiple case design, with dosing of 1, 3, and 5 times/week. Three boys with ASD, 6–8 years of age participated, and counts of target behaviors were collected in each setting and phase of the study. Compared to Baseline, 70 % of the target behaviors were better during Intervention and improvement was retained in 63 % of the behaviors during Withdrawal. Increased doses of therapeutic riding were significant for magnitude of change, and the effect of the therapeutic riding sessions generalized to home and community. PMID:24091469

Exploring the Role of Theory of Mind in Moral Judgment: The Case of Children with Autism Spectrum Disorder.

PubMed

Fadda, Roberta; Parisi, Marinella; Ferretti, Luca; Saba, Gessica; Foscoliano, Maria; Salvago, Azzurra; Doneddu, Giuseppe

2016-01-01

This paper adds to the growing research on moral judgment (MJ) by considering whether theory of mind (ToM) might foster children's autonomous MJ achievement. A group of 30 children with autism spectrum disorder (ASD) was compared in MJ and ToM with 30 typically developing (TD) children. Participants were tested for MJ with a classical Piaget's task and for ToM with a second order False Belief task. In the moral task, children were told two versions of a story: in one version the protagonist acted according to a moral intention but the action resulted in a harmful consequence; in the other version the protagonist acted according to an immoral intention, but the action resulted in a harmless consequence. Children were asked which of the two protagonists was the "naughtier." In line with previous studies, the results indicated that, while the majority of TD participants succeeded in the second order False Belief task, only few individuals with ASD showed intact perspective taking abilities. The analysis of the MJ in relation to ToM showed that children with ASD lacking ToM abilities judged guilty the protagonists of the two versions of the story in the moral task because both of them violated a moral rule or because they considered the consequences of the actions, ignoring any psychological information. These results indicate a heteronomous morality in individuals with ASD, based on the respect of learned moral rules and outcomes rather than others' subjective states.

Age- and sex-related emotional and behavioral problems in children with autism spectrum disorders: comparison with control children.

PubMed

Horiuchi, Fumie; Oka, Yasunori; Uno, Hiroyuki; Kawabe, Kentaro; Okada, Fumi; Saito, Isao; Tanigawa, Takeshi; Ueno, Shu-ichi

2014-07-01

Children with autism spectrum disorders (ASD) often present with emotional and behavioral problems, which could change the clinical course, especially during childhood, and affect future quality of life. The aim of this study was to clarify the age- and sex-related differences of these problems in ASD. The study subjects were 173 patients with ASD (age: 4-16 years) and 173 age- and sex-matched community children (control group). The parent version of the Strengths and Difficulties Questionnaire was used for comparison of the emotional and behavioral problems between the two groups. The Strengths and Difficulties Questionnaire scores were significantly higher in children with ASD than controls at all ages. The score of total difficulties was significantly higher in girls with ASD than in boys, while the score in male controls was significantly higher than in female controls. Age-related differences in emotional and behavioral problems were observed both in children with ASD and controls, but the characteristics were different: in children with ASD, emotional symptoms and peer problems in both sexes and conduct problems in girls increased significantly with age, while none of the problems in the controls changed with age except for a decrease in the score of hyperactivity/inattention developmentally in both sexes. Prosocial behaviors of children with ASD and controls showed small changes with age. Emotional and behavioral problems are common in children with ASD and showed age- and sex-related differences. Our study emphasizes the importance of recognizing those differences among children with ASD for early intervention. © 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.

Age-related differences in cognition across the adult lifespan in autism spectrum disorder.

PubMed

Lever, Anne G; Geurts, Hilde M

2016-06-01

It is largely unknown how age impacts cognition in autism spectrum disorder (ASD). We investigated whether age-related cognitive differences are similar, reduced or increased across the adult lifespan, examined cognitive strengths and weaknesses, and explored whether objective test performance is related to subjective cognitive challenges. Neuropsychological tests assessing visual and verbal memory, generativity, and theory of mind (ToM), and a self-report measure assessing cognitive failures were administered to 236 matched participants with and without ASD, aged 20-79 years (IQ > 80). Group comparisons revealed that individuals with ASD had higher scores on visual memory, lower scores on generativity and ToM, and similar performance on verbal memory. However, ToM impairments were no longer present in older (50+ years) adults with ASD. Across adulthood, individuals with ASD demonstrated similar age-related effects on verbal memory, generativity, and ToM, while age-related differences were reduced on visual memory. Although adults with ASD reported many cognitive failures, those were not associated with neuropsychological test performance. Hence, while some cognitive abilities (visual and verbal memory) and difficulties (generativity and semantic memory) persist across adulthood in ASD, others become less apparent in old age (ToM). Age-related differences characteristic of typical aging are reduced or parallel, but not increased in individuals with ASD, suggesting that ASD may partially protect against an age-related decrease in cognitive functioning. Despite these findings, adults with ASD experience many cognitive daily challenges, which highlights the need for adequate social support and the importance of further research into this topic, including longitudinal studies. Autism Res 2016, 9: 666-676. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

Different verbal learning strategies in autism spectrum disorder: evidence from the Rey Auditory Verbal Learning Test.

PubMed

Bowler, Dermot M; Limoges, Elyse; Mottron, Laurent

2009-06-01

The Rey Auditory Verbal Learning Test, which requires the free recall of the same list of 15 unrelated words over 5 trials, was administered to 21 high-functioning adolescents and adults with autism spectrum disorder (ASD) and 21 matched typical individuals. The groups showed similar overall levels of free recall, rates of learning over trials and subjective organisation of their recall. However, the primacy portion of the serial position curve of the ASD participants showed slower growth over trials than that of the typical participants. The implications of this finding for our understanding of memory in ASD are discussed.

Weighted blankets and sleep in autistic children--a randomized controlled trial.

PubMed

Gringras, Paul; Green, Dido; Wright, Barry; Rush, Carla; Sparrowhawk, Masako; Pratt, Karen; Allgar, Victoria; Hooke, Naomi; Moore, Danielle; Zaiwalla, Zenobia; Wiggs, Luci

2014-08-01

To assess the effectiveness of a weighted-blanket intervention in treating severe sleep problems in children with autism spectrum disorder (ASD). This phase III trial was a randomized, placebo-controlled crossover design. Participants were aged between 5 years and 16 years 10 months, with a confirmed ASD diagnosis and severe sleep problems, refractory to community-based interventions. The interventions were either a commercially available weighted blanket or otherwise identical usual weight blanket (control), introduced at bedtime; each was used for a 2-week period before crossover to the other blanket. Primary outcome was total sleep time (TST) recorded by actigraphy over each 2-week period. Secondary outcomes included actigraphically recorded sleep-onset latency, sleep efficiency, assessments of child behavior, family functioning, and adverse events. Sleep was also measured by using parent-report diaries. Seventy-three children were randomized and analysis conducted on 67 children who completed the study. Using objective measures, the weighted blanket, compared with the control blanket, did not increase TST as measured by actigraphy and adjusted for baseline TST. There were no group differences in any other objective or subjective measure of sleep, including behavioral outcomes. On subjective preference measures, parents and children favored the weighted blanket. The use of a weighted blanket did not help children with ASD sleep for a longer period of time, fall asleep significantly faster, or wake less often. However, the weighted blanket was favored by children and parents, and blankets were well tolerated over this period. Copyright © 2014 by the American Academy of Pediatrics.

Enjoyment, Barriers, and Beliefs About Physical Activity in Adolescents With and Without Autism Spectrum Disorder.

PubMed

Stanish, Heidi; Curtin, Carol; Must, Aviva; Phillips, Sarah; Maslin, Melissa; Bandini, Linda

2015-10-01

The authors compared physical activity enjoyment, perceived barriers, beliefs, and self-efficacy between adolescents with autism spectrum disorder (ASD) and typically developing (TD) adolescents. A questionnaire was verbally administered to 35 adolescents with ASD and 60 TD adolescents. Compared with TD adolescents, fewer adolescents with ASD enjoyed team sports (65% vs. 95%, p < .001) and physical education (84% vs. 98%, p = .02). A greater proportion of adolescents with ASD perceived that physical activities were too hard to learn (16% vs. 0%, p < .01), and fewer believed that physical activity was a way to make friends (68% vs. 97%, p < .001). Fewer adolescents with ASD preferred to do physical activity in their free time (25% vs. 58%, p < .01). Most adolescents with ASD felt that physical activity is fun (84%), but the proportion was lower than in TD adolescents (98%, p = .03). Some perceptions about physical activity were similar between the 2 groups, but differences identified may inform program development.

Neurodiversity, Giftedness, and Aesthetic Perceptual Judgment of Music in Children with Autism

PubMed Central

Masataka, Nobuo

2017-01-01

The author investigated the capability of aesthetic perceptual judgment of music in male children diagnosed with autism spectrum disorder (ASD) when compared to age-matched typically developing (TD) male children. Nineteen boys between 4 and 7 years of age with ASD were compared to 28 TD boys while listening to musical stimuli of different aesthetic levels. The results from two musical experiments using the above participants, are described here. In the first study, responses to a Mozart minuet and a dissonant altered version of the same Mozart minuet were compared. In this first study, the results indicated that both ASD and TD males preferred listening to the original consonant version of the minuet over the altered dissonant version. With the same participants, the second experiment included musical stimuli from four renowned composers: Mozart and Bach’s musical works, both considered consonant in their harmonic structure, were compared with music from Schoenberg and Albinoni, two composers who wrote musical works considered exceedingly harmonically dissonant. In the second study, when the stimuli included consonant or dissonant musical stimuli from different composers, the children with ASD showed greater preference for the aesthetic quality of the highly dissonant music compared to the TD children. While children in both of the groups listened to the consonant stimuli of Mozart and Bach music for the same amount of time, the children with ASD listened to the dissonant music of Schoenberg and Albinoni longer than the TD children. As preferring dissonant music is more aesthetically demanding perceptually, these results suggest that ASD male children demonstrate an enhanced capability of aesthetic judgment of music. Subsidiary data collected after the completion of the experiment revealed that absolute pitch ability was prevalent only in the children with ASD, some of whom also possessed extraordinary musical memory. The implications of these results are discussed with reference to the broader notion of neurodiversity, a term coined to capture potentially gifted qualities in individuals diagnosed with ASD. PMID:29018372

Oral assessment of children with an autism spectrum disorder.

PubMed

DeMattei, R; Cuvo, A; Maurizio, S

2007-01-01

The study assessed the oral health status of children with an autism spectrum disorder (ASD) to help establish the oral health needs of this population. Oral assessments were conducted on 39 children with an ASD and 16 children with other developmental disabilities (DD), solicited from 3 different schools. Conditions assessed were bacterial plaque, gingivitis, dental caries, restorations, bruxism, delayed eruption/missing teeth, oral infection, developmental anomalies, injuries, occlusion, salivary flow, and oral defensiveness. Chi-square and Fisher's exact test of significance were used to compare groups. Young children with an ASD who resided with parents showed significantly more signs of bruxism than the comparison groups. Likewise, older children who lived at the residential school manifested significantly more gingivitis. No other significant differences existed when age and residence were considered for children with an ASD. When comparing children with ASD to those with another DD, the latter group showed significantly more oral injuries, abnormal salivary flow, and developmental anomalies. Children with an ASD displayed the following percentages for clinically visible conditions: plaque (85%), gingivitis (62%), and caries (21%). Approximately half of the children with ASD were orally defensive. Children with an ASD appear to have oral conditions that might increase the risk of developing dental disease. The extent of risk is unclear and needs further investigation.

Self-perception of children with autism spectrum disorders.

PubMed

Nagai, Yukiyo; Uemura, Osamu; Kaneko, Tetsuji; Kanda, Yasushi; Gotoh, Yoshimitsu; Nakagawa, Mayuko; Uzuyama, Shiho; Nomura, Kayo; Iwasa, Mitsuji

2018-02-01

We aimed to evaluate self-perceived competence and self-esteem of primary school children with autism spectrum disorder (ASD) in Japan and compare to those of children with other chronic physical diseases and healthy controls. Data were collected from 227 children: ASD (N.=91), nephrotic syndrome (NS) (N.=52) and asthma (N.=84), using Children's Perceived Competence Scale (CPCS) in 2012-2014. CPCS measures perceived competence in cognitive, social and physical domains, and a general self-worth domain as self-esteem. Scores in the social domain of the ASD group were lower than those of all other groups after adjusting for school age grades and gender. Scores of the ASD group negatively correlated with psychosomatic symptoms in all domains and IQ in the physical domain. These findings are the first data set in Japan on self-perceived competence and self-esteem in primary school children with ASD. Those results were comparable to previous researches in adolescents with ASD. Low social domain scores in the ASD group indicate the CPCS may be one of the useful tools to evaluate difficulty in social competence from the children's point of view. Correlations between CPCS scores and psychosomatic symptoms in the ASD group suggest development of psychosomatic symptoms may be addressed early by attention to low scores, especially in general self-worth.

First impressions of adults with autism improve with diagnostic disclosure and increased autism knowledge of peers.

PubMed

Sasson, Noah J; Morrison, Kerrianne E

2017-10-01

A practical consideration for many intellectually able adults with autism spectrum disorder (ASD) is whether to disclose their diagnostic status or try to mask their autistic characteristics to avoid judgment and discrimination. Here, we assessed first impressions of adults with ASD and typically developing controls ( N = 40) made by typically developing observers ( N = 215) when their diagnostic status was either withheld, accurately provided, or inaccurately provided. First impressions were less favorable for ASD participants compared to typically developing controls across a range of judgments, but were significantly more positive when accurately labeled as ASD compared to when no label was provided, when mislabeled as typically developing, or when mislabeled as having schizophrenia. For typically developing participants, ratings did not change when accurately labeled but improved when mislabeled as ASD. Greater autistic traits for the ASD and typically developing participants were associated with less favorable first impressions, and females were rated more favorably than males. Autism knowledge of the raters, but not age, IQ, or autistic traits, was positively associated with more favorable impressions of ASD participants. Collectively, these findings suggest that first impressions for intellectually able adults with ASD improve with diagnostic disclosure and increased autism understanding on the part of peers.

Cortical Changes Across the Autism Lifespan.

PubMed

Osipowicz, Karol; Bosenbark, Danielle D; Patrick, Kristina E

2015-08-01

Although it is widely accepted that autism spectrum disorder (ASD) involves neuroanatomical abnormalities and atypical neurodevelopmental patterns, there is little consensus regarding the precise pattern of neuroanatomical differences or how these differences relate to autism symptomology. Furthermore, there is limited research related to neuroanatomical correlates of autism symptomology in individuals with ASD and the studies that do exist primarily include small samples. This study was the first to investigate gray matter (GM) changes throughout the ASD lifespan, using voxel-based morphometry to determine whether significant differences exist in the GM volumes of a large sample of individuals with ASD compared to age- and IQ-matched typical controls. We examined GM volume across the lifespan in 531 individuals diagnosed with ASD and 571 neurotypical controls, aged 7-64. We compared groups and correlated GM with age and autism severity in the ASD group. Findings suggest bilateral decreased GM volume for individuals with ASD in regions extending from the thalamus to the cerebellum, anterior medial temporal lobes, and orbitofrontal regions. Higher autism severity was associated with decreased GM volumes in prefrontal cortex, inferior parietal and temporal regions, and temporal poles. Similar relationships were found between GM volume and age. ASD diagnosis and severity were not associated with increased GM volumes in any region. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

Fenestrated Transcatheter ASD Closure in Adults with Diastolic Dysfunction and/or Pulmonary Hypertension: Case Series and Review of the Literature.

PubMed

Abdelkarim, Ayman; Levi, Daniel S; Tran, Bao; Ghobrial, Joanna; Aboulhosn, Jamil

2016-12-01

This study aims to evaluate the safety and efficacy of transcatheter fenestrated ASD closure and to summarize the literature regarding the published techniques and outcomes of transcatheter partial ASD closure. Patients with left ventricular diastolic dysfunction (LVDD) or right ventricular (RV) dysfunction and/or pulmonary hypertension (PHT) may suffer untoward consequences of complete closure of an ostium secundum atrial septal defect (ASD). Therefore, for patients that fall under these categories we suggest partial occlusion of the defect, which may be better tolerated than complete defect closure. After obtaining IRB approval, a search for patients that have undergone percutaneous ASD closure was performed in the Ahmanson/UCLA Adult Congenital Heart Disease Center database to identify which patients received a fenestrated ASD closure device. Eight consecutive patients ranging between 22 and 83 years of age (mean 48 years) with PHT and/or LVDD or RV dysfunction who underwent fenestrated transcatheter ASD closure at UCLA were identified. None of the subjects experienced complications related to the procedure. Postprocedure clinical evaluation showed improvement in symptoms and exercise capacity. Available follow-up transthoracic echocardiography data (mean 4 months, range 0-20 months) demonstrated patent fenestrations in four of eight patients. None of the patients had thromboembolic or infectious complications and there were no device migrations, erosions or embolizations. Partial ASD occlusion in patients with diastolic dysfunction or RV dysfunction and/or PHT is safe and may be better tolerated than complete ASD closure in selected patients. © 2016 Wiley Periodicals, Inc.

Goose-neck snare-assisted transcatheter ASD closure: A safety procedure for large and complex ASDs.

PubMed

Butera, Gianfranco; Lovin, Nicusor; Basile, Domenica Paola; Carminati, Mario

2016-04-01

To report on a new technique that increases the safety of percutaneous atrial septal defect (ASD) closure using a goose-neck snare system. ASD transcatheter closure is a widespread procedure. However, in some cases, ASDs may be large and with soft rims. In these situation, a potential risk exists for device malposition or embolization. When transesophageal echocardiography (TEE) evaluation and balloon sizing showed large defects with floppy rims the chosen Amplatzer device was implanted in a standard way. In large defects with floppy rims, before release a 5-mm goose-neck snare with its 4 Fr catheter was placed across the delivery cable and fixed to catch the screwing mechanism of implanted Amplatzer device. The delivery cable was unscrewed and the device reached its final position without any tension. If the position was considered satisfactory the device was released from the goose-neck snare. Thirteen patients had a snare-assisted ASD transcatheter closure. Median device size was 24 mm (range 14-38 mm). Retrieval or repositioning of the device using the goose-neck snare was performed in four cases: in three patients, because of device malposition after delivery cable release and in one patient, because of unsuitability of closure of a second significant defect. Furthermore, in two subjects with multiple ASDs, a second fenestration looked quite significant with the device still attached to the delivery cable while it appeared smaller after release. Snare-assisted Amplatzer ASD device placement is a new method for ASD percutaneous closure and adds safety to the procedure. © 2016 Wiley Periodicals, Inc.

Biochemical screening and PTEN mutation analysis in individuals with autism spectrum disorders and macrocephaly

PubMed Central

Hobert, Judith A; Embacher, Rebecca; Mester, Jessica L; Frazier, Thomas W; Eng, Charis

2014-01-01

Unlike some other childhood neurodevelopmental disorders, no diagnostic biochemical marker has been identified in all individuals with an autism spectrum disorder (ASD). This deficit likely results from genetic heterogeneity among the population. Therefore, we evaluated a subset of individuals with ASDs, specifically, individuals with or without macrocephaly in the presence or absence of PTEN mutations. We sought to determine if amino or organic acid markers could be used to identify individuals with ASDs with or without macrocephaly in the presence or absence of PTEN mutations, and to establish the degree of macrocephaly in individuals with ASDs and PTEN mutation. Urine, blood and occipital–frontal circumference (OFC) measurements were collected from 69 individuals meeting DSM-IV-TR criteria. Urine and plasma samples were subjected to amino and organic acid analyses. PTEN was Sanger-sequenced from germline genomic DNA. Germline PTEN mutations were identified in 27% (6/22) of the macrocephalic ASD population. All six PTEN mutation-positive individuals were macrocephalic with average OFC+4.35 standard deviations (SDs) above the mean. No common biochemical abnormalities were identified in macrocephalic ASD individuals with or without PTEN mutations. In contrast, among the collective ASD population, elevation of urine aspartic acid (87% 54/62), plasma taurine (69% 46/67) and reduction of plasma cystine (72% 46/64) were observed. PTEN sequencing should be carried out for all individuals with ASDs and macrocephaly with OFC ≥2SDs above the mean. A proportion of individuals with ASDs may have an underlying disorder in sulfur amino acid metabolism. PMID:23695273

A common variant in DRD3 receptor is associated with autism spectrum disorder.

PubMed

de Krom, Mariken; Staal, Wouter G; Ophoff, Roel A; Hendriks, Judith; Buitelaar, Jan; Franke, Barbara; de Jonge, Maretha V; Bolton, Patrick; Collier, David; Curran, Sarah; van Engeland, Herman; van Ree, Jan M

2009-04-01

The presence of specific and common genetic etiologies for autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD) was investigated for 132 candidate genes in a two-stage design-association study. 1,536 single nucleotide polymorphisms (SNPs) covering these candidate genes were tested in ASD (n = 144) and ADHD (n = 110) patients and control subjects (n = 404) from The Netherlands. A second stage was performed with those SNPs from Stage I reaching a significance threshold for association of p < .01 in an independent sample of ASD patients (n = 128) and controls (n = 124) from the United Kingdom and a Dutch ADHD (n = 150) and control (n = 149) sample. No shared association was found between ASD and ADHD. However, in the first and second ASD samples and in a joint statistical analysis, a significant association between SNP rs167771 located in the DRD3 gene was found (joint analysis uncorrected: p = 3.11 x 10(-6); corrected for multiple testing and potential stratification: p = .00162). The DRD3 gene is related to stereotyped behavior, liability to side effects of antipsychotic medication, and movement disorders and may therefore have important clinical implications for ASD.

