Although Autism Spectrum Disorders Research Articles

Environmental Influences Measured by Epigenetic Clock and Vulnerability Components at Birth Impact Clinical ASD Heterogeneity

Although Autism Spectrum Disorders (ASD) is recognized as being heavily influenced by genetic factors, the role of epigenetic and environmental factors is still being established. This study aimed to identify ASD vulnerability components based on familial history and intrauterine environmental stress exposure, explore possible vulnerability subgroups, access DNA methylation age acceleration (AA) as a proxy of stress exposure during life, and evaluate the association of ASD vulnerability components and AA to phenotypic severity measures. Principal Component Analysis (PCA) was used to search the vulnerability components from 67 mothers of autistic children. We found that PC1 had a higher correlation with psychosocial stress (maternal stress, maternal education, and social class), and PC2 had a higher correlation with biological factors (psychiatric family history and gestational complications). Comparing the methylome between above and below PC1 average subgroups we found 11,879 statistically significant differentially methylated probes (DMPs, p < 0.05). DMPs CpG sites were enriched in variably methylated regions (VMRs), most showing environmental and genetic influences. Hypermethylated probes presented higher rates in different regulatory regions associated with functional SNPs, indicating that the subgroups may have different affected regulatory regions and their liability to disease explained by common variations. Vulnerability components score moderated by epigenetic clock AA was associated with Vineland Total score (p = 0.0036, adjR2 = 0.31), suggesting risk factors with stress burden can influence ASD phenotype.

The Episodic Memory Profile in Autism Spectrum Disorder: A Bayesian Meta-Analysis.

Although autism spectrum disorders (ASD) are commonly characterized by diminished episodic memory, the literature in this area is mixed. We address these inconsistent findings by employing multilevel Bayesian meta-analysis to quantify episodic memory differences between individuals with ASD and typically developing (TD) controls. We used meta-regression to evaluate the effects of test modality (e.g., word list, story recall), delay interval (immediate vs. delayed), retrieval demands (recognition vs. recall), and sensory modality (auditory vs. visual) on episodic memory in ASD. A total of 338 effect sizes from 113 empirical articles, including 5,632 unique participants (ASD = 2,777, TD = 2,855), were included. Results show that the memory deficits associated with ASD were larger for recall (g = -0.52, se = 0.04, 95% CrI [-0.60, -0.43]) compared to recognition (g = -0.25, se = 0.05, 95% CrI [-0.35, -0.14]) and differed based on the testing modality. For example, effect sizes were smallest for words (g = -0.28, se = 0.05, 95% CrI [-0.38, -0.18]), pictures (g = -0.38, se = 0.07, 95% CrI [-0.52, -0.24]), and figure reproduction (g = -0.49, se = 0.11, 95% CrI [-0.70, -0.27]). However, effect sizes for sentences (g = -0.59, se = 0.20, 95% CrI [-1.00, -0.21]), stories (Hedges' g = -0.54, se = 0.08, 95% CrI [-0.69, -0.38]) and staged events (g = -0.75, se = 0.10, 95% CrI [-0.95, -0.55]) were much larger. These findings suggest that ASD is associated with a small to medium reduction in scores on episodic memory tests relative to TD controls.

Mice lacking the chromodomain helicase DNA-binding 5 chromatin remodeler display autism-like characteristics

Although autism spectrum disorders (ASDs) share a core set of nosological features, they exhibit substantial genetic heterogeneity. A parsimonious hypothesis posits that dysregulated epigenetic mechanisms represent common pathways in the etiology of ASDs. To investigate this hypothesis, we generated a novel mouse model resulting from brain-specific deletion of chromodomain helicase DNA-binding 5 (Chd5), a chromatin remodeling protein known to regulate neuronal differentiation and a member of a gene family strongly implicated in ASDs. RNA sequencing of Chd5−/− mouse forebrain tissue revealed a preponderance of changes in expression of genes important in cellular development and signaling, sociocommunicative behavior and ASDs. Pyramidal neurons cultured from Chd5−/− cortex displayed alterations in dendritic morphology. Paralleling ASD nosology, Chd5−/− mice exhibited abnormal sociocommunicative behavior and a strong preference for familiarity. Chd5−/− mice further showed deficits in responding to the distress of a conspecific, a mouse homolog of empathy. Thus, dysregulated chromatin remodeling produces a pattern of transcriptional, neuronal and behavioral effects consistent with the presentation of ASDs.

