Findings In Autism Spectrum Disorder Research Articles

Mental representations of speech and musical pitch contours reveal a diversity of profiles in autism spectrum disorder.

As a key auditory attribute of sounds, pitch is ubiquitous in our everyday listening experience involving language, music and environmental sounds. Given its critical role in auditory processing related to communication, numerous studies have investigated pitch processing in autism spectrum disorder. However, the findings have been mixed, reporting either enhanced, typical or impaired performance among autistic individuals. By investigating top-down comparisons of internal mental representations of pitch contours in speech and music, this study shows for the first time that, while autistic individuals exhibit diverse profiles of pitch processing compared to non-autistic individuals, their mental representations of pitch contours are typical across domains. These findings suggest that pitch-processing mechanisms are shared across domains in autism spectrum disorder and provide theoretical implications for using music to improve speech for those autistic individuals who have language problems.

Divergent Associations of Rare De Novo Protein-Truncating Variants and Missense Mutations With Developmental Delays in Autism Spectrum Disorder

One of the most well-established genetic findings in autism spectrum disorder (ASD) is that rare de novo variants substantially increase risk for developmental delays. To our knowledge, no study to date has distinguished between the developmental effects of two classes of constrained rare variants, protein-truncating variants (PTVs) and missense mutations, as the latter class has only been defined recently (Satterstrom et al., Cell, 2020).

Actionable and incidental neuroradiological findings in twins with neurodevelopmental disorders

While previous research has investigated neuroradiological findings in autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD), the entire range of neurodevelopmental disorders (NDDs) has not yet been well-studied using magnetic resonance imaging (MRI). Considering the overlap among NDDs and simultaneous development of the brain and face, guided by molecular signaling, we examined the relationship of actionable and incidental (non-actionable) MRI findings and NDD diagnoses together with facial morphological variants and genetic copy number variants (CNVs). A cross-sectional study was conducted with a twin cohort 8–36 years of age (57% monozygotic, 40% dizygotic), including 372 subjects (46% with NDDs; 47% female) imaged by MRI, 280 with data for facial morphological variants, and 183 for CNVs. Fifty-one percent of participants had MRI findings. Males had a statistically significantly higher percentage of MRI findings (57.7%) compared with females (43.8%, p = 0.03). Twin zygosity was not statistically significantly correlated with incidence or severity of specific MRI findings. No statistically significant association was found between MRI findings and any NDD diagnosis or facial morphological variants; however, MRI findings were statistically significantly associated with the number of CNVs (OR 1.20, 95% CI 1.00–1.44, p = 0.05, adjusted OR for sex 1.24, 95% CI 1.03–1.50, p = 0.02). When combining the presence of MRI findings, facial morphological variants, and CNVs, statistically significant relationships were found with ASD and ADHD diagnoses (p = 0.0006 and p = 0.002, respectively). The results of this study demonstrate that the ability to identify NDDs from combined radiology, morphology, and CNV assessments may be possible. Additionally, twins do not appear to be at increased risk for neuroradiological variants.

Attention Deficits Influence the Development of Motor Abnormalities in High Functioning Autism

Early attentional dysfunction is one of the most consistent findings in autism spectrum disorder (ASD), including the high functioning autism (HFA). There are no studies that assess how the atypical attentional processes affect the motor functioning in HFA. In this study, we evaluated attentional and motor functioning in a sample of 15 drug-naive patients with HFA and 15 healthy children (HC), and possible link between attentional dysfunction and motor impairment in HFA. Compared to HC, HFA group was seriously impaired in a considerable number of attentional processes and showed a greater number of motor abnormalities. Significant correlations between attention deficits and motor abnormalities were observed in HFA group. These preliminary findings suggest that deficit of attentional processes can be implied in motor abnormalities in HFA.