Interdisciplinary Team Evaluation: An Effective Method for the Diagnostic Assessment of Autism Spectrum Disorder.

PubMed

Gerdts, Jennifer; Mancini, James; Fox, Emily; Rhoads, Candace; Ward, Tracey; Easley, Erin; Bernier, Raphael A

2018-05-01

The objective of this research is to assess the feasibility of an interdisciplinary team diagnostic assessment model for autism spectrum disorder (ASD). Medical records from 366 patients evaluated for ASD at the Seattle Children's Autism Center (SCAC) were reviewed. ASD diagnostic outcomes, provider satisfaction, engagement in follow-up care, billed time, and reimbursement amounts were compared in patients evaluated through an interdisciplinary team approach (n = 91) with those seen in multidisciplinary evaluations led by either a psychologist (n = 165) or a physician (n = 110). Diagnostic determination was made in 90% of patients evaluated through the interdisciplinary team model in a single day. Rates of ASD diagnosis were similar across the 3 tracks, ranging from 61% to 72%. Demographic characteristics did not impact the likelihood of ASD diagnosis. Rates of patient follow-up care and provider satisfaction were significantly higher in interdisciplinary versus multidisciplinary teams. Interdisciplinary team evaluations billed 1.8 fewer hours yet generated more net hourly clinic income compared with psychology-led multidisciplinary evaluations. An interdisciplinary team approach, focusing on ruling-in or ruling-out ASD, was sufficient to determine ASD diagnosis in most patients seen at the SCAC Interdisciplinary teams generated more clinic income and decreased the time spent in evaluation compared with a psychology-led approach. They did so while maintaining consistency in diagnostic rates, demonstrating increased provider satisfaction and an increased likelihood of engagement in follow-up care.

Effects of daily maladaptive coping on nightly sleep in mothers.

PubMed

Felder, Jennifer N; Epel, Elissa S; Coccia, Michael; Puterman, Eli; Prather, Aric A

2018-01-01

We examined effects of daily rumination and suppression in response to stressors on objective and subjective sleep among mothers. Participants were 183 mothers, including chronically stressed mothers of children with an autism spectrum disorder (M-ASD; n = 92) and age-matched mothers of neurotypical children (M-NT; n = 91). In an intensive longitudinal design, participants provided reports of daily rumination and suppression, nightly objective actigraphy-defined sleep and nightly subjective sleep quality for seven consecutive days at baseline, 9 months and 18 months. Total sleep time, sleep fragmentation, sleep onset latency, and subjective sleep quality. Among M-NT with above average depressive symptoms, higher daily rumination was associated with shorter total sleep time. Rumination was associated with more sleep fragmentation among M-NT at the trend level. Rumination was not associated with sleep onset latency among M-NT, or with any sleep outcomes among M-ASD. Suppression was not associated with any sleep outcomes. We provide novel evidence of the effect of rumination on objectively measured sleep duration among M-NT. Coping was not related to sleep among M-ASD. Given the prevalence of poor sleep among mothers, future work should examine modifiable factors perpetuating sleep disturbance.

CBT for anxiety disorders in children with and without autism spectrum disorders.

PubMed

van Steensel, F J A; Bögels, S M

2015-06-01

The effectiveness of cognitive-behavioral therapy (CBT) for anxiety disorders in children with autism spectrum disorders (ASD) was examined, and compared with children without ASD. Children with ASD and comorbid anxiety disorders (n = 79, 58 boys; Mage = 11.76) and children with anxiety disorders (n = 95, 46 boys; Mage = 12.85), and their parents, participated. All families were referred to 1 of 7 mental health care centers and received the same CBT. Anxiety, quality of life, ASD-like behaviors, and emotional-behavioral problems were measured at waitlist (ASD-group only, n = 17), pretest, posttest, and 3 months, 1 year, and 2 years after CBT. CBT was more effective than waitlist for treating anxiety disorders (d = -1.45) and anxiety symptoms (d = -0.48) in children with ASD. At 2 years follow-up, 61% of the children with and 64% without ASD were free of their primary anxiety disorder (percentages not significantly different). The decrease in severity of anxiety disorders after CBT (d values ranging between -1.05 and -1.46) was not different for children with and without ASD. Improvements were less in children with ASD for (only) 2 out of 7 continuous outcomes measures: anxiety symptoms (d values ranging between -0.68 and -0.94 vs. d values ranging between -0.98 and -1.25) and quality of life (d values ranging between 0.39 and 0.56 vs. d values ranging between 0.77 and 0.98). CBT for anxiety disorders is effective for children with ASD, also in the long-term. Treatment gains may be somewhat less compared with children without ASD. (c) 2015 APA, all rights reserved).

Family Impacts among Children with Autism Spectrum Disorder: The Role of Health Care Quality

PubMed Central

Zuckerman, Katharine E.; Lindly, Olivia J.; Bethell, Christina D.; Kuhlthau, Karen

2014-01-01

Objectives To compare health care quality and family employment and financial impacts among children with special health care needs (CSHCN) with autism spectrum disorder (CSHCN+ASD), CSHCN with functional limitations (CSHCN+FL), and CSHCN lacking these conditions (other CSHCN). To test whether high health care quality was associated with reduced family impacts among CSHCN+ASD. Methods Data from the 2009-2010 National Survey of CSHCN were used to compare 3025 CSHCN+ASD, 6505 CSHCN+FL, and 28 296 other CSHCN. Weighted multivariate logistic regression analyses examined six age-relevant, federally-defined health care quality indicators and five family financial and employment impact indicators. Two composite measures were additionally used: (1) receipt of care that met all age-relevant quality indicators; and (2) had ≥ two of the five adverse family impacts. Results Across all health care quality indicators CSHCN+ASD fared poorly, with only 7.4% meeting all age-relevant indicators. CSHCN+ASD had worse health care quality than other CSHCN, including CSHCN+FL. CSHCN+ASD also had high rates of adverse family impact, with over half experiencing two or more adverse impacts. Rates of adverse family impact were higher in CSHCN+ASD than other CSHCN, including CSHCN+FL. Among CSHCN+ASD, those whose health care that met federal quality standards were less likely to have multiple adverse family impacts than CSHCN+ASD whose health care did not meet federal quality standards. Conclusions CSHCN+ASD are more prone to experience poor health care quality and family impacts than other CSHCN, even CSHCN+FL. Receipt of care meeting federal quality standards may potentially lessen adverse family impacts for CSHCN+ASD. PMID:24976352

Risk of Autism Spectrum Disorders in Children Born to Mothers With Rheumatoid Arthritis: A Systematic Literature Review.

PubMed

Wojcik, Sophie; Bernatsky, Sasha; Platt, Robert W; Pineau, Christian A; Clarke, Ann E; Fombonne, Éric; Bérard, Anick; Vinet, Évelyne

2017-12-01

There is recent evidence to suggest that in utero exposure to maternal antibodies and cytokines is an important risk factor for autism spectrum disorders (ASDs). We aimed to systematically review the risk of ASDs in children born to mothers with rheumatoid arthritis (RA) compared to children born to mothers without RA. We conducted a systematic review of original articles using the electronic databases PubMed, Embase, and Web of Science. Our literature search yielded a total of 70 articles. Of the potentially relevant studies retrieved, 67 were excluded for lack of relevance and/or because they did not report original data. Three studies were included in the final analysis. A case-control study found no difference in the prevalence of RA in mothers of children with ASDs versus control mothers. Another case-control study showed a statistically significant 8-fold increase in autoimmune disorders, including RA, in mothers of offspring with ASDs compared to controls. Forty-six percent of offspring with ASDs had a first-degree relative with RA, compared to 26% of controls. And in a population-based cohort study, investigators observed an increased risk of ASDs in children with a maternal history of RA compared to children born to unaffected mothers. These studies had methodologic limitations: none controlled for medication exposures, only 1 controlled for obstetric complications and considered the timing of RA diagnosis in relation to pregnancy, and all but 1 used a case-control study design. Observational studies suggest a potentially increased risk of ASDs in children born to mothers with RA compared to children born to mothers without RA, although data are limited. © 2017, American College of Rheumatology.

Evaluating Sex and Age Differences in ADI-R and ADOS Scores in a Large European Multi-site Sample of Individuals with Autism Spectrum Disorder.

PubMed

Tillmann, J; Ashwood, K; Absoud, M; Bölte, S; Bonnet-Brilhault, F; Buitelaar, J K; Calderoni, S; Calvo, R; Canal-Bedia, R; Canitano, R; De Bildt, A; Gomot, M; Hoekstra, P J; Kaale, A; McConachie, H; Murphy, D G; Narzisi, A; Oosterling, I; Pejovic-Milovancevic, M; Persico, A M; Puig, O; Roeyers, H; Rommelse, N; Sacco, R; Scandurra, V; Stanfield, A C; Zander, E; Charman, T

2018-02-21

Research on sex-related differences in Autism Spectrum Disorder (ASD) has been impeded by small samples. We pooled 28 datasets from 18 sites across nine European countries to examine sex differences in the ASD phenotype on the ADI-R (376 females, 1763 males) and ADOS (233 females, 1187 males). On the ADI-R, early childhood restricted and repetitive behaviours were lower in females than males, alongside comparable levels of social interaction and communication difficulties in females and males. Current ADI-R and ADOS scores showed no sex differences for ASD severity. There were lower socio-communicative symptoms in older compared to younger individuals. This large European ASD sample adds to the literature on sex and age variations of ASD symptomatology.

Comparative analysis of three screening instruments for autism spectrum disorder in toddlers at high risk.

PubMed

Oosterling, Iris J; Swinkels, Sophie H; van der Gaag, Rutger Jan; Visser, Janne C; Dietz, Claudine; Buitelaar, Jan K

2009-06-01

Several instruments have been developed to screen for autism spectrum disorders (ASD) in high-risk populations. However, few studies compare different instruments in one sample. Data were gathered from the Early Screening of Autistic Traits Questionnaire, Social Communication Questionnaire, Communication and Symbolic Behavior Scales-Developmental Profile, Infant-Toddler Checklist and key items of the Checklist for Autism in Toddlers in 238 children (mean age = 29.6 months, SD = 6.4) at risk for ASD. Discriminative properties are compared in the whole sample and in two age groups separately (8-24 months and 25-44 months). No instrument or individual item shows satisfying power in discriminating ASD from non-ASD, but pros and cons of instruments and items are discussed and directions for future research are proposed.

Data analysis of response interruption and redirection as a treatment for vocal stereotypy.

PubMed

Wunderlich, Kara L; Vollmer, Timothy R

2015-12-01

Vocal stereotypy, or repetitive, noncontextual vocalizations, is a problematic form of behavior exhibited by many individuals with autism spectrum disorder (ASD). Recent research has evaluated the efficacy of response interruption and redirection (RIRD) in the reduction of vocal stereotypy. Research has indicated that RIRD often results in reductions in the level of vocal stereotypy; however, many previous studies have only presented data on vocal stereotypy that occurred outside RIRD implementation. The current study replicated the procedures of previous studies that have evaluated the efficacy of RIRD and compared 2 data-presentation methods: inclusion of only data collected outside RIRD implementation and inclusion of all vocal stereotypy data from the entirety of each session. Subjects were 7 children who had been diagnosed with ASD. Results indicated that RIRD appeared to be effective when we evaluated the level of vocal stereotypy outside RIRD implementation, but either no reductions or more modest reductions in the level of vocal stereotypy during the entirety of sessions were obtained for all subjects. Results suggest that data-analysis methods used in previous research may overestimate the efficacy of RIRD. © Society for the Experimental Analysis of Behavior.

Employment Interventions for Individuals with ASD: The Relative Efficacy of Supported Employment With or Without Prior Project SEARCH Training.

PubMed

Schall, Carol M; Wehman, Paul; Brooke, Valerie; Graham, Carolyn; McDonough, Jennifer; Brooke, Alissa; Ham, Whitney; Rounds, Rachael; Lau, Stephanie; Allen, Jaclyn

2015-12-01

This paper presents findings from a retrospective observational records review study that compares the outcomes associated with implementation of supported employment (SE) with and without prior Project SEARCH with ASD Supports (PS-ASD) on wages earned, time spent in intervention, and job retention. Results suggest that SE resulted in competitive employment for 45 adults with ASD. Twenty-five individuals received prior intervention through PS-ASD while the other 20 individuals received SE only. Individuals in this sample who received PS-ASD required fewer hours of intervention. Additionally, individuals in the PS-ASD group achieved a mean higher wage and had higher retention rates than their peers who received SE only. Further research with a larger sample is needed to confirm these findings.

Assessing the Dim Light Melatonin Onset in Adults with Autism Spectrum Disorder and No Comorbid Intellectual Disability.

PubMed

Baker, Emma K; Richdale, Amanda L; Hazi, Agnes; Prendergast, Luke A

2017-07-01

This study assessed melatonin levels and the dim light melatonin onset (DLMO) in adults with Autism Spectrum Disorder (ASD) and also investigated the relationships between melatonin and objectively measured sleep parameters. Sixteen adults with ASD (ASD-Only), 12 adults with ASD medicated for comorbid diagnoses of anxiety and/or depression (ASD-Med) and 32 controls participated in the study. Although, the timing of the DLMO did not differ between the two groups, advances and delays of the melatonin rhythm were observed in individual profiles. Overall mean melatonin levels were lower in the ASD-Med group compared to the two other groups. Lastly, greater increases in melatonin in the hour prior to sleep were associated with greater sleep efficiency in the ASD groups.

Elevated Glutamatergic Compounds in Pregenual Anterior Cingulate in Pediatric Autism Spectrum Disorder Demonstrated by 1H MRS and 1H MRSI

PubMed Central

Bejjani, Anthony; O'Neill, Joseph; Kim, John A.; Frew, Andrew J.; Yee, Victor W.; Ly, Ronald; Kitchen, Christina; Salamon, Noriko; McCracken, James T.; Toga, Arthur W.; Alger, Jeffry R.; Levitt, Jennifer G.

2012-01-01

Recent research in autism spectrum disorder (ASD) has aroused interest in anterior cingulate cortex and in the neurometabolite glutamate. We report two studies of pregenual anterior cingulate cortex (pACC) in pediatric ASD. First, we acquired in vivo single-voxel proton magnetic resonance spectroscopy (1H MRS) in 8 children with ASD and 10 typically developing controls who were well matched for age, but with fewer males and higher IQ. In the ASD group in midline pACC, we found mean 17.7% elevation of glutamate + glutamine (Glx) (p<0.05) and 21.2% (p<0.001) decrement in creatine + phosphocreatine (Cr). We then performed a larger (26 subjects with ASD, 16 controls) follow-up study in samples now matched for age, gender, and IQ using proton magnetic resonance spectroscopic imaging (1H MRSI). Higher spatial resolution enabled bilateral pACC acquisition. Significant effects were restricted to right pACC where Glx (9.5%, p<0.05), Cr (6.7%, p<0.05), and N-acetyl-aspartate + N-acetyl-aspartyl-glutamate (10.2%, p<0.01) in the ASD sample were elevated above control. These two independent studies suggest hyperglutamatergia and other neurometabolic abnormalities in pACC in ASD, with possible right-lateralization. The hyperglutamatergic state may reflect an imbalance of excitation over inhibition in the brain as proposed in recent neurodevelopmental models of ASD. PMID:22848344

Spectrum of care: Current management of childhood autism spectrum disorder (ASD) in New Zealand.

PubMed

Thabrew, Hiran; Eggleston, Matthew

2017-07-01

The purpose of this research was to compare the current status of assessment and intervention for New Zealand children and adolescents who have autism spectrum disorder (ASD) with recommendations outlined in the 2008 New Zealand ASD Guideline. ASD coordinators and New Zealand District Health Board (DHB) staff working with children and adolescents who have ASD were electronically surveyed. Responses were received from 32 staff in 17 (85%) surveyed DHBs. Positive findings included the presence of ASD coordinators in 85% of DHBs, clear pathways for management in 73.1% of DHBs and good communications between paediatric, psychiatric and educational teams in some DHBs regions. Areas for improvement included wait times to assessment, access to longer-term support and intervention for families, and training for staff in ASD and cultural issues. Since the launch of the NZ ASD Guidelines, significant progress has been made. However, further work is needed to ensure services for children and adolescents with ASD are accessible, well-coordinated and focussed on both assessment and intervention.

Protracted dendritic growth in the typically developing human amygdala and increased spine density in young ASD brains.

PubMed

Weir, R K; Bauman, M D; Jacobs, B; Schumann, C M

2018-02-01

The amygdala is a medial temporal lobe structure implicated in social and emotional regulation. In typical development (TD), the amygdala continues to increase volumetrically throughout childhood and into adulthood, while other brain structures are stable or decreasing in volume. In autism spectrum disorder (ASD), the amygdala undergoes rapid early growth, making it volumetrically larger in children with ASD compared to TD children. Here we explore: (a) if dendritic arborization in the amygdala follows the pattern of protracted growth in TD and early overgrowth in ASD and (b), if spine density in the amygdala in ASD cases differs from TD from youth to adulthood. The amygdala from 32 postmortem human brains (7-46 years of age) were stained using a Golgi-Kopsch impregnation. Ten principal neurons per case were selected in the lateral nucleus and traced using Neurolucida software in their entirety. We found that both ASD and TD individuals show a similar pattern of increasing dendritic length with age well into adulthood. However, spine density is (a) greater in young ASD cases compared to age-matched TD controls (<18 years old) and (b) decreases in the amygdala as people with ASD age into adulthood, a phenomenon not found in TD. Therefore, by adulthood, there is no observable difference in spine density in the amygdala between ASD and TD age-matched adults (≥18 years old). Our findings highlight the unique growth trajectory of the amygdala and suggest that spine density may contribute to aberrant development and function of the amygdala in children with ASD. © 2017 Wiley Periodicals, Inc.

Magnetoencephalographic Imaging of Auditory and Somatosensory Cortical Responses in Children with Autism and Sensory Processing Dysfunction

PubMed Central

Demopoulos, Carly; Yu, Nina; Tripp, Jennifer; Mota, Nayara; Brandes-Aitken, Anne N.; Desai, Shivani S.; Hill, Susanna S.; Antovich, Ashley D.; Harris, Julia; Honma, Susanne; Mizuiri, Danielle; Nagarajan, Srikantan S.; Marco, Elysa J.

2017-01-01

This study compared magnetoencephalographic (MEG) imaging-derived indices of auditory and somatosensory cortical processing in children aged 8–12 years with autism spectrum disorder (ASD; N = 18), those with sensory processing dysfunction (SPD; N = 13) who do not meet ASD criteria, and typically developing control (TDC; N = 19) participants. The magnitude of responses to both auditory and tactile stimulation was comparable across all three groups; however, the M200 latency response from the left auditory cortex was significantly delayed in the ASD group relative to both the TDC and SPD groups, whereas the somatosensory response of the ASD group was only delayed relative to TDC participants. The SPD group did not significantly differ from either group in terms of somatosensory latency, suggesting that participants with SPD may have an intermediate phenotype between ASD and TDC with regard to somatosensory processing. For the ASD group, correlation analyses indicated that the left M200 latency delay was significantly associated with performance on the WISC-IV Verbal Comprehension Index as well as the DSTP Acoustic-Linguistic index. Further, these cortical auditory response delays were not associated with somatosensory cortical response delays or cognitive processing speed in the ASD group, suggesting that auditory delays in ASD are domain specific rather than associated with generalized processing delays. The specificity of these auditory delays to the ASD group, in addition to their correlation with verbal abilities, suggests that auditory sensory dysfunction may be implicated in communication symptoms in ASD, motivating further research aimed at understanding the impact of sensory dysfunction on the developing brain. PMID:28603492

Idiom Comprehension Deficits in High-Functioning Autism Spectrum Disorder Using a Korean Autism Social Language Task

PubMed Central

Lee, Seul Bee; Song, Seung Ha; Ham, Ju Hyun; Song, Dong Ho

2015-01-01

Purpose High-functioning autism spectrum disorder (ASD) involves pragmatic impairment of language skills. Among numerous tasks for assessing pragmatic linguistic skills, idioms are important to evaluating high-functioning ASD. Nevertheless, no assessment tool has been developed with specific consideration of Korean culture. Therefore, we designed the Korean Autism Social Language Task (KASLAT) to test idiom comprehension in ASD. The aim of the current study was to introduce this novel psychological tool and evaluate idiom comprehension deficits in high-functioning ASD. Materials and Methods The participants included 42 children, ages 6-11 years, who visited our child psychiatric clinic between April 2014 and May 2015. The ASD group comprised 16 children; the attention deficit hyperactivity disorder (ADHD) group consisted of 16 children. An additional 10 normal control children who had not been diagnosed with either disorder participated in this study. Idiom comprehension ability was assessed in these three groups using the KASLAT. Results Both ASD and ADHD groups had significantly lower scores on the matched and mismatched tasks, compared to the normal control children (matched tasks mean score: ASD 11.56, ADHD 11.56, normal control 14.30; mismatched tasks mean score: ASD 6.50, ADHD 4.31, normal control 11.30). However, no significant differences were found in scores of KASLAT between the ADHD and ASD groups. Conclusion These findings suggest that children with ASD exhibit greater impairment in idiom comprehension, compared to normal control children. The KASLAT may be useful in evaluating idiom comprehension ability. PMID:26446644

Atypical spatiotemporal signatures of working memory brain processes in autism.