Intelligence Quotient of Primary School Pupils with Autism Spectrum Disorders in Uyo, Nigeria

Although autism Spectrum Disorders (ASD) have been considered to be associated with intellectual disability, there is no known study on cognitive capacities of primary school aged children with ASD in Nigeria. The objective of this study is to compare the intelligence quotient (IQ) of primary school pupils with autism spectrum disorders with that of their controls in Uyo, Nigeria. Gilliam Autism Rating Scale–second Edition (GARS-2) and Gilliam Asperger Disorder Scale (GADS) were used to identify school children with Autism Spectrum Disorders (ASD). Their intelligence quotient was assessed using the Draw–A–Person–Test (DAPT). The findings were compared with that of their age, social class and gender matched controls. A total of 29 pupils with autism spectrum disorders were identified out of 2,641 studied. Twenty-six out of the 29 children with ASD were suitable for intelligence quotient estimation using DAPT; two of the pupils were less than 4 years of age and one had features suggestive of Down syndrome. Eleven out of 26 pupils (42%) assessed for intelligence quotient had intellectual disability (IQ<75%) while fifteen (58%) had normal intelligence (IQ>75%). The overall mean IQ score of the pupils with ASD of 82.5±22.5 was significantly lower than that of the controls of 108.9±14.8 (p<0.01). Pupils with Asperger’s disorder had the highest mean IQ while those with autistic disorder had the least mean IQ with a statistically significant difference (p<0.01). ASD are associated with low IQ among school children in Uyo, Nigeria.

Optimal outcome in individuals with a history of autism

Although autism spectrum disorders (ASDs) are generally considered lifelong disabilities, literature suggests that a minority of individuals with an ASD will lose the diagnosis. However, the existence of this phenomenon, as well as its frequency and interpretation, is still controversial: were they misdiagnosed initially, is this a rare event, did they lose the full diagnosis, but still suffer significant social and communication impairments or did they lose all symptoms of ASD and function socially within the normal range? The present study documents a group of these optimal outcome individuals (OO group, n=34) by comparing their functioning on standardized measures to age, sex, and nonverbal IQ matched individuals with high-functioning autism (HFA group, n=44) or typical development (TD group, n=34). For this study, 'optimal outcome' requires losing all symptoms of ASD in addition to the diagnosis, and functioning within the nonautistic range of social interaction and communication. Domains explored include language, face recognition, socialization, communication, and autism symptoms. Optimal outcome and TD groups' mean scores did not differ on socialization, communication, face recognition, or most language subscales, although three OO individuals showed below-average scores on face recognition. Early in their development, the OO group displayed milder symptoms than the HFA group in the social domain, but had equally severe difficulties with communication and repetitive behaviors. Although possible deficits in more subtle aspects of social interaction or cognition are not ruled out, the results substantiate the possibility of OO from autism spectrum disorders and demonstrate an overall level of functioning within normal limits for this group.

Increased Glutamate Concentration in the Auditory Cortex of Persons With Autism and First‐Degree Relatives: A 1H‐MRS Study

Increased glutamate levels have been reported in the hippocampal and frontal regions of persons with autism using proton magnetic resonance spectroscopy ((1)H-MRS). Although autism spectrum disorders (ASDs) are highly heritable, MRS studies have not included relatives of persons with ASD. We therefore conducted a study to determine if glutamate levels are elevated in people with autism and parents of children with autism. Single-voxel, point-resolved spectroscopy data were acquired at 3T for left and right hemisphere auditory cortical voxels in 13 adults with autism, 15 parents of children with autism, and 15 adult control subjects. The primary measure was glutamate + glutamine (Glx). Additional measures included n-acetyl-aspartate (NAA), choline (Cho), myoinositol (mI), and creatine (Cr). The autism group had significantly higher Glx, NAA, and Cr concentrations than the control subjects. Parents did not differ from control subjects on any measures. No significant differences in Cho or mI levels were seen among groups. No reliable correlations between autism symptom measures, and MRS variables were seen after Bonferroni correction for multiple comparisons. The elevation in Glx in autism is consistent with prior MRS data in the hippocampus and frontal lobe and may suggest increased cortical excitability. Increased NAA and Cr may indicate brain metabolism disturbances in autism. In the current study, we found no reliable evidence of a familial effect for any spectroscopy measure. This may indicate that these metabolites have no heritable component in autism, the presence of a compensatory factor in parents, or sample-specific limitations such as the participation of singleton families.

De novo mutations, protein–protein interactions and functional regulatory networks toward novel diagnostics in autism

Although autism spectrum disorders (ASD) have a strong genetic component, the genetic cause is still unknown in about 70% of cases [1]. By applying next-generation sequencing (NGS) including whole-...