A social encounter drives gene expression changes linked to neuronal function, brain development, and related disorders in mice expressing the serotonin transporter Ala56 variant

Multiple lines of evidence implicate the serotonin (5-HT) system in social function, including biomarker findings in autism spectrum disorder. In mice, knock-in of a rare Gly56Ala substitution in the serotonin transporter (SERT) causes elevated whole blood 5-HT levels, increased 5-HT clearance in the brain, and altered social and repetitive behavior. To further examine the molecular impact of this variant on social response, SERT Ala56 mutant mice and wildtype littermate controls were exposed to a social or non-social stimulus. We examined the differential activation of the prefrontal cortex, lateral amygdala, and medial amygdala, to social stimuli through RNA sequencing. Differentially expressed genes were enriched in axonal guidance signaling pathways, networks related to nervous system development and function, neurological and psychiatric disorders, and behavior. These identified pathways and networks may shed light on the molecular cascades underlying the impact of altered SERT function on social behavior.

Looking at the eyes interferes with facial emotion recognition in alexithymia.

Alexithymia refers to difficulties in identifying, differentiating, and describing feelings. This personality trait is highly prevalent in many psychiatric conditions and may drive associated social-emotional problems, including the ability to decode emotions in faces. This study probed alexithymic problems with identifying clear and ambiguous blends of emotions in faces and their underlying visual attention patterns. Using the Toronto Alexithymia Scale-20, students with high alexithymia (HA, n = 73) or low alexithymia (LA, n = 76) were enrolled in this study. Participants judged the mixture ratio of emotional expressions while their eye movements were recorded. Controlling for group differences in mood and anxiety, HA showed similar accuracy but a reduced viewing preference of facial eye regions compared to LA (p = .02). More attention to the eye regions was related to lower accuracy in HA (p = .02) but to slightly higher accuracy in LA (p = .07). The current findings point to a role of alexithymia in attentional avoidance of other people's eyes, similar to previous findings in autism spectrum disorder. Eye contact may be perceived as a greater emotional challenge by those with alexithymia, disrupting downstream processing of facial emotions. (PsycINFO Database Record

Reversed gender ratio of autism spectrum disorder in Smith-Magenis syndrome

BackgroundA substantial amount of research shows a higher rate of autistic type of problems in males compared to females. The 4:1 male to female ratio is one of the most consistent findings in autism spectrum disorder (ASD).Lately, the interest in studying ASD in genetic disorders has increased, and research has shown a higher prevalence of ASD in some genetic disorders than in the general population.Smith-Magenis syndrome (SMS) is a rare and complex genetic syndrome caused by an interstitial deletion of chromosome 17p11.2 or a mutation on the retinoic acid induced 1 gene. The disorder is characterised by intellectual disability, multiple congenital anomalies, obesity, neurobehavioural abnormalities and a disrupted circadian sleep-wake pattern.MethodsParents of 28 persons with SMS between 5 and 50 years old participated in this study. A total of 12 of the persons with SMS were above the age of 18 at the time of the study. A total of 11 came from Sweden and 17 were from Norway.We collected information regarding the number of autism spectrum symptoms using the Social Communication Questionnaire (SCQ) and the Social Responsiveness Scale (SRS). Adaptive behaviour was also measured using the Vineland Adaptive Behavior Scale II. The level of intellectual disability was derived from a review of the medical chart.ResultsWe found significant gender differences in ASD symptomatology using the SCQ and SRS questionnaires. We found approximately three females per male above the SCQ cutoff. The same differences were not found in the intellectual level and adaptive behaviour or for behavioural and emotional problems.Gender had an independent contribution in a regression model predicting the total SCQ score, and neither the Vineland Adaptive Behavior Scale II nor the Developmental Behaviour Checklist had an independent contribution to the SCQ scores.ConclusionWe found a clear reversed gender difference in ASD symptomatology in persons with SMS. This may be relevant in the search for female protective factors assumed to explain the male bias in ASD.