PubMed

Urbain, C M; Pang, E W; Taylor, M J

2015-08-11

Working memory (WM) impairments may contribute to the profound behavioural manifestations in children with autism spectrum disorder (ASD). However, previous behavioural results are discrepant as are the few functional magnetic resonance imaging (fMRI) results collected in adults and adolescents with ASD. Here we investigate the precise temporal dynamics of WM-related brain activity using magnetoencephalography (MEG) in 20 children with ASD and matched controls during an n-back WM task across different load levels (1-back vs 2-back). Although behavioural results were similar between ASD and typically developing (TD) children, the between-group comparison performed on functional brain activity showed atypical WM-related brain processes in children with ASD compared with TD children. These atypical responses were observed in the ASD group from 200 to 600 ms post stimulus in both the low- (1-back) and high- (2-back) memory load conditions. During the 1-back condition, children with ASD showed reduced WM-related activations in the right hippocampus and the cingulate gyrus compared with TD children who showed more activation in the left dorso-lateral prefrontal cortex and the insulae. In the 2-back condition, children with ASD showed less activity in the left insula and midcingulate gyrus and more activity in the left precuneus than TD children. In addition, reduced activity in the anterior cingulate cortex was correlated with symptom severity in children with ASD. Thus, this MEG study identified the precise timing and sources of atypical WM-related activity in frontal, temporal and parietal regions in children with ASD. The potential impacts of such atypicalities on social deficits of autism are discussed.

Study of the Characteristics of Pulmonary Trunk in Pulmonary Hypertension Secondary to Left Heart Disease Using Pressure-Velocity Loops (PU-Loops).

PubMed

Hanya, Shizuo; Yoshii, Kengo; Sugawara, Motoaki

2017-09-25

Objectives : Although pulmonary hypertension (PH) caused by left heart disease (PH-LHD) is more common in PH, little is known about its properties of pulmonary artery (PA) in PH-LHD. The purpose of this study was to measure pulmonary regional pulse wave velocity (PWV) and to quantify the magnitude of reflected waves in patients with PH-LHD by the analysis of the pressure-velocity loops (PU-loop). Methods : High-fidelity PA pressure (Pm) and PA velocity (Vm) were measured in 11 subjects with PH-LHD (mean Pm>25 mmHg), 1 subject with atrial septal defect (ASD) without PH and 12 control subjects, using multisensor catheters. PWV was calculated as the slope of the initial part of the PU-loop in early systole. The similarity in the shapes of the pressure and flow velocity waveforms over one PU-loop was quantified as the magnitude of reflected wave by calculating the standard error of the estimate (Sy/x) from linear regression analysis between Pm and corresponding Vm. PWV and Sy/x during a Valsalva maneuver (VM) were also assessed in nine control subjects. Results : The contour of PU-loop was so characteristic between control and PH-LHD. Max. PWV (349 cm/s) was recorded in PH-LHD and min. PWV (111 cm/s) was recorded in ASD. VM increased Pm (12 [7-15] mmHg vs. 50 [18-110] mmHg; p=0.009) and PWV (200 [148-238] cm/s vs. 260 [192-306] cm/s; p=0.009) significantly without significant increase of Sy/x (19.6 [12.7-28.9]% vs. 28.2 [19.3-40.7]%; p=0.079). Although Sy/x was significantly higher in PH-LHD than in control and ASD (31.0 [14.3-36.3]% vs. 17.5 [8.4-28.9]%; p=0.009, ASD: 18.2%) , no significant difference was found in PWV between PH-LHD and control (269 [159-349] cm/s vs. 203 [154-289] cm/s; p=0.089). Conclusions : 1) The magnitude of wave reflection was elevated in PH-LHD significantly as compared with control and ASD. 2) Despite the significant increase in PA-PWV caused by abrupt elevation in Pm during VM in control, chronic elevation in Pm did not increase PA-PWV in PH-LHD significantly. It was hypothesized that the PA constituted a self-regulating system for maintaining the arterial stiffness stable against the chronic elevation in Pm in PH-LHD by a remodeling of increasing proximal pulmonary arterial crosssectional area gradually, which was compatible with the Moens-Korteweg equation. The PU-loop could provide a new simple and conventional method for assessing the pulmonary arterial properties, clinically. (This is a translation of J Jpn Coll Angiol 2016; 56: 45-53.).

Study of the Characteristics of Pulmonary Trunk in Pulmonary Hypertension Secondary to Left Heart Disease Using Pressure–Velocity Loops (PU-Loops)

PubMed Central

Hanya, Shizuo; Yoshii, Kengo; Sugawara, Motoaki

2017-01-01

Objectives: Although pulmonary hypertension (PH) caused by left heart disease (PH-LHD) is more common in PH, little is known about its properties of pulmonary artery (PA) in PH-LHD. The purpose of this study was to measure pulmonary regional pulse wave velocity (PWV) and to quantify the magnitude of reflected waves in patients with PH-LHD by the analysis of the pressure–velocity loops (PU-loop). Methods: High-fidelity PA pressure (Pm) and PA velocity (Vm) were measured in 11 subjects with PH-LHD (mean Pm>25 mmHg), 1 subject with atrial septal defect (ASD) without PH and 12 control subjects, using multisensor catheters. PWV was calculated as the slope of the initial part of the PU-loop in early systole. The similarity in the shapes of the pressure and flow velocity waveforms over one PU-loop was quantified as the magnitude of reflected wave by calculating the standard error of the estimate (Sy/x) from linear regression analysis between Pm and corresponding Vm. PWV and Sy/x during a Valsalva maneuver (VM) were also assessed in nine control subjects. Results: The contour of PU-loop was so characteristic between control and PH-LHD. Max. PWV (349 cm/s) was recorded in PH-LHD and min. PWV (111 cm/s) was recorded in ASD. VM increased Pm (12 [7–15] mmHg vs. 50 [18–110] mmHg; p=0.009) and PWV (200 [148–238] cm/s vs. 260 [192–306] cm/s; p=0.009) significantly without significant increase of Sy/x (19.6 [12.7–28.9]% vs. 28.2 [19.3–40.7]%; p=0.079). Although Sy/x was significantly higher in PH-LHD than in control and ASD (31.0 [14.3–36.3]% vs. 17.5 [8.4–28.9]%; p=0.009, ASD: 18.2%) , no significant difference was found in PWV between PH-LHD and control (269 [159–349] cm/s vs. 203 [154–289] cm/s; p=0.089). Conclusions: 1) The magnitude of wave reflection was elevated in PH-LHD significantly as compared with control and ASD. 2) Despite the significant increase in PA-PWV caused by abrupt elevation in Pm during VM in control, chronic elevation in Pm did not increase PA-PWV in PH-LHD significantly. It was hypothesized that the PA constituted a self-regulating system for maintaining the arterial stiffness stable against the chronic elevation in Pm in PH-LHD by a remodeling of increasing proximal pulmonary arterial crosssectional area gradually, which was compatible with the Moens–Korteweg equation. The PU-loop could provide a new simple and conventional method for assessing the pulmonary arterial properties, clinically. (This is a translation of J Jpn Coll Angiol 2016; 56: 45–53.) PMID:29147168

Comparing Energy Expenditure in Adolescents With and Without Autism While Playing Nintendo(®) Wii(™) Games.

PubMed

Getchell, Nancy; Miccinello, Dannielle; Blom, Michelle; Morris, Lyssa; Szaroleta, Mark

2012-02-01

Obesity rates are on the rise in individuals with autism spectrum disorders (ASD), which underscores the importance of finding new ways in which to engage this population in physical activity. We wanted to explore the energetic expenditure of adolescents with and without ASD while playing Nintendo(®) Wii(™) (Nintendo of America, Inc., Redmond, WA) games compared with more traditional exercise modalities. Specifically, we wanted to compare energy expenditure (EE) among the different activities and to see which activities lead to the greatest amount of time classified as "moderate to vigorous." Two groups of adolescents (15 with ASD [mean age, 17.50±2.4 years], 15 without ASD [mean age, 17.23±4.1 years]) participated in 20-minute bouts of walking, running, and playing Nintendo Wii "Sport(™)," Wii "Fit(™)," and "Dance Dance Revolution" (DDR) (Konami Digital Entertainment, Inc., El Segundo, CA). During each session, EE was calculated using an Actical (Mini Mitter Co., Bend, OR) accelerometer. Groups were compared using multiple t tests. Both groups expended similar amounts of kilcalories in all activities, except for Wii Fit, in which the ASD group expended significantly more kilocalories. For the ASD group, EE was greatest in running, followed by walking, DDR, Wii Fit, and Wii Sport. Walking, running, and DDR all had at least 75 percent of the total time spent in moderate to vigorous intensity levels. We suggest videogame systems, such as the Nintendo Wii, may be viable alternative for individuals with ASD to increase their daily physical activity and help alleviate the growing rates of obesity.

Brief Report: The Prevalence of Neurofibromatosis Type 1 among Children with Autism Spectrum Disorder Identified by the Autism and Developmental Disabilities Monitoring Network

ERIC Educational Resources Information Center

Bilder, Deborah A.; Bakian, Amanda V.; Stevenson, David A.; Carbone, Paul S.; Cunniff, Christopher; Goodman, Alyson B.; McMahon, William M.; Fisher, Nicole P.; Viskochil, David

2016-01-01

Neurofibromatosis type 1 (NF1) is an inherited neurocutaneous disorder associated with neurodevelopmental disorders including autism spectrum disorder (ASD). The frequency of ASD/NF1 co-occurrence has been subject to debate since the 1980s. This relationship was investigated in a large population-based sample of 8-year-old children identified with…

Brief Report: The Dopamine-3-Receptor Gene ("DRD3") Is Associated with Specific Repetitive Behavior in Autism Spectrum Disorder (ASD)

ERIC Educational Resources Information Center

Staal, Wouter G.; de Krom, Mariken; de Jonge, Maretha V.

2012-01-01

Recently the "DRD3" gene has been associated with ASD in two independent samples. Follow up analysis of the risk allele of the SNP rs167771 in 91 subjects revealed a significant association with a specific type of repetitive behavior: the factor "insistence on sameness" (IS) derived from the Autism Diagnostic Interview. This risk allele was…

On the relationship between mouth opening and "broken mirror neurons" in autistic individuals.

PubMed

Pascolo, P B; Cattarinussi, A

2012-02-01

Electromyographies of the mylohyoid muscle (MH) during the execution of the goal-oriented action "grasping to eat" have been used to determine the time relationship between the opening of the mouth and the beginning of the movement. This has been used to distinguish the behaviour of typical developing (TD) children from that of highly functioning autistic (ASD) individuals. The results of previous studies appeared to provide evidence of a deficit in action chain organization in ASD subjects and prompted the hypothesis of a "broken" mirror neuron system (MNS) for these individuals. Our results show the MH activation timing is not reliable in discriminating between TD and ASD children and the distance between the food and the subject plays a key role on the MH activation timing and cannot be neglected when analysing these type of data. The preliminary investigation on the effects of external perturbations also shows that these might have an effect on the results and further investigations are warranted. It appears that there is not enough evidence to support a link between ASD and a broken mirror network system (MNS), and the experimental results must be carefully interpreted before developing therapeutic or rehabilitative protocols. Copyright © 2011 Elsevier Ltd. All rights reserved.

Effectiveness of the Picture Exchange Communication System (PECS) on communication and speech for children with autism spectrum disorders: a meta-analysis.

PubMed

Flippin, Michelle; Reszka, Stephanie; Watson, Linda R

2010-05-01

The Picture Exchange Communication System (PECS) is a popular communication-training program for young children with autism spectrum disorders (ASD). This meta-analysis reviews the current empirical evidence for PECS in affecting communication and speech outcomes for children with ASD. A systematic review of the literature on PECS written between 1994 and June 2009 was conducted. Quality of scientific rigor was assessed and used as an inclusion criterion in computation of effect sizes. Effect sizes were aggregated separately for single-subject and group studies for communication and speech outcomes. Eight single-subject experiments (18 participants) and 3 group studies (95 PECS participants, 65 in other intervention/control) were included. Results indicated that PECS is a promising but not yet established evidence-based intervention for facilitating communication in children with ASD ages 1-11 years. Small to moderate gains in communication were demonstrated following training. Gains in speech were small to negative. This meta-analysis synthesizes gains in communication and relative lack of gains made in speech across the PECS literature for children with ASD. Concerns about maintenance and generalization are identified. Emerging evidence of potential preintervention child characteristics is discussed. Phase IV was identified as a possibly influential program characteristic for speech outcomes.

Grammar Is Differentially Impaired in Subgroups of Autism Spectrum Disorders: Evidence from an Investigation of Tense Marking and Morphosyntax

PubMed Central

Modyanova, Nadezhda; Perovic, Alexandra; Wexler, Ken

2017-01-01

Deficits in the production of verbal inflection (tense marking, or finiteness) are part of the Optional Infinitive (OI) stage of typical grammatical development. They are also a hallmark of language impairment: they have been used as biomarkers in guiding genetic studies of Specific Language Impairment (SLI), and have also been observed in autism spectrum disorders (ASD). To determine the detailed nature of finiteness abilities in subgroups of ASD [autism with impaired language (ALI) vs. autism with normal language (ALN)], we compared tense marking abilities in 46 children with ALI and 37 children with ALN with that of two groups of nonverbal mental age (MA) and verbal MA-matched typically developing (TD) controls, the first such study described in the literature. Our participants' performance on two elicited production tasks, probing third-person-singular -s and past tense -ed, from the Rice/Wexler Test of Early Grammatical Impairment (TEGI, Rice and Wexler, 2001), revealed extensive deficits in the ALI group: their ability to correctly mark tense was significantly worse than their much younger TD controls', and significantly worse than that of the ALN group. In contrast, the ALN group performed similarly to their TD controls. We found good knowledge of the meaning of tense, and of case and agreement, in both ASD groups. Similarly, both ASD groups showed distributions of null or overt subjects with nonfinite and finite verbs in line with those found in young TD children. A key difference, however, was that the ALI group used (rather than simply omitted) the wrong tense in some sentences, a feature not reported in the OI stage for TD or SLI children. Our results confirm a clear distinction in the morphosyntactic abilities of the two subgroups of children with ASD: the language system responsible for finiteness in the ALN group seems to be functioning comparably to that of the TD children, whereas the ALI group, despite showing knowledge of case and agreement, seems to experience an extensive grammatical deficit with respect to finiteness which does not seem to improve with age. Crucially, our ALI group seems to have worse grammatical abilities even than those reported for SLI. PMID:28400738

Inhibition, flexibility, working memory and planning in autism spectrum disorders with and without comorbid ADHD-symptoms

PubMed Central

Sinzig, Judith; Morsch, Dagmar; Bruning, Nicole; Schmidt, Martin H; Lehmkuhl, Gerd

2008-01-01

Background Recent studies have not paid a great deal of attention to comorbid attention-deficit/hyperactivity disorder (ADHD) symptoms in autistic children even though it is well known that almost half of children with autism spectrum disorder (ASD) suffer from hyperactivity, inattention and impulsivity. The goal of this study was to evaluate and compare executive functioning (EF) profiles in children with ADHD and in children with ASD with and without comorbid ADHD. Methods Children aged 6 to 18 years old with ADHD (n = 20) or ASD (High-Functioning autism or Asperger syndrome) with (n = 20) and without (n = 20) comorbid ADHD and a typically developing group (n = 20) were compared on a battery of EF tasks comprising inhibition, flexibility, working memory and planning tasks. A MANOVA, effect sizes as well as correlations between ADHD-symptomatology and EF performance were calculated. Age- and IQ-corrected z scores were used. Results There was a significant effect for the factor group (F = 1.55; dF = 42; p = .02). Post-hoc analysis revealed significant differences between the ADHD and the TD group on the inhibition task for false alarms (p = .01) and between the ADHD group, the ASD+ group (p = .03), the ASD- group (p = .02) and the TD group (p = .01) for omissions. Effect sizes showed clear deficits of ADHD children in inhibition and working memory tasks. Participants with ASD were impaired in planning and flexibility abilities. The ASD+ group showed compared to the ASD- group more problems in inhibitory performance but not in the working memory task. Conclusion Our findings replicate previous results reporting impairment of ADHD children in inhibition and working memory tasks and of ASD children in planning and flexibility abilities. The ASD + group showed similarities to the ADHD group with regard to inhibitory but not to working memory deficits. Nevertheless the heterogeneity of these and previous results shows that EF assessment is not useful for differential diagnosis between ADHD and ASD. It might be useful for evaluating strengths and weaknesses in individual children. PMID:18237439

Exploring the neural correlates of lexical stress perception in english among Chinese-English bilingual children with autism spectrum disorder: An ERP study.

PubMed

Zhang, Juan; Meng, Yaxuan; Tong, Xiuhong; Yuan, Zhen; Wu, Chenggang; Ieong, Sao Leng

2018-02-14

Previous studies found that individuals with autism spectrum disorder (ASD) were less sensitive to the variations of lexical stress in their native language than typically developing controls. However, no study has been conducted to explore the perception of lexical stress in the second language among individuals with ASD. Using ERPs (event-related potentials) measurement with an oddball paradigm, the current study examined and compared the neural responses by Chinese-English bilingual children with ASD and typically developing controls in the processing of English lexical stress. The results showed that when compared with typically developing controls, children with ASD manifested reduced MMN (mismatch negativity) amplitude at the left temporal-parietal and parietal sites, indicating that they were less sensitive to lexical stress. However, a more negative MMN response was found for ASD group than for typically developing group at the right central-parietal, temporal-parietal, and temporal sites. In addition, the right hemisphere was more activated than the left hemisphere for ASD group, which might be derived from the reversed asymmetry of brain activation for individuals with ASD when processing language-related stimuli. Copyright © 2017 Elsevier B.V. All rights reserved.

Experiences of Dental Care and Dental Anxiety in Adults with Autism Spectrum Disorder

PubMed Central

Dahllöf, Göran; Bejerot, Susanne

2014-01-01

Dental anxiety is associated with previous distressing dental experiences, such as lack of understanding of the dentist intentions, perceptions of uncontrollability and experiences of pain during dental treatment. People with autism spectrum disorder (ASD) are impaired in building flexible predictions and expectations, which is very much needed during a dental visit. The aims of the study were to investigate if people with ASD have more negative dental experiences and a higher level of dental anxiety compared to a matched control group. Forty-seven adults with ASD and of normal intellectual performance, and 69 age- and sex-matched typically developing controls completed questionnaires on previous dental experiences and dental anxiety, the Dental Anxiety Scale, and the Dental Beliefs Survey. The ASD group experienced pain during dental treatments more often than the controls and 22% had repeatedly experienced being forced to dental treatment they were not prepared for, compared to 3% of the controls. A higher level of dental anxiety was reported by the ASD group. Dental treatment and methods for supporting the communication with patients with ASD need to be developed, in order to reduce the negative dental experiences and dental anxiety in people with ASD. PMID:25530879

Child Eating Behaviors and Caregiver Feeding Practices in Children with Autism Spectrum Disorders.

PubMed

Kral, Tanja V E; Souders, Margaret C; Tompkins, Victoria H; Remiker, Adriane M; Eriksen, Whitney T; Pinto-Martin, Jennifer A

2015-01-01

This pilot study compared children with autism spectrum disorders (ASD) and typically developing children (TDC) on weight-related outcomes and caregiver-reported child eating behaviors and feeding practices. Cross-sectional study. Caregivers of 25 children with ASD and 30 TDC, ages 4-6. Caregivers completed validated questionnaires that assessed child eating behaviors and feeding practices. Children's height, weight, and waist circumference were measured. Children with ASD, when compared to TDC, showed significantly greater abdominal waist circumferences (p = .01) and waist-to-height ratios (p < .001). Children with ASD with atypical oral sensory sensitivity exhibited greater food avoidance behaviors, including reluctance to eat novel foods (p = .004), being selective about the range of foods they accept (p = .03), and undereating due to negative emotions (p = .02), than children with ASD with typical oral sensory sensitivity. Caregivers of children with ASD with atypical oral sensory sensitivity reported using food to regulate negative child emotions to a greater extent than caregivers of children with typical oral sensory sensitivity (p = .02). Children with ASD, especially those with atypical oral sensory sensitivity, are at increased risk for food avoidance behaviors and may require additional support in several feeding domains. © 2014 Wiley Periodicals, Inc.

