Developmental brain structural atypicalities in autism: A voxel-based morphometry analysis

Background Accumulating structural Magnetic Resonance Imaging (sMRI) studies have showed atypicalities in developmental changes of structural regional brain in autism, with largely inconsistent results. Methods The current study investigated the brain structural abnormal features of autistic individuals aged 6~30 years. We included 52 autism individuals and 50 age, gender, and IQ matched typically developing individuals (TD), who were divided into three groups: childhood (6-12 years old), adolescent (13-18 years old) and adulthood (19-30 years old). Whole brain volume and Voxel-Based Morphometry (VBM) analyses were employed on the sMRI data collected from our participants. Results We found no significant difference in the volume of whole brain, gray matter and white matter between autism and TD groups of the three age groups. For VBM analyses, the volumes of gray matter in right superior temporal gyrus and right inferior parietal lobule in children autism group were smaller than those in TD group; the volume of gray matter in left inferior parietal lobule in adolescent autism group was larger than that in TD group; the volume of gray matter in right middle occipital gyrus in adult autism group was larger than that in TD group, and the gray matter in left posterior cingulate gyrus was smaller than that in TD group. Conclusions Findings suggest autism individuals showed different atypical brain regions of gray matter volume in childhood, adolescent, and adulthood relative to their normal peers respectively, indiciating that it is essential to take developmental perspectives into consideration when exploring brain structural abnormalities in autism.

A potential role for the adrenal gland in autism

Androgens have been implicated in autism pathophysiology as recently, prenatal exposure to elevated androgens has been proposed as risk factor. However, published data on postnatal sex hormone levels in autistic children are controversial and the source of prenatal androgen exposure in autism remains unknown. Therefore, this study investigated postnatal sex hormone levels and dehydroepiandrosterone (DHEA) to shed light on a potential role for the adrenal gland in autism pathophysiology. A case-control study investigating estradiol (E2), DHEA, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels was conducted with 31 Saudi males with autism and 28 healthy, age-matched boys plasma. Moreover, correlation analysis with measured hormones and previously measured total testosterone (TT) and free testosterone (FT) in the same group of autism was conducted. DHEA was significantly higher (p < 0.05) in the autism group compared to controls. DHEA positively correlated with previously measured TT (r = + 0.79, p < 0.001) and FT (r = + 0.72, p < 0.001) levels in the same autism group. FSH levels were also significantly higher in the autism group than in the control group (p < 0.01). To the best of our knowledge, this is the first study to report a strong positive correlation between TT, FT and DHEA, suggesting an adrenal source for elevated androgen levels.

Real-world executive functioning for autistic children in school and home settings

Executive function challenges are commonly reported in the home setting for children with an autism spectrum disorder diagnosis (hereafter, autism), but little is known about these challenges in the school setting. A total of 337 youth (autism, N = 241 and typically developing, N = 96) were assessed using Behavior Rating Inventory of Executive Function ratings from home and school settings. Within each setting, we examined differences in specific executive function skills between diagnostic groups. Then, we examined if the autism group showed similar peak executive function impairments, associations with age, and relationships with adaptive behavior across settings. Finally, we examined inter-rater reliability. Autism and typically developing groups differed on all Behavior Rating Inventory of Executive Function scales in both settings. The Shift scale was the peak impairment in the autism group in both settings. There was also an effect of age on executive function impairment in both settings, and executive function ratings in both settings significantly predicted individual adaptive behavior domains. Inter-rater correlations for autistic participants were similar to inter-rater reliability correlations from the Behavior Rating Inventory of Executive Function standardization sample. This study shows that autistic children experience similar but not identical real-world executive function challenges across school and home settings and that supports may vary by setting. Lay abstract Executive functioning skills are important for children to be able to control thoughts, emotions, and actions, and for their ability to adapt to different settings. Previous studies have found that autistic children have difficulty with executive functioning, but most of these studies took place in the home setting. Executive functioning skills in autistic children have not yet been fully examined in the school setting. This is a knowledge gap that needs to be addressed because the school setting is potentially one of the most demanding in terms of executive functioning and is a setting where executive function interventions are already being used for autistic children. In order to learn more about executive functioning for autistic children in the school setting, this study compared ratings of executive function from autistic children’s caregivers and school professionals. The study found that autistic children experience similar but not identical executive function challenges across school and home settings and that supports may differ in each setting. Having information about differences in executive functioning challenges and supports for autistic children across settings can help lead to development of supports that are tailored to each setting.