Impaired Value Learning for Faces in Preschoolers With Autism Spectrum Disorder

One of the common findings in autism spectrum disorder (ASD) is limited selective attention toward social objects, such as faces. Evidence from both human and nonhuman primate studies suggests that selection of objects for processing is guided by the appraisal of object values. We hypothesized that impairments in selective attention in ASD may reflect a disruption of a system supporting learning about object values in the social domain. We examined value learning in social (faces) and nonsocial (fractals) domains in preschoolers with ASD (n= 25) and typically developing (TD) controls (n= 28), using a novel value learning task implemented on a gaze-contingent eye-tracking platform consisting of value learning and a selective attention choice test. Children with ASD performed more poorly than TD controls on the social value learning task, but both groups performed similarly on the nonsocial task. Within-group comparisons indicated that value learning in TD children was enhanced on the social compared to the nonsocial task, but no such enhancement was seen in children with ASD. Performance in the social and nonsocial conditions was correlated in the ASD but not in the TD group. The study provides support for a domain-specific impairment in value learning for faces in ASD, and suggests that, in ASD, value learning in social and nonsocial domains may rely on a shared mechanism. These findings have implications both for models of selective social attention deficits in autism and for identification of novel treatment targets.

Genetic research in autism spectrum disorders.

Purpose of reviewThe recent explosion of genetic findings in autism spectrum disorder (ASD) research has improved knowledge of the disorder's underlying biology and etiologic architecture. This review introduces concepts and results from recent genetic studies and discusses the manner in which those findings can influence the trajectory of ASD research.Recent findingsLarge consortium studies have associated ASDs with many types of genetic risk factors, including common polygenic risk, de novo single nucleotide variants, copy number variants, and rare inherited variants. In aggregate, these results confirm the heterogeneity and complexity of ASDs. The rare variant findings in particular point to genes and pathways that begin to bridge the gap between behavior and biology.SummaryGenetic studies have the potential to identify the biological underpinnings of ASDs and other neuropsychiatric disorders. The data they generate are already being used to examine disease pathways and pathogenesis. The results also speak to ASD heterogeneity and, in the future, may be used to stratify research studies and treatment trials.

Sex and gender differences in autism spectrum disorder: summarizing evidence gaps and identifying emerging areas of priority.

One of the most consistent findings in autism spectrum disorder (ASD) research is a higher rate of ASD diagnosis in males than females. Despite this, remarkably little research has focused on the reasons for this disparity. Better understanding of this sex difference could lead to major advancements in the prevention or treatment of ASD in both males and females. In October of 2014, Autism Speaks and the Autism Science Foundation co-organized a meeting that brought together almost 60 clinicians, researchers, parents, and self-identified autistic individuals. Discussion at the meeting is summarized here with recommendations on directions of future research endeavors.Electronic supplementary materialThe online version of this article (doi:10.1186/s13229-015-0019-y) contains supplementary material, which is available to authorized users.

Corpus callosum area and brain volume in autism spectrum disorder: quantitative analysis of structural MRI from the ABIDE database.

Reduced corpus callosum area and increased brain volume are two commonly reported findings in autism spectrum disorder (ASD). We investigated these two correlates in ASD and healthy controls using T1-weighted MRI scans from the Autism Brain Imaging Data Exchange (ABIDE). Automated methods were used to segment the corpus callosum and intracranial region. No difference in the corpus callosum area was found between ASD participants and healthy controls (ASD 598.53±109mm(2); control 596.82±102mm(2); p=0.76). The ASD participants had increased intracranial volume (ASD 1,508,596±170,505mm(3); control 1,482,732±150,873.5mm(3); p=0.042). No evidence was found for overall ASD differences in the corpus callosum subregions.

Cerebellar gray matter and lobular volumes correlate with core autism symptoms.