Investigating the Grammatical and Pragmatic Origins of Wh-Questions in Children with Autism Spectrum Disorders

PubMed Central

Jyotishi, Manya; Fein, Deborah; Naigles, Letitia

2017-01-01

Compared to typically developing children, children with autism (ASD) show delayed production of wh-questions. It is currently controversial the degree to which such deficits derive from social-pragmatic requirements and/or because these are complex grammatical structures. The current study employed the intermodal preferential looking (IPL) paradigm, which reduces social-pragmatic demands. The IPL paradigm can help distinguish these proposals, as successful comprehension promotes the “pragmatics-origins” argument whereas comprehension difficulties would implicate a “grammatical-origins” argument. Additionally, we tested both the linguistic and social explanations by assessing the contributions of children's early grammatical knowledge (i.e., SVO word order) and their social-pragmatic scores on the Vineland to their later wh-question comprehension. Fourteen children with ASD and 17 TD children, matched on language level, were visited in their homes at 4-month intervals. Comprehension of wh-questions and SVO word order were tested via IPL: the wh-question video showed a costumed horse and bird serving as agents or patients of familiar transitive actions. During the test trials, they were displayed side by side with directing audios (e.g., “What did the horse tickle?”, “What hugged the bird?”, “Where is the horse/bird?”). Children's eye movements were coded offline; the DV was their percent looking to the named item during test. To show comprehension, children should look longer at the named item during a where-question than during a subject-wh or object-wh question. Results indicated that TD children comprehended both subject and object wh-questions at 32 months of age. Comprehension of object-wh questions emerged chronologically later in children with ASD compared to their TD peers, but at similar levels of language. Moreover, performance on word order and social-pragmatic scores independently predicted both groups' later performance on wh-question comprehension. Our findings indicate that both grammar and social-pragmatics are implicated in the comprehension of wh-questions. The “grammatical-origins” argument is supported because the ASD group did not reveal earlier and stable comprehension of wh-questions; furthermore, their performance on SVO word order predicted their later success in linguistic processing of wh-questions. The “pragmatic-origins” argument is also supported because children's earlier socialization and communication scores strongly predicted their successful performance on wh-question comprehension. PMID:28344564

A Cost of Illness Study of Children with High-Functioning Autism Spectrum Disorders and Comorbid Anxiety Disorders as Compared to Clinically Anxious and Typically Developing Children

ERIC Educational Resources Information Center

Steensel, Francisca J.; Dirksen, Carmen D.; Bögels, Susan M.

2013-01-01

The study's aim was to estimate the societal costs of children with high-functioning ASD and comorbid anxiety disorder(s) (ASD + AD-group; n = 73), and to compare these costs to children with anxiety disorders (AD-group; n = 34), and typically developing children (controls; n = 87). Mean total costs for the ASD + AD-group amounted €17,380 per…

Screening of Autism Spectrum Disorders in Geriatric Psychiatry

ERIC Educational Resources Information Center

Heijnen-Kohl, S. M. J.; Kok, R. M.; Wilting, R. M. H. J.; Rossi, G.; van Alphen, S. S. J.

2017-01-01

Autism spectrum disorders (ASD) are difficult to detect in old age. This study examined if ASD symptoms in older adults (age > 60) can be detected with the Dutch informant personality questionnaire, (Hetero-Anamnestische Persoonlijkheidsvragenlijst, HAP) in a mental health setting. Patients with ASD (N = 40) were compared to patients with a…

Increased burden of deleterious variants in essential genes in autism spectrum disorder.

PubMed

Ji, Xiao; Kember, Rachel L; Brown, Christopher D; Bućan, Maja

2016-12-27

Autism spectrum disorder (ASD) is a heterogeneous, highly heritable neurodevelopmental syndrome characterized by impaired social interaction, communication, and repetitive behavior. It is estimated that hundreds of genes contribute to ASD. We asked if genes with a strong effect on survival and fitness contribute to ASD risk. Human orthologs of genes with an essential role in pre- and postnatal development in the mouse [essential genes (EGs)] are enriched for disease genes and under strong purifying selection relative to human orthologs of mouse genes with a known nonlethal phenotype [nonessential genes (NEGs)]. This intolerance to deleterious mutations, commonly observed haploinsufficiency, and the importance of EGs in development suggest a possible cumulative effect of deleterious variants in EGs on complex neurodevelopmental disorders. With a comprehensive catalog of 3,915 mammalian EGs, we provide compelling evidence for a stronger contribution of EGs to ASD risk compared with NEGs. By examining the exonic de novo and inherited variants from 1,781 ASD quartet families, we show a significantly higher burden of damaging mutations in EGs in ASD probands compared with their non-ASD siblings. The analysis of EGs in the developing brain identified clusters of coexpressed EGs implicated in ASD. Finally, we suggest a high-priority list of 29 EGs with potential ASD risk as targets for future functional and behavioral studies. Overall, we show that large-scale studies of gene function in model organisms provide a powerful approach for prioritization of genes and pathogenic variants identified by sequencing studies of human disease.

Investigating the Microstructural Correlation of White Matter in Autism Spectrum Disorder.

PubMed

Dean, Douglas C; Travers, Brittany G; Adluru, Nagesh; Tromp, Do P M; Destiche, Daniel J; Samsin, Danica; Prigge, Molly B; Zielinski, Brandon A; Fletcher, P Thomas; Anderson, Jeffrey S; Froehlich, Alyson L; Bigler, Erin D; Lange, Nicholas; Lainhart, Janet E; Alexander, Andrew L

2016-06-01

White matter microstructure forms a complex and dynamical system that is critical for efficient and synchronized brain function. Neuroimaging findings in children with autism spectrum disorder (ASD) suggest this condition is associated with altered white matter microstructure, which may lead to atypical macroscale brain connectivity. In this study, we used diffusion tensor imaging measures to examine the extent that white matter tracts are interrelated within ASD and typical development. We assessed the strength of inter-regional white matter correlations between typically developing and ASD diagnosed individuals. Using hierarchical clustering analysis, clustering patterns of the pairwise white matter correlations were constructed and revealed to be different between the two groups. Additionally, we explored the use of graph theory analysis to examine the characteristics of the patterns formed by inter-regional white matter correlations and compared these properties between ASD and typical development. We demonstrate that the ASD sample has significantly less coherence in white matter microstructure across the brain compared to that in the typical development sample. The ASD group also presented altered topological characteristics, which may implicate less efficient brain networking in ASD. These findings highlight the potential of graph theory based network characteristics to describe the underlying networks as measured by diffusion magnetic resonance imaging and furthermore indicates that ASD may be associated with altered brain network characteristics. Our findings are consistent with those of a growing number of studies and hypotheses that have suggested disrupted brain connectivity in ASD.

Investigating the Microstructural Correlation of White Matter in Autism Spectrum Disorder

PubMed Central

Travers, Brittany G.; Adluru, Nagesh; Tromp, Do P.M.; Destiche, Daniel J.; Samsin, Danica; Prigge, Molly B.; Zielinski, Brandon A.; Fletcher, P. Thomas; Anderson, Jeffrey S.; Froehlich, Alyson L.; Bigler, Erin D.; Lange, Nicholas; Lainhart, Janet E.; Alexander, Andrew L.

2016-01-01

Abstract White matter microstructure forms a complex and dynamical system that is critical for efficient and synchronized brain function. Neuroimaging findings in children with autism spectrum disorder (ASD) suggest this condition is associated with altered white matter microstructure, which may lead to atypical macroscale brain connectivity. In this study, we used diffusion tensor imaging measures to examine the extent that white matter tracts are interrelated within ASD and typical development. We assessed the strength of inter-regional white matter correlations between typically developing and ASD diagnosed individuals. Using hierarchical clustering analysis, clustering patterns of the pairwise white matter correlations were constructed and revealed to be different between the two groups. Additionally, we explored the use of graph theory analysis to examine the characteristics of the patterns formed by inter-regional white matter correlations and compared these properties between ASD and typical development. We demonstrate that the ASD sample has significantly less coherence in white matter microstructure across the brain compared to that in the typical development sample. The ASD group also presented altered topological characteristics, which may implicate less efficient brain networking in ASD. These findings highlight the potential of graph theory based network characteristics to describe the underlying networks as measured by diffusion magnetic resonance imaging and furthermore indicates that ASD may be associated with altered brain network characteristics. Our findings are consistent with those of a growing number of studies and hypotheses that have suggested disrupted brain connectivity in ASD. PMID:27021440

Increased burden of deleterious variants in essential genes in autism spectrum disorder

PubMed Central

Kember, Rachel L.; Brown, Christopher D.; Bućan, Maja

2016-01-01

Autism spectrum disorder (ASD) is a heterogeneous, highly heritable neurodevelopmental syndrome characterized by impaired social interaction, communication, and repetitive behavior. It is estimated that hundreds of genes contribute to ASD. We asked if genes with a strong effect on survival and fitness contribute to ASD risk. Human orthologs of genes with an essential role in pre- and postnatal development in the mouse [essential genes (EGs)] are enriched for disease genes and under strong purifying selection relative to human orthologs of mouse genes with a known nonlethal phenotype [nonessential genes (NEGs)]. This intolerance to deleterious mutations, commonly observed haploinsufficiency, and the importance of EGs in development suggest a possible cumulative effect of deleterious variants in EGs on complex neurodevelopmental disorders. With a comprehensive catalog of 3,915 mammalian EGs, we provide compelling evidence for a stronger contribution of EGs to ASD risk compared with NEGs. By examining the exonic de novo and inherited variants from 1,781 ASD quartet families, we show a significantly higher burden of damaging mutations in EGs in ASD probands compared with their non-ASD siblings. The analysis of EGs in the developing brain identified clusters of coexpressed EGs implicated in ASD. Finally, we suggest a high-priority list of 29 EGs with potential ASD risk as targets for future functional and behavioral studies. Overall, we show that large-scale studies of gene function in model organisms provide a powerful approach for prioritization of genes and pathogenic variants identified by sequencing studies of human disease. PMID:27956632

Normal variation in fronto-occipital circuitry and cerebellar structure with an autism-associated polymorphism of CNTNAP2

PubMed Central

Tan, Geoffrey C.Y.; Doke, Thomas F.; Ashburner, John; Wood, Nicholas W.; Frackowiak, Richard S.J.

2010-01-01

Recent genetic studies have implicated a number of candidate genes in the pathogenesis of Autism Spectrum Disorder (ASD). Polymorphisms of CNTNAP2 (contactin-associated like protein-2), a member of the neurexin family, have already been implicated as a susceptibility gene for autism by at least 3 separate studies. We investigated variation in white and grey matter morphology using structural MRI and diffusion tensor imaging. We compared volumetric differences in white and grey matter and fractional anisotropy values in control subjects characterised by genotype at rs7794745, a single nucleotide polymorphism in CNTNAP2. Homozygotes for the risk allele showed significant reductions in grey and white matter volume and fractional anisotropy in several regions that have already been implicated in ASD, including the cerebellum, fusiform gyrus, occipital and frontal cortices. Male homozygotes for the risk alleles showed greater reductions in grey matter in the right frontal pole and in FA in the right rostral fronto-occipital fasciculus compared to their female counterparts who showed greater reductions in FA of the anterior thalamic radiation. Thus a risk allele for autism results in significant cerebral morphological variation, despite the absence of overt symptoms or behavioural abnormalities. The results are consistent with accumulating evidence of CNTNAP2's function in neuronal development. The finding suggests the possibility that the heterogeneous manifestations of ASD can be aetiologically characterised into distinct subtypes through genetic-morphological analysis. PMID:20176116

How Useful Is Electroencephalography in the Diagnosis of Autism Spectrum Disorders and the Delineation of Subtypes: A Systematic Review

PubMed Central

Gurau, Oana; Bosl, William J.; Newton, Charles R.

2017-01-01

Autism spectrum disorders (ASD) are thought to be associated with abnormal neural connectivity. Presently, neural connectivity is a theoretical construct that cannot be easily measured. Research in network science and time series analysis suggests that neural network structure, a marker of neural activity, can be measured with electroencephalography (EEG). EEG can be quantified by different methods of analysis to potentially detect brain abnormalities. The aim of this review is to examine evidence for the utility of three methods of EEG signal analysis in the ASD diagnosis and subtype delineation. We conducted a review of literature in which 40 studies were identified and classified according to the principal method of EEG analysis in three categories: functional connectivity analysis, spectral power analysis, and information dynamics. All studies identified significant differences between ASD patients and non-ASD subjects. However, due to high heterogeneity in the results, generalizations could not be inferred and none of the methods alone are currently useful as a new diagnostic tool. The lack of studies prevented the analysis of these methods as tools for ASD subtypes delineation. These results confirm EEG abnormalities in ASD, but as yet not sufficient to help in the diagnosis. Future research with larger samples and more robust study designs could allow for higher sensitivity and consistency in characterizing ASD, paving the way for developing new means of diagnosis. PMID:28747892

Mirror neuron activity associated with social impairments but not age in autism spectrum disorder.

PubMed

Enticott, Peter G; Kennedy, Hayley A; Rinehart, Nicole J; Tonge, Bruce J; Bradshaw, John L; Taffe, John R; Daskalakis, Zafiris J; Fitzgerald, Paul B

2012-03-01

The neurobiology of autism spectrum disorder (ASD) is not particularly well understood, and biomedical treatment approaches are therefore extremely limited. A prominent explanatory model suggests that social-relating symptoms may arise from dysfunction within the mirror neuron system, while a recent neuroimaging study suggests that these impairments in ASD might reduce with age. Participants with autism spectrum disorder (i.e., DSM-IV autistic disorder or Asperger's disorder) (n = 34) and matched control subjects (n = 36) completed a transcranial magnetic stimulation study in which corticospinal excitability was assessed during the observation of hand gestures. Regression analyses revealed that the ASD group presented with significantly reduced corticospinal excitability during the observation of a transitive hand gesture (relative to observation of a static hand) (p < .05), which indicates reduced putative mirror neuron system activity within ventral premotor cortex/inferior frontal gyrus. Among the ASD group, there was also a negative association between putative mirror neuron activity and self-reported social-relating impairments, but there was no indication that mirror neuron impairments in ASD decrease with age. These data provide general support for the mirror neuron hypothesis of autism; researchers now must clarify the precise functional significance of mirror neurons to truly understand their role in the neuropathophysiology of ASD and to determine whether they should be used as targets for the treatment of ASD.

Self-face recognition in children with autism spectrum disorders: a near-infrared spectroscopy study.

PubMed

Kita, Yosuke; Gunji, Atsuko; Inoue, Yuki; Goto, Takaaki; Sakihara, Kotoe; Kaga, Makiko; Inagaki, Masumi; Hosokawa, Toru

2011-06-01

It is assumed that children with autism spectrum disorders (ASD) have specificities for self-face recognition, which is known to be a basic cognitive ability for social development. In the present study, we investigated neurological substrates and potentially influential factors for self-face recognition of ASD patients using near-infrared spectroscopy (NIRS). The subjects were 11 healthy adult men, 13 normally developing boys, and 10 boys with ASD. Their hemodynamic activities in the frontal area and their scanning strategies (eye-movement) were examined during self-face recognition. Other factors such as ASD severities and self-consciousness were also evaluated by parents and patients, respectively. Oxygenated hemoglobin levels were higher in the regions corresponding to the right inferior frontal gyrus than in those corresponding to the left inferior frontal gyrus. In two groups of children these activities reflected ASD severities, such that the more serious ASD characteristics corresponded with lower activity levels. Moreover, higher levels of public self-consciousness intensified the activities, which were not influenced by the scanning strategies. These findings suggest that dysfunction in the right inferior frontal gyrus areas responsible for self-face recognition is one of the crucial neural substrates underlying ASD characteristics, which could potentially be used to evaluate psychological aspects such as public self-consciousness. Copyright © 2010 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Maternal and Neonatal Birth Factors Affecting the Age of ASD Diagnosis.

PubMed

Darcy-Mahoney, Ashley; Minter, Bonnie; Higgins, Melinda; Guo, Ying; Zauche, Lauren Head; Hirst, Jessica

2016-12-01

Early diagnosis of autism spectrum disorders (ASD) enables early intervention that improves long term functioning of children with ASD but is often delayed until age of school entry. Few studies have identified factors that affect timely diagnosis. This study addressed how maternal education, race, age, marital status as well as neonatal birth factors affect the age at which a child is diagnosed with ASD. This study involved a retrospective analysis of 664 records of children treated at one of the largest autism treatment centers in the United States from March 1, 2009 to December 30, 2010. Logistic regression and Cox proportional hazards regression were used to identify maternal and neonatal factors associated with age of diagnosis. Infant gender, maternal race, marital status, and maternal age were identified as significant factors for predicting the age of ASD diagnosis. In the Cox proportional hazards regression model, only maternal race and marital status were included. Median survival age till diagnosis of children born to married mothers was 53.4 months compared to 57.8 months and 63.7 months of children born to single and divorced or widowed mothers respectively. Median survival age till diagnosis for children of African American mothers was 53.8 months compared to 57.2 months for children of Caucasian mothers. No statistically significant difference of timing of ASD diagnosis was found for children of varying gestational age. Children born to older or married mothers and mothers of minority races were more likely to have an earlier ASD diagnosis. No statistically significant differences in timing of ASD diagnosis were found for children born at varying gestational ages. Identification of these factors has the potential to inform public health outreach aimed at promoting timely ASD diagnosis. This work could enhance clinical practice for timelier diagnoses of ASD by supporting parents and clinicians around the world in identifying risk factors beyond gender and SES and developing strategies to recognize earlier signs of ASD and contribute to improved development outcomes in children with ASD.

Correlation between Nutrition and Symptoms: Nutritional Survey of Children with Autism Spectrum Disorder in Chongqing, China

PubMed Central

Liu, Xiao; Liu, Juan; Xiong, Xueqin; Yang, Ting; Hou, Nali; Liang, Xiaohua; Chen, Jie; Cheng, Qian; Li, Tingyu

2016-01-01

Restricted diets and inadequate nutrient intake of children with autism spectrum disorder (ASD) have been reported. This study examined the nutritional statuses of children with ASD and the relationships between their behaviors and nutritional intake. A total of 154 children with ASD (age = 5.21 ± 1.83 years) and 73 typically-developing (TD) children (age = 4.83 ± 0.84 years) from Chongqing, China, were enrolled. The severity of ASD was evaluated using the Childhood Autism Rating Scale (CARS). The serum ferritin, folate, vitamin B12, 25(OH) vitamin D, and vitamin A concentrations in the children with ASD were determined. All participants underwent anthropometric examinations, dietary assessments, and questionnaire assessments about their feeding behaviors, and gastrointestinal symptoms. The ZHA, ZWA, and ZBMIA were found to be significantly lower in the children with ASD compared with those without ASD. In addition, the percentages of children exhibiting severe picky eating and severe resistance to new foods, as well as those with a reported general impression of severe eating problems and constipation, were higher among the children with ASD. These children consumed significantly fewer macronutrients compared with the children without ASD. In addition, the children with ASD had the highest rate of vitamin A deficiency, followed by iron deficiency. After adjusting for sex, the vitamin A concentration was found to be negatively correlated with the CARS score (rs = −0.222, p = 0.021). No correlation between the ferritin, folate, vitamin D, or vitamin B12 concentration and the CARS score was found. These results suggest that reduced macronutrient intakes, severe feeding behavior issues, constipation, and vitamin A deficiency are quite common among children with ASD. Further, a low serum vitamin A level may be a risk factor for symptoms of ASD. However, the underlying mechanism should be further studied. PMID:27187463

Behavior change in a student with a dual diagnosis of deafness and pervasive developmental disorder: a case study.

PubMed

Easterbrooks, Susan R; Handley, C Michele

The broad term pervasive developmental disorder (PPD) describes a set of symptoms that occur along a continuum of severity; these symptoms are often referred to as autism spectrum disorders (ASDs). Little is known about the incidence and prevalence of ASDs among students who are deaf or hard of hearing (DHH). Teachers of DHH students, who must work with individuals with dual diagnoses, are at a loss for guidance from the literature. The authors review the literature on ASDs (also referred to as PDD) within the DHH population, provide results of a single-subject study to reduce PDD-type behaviors in a child with hearing loss, and argue that teachers of students who are DHH must learn about practices associated with applied behavior analysis as an tool for intervening therapeutically with children with dual diagnoses of hearing loss plus an ASD.

Integrative approaches utilizing oxytocin to enhance prosocial behavior: from animal and human social behavior to autistic social dysfunction.

PubMed

Yamasue, Hidenori; Yee, Jason R; Hurlemann, René; Rilling, James K; Chen, Frances S; Meyer-Lindenberg, Andreas; Tost, Heike

2012-10-10

The prevalence of autism spectrum disorder (ASD) is as high as 1 in 100 individuals and is a heavy burden to society. Thus, identifying causes and treatments is imperative. Here, we briefly review the topics covered in our 2012 Society for Neuroscience Mini-Symposium entitled "Integrative Approaches Using Oxytocin to Enhance Prosocial Behavior: From Animal and Human Social Behavior to ASD's Social Dysfunction." This work is not meant to be a comprehensive review of oxytocin and prosocial behavior. Instead, we wish to share the newest findings on the effects of oxytocin on social behavior, the brain, and the social dysfunction of ASD at the molecular, genetic, systemic, and behavior levels, in varied subjects ranging from animal models to humans suffering from autism for the purpose of promoting further study for developing the clinical use of oxytocin in treating ASD.

An improved asynchronous brain interface: making use of the temporal history of the LF-ASD feature vectors

NASA Astrophysics Data System (ADS)

Bashashati, Ali; Mason, Steve; Ward, Rabab K.; Birch, Gary E.

2006-06-01

The low-frequency asynchronous switch design (LF-ASD) has been introduced as a direct brain interface (BI) for asynchronous control applications. Asynchronous interfaces, as opposed to synchronous interfaces, have the advantage of being operational at all times and not only at specific system-defined periods. This paper modifies the LF-ASD design by incorporating into the system more knowledge about the attempted movements. Specifically, the history of feature values extracted from the EEG signal is used to detect a right index finger movement attempt. Using data collected from individuals with high-level spinal cord injuries and able-bodied subjects, it is shown that the error characteristics of the modified design are significantly better than the previous LF-ASD design. The true positive rate percentage increased by up to 15 which corresponds to 50% improvement when the system is operating with false positive rates in the 1-2% range.