Health-related risky behaviors in Chinese adolescents with autism: a cross-sectional study

Background Health-related risky behaviors (HRB) generally refer to behaviors that have a negative influence on health and quality of life. HRB in adolescents with autism have not been well understood so far. We aim to explore health-related risky behaviors and their risk factors with autistic adolescents. Methods In this study, 150 adolescents with autism and 150 neurotypical adolescents were enrolled. Participants in both groups completed the Adolescent Health-Related Risky Behavior Inventory (AHRBI). Autism Spectrum Screening Questionnaire (ASSQ), Wechsler Intelligence Scale, Theory of Mind (ToM) Test, Zung Self-rating Anxiety Scale (SAS), Zung Self-rating Depression Scale (SDS), and Self-Esteem Scale (SES) were also assessed in the autism group to explore risk factors. Results The results showed that the total score of AHRBI and scores of "aggression and violence (AV)", "suicide or self-injury (SS)", "health-compromising behavior (HCB)", and "unprotected sex (US)" subscales in the autism group were significantly higher than those in the control group (Z value = − 4.58 ~ − 2.26, all P < 0.05). Anxiety, depression, low self-esteem, low IQ score, low ToM test score, increasing age, and communication disorder were found as risk factors for health-related risky behaviors in autistic adolescents. Conclusions Adolescents with autism have more health-related risky behaviors than neurotypical adolescents. We should pay attention to the emotional state, self-esteem, cognitive function, and verbal communication levels of autistic adolescent with health-related risky behaviors.

Neurite orientation dispersion and density imaging reveals white matter microstructural alterations in adults with autism

Background Evidences suggesting the association between behavioral anomalies in autism and white matter (WM) microstructural alterations are increasing. Diffusion tensor imaging (DTI) is widely used to infer tissue microstructure. However, due to its lack of specificity, the underlying pathology of reported differences in DTI measures in autism remains poorly understood. Herein, we applied neurite orientation dispersion and density imaging (NODDI) to quantify and define more specific causes of WM microstructural changes associated with autism in adults. Methods NODDI (neurite density index [NDI], orientation dispersion index, and isotropic volume fraction [ISOVF]) and DTI (fractional anisotropy [FA], mean diffusivity [MD], axial diffusivity, and radial diffusivity [RD]) measures were compared between autism (N = 26; 19 males and 7 females; 32.93 ± 9.24 years old) and age- and sex-matched typically developing (TD; N = 25; 17 males and 8 females; 34.43 ± 9.02 years old) groups using tract-based spatial statistics and region-of-interest analyses. Linear discriminant analysis using leave-one-out cross-validation (LDA-LOOCV) was also performed to assess the discriminative power of diffusion measures in autism and TD. Results Significantly lower NDI and higher ISOVF, suggestive of decreased neurite density and increased extracellular free-water, respectively, were demonstrated in the autism group compared with the TD group, mainly in commissural and long-range association tracts, but with distinct predominant sides. Consistent with previous reports, the autism group showed lower FA and higher MD and RD when compared with TD group. Notably, LDA-LOOCV suggests that NDI and ISOVF have relatively higher accuracy (82%) and specificity (NDI, 84%; ISOVF, 88%) compared with that of FA, MD, and RD (accuracy, 67–73%; specificity, 68–80%). Limitations The absence of histopathological confirmation limit the interpretation of our findings. Conclusions Our results suggest that NODDI measures might be useful as imaging biomarkers to diagnose autism in adults and assess its behavioral characteristics. Furthermore, NODDI allows interpretation of previous findings on changes in WM diffusion tensor metrics in individuals with autism.

Developmental Language Disorder and Autism: Commonalities and Differences on Language

Language and communication deficits characterize both autism spectrum disorder and developmental language disorder, and the possibility of there being a common profile of these is a matter of tireless debate in the research community. This experimental study addresses the relation of these two developmental conditions in the critical topic of language. Α total of 103 children (79 males, 24 females) participated in the present study. Specifically, the study’s sample consisted of 40 children with autism, 28 children with developmental language disorder, and 35 typically developing children between 6 and 12 years old. All children completed language and cognitive measures. The results showed that there is a subgroup inside the autism group of children who demonstrate language difficulties similar to children with developmental language disorder. Specifically, two different subgroups were derived from the autism group; those with language impairment and those without. Both autism and language-impaired groups scored lower than typically developing children on all language measures indicating a common pathology in language ability. The results of this study shed light on the relation between the two disorders, supporting the assumption of a subgroup with language impairment inside the autism spectrum disorder population. The common picture presented by the two developmental conditions highlights the need for further research in the field.