Neuroanatomical differences in the cerebellum are among the most consistent findings in autism spectrum disorder (ASD), but little is known about the relationship between cerebellar dysfunction and core ASD symptoms. The newly-emerging existence of cerebellar sensorimotor and cognitive subregions provides a new framework for interpreting the functional significance of cerebellar findings in ASD. Here we use two complementary analyses — whole-brain voxel-based morphometry (VBM) and the SUIT cerebellar atlas — to investigate cerebellar regional gray matter (GM) and volumetric lobular measurements in 35 children with ASD and 35 typically-developing (TD) children (mean age 10.4 ± 1.6 years; range 8–13 years). To examine the relationships between cerebellar structure and core ASD symptoms, correlations were calculated between scores on the Autism Diagnostic Observation Schedule (ADOS) and Autism Diagnostic Interview (ADI) and the VBM and volumetric data. Both VBM and the SUIT analyses revealed reduced GM in ASD children in cerebellar lobule VII (Crus I/II). The degree of regional and lobular gray matter reductions in different cerebellar subregions correlated with the severity of symptoms in social interaction, communication, and repetitive behaviors. Structural differences and behavioral correlations converged on right cerebellar Crus I/II, a region which shows structural and functional connectivity with fronto-parietal and default mode networks. These results emphasize the importance of the location within the cerebellum to the potential functional impact of structural differences in ASD, and suggest that GM differences in cerebellar right Crus I/II are associated with the core ASD profile.

Neural networks related to dysfunctional face processing in autism spectrum disorder.

One of the most consistent neuropsychological findings in autism spectrum disorders (ASD) is a reduced interest in and impaired processing of human faces. We conducted an activation likelihood estimation meta-analysis on 14 functional imaging studies on neural correlates of face processing enrolling a total of 164 ASD patients. Subsequently, normative whole-brain functional connectivity maps for the identified regions of significant convergence were computed for the task-independent (resting-state) and task-dependent (co-activations) state in healthy subjects. Quantitative functional decoding was performed by reference to the BrainMap database. Finally, we examined the overlap of the delineated network with the results of a previous meta-analysis on structural abnormalities in ASD as well as with brain regions involved in human action observation/imitation. We found a single cluster in the left fusiform gyrus showing significantly reduced activation during face processing in ASD across all studies. Both task-dependent and task-independent analyses indicated significant functional connectivity of this region with the temporo-occipital and lateral occipital cortex, the inferior frontal and parietal cortices, the thalamus and the amygdala. Quantitative reverse inference then indicated an association of these regions mainly with face processing, affective processing, and language-related tasks. Moreover, we found that the cortex in the region of right area V5 displaying structural changes in ASD patients showed consistent connectivity with the region showing aberrant responses in the context of face processing. Finally, this network was also implicated in the human action observation/imitation network. In summary, our findings thus suggest a functionally and structurally disturbed network of occipital regions related primarily to face (but potentially also language) processing, which interact with inferior frontal as well as limbic regions and may be the core of aberrant face processing and reduced interest in faces in ASD.

Impact of methodological variables on functional connectivity findings in autism spectrum disorders

Growing evidence suggests that Autism Spectrum Disorder (ASD) involves abnormalities of multiple functional networks. Neuroimaging studies of ASD have therefore increasingly focused on connectivity. Many functional connectivity (fcMRI) studies have reported network underconnectivity in children and adults with ASD. However, there are notable inconsistencies, with some studies reporting overconnectivity. A previous literature survey suggested that a few methodological factors play a crucial role in differential fcMRI outcomes. Using three ASD data sets (two task-related, one resting state) from 54 ASD and 51 typically developing (TD) participants (ages 9-18 years), we examined the impact of four methodological factors: type of pipeline (co-activation vs. intrinsic analysis, related to temporal filtering and removal of task-related effects), seed selection, field of view (whole brain vs. limited ROIs), and dataset. Significant effects were found for type of pipeline, field of view, and dataset. Notably, for each dataset results ranging from robust underconnectivity to robust overconnectivity were detected, depending on the type of pipeline, with intrinsic fcMRI analyses (low bandpass filter and task regressor) predominantly yielding overconnectivity in ASD, but co-activation analyses (no low bandpass filter or task removal) mostly generating underconnectivity findings. These results suggest that methodological variables have dramatic impact on group differences reported in fcMRI studies. Improved awareness of their implications appears indispensible in fcMRI studies when inferences about "underconnectivity" or "overconnectivity" in ASD are made. In the absence of a gold standard for functional connectivity, the combination of different methodological approaches promises a more comprehensive understanding of connectivity in ASD.