Psychosocial Adjustment and Sibling Relationships in Siblings of Children with Autism Spectrum Disorder: Risk and Protective Factors.

PubMed

Walton, Katherine M; Ingersoll, Brooke R

2015-09-01

This study compared sibling adjustment and relationships in siblings of children with Autism Spectrum Disorder (ASD-Sibs; n = 69) and siblings of children with typical development (TD-Sibs; n = 93). ASD-Sibs and TD-Sibs demonstrated similar emotional/behavioral adjustment. Older male ASD-Sibs were at increased risk for difficulties. Sibling relationships of ASD-Sibs involved less aggression, less involvement, and more avoidance than those of TD-Sibs. Partial support for a diathesis-stress conceptualization of sibling difficulties was found for ASD-Sibs. For TD-Sibs, broader autism phenotype (BAP) was related to psychosocial difficulties regardless of family stressors. For ASD-Sibs, BAP was related to difficulties only when family stressors were present. This suggests that having a sibling with ASD may be a protective factor that attenuates the negative impact of sibling BAP.

Physiological Arousal in Autism and Fragile X Syndrome: Group Comparisons and Links With Pragmatic Language

PubMed Central

Klusek, Jessica; Martin, Gary E.; Losh, Molly

2014-01-01

This study tested the hypothesis that pragmatic (i.e., social) language impairment is linked to arousal dysregulation in autism spectrum disorder (ASD) and fragile X syndrome (FXS). Forty boys with ASD, 39 with FXS, and 28 with typical development (TD), aged 4–15 years, participated. Boys with FXS were hyperaroused compared to boys with TD but did not differ from boys with ASD. Dampened vagal tone predicted pragmatic impairment in ASD, and associations emerged between cardiac activity and receptive/expressive vocabulary across groups. Findings support autonomic dysfunction as a mechanism underlying pragmatic impairment in ASD and suggest that biophysiological profiles are shared in ASD and FXS, which has implications for understanding the role of fragile X mental retardation-1 (FMR1, the FXS gene) in the pathophysiology of ASD. PMID:24432860

Social communication competence and functional adaptation in a general population of children: preliminary evidence for sex-by-verbal IQ differential risk.

PubMed

Skuse, David H; Mandy, William; Steer, Colin; Miller, Laura L; Goodman, Robert; Lawrence, Kate; Emond, Alan; Golding, Jean

2009-02-01

The proportion of schoolchildren with mild social communicative deficits far exceeds the number diagnosed with an autistic spectrum disorder (ASD). We aimed to ascertain both the population distribution of such deficits and their association with functional adaptation and cognitive ability in middle childhood. The parent-report Social and Communication Disorders Checklist was administered to participants (n = 8,094) in the Avon Longitudinal Study of Parents and Children. We correlated impairment severity with independent clinical diagnoses of ASD, cognitive abilities, and teacher-rated maladaptive behavior. Social and Communication Disorders Checklist scores were continuously distributed in the general population; boys had mean scores 30% higher than girls. Social communicative deficits were associated with functional impairment at school, especially in domains of hyperactivity and conduct disorders. A sex-by-verbal IQ interaction effect occurred: verbal IQ was protective against social communication impairments across the range of abilities in female subjects only. In male subjects, this protective effect did not exist for those with above-average verbal IQ. Social communicative deficits are of prognostic significance, in terms of behavioral adjustment at school, for boys and girls. Their high general population prevalence emphasizes the importance of measuring such traits among clinically referred children who do not meet diagnostic ASD criteria. Above-average verbal IQ seems to confer protection against social communication impairments in female subjects but not in male subjects.

Childhood vision impairment, hearing loss and co-occurring autism spectrum disorder

PubMed Central

Kancherla, Vijaya; Van Naarden Braun, Kim; Yeargin-Allsopp, Marshalyn

2015-01-01

Background Limited population-based data on prevalence of childhood vision impairment (VI) and hearing loss (HL), and their co-occurrence with autism spectrum disorder (ASD) exists. Objective To examine prevalence and characteristics of VI, HL and co-occurring ASD among 8-year-olds in metropolitan Atlanta 2000–2008. Methods We used data from the population-based Metropolitan Atlanta Developmental Disabilities Surveillance Program. Prevalence, birth and parental characteristics, presence and severity of other co-occurring developmental disabilities, and age of earliest identification of ASD, were examined for children with VI and HL, by co-occurring ASD. Results VI and HL prevalences were 1.2 and 1.3 per 1000 8-year-olds, respectively. Approximately 6–7% of children with VI or HL had co-occurring ASD. Children with VI or HL with co-occurring ASD differed from those without co-occurring ASD by select birth characteristics and the presence of other co-occurring DDs. The median age of earliest known ASD diagnosis was significantly later among children with VI and ASD compared to children with ASD without VI (79 vs. 56 months). Children with HL and ASD were first evaluated by a community provider significantly earlier than those with ASD without HL (40 vs. 50 months). Conclusions The frequency of co-occurring ASD with VI and HL is higher than the population prevalence of ASD. The significant delays in diagnosis of ASD in children with VI and lack of earlier diagnosis of ASD among children with HL despite earlier evaluation highlight the importance of developing screening tools for early identification of ASD among children with VI and HL. PMID:24060256

[Quality of life in children and adolescents with autism spectrum disorder without intellectual disability].

PubMed

Cuesta-Gomez, J L; Vidriales-Fernandez, R; Carvajal-Molina, F

2016-01-01

The concept of quality of life is of great importance for interventions directed at people living with disabilities. It is undeniable that the achievement of a satisfactory quality of life should be the objective of clinical interventions that are directed at the group of people with autism spectrum disorder (ASD) and should be a key element in the design of the treatments that are needed to improve the prognosis of future development. Nevertheless, knowledge of both the objective and the subjective conditions that predict greater quality of life satisfaction in people with ASD is still very limited. To explore the perception of the quality of life experienced by a group of children and adolescents with ASD without intellectual disability. A sample of 12 children and 11 adolescents with ASD without intellectual disability. In accordance with their age, they were administered the corresponding quality of life questionnaires. Both groups reported positively on their quality of life, without any differences in the basic dimensions. Nevertheless, in the case of adolescents, very low scores were obtained in the area of self-determination in comparison with their scores in other areas. The discussion centers on the identification of the most relevant dimensions for quality of life, the implications for intervention, and the need to adapt the methodologies in use for the subjective evaluation of those factors, due to the characteristics of ASD that can affect the capabilities necessary for the evaluation of personal experience, and may require the adaptation of the procedures that are employed.

Idiom, syntax, and advanced theory of mind abilities in children with autism spectrum disorders.

PubMed

Whyte, Elisabeth M; Nelson, Keith E; Scherf, K Suzanne

2014-02-01

When researchers investigate figurative language abilities (including idioms) in children with autism spectrum disorder (ASD), syntax abilities may be more important than once considered. In addition, there are limitations to the overreliance on false-belief tasks to measure theory of mind (TOM) abilities. In the current study, the authors investigated idiom, syntax, and advanced TOM abilities in children with ASD compared to children with typical development (TD). Twenty-six children with ASD, ages 5 to 12 years, were compared to individuals in each of 2 control groups of children with TD: 1 matched on chronological age and nonverbal IQ, and 1 matched on syntax age-equivalence and raw scores. Idiom comprehension, syntax, vocabulary, and 2 measures of advanced TOM abilities were examined. Although children with ASD performed worse on idiom comprehension compared to the age-matched group with TD, they exhibited comparable idiom performance to the syntax-matched group with TD. Advanced TOM abilities were related to idiom comprehension for children with ASD, but not for children with TD, above the contributions of basic language abilities. Syntax abilities should be used as a matching variable when examining figurative or other late-developing language skills.

Comparison of ICD-10R, DSM-IV-TR and DSM-5 in an Adult Autism Spectrum Disorder Diagnostic Clinic

ERIC Educational Resources Information Center

Wilson, C. Ellie; Gillan, Nicola; Spain, Deborah; Robertson, Dene; Roberts, Gedeon; Murphy, Clodagh M.; Maltezos, Stefanos; Zinkstok, Janneke; Johnston, Katie; Dardani, Christina; Ohlsen, Chris; Deeley, P. Quinton; Craig, Michael; Mendez, Maria A.; Happé, Francesca; Murphy, Declan G. M.

2013-01-01

An Autism Spectrum Disorder (ASD) diagnosis is often used to access services. We investigated whether ASD diagnostic outcome varied when DSM-5 was used compared to ICD-10R and DSM-IV-TR in a clinical sample of 150 intellectually able adults. Of those diagnosed with an ASD using ICD-10R, 56% met DSM-5 ASD criteria. A further 19% met DSM-5 (draft)…

Multiplex ligation-dependent probe amplification for genetic screening in autism spectrum disorders: Efficient identification of known microduplications and identification of a novel microduplication in ASMT

PubMed Central

Cai, Guiqing; Edelmann, Lisa; Goldsmith, Juliet E; Cohen, Ninette; Nakamine, Alisa; Reichert, Jennifer G; Hoffman, Ellen J; Zurawiecki, Danielle M; Silverman, Jeremy M; Hollander, Eric; Soorya, Latha; Anagnostou, Evdokia; Betancur, Catalina; Buxbaum, Joseph D

2008-01-01

Background It has previously been shown that specific microdeletions and microduplications, many of which also associated with cognitive impairment (CI), can present with autism spectrum disorders (ASDs). Multiplex ligation-dependent probe amplification (MLPA) represents an efficient method to screen for such recurrent microdeletions and microduplications. Methods In the current study, a total of 279 unrelated subjects ascertained for ASDs were screened for genomic disorders associated with CI using MLPA. Fluorescence in situ hybridization (FISH), quantitative polymerase chain reaction (Q-PCR) and/or direct DNA sequencing were used to validate potential microdeletions and microduplications. Methylation-sensitive MLPA was used to characterize individuals with duplications in the Prader-Willi/Angelman (PWA) region. Results MLPA showed two subjects with typical ASD-associated interstitial duplications of the 15q11-q13 PWA region of maternal origin. Two additional subjects showed smaller, de novo duplications of the PWA region that had not been previously characterized. Genes in these two novel duplications include GABRB3 and ATP10A in one case, and MKRN3, MAGEL2 and NDN in the other. In addition, two subjects showed duplications of the 22q11/DiGeorge syndrome region. One individual was found to carry a 12 kb deletion in one copy of the ASPA gene on 17p13, which when mutated in both alleles leads to Canavan disease. Two subjects showed partial duplication of the TM4SF2 gene on Xp11.4, previously implicated in X-linked non-specific mental retardation, but in our subsequent analyses such variants were also found in controls. A partial duplication in the ASMT gene, located in the pseudoautosomal region 1 (PAR1) of the sex chromosomes and previously suggested to be involved in ASD susceptibility, was observed in 6–7% of the cases but in only 2% of controls (P = 0.003). Conclusion MLPA proves to be an efficient method to screen for chromosomal abnormalities. We identified duplications in 15q11-q13 and in 22q11, including new de novo small duplications, as likely contributing to ASD in the current sample by increasing liability and/or exacerbating symptoms. Our data indicate that duplications in TM4SF2 are not associated with the phenotype given their presence in controls. The results in PAR1/PAR2 are the first large-scale studies of gene dosage in these regions, and the findings at the ASMT locus indicate that further studies of the duplication of the ASMT gene are needed in order to gain insight into its potential involvement in ASD. Our studies also identify some limitations of MLPA, where single base changes in probe binding sequences alter results. In summary, our studies indicate that MLPA, with a focus on accepted medical genetic conditions, may be an inexpensive method for detection of microdeletions and microduplications in ASD patients for purposes of genetic counselling if MLPA-identified deletions are validated by additional methods. PMID:18925931

Abnormal melatonin synthesis in autism spectrum disorders.

PubMed

Melke, J; Goubran Botros, H; Chaste, P; Betancur, C; Nygren, G; Anckarsäter, H; Rastam, M; Ståhlberg, O; Gillberg, I C; Delorme, R; Chabane, N; Mouren-Simeoni, M-C; Fauchereau, F; Durand, C M; Chevalier, F; Drouot, X; Collet, C; Launay, J-M; Leboyer, M; Gillberg, C; Bourgeron, T

2008-01-01

Melatonin is produced in the dark by the pineal gland and is a key regulator of circadian and seasonal rhythms. A low melatonin level has been reported in individuals with autism spectrum disorders (ASD), but the underlying cause of this deficit was unknown. The ASMT gene, encoding the last enzyme of melatonin synthesis, is located on the pseudo-autosomal region 1 of the sex chromosomes, deleted in several individuals with ASD. In this study, we sequenced all ASMT exons and promoters in individuals with ASD (n=250) and compared the allelic frequencies with controls (n=255). Non-conservative variations of ASMT were identified, including a splicing mutation present in two families with ASD, but not in controls. Two polymorphisms located in the promoter (rs4446909 and rs5989681) were more frequent in ASD compared to controls (P=0.0006) and were associated with a dramatic decrease in ASMT transcripts in blood cell lines (P=2 x 10(-10)). Biochemical analyses performed on blood platelets and/or cultured cells revealed a highly significant decrease in ASMT activity (P=2 x 10(-12)) and melatonin level (P=3 x 10(-11)) in individuals with ASD. These results indicate that a low melatonin level, caused by a primary deficit in ASMT activity, is a risk factor for ASD. They also support ASMT as a susceptibility gene for ASD and highlight the crucial role of melatonin in human cognition and behavior.

Features of the broader autism phenotype in people with epilepsy support shared mechanisms between epilepsy and autism spectrum disorder.

PubMed

Richard, Annie E; Scheffer, Ingrid E; Wilson, Sarah J

2017-04-01

Richard, A.E., I.E. Scheffer and S.J. Wilson. Features of the broader autism phenotype in people with epilepsy support shared mechanisms between epilepsy and autism spectrum disorder. NEUROSCI BIOBEHAV REV 21(1) XXX-XXX, 2016. To inform on mechanisms underlying the comorbidity of epilepsy and autism spectrum disorder (ASD), we conducted meta-analyses to test whether impaired facial emotion recognition (FER) and theory of mind (ToM), key phenotypic traits of ASD, are more common in people with epilepsy (PWE) than controls. We contrasted these findings with those of relatives of individuals with ASD (ASD-relatives) compared to controls. Furthermore, we examined the relationship of demographic (age, IQ, sex) and epilepsy-related factors (epilepsy onset age, duration, seizure laterality and origin) to FER and ToM. Thirty-one eligible studies of PWE (including 1449 individuals: 77% with temporal lobe epilepsy), and 22 of ASD-relatives (N=1295) were identified by a systematic database search. Analyses revealed reduced FER and ToM in PWE compared to controls (p<0.001), but only reduced ToM in ASD-relatives (p<0.001). ToM was poorer in PWE than ASD-relatives. Only weak associations were found between FER and ToM and epilepsy-related factors. These findings suggest shared mechanisms between epilepsy and ASD, independent of intellectual disability. Copyright © 2017 Elsevier Ltd. All rights reserved.

Parenting adolescents with ASD: A multimethod study.

PubMed

van Esch, Lotte; Vanmarcke, Steven; Ceulemans, Eva; Van Leeuwen, Karla; Noens, Ilse

2018-05-15

A number of studies have concluded that parents of children with ASD experience high levels of parenting stress. However, little is known about their parenting behaviors. Especially few studies investigated parenting in adolescence, although this period is associated with additional challenges for both adolescents and their parents. In the present study, a multi-method approach was used, combining data from a self-report questionnaire and observation of mother-child interactions during different semi-structured (e.g., inventing and building a vehicle of the future with construction toys) and structured tasks (e.g., solving marble maze). Linear mixed models (LMM) were used to compare the means of parenting behaviors among mothers of adolescents with (n = 44) and without ASD (n = 38), aged 12 to 16 years old. During the observations, mothers of adolescents with ASD showed more sensitivity and creativity, compared to the general population control group. In addition, mothers in the ASD group reported on the self-report questionnaire to adapt the environment more, for example, by establishing routines. Furthermore, this study investigated the role of maternal characteristics, that is, ASD characteristics and parenting stress. Parenting stress was associated with less self-reported positive parenting. Higher levels of ASD characteristics of the mother were related to more negativity and less sensitivity during the observation, and more self-reported harsh punishment and adapting the environment. This study additionally examined whether the impact of these maternal characteristics was the same across the two groups. Whereas group by parenting stress interaction effects were not significant for any of the observed and self-reported parenting behaviors, significant group by ASD characteristics interaction effects were noticed for self-reported harsh punishment and adapting the environment. Autism Res 2018. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. A number of studies have concluded that parents of children with ASD experience high levels of parenting stress. However, little is known about their parenting behaviors. Especially parenting in adolescence remains under investigated, although this period is associated with additional challenges for both adolescents and their parents. In this study, 44 adolescents with ASD and a control group of 38 adolescents without ASD, aged 12-16 years old, participated together with their mother. We compared parenting behaviors between the two groups, based on observations of mother-child interactions and a questionnaire that was filled out by the mother. During the observation, mothers of adolescents with ASD showed more sensitivity and creativity, compared to the control group. In addition, the questionnaire responses indicated that mothers in the ASD group adapted the environment more by for example, establishing routines. Furthermore, this study investigated the role of parenting stress and ASD characteristics of the mother on parenting behavior. Parenting stress was associated with less self-reported positive parenting. Higher levels of ASD characteristics of the mother were related to more negativity and less sensitivity during the observation in both groups, and more self-reported harsh punishment and adapting the environment in the control group only. © 2018 International Society for Autism Research, Wiley Periodicals, Inc.

Abnormal motor cortex excitability during linguistic tasks in adductor-type spasmodic dysphonia.

PubMed

Suppa, A; Marsili, L; Giovannelli, F; Di Stasio, F; Rocchi, L; Upadhyay, N; Ruoppolo, G; Cincotta, M; Berardelli, A

2015-08-01

In healthy subjects (HS), transcranial magnetic stimulation (TMS) applied during 'linguistic' tasks discloses excitability changes in the dominant hemisphere primary motor cortex (M1). We investigated 'linguistic' task-related cortical excitability modulation in patients with adductor-type spasmodic dysphonia (ASD), a speech-related focal dystonia. We studied 10 ASD patients and 10 HS. Speech examination included voice cepstral analysis. We investigated the dominant/non-dominant M1 excitability at baseline, during 'linguistic' (reading aloud/silent reading/producing simple phonation) and 'non-linguistic' tasks (looking at non-letter strings/producing oral movements). Motor evoked potentials (MEPs) were recorded from the contralateral hand muscles. We measured the cortical silent period (CSP) length and tested MEPs in HS and patients performing the 'linguistic' tasks with different voice intensities. We also examined MEPs in HS and ASD during hand-related 'action-verb' observation. Patients were studied under and not-under botulinum neurotoxin-type A (BoNT-A). In HS, TMS over the dominant M1 elicited larger MEPs during 'reading aloud' than during the other 'linguistic'/'non-linguistic' tasks. Conversely, in ASD, TMS over the dominant M1 elicited increased-amplitude MEPs during 'reading aloud' and 'syllabic phonation' tasks. CSP length was shorter in ASD than in HS and remained unchanged in both groups performing 'linguistic'/'non-linguistic' tasks. In HS and ASD, 'linguistic' task-related excitability changes were present regardless of the different voice intensities. During hand-related 'action-verb' observation, MEPs decreased in HS, whereas in ASD they increased. In ASD, BoNT-A improved speech, as demonstrated by cepstral analysis and restored the TMS abnormalities. ASD reflects dominant hemisphere excitability changes related to 'linguistic' tasks; BoNT-A returns these excitability changes to normal. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Screening for attention deficit and hyperactivity disorder, autism spectrum disorder, and developmental delay in Taiwanese aboriginal preschool children

PubMed Central

Chan, Hsiang-Lin; Liu, Wen-Sheng; Hsieh, Yi-Hsuan; Lin, Chiao-Fan; Ling, Tiing-Soon; Huang, Yu-Shu

2016-01-01

Objectives This study aimed to estimate the percentages of attention deficit and hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in Taiwanese aboriginal preschool children. Child development level was compared between the two groups. Methods Teachers completed screening questionnaires for ADHD, ASD, and development level for 36- to 72-month-old children in kindergartens in Taiwan. The questionnaire results were compared between the aboriginal and nonaboriginal children. One child psychiatrist then interviewed the aboriginal preschool children to determine if they had ADHD and/or ASD. Results We collected 93 questionnaires from the aboriginal group and 60 from the nonaboriginal group. In the aboriginal group, 5.37% of the children were identified to have ADHD, while 1.08% were identified to have ASD. Significantly fewer aboriginal children had developmental delays for situation comprehension and personal–social development (P=0.012 and 0.002, respectively) than nonaboriginal children. Conclusion Aboriginal children in Taiwan had typical percentages of ADHD and ASD compared to those published in the literature. Aboriginal children showed relative strengths in situation comprehension and personal–social skills. Further studies are required to understand the learning styles of the aboriginal children and to develop effective screening and intervention strategies for ADHD and ASD. PMID:27785028

Impaired social brain network for processing dynamic facial expressions in autism spectrum disorders.