Dysregulation of mTOR Signaling in Neuropsychiatric Disorders: Therapeutic Implications

Autism is a widespread disorder characterized by deficits in social interactions, impairments in communication, and repetitive and stereotypic behaviors. Identification of genetic markers has proved difficult, owing to the highly complex and variable nature of the disease. Although autism spectrum disorders (ASDs) arise as a consequence of mutations in genes with multiple molecular functions, they appear to converge on common biological pathways to give rise to autism-relevant behaviors (Abrahams and Geschwind, 2008). One such pathway is the PI3K-mammalian target of rapamycin (mTOR) signaling cascade. The mTOR pathway is a central regulator of cell growth, proliferation, survival, and cap-dependent protein translation. In brain, components of the mTOR pathway are present at synapses, where they regulate dendritic spine morphology, and are essential to synaptogenesis. Growing evidence indicates that dysregulation of mTOR is involved in human diseases, including cancer, diabetes, and autism. Mutations in tuberous sclerosis complex (TSC)1, TSC2, neurofibromatosis 1 (NF1), and PTEN lead to overactivated PI3K-mTOR pathway, autism-relevant behaviors, and tuberous sclerosis, neurofibromatosis, or macrocephaly.

Sex differences in Arab children with Autism spectrum disorders

Although autism spectrum disorders (ASD) prevalence is higher in males than females in Arab countries, few studies address sex differences in autistic symptoms and coexiting behavioral problems. A total of 37 boys and 23 girls recruited from three Arab countries (Egypt, Saudi Arabia, Jordan) matched for age and IQ. They were compared using Indian Scale for Assessment of Autism (ISAA) and the Child Behavior Checklist (CBCL). The boys had poor emotional responsiveness and the girls had more cognitive problems. With regard to coexisting psychopathology boys exhibited significantly more delinquent behavior problems. Longitudinal, representative studies are needed to elucidate etiological significance of the observed sex differences.

A genome-wide scan for common alleles affecting risk for autism

Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10−8. When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10−8 threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.

Brief Report: Executive Functioning in Autism Spectrum Disorders: A Gender Comparison of Response Inhibition

Although autism spectrum disorders (ASD) affect more males than females, it is not clear whether neurobehavioural correlates of ASD are equivalent across genders. This study examined gender differences in neurobehavioural functioning in boys and girls with ASD. Participants were males with ASD (n=10), females with ASD (n=13), typically developing males (n=8), and typically developing females (n=14). Each completed the stop task, a common measure of response inhibition. Females with ASD demonstrated a significant increase in stopping time (indicating poorer inhibition). By contrast, no response inhibition impairments were evident among males with ASD. Females with ASD may have a different neurobehavioural profile, and therefore different clinical needs, when compared with males with ASD.

Can Children with Autism Recover? If So, How?

Although Autism Spectrum Disorders (ASD) are generally assumed to be lifelong, we review evidence that between 3% and 25% of children reportedly lose their ASD diagnosis and enter the normal range of cognitive, adaptive and social skills. Predictors of recovery include relatively high intelligence, receptive language, verbal and motor imitation, and motor development, but not overall symptom severity. Earlier age of diagnosis and treatment, and a diagnosis of Pervasive Developmental Disorder-Not Otherwise Specified are also favorable signs. The presence of seizures, mental retardation and genetic syndromes are unfavorable signs, whereas head growth does not predict outcome. Controlled studies that report the most recovery came about after the use of behavioral techniques. Residual vulnerabilities affect higher-order communication and attention. Tics, depression and phobias are frequent residual co-morbidities after recovery. Possible mechanisms of recovery include: normalizing input by forcing attention outward or enriching the environment; promoting the reinforcement value of social stimuli; preventing interfering behaviors; mass practice of weak skills; reducing stress and stabilizing arousal. Improving nutrition and sleep quality is non-specifically beneficial.

Sex Differences in Toddlers with Autism Spectrum Disorders

Although autism spectrum disorders (ASD) prevalence is higher in males than females, few studies address sex differences in developmental functioning or clinical manifestations. Participants in this study of sex differences in developmental profiles and clinical symptoms were 22 girls and 68 boys with ASD (mean age = 28 months). All children achieved strongest performance in visual reception and fine motor followed by gross motor and language functioning. Sex differences emerged in developmental profiles. Controlling for language, girls achieved higher visual reception scores than boys; boys attained higher language and motor scores and higher social-competence ratings than girls, particularly when controlling for visual reception. Longitudinal, representative studies are needed to elucidate the developmental and etiological significance of the observed sex differences.