Understanding the brain–behaviour relationship in persons with ASD: Implications for PECS as a treatment choice

Introduction: This article presents emerging neurological findings in Autism Spectrum Disorders (ASD) with particular attention to how this information might inform treatment practices addressing communication impairments.Methods: The article begins with a general discussion of the brain–behaviour relationship and moves to the presentation of recent research findings related to ASD. There is particular attention to individuals with autism who are either non-verbal or present emergent verbal abilities.Results/Discussion: A specific communication treatment, the Picture Exchange Communication System (PECS), is presented as an example of an intervention that addresses the learner needs of many individuals with ASD. The success of PECS is discussed within the context of its fit with brain-based learner characteristics.

Evaluation of enhanced attention to local detail in anorexia nervosa using the embedded figures test; an FMRI study.

The behavioural literature in anorexia nervosa and autism spectrum disorders has indicated an overlap in cognitive profiles. One such domain is the enhancement of local processing over global processing. While functional imaging studies of autism spectrum disorder have revealed differential neural patterns compared to controls in response to tests of local versus global processing, no studies have explored such effects in anorexia nervosa. This study uses functional magnetic resonance imaging in conjunction with the embedded figures test, to explore the neural correlates of this enhanced attention to detail in the largest anorexia nervosa cohort to date. On the embedded figures tests participants are required to indicate which of two complex figures contains a simple geometrical shape. The findings indicate that whilst healthy controls showed greater accuracy on the task than people with anorexia nervosa, different brain regions were recruited. Healthy controls showed greater activation in the precuneus whilst people with anorexia nervosa showed greater activation in the fusiform gyrus. This suggests that different cognitive strategies were used to perform the task, i.e. healthy controls demonstrated greater emphasis on visuospatial searching and people with anorexia nervosa employed a more object recognition-based approach. This is in accordance with previous findings in autism spectrum disorder using a similar methodology and has implications for therapies addressing the appropriate adjustment of cognitive strategies in anorexia nervosa.

Minor Fetal Sonographic Findings in Autism Spectrum Disorder

Autism spectrum disorder (ASD) is more prevalent in the population than ever before. It is debatable whether this is a real increase in incidence, a change in the diagnostic criteria, or both. The diagnosis is usually made by age 3 years; therefore, obstetricians and fetal-maternal specialists generally display limited awareness of the disorder. Unlike fetuses with chromosomal diseases, which have distinctive physical anomalies, some fetuses that eventually will develop ASD have minor physical anomalies. This is even truer in pregnant women who already have a child with ASD. Those fetuses have a 20 times higher risk of developing ASD than the general population. The more frequent minor physical changes that may be potentially detected by ultrasound are as follows: changes in head circumference (that become more noticeable after 6 months of age), the ratio between the second and the fourth digits, left handedness, and palatal changes. Obstetricians, Maternal - Fetal Medicine specialists, Pediatricians, Sonographers After completing this CME activity, physicians should better able to classify the increasing prevalence of this disorder, and to assess the minor physical changes in fetuses that some may be seen on ultrasound during pregnancy.

Age-related change in brain metabolite abnormalities in autism: a meta-analysis of proton magnetic resonance spectroscopy studies.

Abnormal trajectory of brain development has been suggested by previous structural magnetic resonance imaging and head circumference findings in autism spectrum disorders (ASDs); however, the neurochemical backgrounds remain unclear. To elucidate neurochemical processes underlying aberrant brain growth in ASD, we conducted a comprehensive literature search and a meta-analysis of 1H-magnetic resonance spectroscopy (1H-MRS) studies in ASD. From the 22 articles identified as satisfying the criteria, means and s.d. of measure of N-acetylaspartate (NAA), creatine, choline-containing compounds, myo-Inositol and glutamate+glutamine in frontal, temporal, parietal, amygdala-hippocampus complex, thalamus and cerebellum were extracted. Random effect model analyses showed significantly lower NAA levels in all the examined brain regions but cerebellum in ASD children compared with typically developed children (n=1295 at the maximum in frontal, P<0.05 Bonferroni-corrected), although there was no significant difference in metabolite levels in adulthood. Meta-regression analysis further revealed that the effect size of lower frontal NAA levels linearly declined with older mean age in ASD (n=844, P<0.05 Bonferroni-corrected). The significance of all frontal NAA findings was preserved after considering between-study heterogeneities (P<0.05 Bonferroni-corrected). This first meta-analysis of 1H-MRS studies in ASD demonstrated robust developmental changes in the degree of abnormality in NAA levels, especially in frontal lobes of ASD. Previously reported larger-than-normal brain size in ASD children and the coincident lower-than-normal NAA levels suggest that early transient brain expansion in ASD is mainly caused by an increase in non-neuron tissues, such as glial cell proliferation.