PubMed

Sato, Wataru; Toichi, Motomi; Uono, Shota; Kochiyama, Takanori

2012-08-13

Impairment of social interaction via facial expressions represents a core clinical feature of autism spectrum disorders (ASD). However, the neural correlates of this dysfunction remain unidentified. Because this dysfunction is manifested in real-life situations, we hypothesized that the observation of dynamic, compared with static, facial expressions would reveal abnormal brain functioning in individuals with ASD.We presented dynamic and static facial expressions of fear and happiness to individuals with high-functioning ASD and to age- and sex-matched typically developing controls and recorded their brain activities using functional magnetic resonance imaging (fMRI). Regional analysis revealed reduced activation of several brain regions in the ASD group compared with controls in response to dynamic versus static facial expressions, including the middle temporal gyrus (MTG), fusiform gyrus, amygdala, medial prefrontal cortex, and inferior frontal gyrus (IFG). Dynamic causal modeling analyses revealed that bi-directional effective connectivity involving the primary visual cortex-MTG-IFG circuit was enhanced in response to dynamic as compared with static facial expressions in the control group. Group comparisons revealed that all these modulatory effects were weaker in the ASD group than in the control group. These results suggest that weak activity and connectivity of the social brain network underlie the impairment in social interaction involving dynamic facial expressions in individuals with ASD.

Oral health challenges facing Dubai children with Autism Spectrum Disorder at home and in accessing oral health care.

PubMed

Mansoor, D; Al Halabi, M; Khamis, A H; Kowash, M

2018-06-01

To investigate the challenges faced by Autism Spectrum Disorder (ASD) children and their families in Dubai from three different perspectives of dental care: oral care at home, oral care at the dentist and access to oral care, and to compare the results to their normally developing peers. A case-control comparative study of 84 ASD and 53 healthy children attending special needs centres and schools in Dubai including siblings of the autistic children. Data collection was by a survey questionnaire completed by parents or guardians. More parents of ASD children compared to parents of healthy children reported difficulties across almost all oral care variables explored. The majority of ASD children's parents (83.3%) reported that their children need assistance in brushing their teeth compared with 15.4% of the healthy controls (p-value < 0.001). The ASD children's uncooperative behaviour increased during dental visits and significantly more parents (37%) rated their child's experience as negative compared with 9.5% among the parents of control children (p-value=0.006). The autistic children had visited a dentist mostly for extractions. This study indicates that autistic children in Dubai experience more challenges and barriers to oral care than their typically developing healthy peers.

Maternal Exposure to Occupational Asthmagens During Pregnancy and Autism Spectrum Disorder in the Study to Explore Early Development.

PubMed

Singer, Alison B; Windham, Gayle C; Croen, Lisa A; Daniels, Julie L; Lee, Brian K; Qian, Yinge; Schendel, Diana E; Fallin, M Daniele; Burstyn, Igor

2016-11-01

Maternal immune activity has been linked to children with autism spectrum disorder (ASD). We examined maternal occupational exposure to asthma-causing agents during pregnancy in relation to ASD risk. Our sample included 463 ASD cases and 710 general population controls from the Study to Explore Early Development whose mothers reported at least one job during pregnancy. Asthmagen exposure was estimated from a published job-exposure matrix. The adjusted odds ratio for ASD comparing asthmagen-exposed to unexposed was 1.39 (95 % CI 0.96-2.02). Maternal workplace asthmagen exposure was not associated with ASD risk in this study, but this result does not exclude some involvement of maternal exposure to asthma-causing agents in ASD.

Otitis Media and Related Complications Among Children with Autism Spectrum Disorders.

PubMed

Adams, Daniel J; Susi, Apryl; Erdie-Lalena, Christine R; Gorman, Gregory; Hisle-Gorman, Elizabeth; Rajnik, Michael; Elrod, Marilisa; Nylund, Cade M

2016-05-01

Acute otitis media (AOM) symptoms can be masked by communication deficits, common to children with autism spectrum disorders (ASD). We sought to evaluate the association between ASD and otitis media. Using ICD-9-CM diagnostic codes, we performed a retrospective case-cohort study comparing AOM, and otitis-related diagnoses among children with and without ASD. Children with ASD had a significantly increased rate of AOM, otitis media with effusion, otorrhea, and PE tube placement. Children with ASD were more than twice as likely to develop mastoiditis, and to undergo mastoidectomy and tympanoplasty. Children with ASD are more likely to have middle ear infections and otitis-related complications, highlighting the importance of routine middle ear examinations and close attention to hearing impairment in this population.

Coping and Well-Being in Parents of Children with Autism Spectrum Disorders (ASD).

PubMed

Lai, Wei Wei; Goh, Tze Jui; Oei, Tian P S; Sung, Min

2015-08-01

This study examined psychological well-being and coping in parents of children with ASD and parents of typically developing children. 73 parents of children with ASD and 63 parents of typically developing children completed a survey. Parents of children with ASD reported significantly more parenting stress symptoms (i.e., negative parental self-views, lower satisfaction with parent-child bond, and experiences of difficult child behaviors), more depression symptoms, and more frequent use of Active Avoidance coping, than parents of typically developing children. Parents of children with ASD did not differ significantly in psychological well-being and coping when compared as according to child's diagnosis. Study results reinforced the importance of addressing well-being and coping needs of parents of children with ASD.

Vicarious Effort-Based Decision-Making in Autism Spectrum Disorders.

PubMed

Mosner, Maya G; Kinard, Jessica L; McWeeny, Sean; Shah, Jasmine S; Markiewitz, Nathan D; Damiano-Goodwin, Cara R; Burchinal, Margaret R; Rutherford, Helena J V; Greene, Rachel K; Treadway, Michael T; Dichter, Gabriel S

2017-10-01

This study investigated vicarious effort-based decision-making in 50 adolescents with autism spectrum disorders (ASD) compared to 32 controls using the Effort Expenditure for Rewards Task. Participants made choices to win money for themselves or for another person. When choosing for themselves, the ASD group exhibited relatively similar patterns of effort-based decision-making across reward parameters. However, when choosing for another person, the ASD group demonstrated relatively decreased sensitivity to reward magnitude, particularly in the high magnitude condition. Finally, patterns of responding in the ASD group were related to individual differences in consummatory pleasure capacity. These findings indicate atypical vicarious effort-based decision-making in ASD and more broadly add to the growing body of literature addressing social reward processing deficits in ASD.

External validation of the adult spinal deformity (ASD) frailty index (ASD-FI).

PubMed

Miller, Emily K; Vila-Casademunt, Alba; Neuman, Brian J; Sciubba, Daniel M; Kebaish, Khaled M; Smith, Justin S; Alanay, Ahmet; Acaroglu, Emre R; Kleinstück, Frank; Obeid, Ibrahim; Sánchez Pérez-Grueso, Francisco Javier; Carreon, Leah Y; Schwab, Frank J; Bess, Shay; Scheer, Justin K; Lafage, Virginie; Shaffrey, Christopher I; Pellisé, Ferran; Ames, Christopher P

2018-03-30

To assess the ability of the recently developed adult spinal deformity frailty index (ASD-FI) to predict odds of perioperative complications, odds of reoperation, and length of hospital stay after adult spinal deformity (ASD) surgery using a database other than the one used to create the index. We used the ASD-FI to calculate frailty scores for 266 ASD patients who had minimum postoperative follow-up of 2 years in the European Spine Study Group (ESSG) database. Patients were enrolled from 2012 through 2013. Using ASD-FI scores, we categorized patients as not frail (NF) (< 0.3 points), frail (0.3-0.5 points), or severely frail (SF) (> 0.5 points). Multivariable logistic regression, adjusted for preoperative and surgical factors such as operative time and blood loss, was performed to determine the relationship between ASD-FI category and odds of major complications, odds of reoperation, and length of hospital stay. We categorized 135 patients (51%) as NF, 90 patients (34%) as frail, and 41 patients (15%) as SF. Overall mean ASD-FI score was 0.29 (range 0-0.8). The adjusted odds of experiencing a major intraoperative or postoperative complication (OR 4.5, 95% CI 2.0-10) or having a reoperation (OR 3.9, 95% CI 1.7-8.9) were higher for SF patients compared with NF patients. Mean hospital stay was 2.1 times longer (95% CI 1.8-2.4) for SF patients compared with NF patients. Greater patient frailty, as measured by the ASD-FI, is associated with longer hospital stays and greater odds of major complications and reoperation. These slides can be retrieved under Electronic Supplementary Material.

The influence of parental concern on the utility of autism diagnostic instruments.

PubMed

Havdahl, Karoline Alexandra; Bishop, Somer L; Surén, Pål; Øyen, Anne-Siri; Lord, Catherine; Pickles, Andrew; von Tetzchner, Stephen; Schjølberg, Synnve; Gunnes, Nina; Hornig, Mady; Lipkin, W Ian; Susser, Ezra; Bresnahan, Michaeline; Magnus, Per; Stenberg, Nina; Reichborn-Kjennerud, Ted; Stoltenberg, Camilla

2017-10-01

The parental report-based Autism Diagnostic Interview-Revised (ADI-R) and the clinician observation-based Autism Diagnostic Observation Schedule (ADOS) have been validated primarily in U.S. clinics specialized in autism spectrum disorder (ASD), in which most children are referred by their parents because of ASD concern. This study assessed diagnostic agreement of the ADOS-2 and ADI-R toddler algorithms in a more broadly based sample of 679 toddlers (age 35-47 months) from the Norwegian Mother and Child Cohort. We also examined whether parental concern about ASD influenced instrument performance, comparing toddlers identified based on parental ASD concern (n = 48) and parent-reported signs of developmental problems (screening) without a specific concern about ASD (n = 400). The ADOS cutoffs showed consistently well-balanced sensitivity and specificity. The ADI-R cutoffs demonstrated good specificity, but reduced sensitivity, missing 43% of toddlers whose parents were not specifically concerned about ASD. The ADI-R and ADOS dimensional scores agreed well with clinical diagnoses (area under the curve ≥ 0.85), contributing additively to their prediction. On the ADI-R, different cutoffs were needed according to presence or absence of parental ASD concern, in order to achieve comparable balance of sensitivity and specificity. These results highlight the importance of taking parental concern about ASD into account when interpreting scores from parental report-based instruments such as the ADI-R. While the ADOS cutoffs performed consistently well, the additive contributions of ADI-R and ADOS scores to the prediction of ASD diagnosis underscore the value of combining instruments based on parent accounts and clinician observation in evaluation of ASD. Autism Res 2017, 10: 1672-1686. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

Acute sleep deprivation preconditions the heart against ischemia/ reperfusion injury: the role of central GABA-A receptors

PubMed Central

Parsa, Hoda; Imani, Alireza; Faghihi, Mahdieh; Riahi, Esmail; Badavi, Mohammad; Shakoori, Abbas; Rastegar, Tayebeh; Aghajani, Marjan; Rajani, Sulail Fatima

2017-01-01

Objective(s): Central γ-aminobutyric acid (GABA) neurotransmission modulates cardiovascular functions and sleep. Acute sleep deprivation (ASD) affects functions of various body organs via different mechanisms. Here, we evaluated the effect of ASD on cardiac ischemia/reperfusion injury (IRI), and studied the role of GABA-A receptor inhibition in central nucleus of amygdala (CeA) by assessing nitric oxide (NO) and oxidative stress. Materials and Methods: The CeA in sixty male Wistar rats was cannulated for saline or bicuculline (GABA-A receptor antagonist) administration. All animals underwent 30 min of coronary occlusion (ischemia), followed by 2 hr reperfusion (IR). The five experimental groups (n=12) included are as follows: IR: received saline; BIC+IR: received Bicuculline; MLP+IR: received saline, followed by the placement of animals in an aquarium with multiple large platforms; ASD+IR: underwent ASD in an aquarium with multiple small platforms; and BIC+ASD+IR: received bicuculline prior to ASD. Results: Bicuculline administration increased the malondialdehyde levels and infarct size, and decreased the NO metabolites levels and endothelial nitric oxide synthase (eNOS) gene expression in infarcted and non-infarcted areas in comparison to IR group. ASD reduced malondialdehyde levels and infarct size and increased NO metabolites, corticosterone levels and eNOS expression in infarcted and non-infarcted areas as compared to the IR group. Levels of malondialdehyde were increased while levels of NO metabolites, corticosterone and eNOS expression in infarcted and non-infarcted areas were reduced in the BIC+ASD+IR as compared to the ASD+IR group. Conclusion: Blockade of GABA-A receptors in the CeA abolishes ASD-induced cardioprotection by suppressing oxidative stress and NO production. PMID:29299201

Acute sleep deprivation preconditions the heart against ischemia/ reperfusion injury: the role of central GABA-A receptors.

PubMed

Parsa, Hoda; Imani, Alireza; Faghihi, Mahdieh; Riahi, Esmail; Badavi, Mohammad; Shakoori, Abbas; Rastegar, Tayebeh; Aghajani, Marjan; Rajani, Sulail Fatima

2017-11-01

Central γ-aminobutyric acid (GABA) neurotransmission modulates cardiovascular functions and sleep. Acute sleep deprivation (ASD) affects functions of various body organs via different mechanisms. Here, we evaluated the effect of ASD on cardiac ischemia/reperfusion injury (IRI), and studied the role of GABA-A receptor inhibition in central nucleus of amygdala (CeA) by assessing nitric oxide (NO) and oxidative stress. The CeA in sixty male Wistar rats was cannulated for saline or bicuculline (GABA-A receptor antagonist) administration. All animals underwent 30 min of coronary occlusion (ischemia), followed by 2 hr reperfusion (IR). The five experimental groups (n=12) included are as follows: IR: received saline; BIC+IR: received Bicuculline; MLP+IR: received saline, followed by the placement of animals in an aquarium with multiple large platforms; ASD+IR: underwent ASD in an aquarium with multiple small platforms; and BIC+ASD+IR: received bicuculline prior to ASD. Bicuculline administration increased the malondialdehyde levels and infarct size, and decreased the NO metabolites levels and endothelial nitric oxide synthase (eNOS) gene expression in infarcted and non-infarcted areas in comparison to IR group. ASD reduced malondialdehyde levels and infarct size and increased NO metabolites, corticosterone levels and eNOS expression in infarcted and non-infarcted areas as compared to the IR group. Levels of malondialdehyde were increased while levels of NO metabolites, corticosterone and eNOS expression in infarcted and non-infarcted areas were reduced in the BIC+ASD+IR as compared to the ASD+IR group. Blockade of GABA-A receptors in the CeA abolishes ASD-induced cardioprotection by suppressing oxidative stress and NO production.

Longitudinal Course of Bipolar Disorder in Youth With High-Functioning Autism Spectrum Disorder

PubMed Central

Borue, Xenia; Mazefsky, Carla; Rooks, Brian T.; Strober, Michael; Keller, Martin B.; Hower, Heather; Yen, Shirley; Gill, Mary Kay; Diler, Rasim S.; Axelson, David A.; Goldstein, Benjamin I.; Goldstein, Tina R.; Ryan, Neal; Liao, Fangzi; Hunt, Jeffrey I.; Dickstein, Daniel P.; Birmaher, Boris

2016-01-01

Objective To provide the first longitudinal characterization of mood and psychosocial functioning in youth with comorbid bipolar (BD) and autism spectrum (ASD) disorders. Method The Course and Outcome of Bipolar Youth study followed 368 youth (7–17 years) with DSM-IV bipolar I (BP-I), -II, or Not Otherwise Specified (NOS) for, on average, 9 years using the Longitudinal Interval Follow-up Evaluation. This subgroup analysis compared youth with and without ASD on clinical presentation, percentage of time with mood symptomatology, and psychosocial functioning. Results Thirty youth (~8%) met DSM-IV criteria for Asperger disorder or pervasive developmental disorder-NOS (referred to here as ASD). Lifetime worst episode severity was similar in both groups, but youth with both BD and ASD (BD+ASD) had elevated rates of comorbid attention-deficit/hyperactivity and obsessive-compulsive disorders, were younger at intake, and had an earlier onset of mood symptoms. Over time, in both groups, the proportion of predominantly euthymic youth increased, and episode recurrence decreased. Compared to youth with BD, the clinical presentation of youth with BD+ASD more frequently involved distractibility, racing thoughts, depressed mood, social withdrawal, and low reactivity of negative mood states. ASD-related symptomatic differences were generally strongest early and decreased over time. Youth with BD+ASD had significantly greater impairment in friendships throughout follow-up. Conclusion Youth with BD+ASD exhibit typical BD mood symptoms but with earlier onset, mixed symptom presentation, and additive functional impairments. Significant amelioration of clinical symptoms occurred over time, suggesting that early recognition and treatment of mood disorders in youth with ASD may improve clinical outcomes. PMID:27871641

Comparing Children with ASD and Their Peers' Growth in Print Knowledge

ERIC Educational Resources Information Center

Dynia, Jaclyn M.; Brock, Matthew E.; Logan, Jessica A.; Justice, Laura M.; Kaderavek, Joan N.

2016-01-01

Many children with autism spectrum disorder (ASD) struggle with reading. An increased focus on emergent literacy skills--particularly print knowledge--might improve later reading outcomes. We analyzed longitudinal measures of print knowledge (i.e., alphabet knowledge and print-concept knowledge) for 35 preschoolers with ASD relative to a sample of…

Neural Correlates of Explicit versus Implicit Facial Emotion Processing in ASD

ERIC Educational Resources Information Center

Luckhardt, Christina; Kröger, Anne; Cholemkery, Hannah; Bender, Stephan; Freitag, Christine M.

2017-01-01

The underlying neural mechanisms of implicit and explicit facial emotion recognition (FER) were studied in children and adolescents with autism spectrum disorder (ASD) compared to matched typically developing controls (TDC). EEG was obtained from N = 21 ASD and N = 16 TDC. Task performance, visual (P100, N170) and cognitive (late positive…

Cardiac Reactivity and Stimulant Use in Adolescents with Autism Spectrum Disorders with Comorbid ADHD Versus ADHD

ERIC Educational Resources Information Center

Bink, M.; Popma, A.; Bongers, I. L.; van Boxtel, G. J. M.; Denissen, A.; van Nieuwenhuizen, Ch.

2015-01-01

A large number of youngsters with autism spectrum disorders (ASD) display comorbid attention deficit/hyperactivity disorder (ADHD) symptoms. However, previous studies are not conclusive whether psychophysiological correlates, like cardiac reactivity, are different for ASD with comorbid ADHD (ASD+) compared to ADHD. Therefore, the current study…

Comparative Language Development in Bilingual and Monolingual Children with Autism Spectrum Disorder: A Systematic Review

ERIC Educational Resources Information Center

Lund, Emily M.; Kohlmeier, Theresa L.; Durán, Lillian K.

2017-01-01

The prevalence of both bilingual children and children with autism spectrum disorder (ASD) is growing rapidly, and early childhood educators may be increasingly likely to encounter bilingual children with ASD in their classrooms. Because ASD significantly affects communication, many parents and professionals may have questions or concerns about…

Evaluating and Enhancing Driving Ability Among Teens with Autism Spectrum Disorder (ASD)

DTIC Science & Technology

2014-10-01

impact. 15. SUBJECT TERMS Autism, Driving Safety , Driving Simulation, Automated Feedback, Eye Tracking 16. SECURITY CLASSIFICATION OF: 17...driving training (RT) required by the DMV, VRDS training + RT (VRDS-T) would lead to greater improvement in driving safety and less driving anxiety, 2...the Idea Development award we learned that VRDS-T can significantly improve the driving safety of novice drivers with ASD, and this is not enhanced by

Association between amygdala response to emotional faces and social anxiety in autism spectrum disorders.

PubMed

Kleinhans, Natalia M; Richards, Todd; Weaver, Kurt; Johnson, L Clark; Greenson, Jessica; Dawson, Geraldine; Aylward, Elizabeth

2010-10-01

Difficulty interpreting facial expressions has been reported in autism spectrum disorders (ASD) and is thought to be associated with amygdala abnormalities. To further explore the neural basis of abnormal emotional face processing in ASD, we conducted an fMRI study of emotional face matching in high-functioning adults with ASD and age, IQ, and gender matched controls. In addition, we investigated whether there was a relationship between self-reported social anxiety and fMRI activation. During fMRI scanning, study participants were instructed to match facial expressions depicting fear or anger. The control condition was a comparable shape-matching task. The control group evidenced significantly increased left prefrontal activation and decreased activation in the occipital lobes compared to the ASD group during emotional face matching. Further, within the ASD group, greater social anxiety was associated with increased activation in right amygdala and left middle temporal gyrus, and decreased activation in the fusiform face area. These results indicate that level of social anxiety mediates the neural response to emotional face perception in ASD. Copyright © 2010 Elsevier Ltd. All rights reserved.

Children with autism spectrum disorder (ASD) attend typically to faces and objects presented within their picture communication systems.

PubMed

Gillespie-Smith, K; Riby, D M; Hancock, P J B; Doherty-Sneddon, G

2014-05-01

Children with autism spectrum disorder (ASD) may require interventions for communication difficulties. One type of intervention is picture communication symbols which are proposed to improve comprehension of linguistic input for children with ASD. However, atypical attention to faces and objects is widely reported across the autism spectrum for several types of stimuli. In this study we used eye-tracking methodology to explore fixation duration and time taken to fixate on the object and face areas within picture communication symbols. Twenty-one children with ASD were compared with typically developing matched groups. Children with ASD were shown to have similar fixation patterns on face and object areas compared with typically developing matched groups. It is proposed that children with ASD attend to the images in a manner that does not differentiate them from typically developing individuals. Therefore children with and without autism have the same opportunity to encode the available information. We discuss what this may imply for interventions using picture symbols. © 2013 The Authors. Journal of Intellectual Disability Research © 2013 John Wiley & Sons Ltd, MENCAP & IASSIDD.

Contrasting Complement Control, Temporal Adjunct Control and Controlled Verbal Gerund Subjects in ASD: The Role of Contextual Cues in Reference Assignment.

PubMed

Janke, Vikki; Perovic, Alexandra

2017-01-01

This study examines two complex syntactic dependencies (complement control and sentence-final temporal adjunct control) and one pragmatic dependency (controlled verbal gerund subjects) in children with ASD. Sixteen high-functioning (HFA) children (aged 6-16) with a diagnosis of autism and no language impairment, matched on age, gender and non-verbal MA to one TD control group, and on age, gender and verbal MA to another TD control group, undertook three picture-selection tasks. Task 1 measured their base-line interpretations of the empty categories ( ec ). Task 2 preceded these sentence sets with a weakly established topic cueing an alternative referent and Task 3 with a strongly established topic cueing an alternative referent. In complement control (Ron persuaded Hermione ec to kick the ball) and sentence-final temporal adjunct control (Harry tapped Luna while ec feeding the owl), the reference of the ec is argued to be related obligatorily to the object and subject respectively. In controlled verbal-gerund subjects (VGS) ( ec Rowing the boat clumsily made Luna seasick), the ec 's reference is resolved pragmatically. Referent choices across the three tasks were compared. TD children chose the object uniformly in complement control across all tasks but in adjunct control, preferences shifted toward the object in Task 3. In controlled VGSs, they exhibited a strong preference for an internal-referent interpretation in Task 1, which shifted in the direction of the cues in Tasks 2 and 3. HFA children gave a mixed performance. They patterned with their TD counterparts on complement control and controlled VGSs but performed marginally differently on adjunct control: no TD groups were influenced by the weakly established topic in Task 2 but all groups were influenced by the strongly established topic in Task 3. HFA children were less influenced than the TD children, resulting in their making fewer object choices overall but revealing parallel patterns of performance. In this first study of three sub-types of control in ASD, we demonstrate that HFA children consult the same pragmatic cues to the same degree as TD children, in spite of the diverse pragmatic deficits reported for this population.

Contrasting Complement Control, Temporal Adjunct Control and Controlled Verbal Gerund Subjects in ASD: The Role of Contextual Cues in Reference Assignment

PubMed Central

Janke, Vikki; Perovic, Alexandra

2017-01-01

This study examines two complex syntactic dependencies (complement control and sentence-final temporal adjunct control) and one pragmatic dependency (controlled verbal gerund subjects) in children with ASD. Sixteen high-functioning (HFA) children (aged 6–16) with a diagnosis of autism and no language impairment, matched on age, gender and non-verbal MA to one TD control group, and on age, gender and verbal MA to another TD control group, undertook three picture-selection tasks. Task 1 measured their base-line interpretations of the empty categories (ec). Task 2 preceded these sentence sets with a weakly established topic cueing an alternative referent and Task 3 with a strongly established topic cueing an alternative referent. In complement control (Ron persuaded Hermione ec to kick the ball) and sentence-final temporal adjunct control (Harry tapped Luna while ec feeding the owl), the reference of the ec is argued to be related obligatorily to the object and subject respectively. In controlled verbal-gerund subjects (VGS) (ec Rowing the boat clumsily made Luna seasick), the ec's reference is resolved pragmatically. Referent choices across the three tasks were compared. TD children chose the object uniformly in complement control across all tasks but in adjunct control, preferences shifted toward the object in Task 3. In controlled VGSs, they exhibited a strong preference for an internal-referent interpretation in Task 1, which shifted in the direction of the cues in Tasks 2 and 3. HFA children gave a mixed performance. They patterned with their TD counterparts on complement control and controlled VGSs but performed marginally differently on adjunct control: no TD groups were influenced by the weakly established topic in Task 2 but all groups were influenced by the strongly established topic in Task 3. HFA children were less influenced than the TD children, resulting in their making fewer object choices overall but revealing parallel patterns of performance. In this first study of three sub-types of control in ASD, we demonstrate that HFA children consult the same pragmatic cues to the same degree as TD children, in spite of the diverse pragmatic deficits reported for this population. PMID:28400743

Motor competency and social communication skills in preschool children with autism spectrum disorder.

PubMed

Craig, Francesco; Lorenzo, Alessandro; Lucarelli, Elisabetta; Russo, Luigi; Fanizza, Isabella; Trabacca, Antonio

2018-06-01

This study aimed to investigate the association between motor competency and social communication in children with Autism Spectrum Disorder (ASD) compared with children with Intellectual Disabilities (ID) and typically developing (TD) children. Motor competency, ASD symptoms, and nonverbal Intelligent Quotient (IQ) were investigated through the following tests: Movement Assessment Battery for Children, second edition (MABC-2), Social Communication Questionnaire (SCQ), Autism Classification System of Functioning: Social Communication (ACSF:SC) and Leiter International Performances Scale Revised (Leiter-R). The ASD + ID and ID groups had lower MABC-2-manual dexterity mean scores, MABC-2-aiming and catching mean scores, MABC-2-static and dynamic balance mean scores and MABC-2-TTS compared with the TD group (P < 0.05). In addition, the ASD + ID group had lower MABC-2-aiming and catching mean scores compared with the ID group. In the ASD + ID group, we found a significant negative correlation (P < 0.001) between MABC-2-aiming and catching scores with SCQ scores, nonverbal IQ and ACSF:SC levels. Our findings provide new insight into the common neuropsychological mechanisms underlying social communication and motor deficits in ASD. Multiple deficits in motor functioning may be present in ASD and ID, however deficits involving the ability to integrate motor and social cues are somewhat specific to ASD. Autism Res 2018, 11: 893-902. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. This study highlighted the specificity of motor impairment in ASD comparing performances on a frequently used measure of motor impairment between clinical groups (ASD + ID and ID) and a non-clinical group. While previous research has suggested that multiple deficits in motor functioning may be present in ASD, our findings suggest that deficits in tasks involving the ability to integrate visual and motor cues (aiming and catching task) are somewhat specific to ASD. © 2018 International Society for Autism Research, Wiley Periodicals, Inc.

Skeletal Growth Dysregulation in Australian Male Infants and Toddlers With Autism Spectrum Disorder.

PubMed

Green, Cherie C; Dissanayake, Cheryl; Loesch, Danuta Z; Bui, Minh; Barbaro, Josephine

2018-06-01

Recent findings suggest that children with Autism Spectrum Disorder (ASD) are larger in size for head circumference (HC), height, and weight compared to typically developing (TD) children; however, little is known about their rate of growth, especially in height and weight. The current study aimed to: (a) confirm and extend upon previous findings of early generalized overgrowth in ASD; and (b) determine if there were any differences in the rate of growth between infants and toddlers with ASD compared to their TD peers. Measurements of HC, height, and weight were available for 135 boys with ASD and 74 TD boys, from birth through 3 years of age. Size and growth rate in HC, height, and weight were analyzed using a linear mixed-effects model. Infants with ASD were significantly smaller in size at birth for HC, body length, and weight compared to TD infants (all P < 0.05); however, they grew at a significantly faster rate in HC and height in comparison to the TD children (P < 0.001); there was no significant difference between the groups in growth rate for weight (P > 0.05). The results confirmed that male infants and toddlers with ASD exhibit skeletal growth dysregulation early in life. Autism Res 2018, 11: 846-856. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. Recent findings suggest that infants with Autism Spectrum Disorder (ASD) are smaller in size at birth compared to typically developing infants but grow larger than their peers during the first year. Little is known about their rate of growth, especially for height and weight. Our findings confirmed that infants with ASD are smaller in size at birth for head circumference (HC), height, and weight, but grow at a faster rate in HC and height than their peers from birth to 3 years. © 2018 International Society for Autism Research, Wiley Periodicals, Inc.

Gender differences in emotionality and sociability in children with autism spectrum disorders

PubMed Central

2014-01-01

Background Four times as many males are diagnosed with high functioning autism compared to females. A growing body of research that focused on females with autism spectrum disorder (ASD) questions the assumption of gender invariance in ASD. Clinical observations suggest that females with ASD superficially demonstrate better social and emotional skills than males with ASD, which may camouflage other diagnostic features. This may explain the under-diagnosis of females with ASD. Methods We hypothesised that females with ASD would display better social skills than males with ASD on a test of friendship and social function. One hundred and one 10- to 16-year-olds (ASD females, n = 25; typically developing (TD) females, n = 25; ASD males, n = 25; TD males, n = 26) were interviewed (using the friendship questionnaire (FQ)) with high scores indicating the child has close, empathetic and supportive relationships. One parent of each child completed the FQ to assess whether there are differences in perception of friendships between parents and children. Results It was found that, independent of diagnosis, females demonstrated higher scores on the FQ than males. Further, regardless of gender, children with ASD demonstrated lower scores than TD children. Moreover, the effect of ASD was independent of gender. Interestingly, females with ASD and TD males displayed similar scores on the FQ. Conclusions This finding is supported by clinical reports that females with ASD have more developed social skills than males with ASD. Further research is now required to examine the underlying causes for this phenomenon in order to develop gender-appropriate diagnostic criteria and interventions for ASD. PMID:24576331

Symptoms of ADHD Affect Intrasubject Variability in Youths with Autism Spectrum Disorder: An Ex-Gaussian Analysis.

PubMed

Hwang-Gu, Shoou-Lian; Lin, Hsiang-Yuan; Chen, Yu-Chi; Tseng, Yu-Han; Hsu, Wen-Yau; Chou, Miao-Chun; Chou, Wen-Jun; Wu, Yu-Yu; Gau, Susan Shur-Fen

2018-05-30

Increased intrasubject variability in reaction times (RT-ISV) is frequently found in individuals with autism spectrum disorder (ASD). However, how dimensional attention deficit/hyperactivity disorder (ADHD) symptoms impact RT-ISV in individuals with ASD remains elusive. We assessed 97 high-functioning youths with co-occurring ASD and ADHD (ASD+ADHD), 124 high-functioning youths with ASD only, 98 youths with ADHD only, and 249 typically developing youths, 8-18 years of age, using the Conners Continuous Performance Test (CCPT). We compared the conventional CCPT parameters (omission errors, commission errors, mean RT and RT standard error (RTSE) as well as the ex-Gaussian parameters of RT (mu, sigma, and tau) across the four groups. We also conducted regression analyses to assess the relationships between RT indices and symptoms of ADHD and ASD in the ASD group (i.e., the ASD+ADHD and ASD-only groups). The ASD+ADHD and ADHD-only groups had higher RT-ISV than the other two groups. RT-ISV, specifically RTSE and tau, was significantly associated with ADHD symptoms rather than autistic traits in the ASD group. Regression models also revealed that sex partly accounted for RT-ISV variance in the ASD group. A post hoc analysis showed girls with ASD had higher tau and RTSE values than their male counterparts. Our results suggest that RT-ISV is primarily associated with co-occurring ADHD symptoms/diagnosis in children and adolescents with ASD. These results do not support the hypothesis of response variability as a transdiagnostic phenotype for ASD and ADHD and warrant further validation at a neural level.

The peer relationships of girls with ASD at school: comparison to boys and girls with and without ASD.

PubMed

Dean, Michelle; Kasari, Connie; Shih, Wendy; Frankel, Fred; Whitney, Rondalyn; Landa, Rebecca; Lord, Catherine; Orlich, Felice; King, Bryan; Harwood, Robin

2014-11-01

This study examines the social relationships of elementary school children with high-functioning autism, focusing on how gender relates to social preferences and acceptance, social connections, reciprocal friendships, and rejection. Peer nomination data were analyzed for girls with and without ASD (n = 50) and boys with and without ASD (n = 50). Girls and boys with ASD were matched by age, gender, and IQ. Each child with ASD was matched by age and gender to a typically developing classmate. Consistent with typically developing populations, children with ASD preferred, were accepted by, and primarily socialized with same-gender friends. With fewer nominations and social relationships, girls and boys with ASD appear more socially similar to each other than to the same-gender control group. Additionally, girls and boys with ASD showed higher rates of social exclusion than their typically developing peers. However, boys with ASD were more overtly socially excluded compared to girls with ASD, who seemed to be overlooked, rather than rejected. Our data suggest a number of interesting findings in the social relationships of children with ASD in schools. Like typically developing populations, children with ASD identify with their own gender when socializing and choosing friends. But given the social differences between genders, it is likely that girls with ASD are experiencing social challenges that are different from boys with ASD. Therefore, gender is an important environmental factor to consider when planning social skills interventions at school. © 2014 The Authors. Journal of Child Psychology and Psychiatry. © 2014 Association for Child and Adolescent Mental Health.

Risk of epilepsy and autism in full and half siblings-A population-based cohort study.

PubMed

Christensen, Jakob; Overgaard, Morten; Parner, Erik T; Vestergaard, Mogens; Schendel, Diana

2016-12-01

Epilepsy and autism spectrum disorder (ASD) often occur together in the same individual. However, it remains unknown whether siblings of children with ASD have an increased risk of epilepsy and vice versa. This study determines the risk of ASD and epilepsy among younger siblings of children with ASD and epilepsy. The study included all children born in Denmark between January 1, 1980 and 31 December 2006 who participated in follow-up until December 31, 2012 (1,663,302 children). We used Cox regression to calculate the adjusted hazard ratio (aHR) and the Kaplan-Meier method to calculate the cumulative incidence. The overall aHR of epilepsy in younger siblings increased by 70% (aHR 1.70, 95% confidence interval [CI] 1.34-2.16%) if the older sibling had ASD compared with siblings where the older sibling did not have ASD. The cumulative incidence of epilepsy at 20 years of age was 2.54% (95% CI 1.97-3.26%) if the older sibling had ASD, whereas the cumulative incidence of epilepsy at 20 years of age was 1.63% (95% CI 1.60-1.66%) if the older sibling did not have ASD. The overall aHR of ASD in younger siblings increased by 54% if the older sibling had epilepsy (aHR 1.54, 95% CI 1.32-1.80) compared with siblings where the older sibling did not have epilepsy. The cumulative incidence of ASD at 20 years of age was 2.06% (95% CI 1.84-2.32%) if the older sibling had epilepsy, whereas the cumulative incidence of ASD at 20 years of age was 1.27% (95% CI 1.25-1.29%) if the older sibling did not have epilepsy. The cross-disorder sibling risk of epilepsy and ASD was increased for the two disorders, which suggests that genes or environmental factors shared by family members may play a causal role in the co-occurrence of ASD and epilepsy. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

Meta-analysis of social cognition in attention-deficit/hyperactivity disorder (ADHD): comparison with healthy controls and autistic spectrum disorder.

PubMed

Bora, E; Pantelis, C

2016-03-01

Impairment in social cognition is an established finding in autism spectrum disorders (ASD). Emerging evidence suggests that attention-deficit/hyperactivity disorder (ADHD) might be also associated with deficits in theory of mind (ToM) and emotion recognition. However, there are inconsistent findings, and it has been debatable whether such deficits persist beyond childhood and how similar social cognitive deficits are in ADHD v. ASD. We conducted a meta-analysis of social cognition, including emotion recognition and ToM, studies in ADHD compared with healthy controls and ASD. The current meta-analysis involved 44 studies comparing ADHD (n = 1999) with healthy controls (n = 1725) and 17 studies comparing ADHD (n = 772) with ASD (n = 710). Facial and vocal emotion recognition (d = 0.40-0.44) and ToM (d = 0.43) abilities were significantly impaired in ADHD. The most robust facial emotion recognition deficits were evident in anger and fear. Social cognitive deficits were either very subtle (emotion recognition) or non-significant (ToM) in adults with ADHD. Deficits in social cognition, especially ToM, were significantly more pronounced in ASD compared with ADHD. General cognitive impairment has contributed to social cognitive deficits in ADHD. Performance of individuals with ADHD on social cognition lies intermediate between ASD and healthy controls. However, developmental trajectories of social cognition probably differ between ADHD and ASD as social cognitive deficits in ADHD might be improving with age in most individuals. There is a need for studies investigating a potential subtype of ADHD with persistent social cognitive deficits and exploring longitudinal changes in social cognition during development.

Superior haptic-to-visual shape matching in autism spectrum disorders.

PubMed

Nakano, Tamami; Kato, Nobumasa; Kitazawa, Shigeru

2012-04-01

A weak central coherence theory in autism spectrum disorder (ASD) proposes that a cognitive bias toward local processing in ASD derives from a weakness in integrating local elements into a coherent whole. Using this theory, we hypothesized that shape perception through active touch, which requires sequential integration of sensorimotor traces of exploratory finger movements into a shape representation, would be impaired in ASD. Contrary to our expectation, adults with ASD showed superior performance in a haptic-to-visual delayed shape-matching task compared to adults without ASD. Accuracy in discriminating haptic lengths or haptic orientations, which lies within the somatosensory modality, did not differ between adults with ASD and adults without ASD. Moreover, this superior ability in inter-modal haptic-to-visual shape matching was not explained by the score in a unimodal visuospatial rotation task. These results suggest that individuals with ASD are not impaired in integrating sensorimotor traces into a global visual shape and that their multimodal shape representations and haptic-to-visual information transfer are more accurate than those of individuals without ASD. Copyright © 2012 Elsevier Ltd. All rights reserved.

A New Methodology of Viewing Extra-Axial Fluid and Cortical Abnormalities in Children with Autism via Transcranial Ultrasonography

PubMed Central

Bradstreet, James Jeffrey; Pacini, Stefania; Ruggiero, Marco

2014-01-01

Background: Autism spectrum disorders (ASDs) are developmental conditions of uncertain etiology which have now affected more than 1% of the school-age population of children in many developed nations. Transcranial ultrasonography (TUS) via the temporal bone appeared to be a potential window of investigation to determine the presence of both cortical abnormalities and increased extra-axial fluid (EAF). Methods: TUS was accomplished using a linear probe (10–5 MHz). Parents volunteered ASD subjects (N = 23; males 18, females 5) for evaluations (mean = 7.46 years ± 3.97 years), and 15 neurotypical siblings were also examined (mean = 7.15 years ± 4.49 years). Childhood Autism Rating Scale (CARS2®) scores were obtained and the ASD score mean was 48.08 + 6.79 (Severe). Results: Comparisons of the extra-axial spaces indicated increases in the ASD subjects. For EAF we scored based on the gyral summit distances between the arachnoid membrane and the cortical pia layer (subarachnoid space): (1) <0.05 cm, (2) 0.05–0.07 cm, (3) 0.08–0.10 cm, (4) >0.10 cm. All of the neurotypical siblings scored 1, whereas the ASD mean score was 3.41 ± 0.67. We also defined cortical dysplasia as the following: hypoechoic lesions within the substance of the cortex, or disturbed layering within the gray matter. For cortical dysplasia we scored: (1) none observed, (2) rare hypoechogenic lesions and/or mildly atypical cortical layering patterns, (3) more common, but separated areas of cortical hypoechogenic lesions, (4) very common or confluent areas of cortical hypoechogenicity. Again all of the neurotypical siblings scored 1, while the ASD subjects’ mean score was 2.79 ± 0.93. Conclusion: TUS may be a useful screening technique for children at potential risk of ASDs which, if confirmed with repeated studies and high resolution MRI, provides rapid, non-invasive qualification of EAF, and cortical lesions. PMID:24459462

The clinical implications of high levels of autism spectrum disorder features in anorexia nervosa: a pilot study.

PubMed

Huke, Vanessa; Turk, Jeremy; Saeidi, Saeideh; Kent, Andrew; Morgan, John F

2014-03-01

This study examined autism spectrum disorder (ASD) features in relation to treatment completion and eating disorder psychopathology in anorexia nervosa (AN). Thirty-two adult women were recruited from specialist eating disorder services. Features of ASD and disordered eating were measured. Premature termination of treatment was recorded to explore whether ASD traits had impact on early discharge. A healthy control group was also recruited to investigate ASD traits between clinical and nonclinical samples. Significant differences were found between the AN group and the healthy control group in obsessive-compulsive disorder traits, depression and anxiety and ASD traits, with significant differences between groups in Social Skill and Attention Switching. The AN group reported no significant relationship between disordered eating severity and ASD traits. No significant effect was found between ASD features and treatment completion. Raw data on premature termination of treatment, despite no statistic impact, showed that seven out of the eight participants with high features of ASD completed treatment as planned compared with 50% of those with low ASD traits. Unexpectedly, this suggests enhanced treatment adherence in ASD. Copyright © 2013 John Wiley & Sons, Ltd and Eating Disorders Association.

Gender Profiles of Behavioral Attention in Children With Autism Spectrum Disorder.

PubMed

May, Tamara; Cornish, Kim; Rinehart, Nicole J

2016-07-01

The attention profile of girls with autism spectrum disorder (ASD) is unclear compared with boys with ASD and typical children. This study aimed to investigate parent-reported ASD and ADHD symptoms in a large sample of boys and girls with and without ASD. A total of 124 normally intelligent children, half of them girls, 64 with autistic disorder or Asperger's disorder, and 60 age- and gender-matched typically developing, aged 7 to 12 years, were recruited. Parents completed questionnaires regarding autistic and ADHD symptoms. No gender differences in social difficulties but more repetitive motor movements, communication difficulties, and inattention were reported in males, regardless of group. Younger boys with ASD had more elevated levels of hyperactivity-impulsivity than younger girls with ASD. Gender differences in autistic symptoms and inattention in ASD reflected gender differences in typical children. More pronounced hyperactivity in younger boys with ASD could contribute to higher rates of clinical referral than girls. © The Author(s) 2012.