Update on neuroimaging findings in autism spectrum disorder

Purpose – Autism spectrum disorder (ASD) has been studied as a neurodevelopmental disorder since Leo Kanner's early observations of abnormal head circumference in autistic children. In the past few years, there has been much progress made in elucidating the anatomical and functional abnormalities in ASD. This paper aims to summarise the extant research.Design/methodology/approach – This paper provides a summary of relevant research findings in the neuroimaging of autism for the past 12 month period. Papers were identified using the Medline search terms: autism; ASD (functional); magnetic resonance imaging (MRI); neuroimaging; diffusion tensor imaging (DTI); and endophenotype.Findings – Relatively recent techniques such as functional MRI and DTI have furthered the initial work derived from early histological and structural imaging studies. Even newer techniques, such as DTI tractography and support vector machine analysis, and other computer‐based learning methods have allowed us to move beyond regional va...

Melatonin in autism spectrum disorders: a systematic review and meta‐analysis

The aim of this study was to investigate melatonin-related findings in autism spectrum disorders (ASD), including autistic disorder, Asperger syndrome, Rett syndrome, and pervasive developmental disorders, not otherwise specified. Comprehensive searches were conducted in the PubMed, Google Scholar, CINAHL, EMBASE, Scopus, and ERIC databases from their inception to October 2010. Two reviewers independently assessed 35 studies that met the inclusion criteria. Of these, meta-analysis was performed on five randomized double-blind, placebo-controlled studies, and the quality of these trials was assessed using the Downs and Black checklist. Nine studies measured melatonin or melatonin metabolites in ASD and all reported at least one abnormality, including an abnormal melatonin circadian rhythm in four studies, below average physiological levels of melatonin and/or melatonin derivates in seven studies, and a positive correlation between these levels and autistic behaviors in four studies. Five studies reported gene abnormalities that could contribute to decreased melatonin production or adversely affect melatonin receptor function in a small percentage of children with ASD. Six studies reported improved daytime behavior with melatonin use. Eighteen studies on melatonin treatment in ASD were identified; these studies reported improvements in sleep duration, sleep onset latency, and night-time awakenings. Five of these studies were randomized double-blind, placebo-controlled crossover studies; two of the studies contained blended samples of children with ASD and other developmental disorders, but only data for children with ASD were used in the meta-analysis. The meta-analysis found significant improvements with large effect sizes in sleep duration (73 min compared with baseline, Hedge's g 1.97 [95% confidence interval {CI} CI 1.10-2.84], Glass's Δ 1.54 [95% CI 0.64-2.44]; 44 min compared with placebo, Hedge's g 1.07 [95% CI 0.49-1.65], Glass's Δ 0.93 [95% CI 0.33-1.53]) and sleep onset latency (66 min compared with baseline, Hedge's g-2.42 [95% CI -1.67 to -3.17], Glass's Δ-2.18 [95% CI -1.58 to -2.76]; 39 min compared with placebo, Hedge's g-2.46 [95% CI -1.96 to -2.98], Glass's Δ-1.28 [95% CI -0.67 to -1.89]) but not in night-time awakenings. The effect size varied significantly across studies but funnel plots did not indicate publication bias. The reported side effects of melatonin were minimal to none. Some studies were affected by limitations, including small sample sizes and variability in the protocols that measured changes in sleep parameters. Melatonin administration in ASD is associated with improved sleep parameters, better daytime behavior, and minimal side effects. Additional studies of melatonin would be helpful to confirm and expand on these findings.