Profile of refractive errors in European Caucasian children with Autistic Spectrum Disorder; increased prevalence and magnitude of astigmatism.

PubMed

Anketell, Pamela M; Saunders, Kathryn J; Gallagher, Stephen; Bailey, Clare; Little, Julie-Anne

2016-07-01

Autistic Spectrum Disorder (ASD) is a common neurodevelopmental disorder characterised by impairment of communication, social interaction and repetitive behaviours. Only a small number of studies have investigated fundamental clinical measures of vision including refractive error. The aim of this study was to describe the refractive profile of a population of children with ASD compared to typically developing (TD) children. Refractive error was assessed using the Shin-Nippon NVision-K 5001 open-field autorefractor following the instillation of cyclopentolate hydrochloride 1% eye drops. A total of 128 participants with ASD (mean age 10.9 ± 3.3 years) and 206 typically developing participants (11.5 ± 3.1 years) were recruited. There was no significant difference in median refractive error, either by spherical equivalent or most ametropic meridian between the ASD and TD groups (Spherical equivalent, Mann-Whitney U307 = 1.15, p = 0.25; Most Ametropic Meridian, U305 = 0.52, p = 0.60). Median refractive astigmatism was -0.50DC (range 0.00 to -3.50DC) for the ASD group and -0.50DC (Range 0.00 to -2.25DC) for the TD group. Magnitude and prevalence of refractive astigmatism (defined as astigmatism ≥1.00DC) was significantly greater in the ASD group compared to the typically developing group (ASD 26%, TD 8%, magnitude U305 = 3.86, p = 0.0001; prevalence (χ12=17.71 , p < 0.0001). This is the first study to describe the refractive profile of a population of European Caucasian children with ASD compared to a TD population of children. Unlike other neurodevelopmental conditions, there was no increased prevalence of spherical refractive errors in ASD but astigmatic errors were significantly greater in magnitude and prevalence. This highlights the need to examine refractive errors in this population. © 2016 The Authors Ophthalmic & Physiological Optics © 2016 The College of Optometrists.

Amplitude spectrum distance: measuring the global shape divergence of protein fragments.

PubMed

Galiez, Clovis; Coste, François

2015-08-14

In structural bioinformatics, there is an increasing interest in identifying and understanding the evolution of local protein structures regarded as key structural or functional protein building blocks. A central need is then to compare these, possibly short, fragments by measuring efficiently and accurately their (dis)similarity. Progress towards this goal has given rise to scores enabling to assess the strong similarity of fragments. Yet, there is still a lack of more progressive scores, with meaningful intermediate values, for the comparison, retrieval or clustering of distantly related fragments. We introduce here the Amplitude Spectrum Distance (ASD), a novel way of comparing protein fragments based on the discrete Fourier transform of their C(α) distance matrix. Defined as the distance between their amplitude spectra, ASD can be computed efficiently and provides a parameter-free measure of the global shape dissimilarity of two fragments. ASD inherits from nice theoretical properties, making it tolerant to shifts, insertions, deletions, circular permutations or sequence reversals while satisfying the triangle inequality. The practical interest of ASD with respect to RMSD, RMSDd, BC and TM scores is illustrated through zinc finger retrieval experiments and concrete structure examples. The benefits of ASD are also illustrated by two additional clustering experiments: domain linkers fragments and complementarity-determining regions of antibodies. Taking advantage of the Fourier transform to compare fragments at a global shape level, ASD is an objective and progressive measure taking into account the whole fragments. Its practical computation time and its properties make ASD particularly relevant for applications requiring meaningful measures on distantly related protein fragments, such as similar fragments retrieval asking for high recalls as shown in the experiments, or for any application taking also advantage of triangle inequality, such as fragments clustering. ASD program and source code are freely available at: http://www.irisa.fr/dyliss/public/ASD/.

HERVs Expression in Autism Spectrum Disorders

PubMed Central

Balestrieri, Emanuela; Arpino, Carla; Matteucci, Claudia; Sorrentino, Roberta; Pica, Francesca; Alessandrelli, Riccardo; Coniglio, Antonella; Curatolo, Paolo; Rezza, Giovanni; Macciardi, Fabio; Garaci, Enrico; Gaudi, Simona; Sinibaldi-Vallebona, Paola

2012-01-01

Background Autistic Spectrum Disorder (ASD) is a heterogeneous neurodevelopmental disorder, resulting from complex interactions among genetic, genomic and environmental factors. Here we have studied the expression of Human Endogenous Retroviruses (HERVs), non-coding DNA elements with potential regulatory functions, and have tested their possible implication in autism. Methods The presence of retroviral mRNAs from four HERV families (E, H, K and W), widely implicated in complex diseases, was evaluated in peripheral blood mononuclear cells (PBMCs) from ASD patients and healthy controls (HCs) by qualitative RT-PCR. We also analyzed the expression of the env sequence from HERV-H, HERV-W and HERV-K families in PBMCs at the time of sampling and after stimulation in culture, in both ASD and HC groups, by quantitative Real-time PCR. Differences between groups were evaluated using statistical methods. Results The percentage of HERV-H and HERV-W positive samples was higher among ASD patients compared to HCs, while HERV-K was similarly represented and HERV-E virtually absent in both groups. The quantitative evaluation shows that HERV-H and HERV-W are differentially expressed in the two groups, with HERV-H being more abundantly expressed and, conversely, HERV-W, having lower abundance, in PBMCs from ASDs compared to healthy controls. PMBCs from ASDs also showed an increased potential to up-regulate HERV-H expression upon stimulation in culture, unlike HCs. Furthermore we report a negative correlation between expression levels of HERV-H and age among ASD patients and a statistically significant higher expression in ASD patients with Severe score in Communication and Motor Psychoeducational Profile-3. Conclusions Specific HERV families have a distinctive expression profile in ASD patients compared to HCs. We propose that HERV-H expression be explored in larger samples of individuals with autism spectrum in order to determine its utility as a novel biological trait of this complex disorder. PMID:23155411

Severity of ASD symptoms and their correlation with the presence of copy number variations and exposure to first trimester ultrasound.

PubMed

Webb, Sara Jane; Garrison, Michelle M; Bernier, Raphael; McClintic, Abbi M; King, Bryan H; Mourad, Pierre D

2017-03-01

Current research suggests that incidence and heterogeneity of autism spectrum disorder (ASD) symptoms may arise through a variety of exogenous and/or endogenous factors. While subject to routine clinical practice and generally considered safe, there exists speculation, though no human data, that diagnostic ultrasound may also contribute to ASD severity, supported by experimental evidence that exposure to ultrasound early in gestation could perturb brain development and alter behavior. Here we explored a modified triple hit hypothesis [Williams & Casanova, ] to assay for a possible relationship between the severity of ASD symptoms and (1) ultrasound exposure (2) during the first trimester of pregnancy in fetuses with a (3) genetic predisposition to ASD. We did so using retrospective analysis of data from the SSC (Simon's Simplex Collection) autism genetic repository funded by the Simons Foundation Autism Research Initiative. We found that male children with ASD, copy number variations (CNVs), and exposure to first trimester ultrasound had significantly decreased non-verbal IQ and increased repetitive behaviors relative to male children with ASD, with CNVs, and no ultrasound. These data suggest that heterogeneity in ASD symptoms may result, at least in part, from exposure to diagnostic ultrasound during early prenatal development of children with specific genetic vulnerabilities. These results also add weight to on-going concerns expressed by the FDA about non-medical use of diagnostic ultrasound during pregnancy. Autism Res 2017, 10: 472-484. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

Electrophysiological signatures of atypical intrinsic brain connectivity networks in autism

NASA Astrophysics Data System (ADS)

Shou, Guofa; Mosconi, Matthew W.; Wang, Jun; Ethridge, Lauren E.; Sweeney, John A.; Ding, Lei

2017-08-01

Objective. Abnormal local and long-range brain connectivity have been widely reported in autism spectrum disorder (ASD), yet the nature of these abnormalities and their functional relevance at distinct cortical rhythms remains unknown. Investigations of intrinsic connectivity networks (ICNs) and their coherence across whole brain networks hold promise for determining whether patterns of functional connectivity abnormalities vary across frequencies and networks in ASD. In the present study, we aimed to probe atypical intrinsic brain connectivity networks in ASD from resting-state electroencephalography (EEG) data via characterizing the whole brain network. Approach. Connectivity within individual ICNs (measured by spectral power) and between ICNs (measured by coherence) were examined at four canonical frequency bands via a time-frequency independent component analysis on high-density EEG, which were recorded from 20 ASD and 20 typical developing (TD) subjects during an eyes-closed resting state. Main results. Among twelve identified electrophysiological ICNs, individuals with ASD showed hyper-connectivity in individual ICNs and hypo-connectivity between ICNs. Functional connectivity alterations in ASD were more severe in the frontal lobe and the default mode network (DMN) and at low frequency bands. These functional connectivity measures also showed abnormal age-related associations in ICNs related to frontal, temporal and motor regions in ASD. Significance. Our findings suggest that ASD is characterized by the opposite directions of abnormalities (i.e. hypo- and hyper-connectivity) in the hierarchical structure of the whole brain network, with more impairments in the frontal lobe and the DMN at low frequency bands, which are critical for top-down control of sensory systems, as well as for both cognition and social skills.

Two single-nucleotide polymorphisms of the RELN gene and symptom-based and developmental deficits among children and adolescents with autistic spectrum disorders in the Tianjin, China.

PubMed

Wang, Geng-Fu; Ye, Sheng; Gao, Lei; Han, Yu; Guo, Xuan; Dong, Xiao-Peng; Su, Yuan-Yuan; Zhang, Xin

2018-05-10

Increasing evidence has revealed that genetic variants in Reelin (RELN) gene, especially single-nucleotide polymorphisms (SNPs), correlate with autistic spectrum disorders (ASD) risk; however, no consensus have been reached. This study aimed to provide additional evidence for the association between two SNPs of RELN (i.e., rs736707, rs2229864) and ASD risk, as well as the relationship between RELN gene and symptom-based and developmental deficits of ASD patients in Chinese Han children and adolescents. 157 ASD subjects and 256 typical development (TD) controls were genotyped by TaqMan® genotyping assay. ASD patients were assessed by Childhood Autism Rating Scale (CARS), Autism Behavior Checklist (ABC), and Early Childhood Development Questionnaire (ECDQ). We found that SNP rs2229864 was associated with the genetic predisposition of ASD, whereas a negative association between SNP rs2229864 and symptom-based and developmental features was detected. In contrast, RELN rs736707 correlated with the sensory subscale of the ABC, the relating subscale of the ABC and the total score of ABC, although we did not detect a significant association between SNP rs736707 and ASD risk. Furthermore, a significant rs736707-rs2229864 haplotype was detected. Individuals with a CC haplotype were more likely to have ASD, but individuals with a CT haplotype had more chance be TD controls. Further studies using more samples and including more gene variants in RELN are warranted to confirm our results. Copyright © 2018 Elsevier B.V. All rights reserved.

Increased Intra-Participant Variability in Children with Autistic Spectrum Disorders: Evidence from Single-Trial Analysis of Evoked EEG

PubMed Central

Milne, Elizabeth

2011-01-01

Intra-participant variability in clinical conditions such as autistic spectrum disorder (ASD) is an important indicator of pathophysiological processing. The data reported here illustrate that trial-by-trial variability can be reliably measured from EEG, and that intra-participant EEG variability is significantly greater in those with ASD than in neuro-typical matched controls. EEG recorded at the scalp is a linear mixture of activity arising from muscle artifacts and numerous concurrent brain processes. To minimize these additional sources of variability, EEG data were subjected to two different methods of spatial filtering. (i) The data were decomposed using infomax independent component analysis, a method of blind source separation which un-mixes the EEG signal into components with maximally independent time-courses, and (ii) a surface Laplacian transform was performed (current source density interpolation) in order to reduce the effects of volume conduction. Data are presented from 13 high functioning adolescents with ASD without co-morbid ADHD, and 12 neuro-typical age-, IQ-, and gender-matched controls. Comparison of variability between the ASD and neuro-typical groups indicated that intra-participant variability of P1 latency and P1 amplitude was greater in the participants with ASD, and inter-trial α-band phase coherence was lower in the participants with ASD. These data support the suggestion that individuals with ASD are less able to synchronize the activity of stimulus-related cell assemblies than neuro-typical individuals, and provide empirical evidence in support of theories of increased neural noise in ASD. PMID:21716921

Copy number variation in 19 Italian multiplex families with autism spectrum disorder: Importance of synaptic and neurite elongation genes.

PubMed

Lintas, Carla; Picinelli, Chiara; Piras, Ignazio Stefano; Sacco, Roberto; Brogna, Claudia; Persico, Antonio M

2017-03-17

Autism Spectrum Disorder (ASD) is endowed with impressive heritability estimates and high recurrence rates. Its genetic underpinnings are nonetheless very heterogeneous, with common, and rare contributing variants located in hundreds of different loci, each characterized by variable levels of penetrance. Multiplex families from single ethnic groups represent a useful means to reduce heterogeneity and enhance genetic load. We screened 19 Italian ASD multiplex families (3 triplets and 16 duplets, total N = 41 ASD subjects), using array-CGH (Agilent 180 K). Causal or ASD-relevant CNVs were detected in 36.6% (15/41) of ASD probands, corresponding to 36.8% (7/19) multiplex families with at least one affected sibling genetically positive. However, only in less than half (3/7) of positive families, affected siblings share the same causal or ASD-relevant CNV. Even in these three families, additional potentially relevant CNVs not shared by affected sib pairs were also detected. These results provide further evidence of genetic heterogeneity in ASD even within multiplex families belonging to a single ethnic group. Differences in CNV burden may likely contribute to the substantial clinical heterogeneity observed between affected siblings. In addition, Gene Ontology enrichment analysis indicates that most potentially causal or relevant ASD genes detected in our cohort belong to nervous system-specific categories, especially involved in neurite elongation and synaptic structure/function. These findings point toward the existence of genomic instability in these families, whose underlying genetic and epigenetic mechanisms deserve further scrutiny. © 2017 Wiley Periodicals, Inc.

Convergence of circuit dysfunction in ASD: a common bridge between diverse genetic and environmental risk factors and common clinical electrophysiology.

PubMed

Port, Russell G; Gandal, Michael J; Roberts, Timothy P L; Siegel, Steven J; Carlson, Gregory C

2014-01-01

Most recent estimates indicate that 1 in 68 children are affected by an autism spectrum disorder (ASD). Though decades of research have uncovered much about these disorders, the pathological mechanism remains unknown. Hampering efforts is the seeming inability to integrate findings over the micro to macro scales of study, from changes in molecular, synaptic and cellular function to large-scale brain dysfunction impacting sensory, communicative, motor and cognitive activity. In this review, we describe how studies focusing on neuronal circuit function provide unique context for identifying common neurobiological disease mechanisms of ASD. We discuss how recent EEG and MEG studies in subjects with ASD have repeatedly shown alterations in ensemble population recordings (both in simple evoked related potential latencies and specific frequency subcomponents). Because these disease-associated electrophysiological abnormalities have been recapitulated in rodent models, studying circuit differences in these models may provide access to abnormal circuit function found in ASD. We then identify emerging in vivo and ex vivo techniques, focusing on how these assays can characterize circuit level dysfunction and determine if these abnormalities underlie abnormal clinical electrophysiology. Such circuit level study in animal models may help us understand how diverse genetic and environmental risks can produce a common set of EEG, MEG and anatomical abnormalities found in ASD.

Neurodevelopmental Delay Diagnosis Rates Are Increased in a Region with Aerial Pesticide Application.

PubMed

Hicks, Steven D; Wang, Ming; Fry, Katherine; Doraiswamy, Vignesh; Wohlford, Eric M

2017-01-01

A number of studies have implicated pesticides in childhood developmental delay (DD) and autism spectrum disorder (ASD). The influence of the route of pesticide exposure on neurodevelopmental delay is not well defined. To study this factor, we examined ASD/DD diagnoses rates in an area near our regional medical center that employs yearly aerial pyrethroid pesticide applications to combat mosquito-borne encephalitis. The aim of this study was to determine if areas with aerial pesticide exposure had higher rates of ASD/DD diagnoses. This regional study identified higher rates of ASD/DD diagnoses in an area with aerial pesticides application. Zip codes with aerial pyrethroid exposure were 37% more likely to have higher rates of ASD/DD (adjusted RR = 1.37, 95% CI = 1.06-1.78, p  = 0.02). A Poisson regression model controlling for regional characteristics (poverty, pesticide use, population density, and distance to medical center), subject characteristics (race and sex), and local birth characteristics (prematurity, low birthweight, and birth rates) identified a significant relationship between aerial pesticide use and ASD/DD rates. The relationship between pesticide application and human neurodevelopment deserves additional study to develop safe and effective methods of mosquito prevention, particularly as communities develop plans for Zika virus control.

The relationship between carers' report of autistic traits and clinical diagnoses of autism spectrum disorders in adults with intellectual disability.

PubMed

Bhaumik, Sabyasachi; Tyrer, Freya; Barrett, Mary; Tin, Nyunt; McGrother, Catherine W; Kiani, Reza

2010-01-01

It is often difficult to determine the triad of impairments and whether autistic features are the consequence of intellectual impairment or autism spectrum disorders in people with intellectual disability (ID). The aim of the current study was to investigate the relationship between carer-reported autistic traits and independent diagnoses of autism spectrum disorders (ASD). Data were collected on carers' subjective report of autistic traits and clinical diagnoses of ASD. Of 1145 adults with ID identified, 220 (19%) individuals had a diagnosis of ASD, and 778 (68%) individuals had at least one autistic trait. Optimal sensitivity and specificity were achieved with two or more autistic traits (sensitivity 63%; specificity 79%) and the positive predictive value increased substantially as the number of autistic traits increased. However, a significant proportion of individuals with ID who did not have a diagnosis of ASD also displayed autistic traits. Our findings suggest that in the absence of other measures, the presence of autistic traits can serve as a useful proxy measure for ASD in research (and/or clinical settings). However, although information on autistic traits may help healthcare practitioners to identify people with possible ASD, it cannot be used alone to make a formal diagnosis. 2010 Elsevier Ltd. All rights reserved.

Motor demands impact speed of information processing in Autism Spectrum Disorders

PubMed Central

Kenworthy, Lauren; Yerys, Benjamin E.; Weinblatt, Rachel; Abrams, Danielle N.; Wallace, Gregory L.

2015-01-01

Objective The apparent contradiction between preserved or even enhanced perceptual processing speed on inspection time tasks in autism spectrum disorders (ASD) and impaired performance on complex processing speed tasks that require motor output (e.g. Wechsler Processing Speed Index) has not yet been systematically investigated. This study investigates whether adding motor output demands to an inspection time task impairs ASD performance compared to that of typically developing control (TDC) children. Method The performance of children with ASD (n=28; mean FSIQ=115) and TDC (n=25; mean FSIQ=122) children was compared on processing speed tasks with increasing motor demand. Correlations were run between ASD task performance and Autism Diagnostic Observation Schedule (ADOS) Communication scores. Results Performance by the ASD and TDC groups on a simple perceptual processing speed task with minimal motor demand was equivalent, though it diverged (ASD worse than TDC) on two tasks with the same stimuli, but increased motor output demands. ASD performance on the moderate but not the high speeded motor output demand task was negatively correlated with ADOS communication symptoms. Conclusions These data address the apparent contradiction between preserved inspection time in the context of slowed “processing speed” in ASD. They show that processing speed is preserved when motor demands are minimized, but that increased motor output demands interfere with the ability to act on perceptual processing of simple stimuli. Reducing motor demands (e.g. through the use of computers) may increase the capacity of people with ASD to demonstrate good perceptual processing in a variety of educational, vocational and social settings. PMID:23937483

Driving Comparisons Between Young Adults with Autism Spectrum Disorder and Typical Development.

PubMed

Patrick, Kristina E; Hurewitz, Felicia; McCurdy, Mark D; Agate, Frederic Taylor; Daly, Brian P; Tarazi, Reem A; Chute, Douglas L; Schultheis, Maria T

2018-05-18

Many individuals with autism spectrum disorder (ASD) are reluctant to pursue driving because of concerns about their ability to drive safely. This study aimed to assess differences in simulated driving performance in young adults with ASD and typical development, examining relationships between driving performance and the level of experience (none, driver's permit, licensed) across increasingly difficult driving environments. Participants included 50 English-speaking young adults (16-26 years old) with ASD matched for sex, age, and licensure with 50 typically-developing (TD) peers. Participants completed a structured driving assessment using a virtual-reality simulator that included increasingly complex environmental demands. Differences in mean speed and speed and lane variability by diagnostic group and driving experience were analyzed using multilevel linear modeling. Young adults with ASD demonstrated increased variability in speed and lane positioning compared with controls, even during low demand tasks. When driving demands became more complex, group differences were moderated by driving experience such that licensed drivers with ASD drove similarly to TD licensed drivers for most tasks, whereas unlicensed drivers with ASD had more difficulty with speed and lane management than TD drivers. Findings suggest that young adults with ASD may have more difficulty with basic driving skills than peers, particularly in the early stages of driver training. Increased difficulty compared with peers increases as driving demands become more complex, suggesting that individuals with ASD may benefit from a slow and gradual approach to driver training. Future studies should evaluate predictors of driving performance, on-road driving, and ASD-specific driving interventions.