Gray matter covariations and core symptoms of autism: the EU-AIMS Longitudinal European Autism Project

Background Voxel-based morphometry (VBM) studies in autism spectrum disorder (autism) have yielded diverging results. This might partly be attributed to structural alterations being associating with the combined influence of several regions rather than with a single region. Further, these structural covariation differences may relate to continuous measures of autism rather than with categorical case–control contrasts. The current study aimed to identify structural covariation alterations in autism, and assessed canonical correlations between brain covariation patterns and core autism symptoms. Methods We studied 347 individuals with autism and 252 typically developing individuals, aged between 6 and 30 years, who have been deeply phenotyped in the Longitudinal European Autism Project. All participants’ VBM maps were decomposed into spatially independent components using independent component analysis. A generalized linear model (GLM) was used to examine case–control differences. Next, canonical correlation analysis (CCA) was performed to separately explore the integrated effects between all the brain sources of gray matter variation and two sets of core autism symptoms. Results GLM analyses showed significant case–control differences for two independent components. The first component was primarily associated with decreased density of bilateral insula, inferior frontal gyrus, orbitofrontal cortex, and increased density of caudate nucleus in the autism group relative to typically developing individuals. The second component was related to decreased densities of the bilateral amygdala, hippocampus, and parahippocampal gyrus in the autism group relative to typically developing individuals. The CCA results showed significant correlations between components that involved variation of thalamus, putamen, precentral gyrus, frontal, parietal, and occipital lobes, and the cerebellum, and repetitive, rigid and stereotyped behaviors and abnormal sensory behaviors in autism individuals. Limitations Only 55.9% of the participants with autism had complete questionnaire data on continuous parent-reported symptom measures. Conclusions Covaried areas associated with autism diagnosis and/or symptoms are scattered across the whole brain and include the limbic system, basal ganglia, thalamus, cerebellum, precentral gyrus, and parts of the frontal, parietal, and occipital lobes. Some of these areas potentially subserve social-communicative behavior, whereas others may underpin sensory processing and integration, and motor behavior.

Fundamental Role of Neurochemicals Aberration in the Pathogenesis of Autism Spectrum Disorders

AIM: The aim of this research was to establish the perturbation of reliable biomarkers implicated in the pathophysiology of autism to help in the early diagnosis and to be as targets in the treatment of autism spectrum disorders (ASDs) in children and to spotlight into the complex crosstalk between these biomarkers. PATIENS AND METHODS: This study included 90 autistic children aged from 2 to 7 years old, who were classified into two groups, the atypical autism of 30 children and the childhood autism. The childhood autism group was further divided into mild-moderate autism group and severe autism group each of 30 children. The control group included 30 matched healthy children. All the participants were subjected to full psychiatric examinations, psychological investigations, and biochemical measurements, including gamma-aminobutaric acid (GABA), serotonin, dopamine (DA) in plasma, and brain-derived neurotrophic factor (BDNF) in serum. RESULTS: The autistic groups showed a highly significant increase in GABA, serotonin, DA, and BDNF levels compared to the control. Of note, the levels of GABA, DA, and BDNF were significantly increased with the increased disease severity. Furthermore, a significant positive correlation between BDNF levels and both GABA and DA levels in the childhood autism group has been recorded. CONCLUSION: The present clinical setting provides new insight into the fundamental role of BDNF in the brain of autistic children as any alterations of its level due to GABA increment cause change in serotonin and DA levels which have empirical evidence in the pathophysiology of ASD. The results received in this research, create a fertile base for the setup of particular targets in the intervention of this ailment.

Sensory processing and participation in childhood occupation in Autism and Typically developing children - A cross sectional case control

BackgroundSensory processing difficulties and participation in childhood occupation in children impact their development, but the association among Malaysian children is unknown. The aim of this study is to provide empirical evidences on sensory processing and participation in childhood occupation, in children with autism and compare them with typical children without autism /’typical’.MethodTwo groups of participants (parents of children with autism and parents of ‘normal’ children were recruited from 5 hospitals, and from tuition/care centre/school respectively. Children with autism, age 6 to 10 years were matched (age/gender) with ‘typical’ children. The Participation of childhood occupation (PICO) and Sensory Processing (SSP) measures were used. Data were analysed descriptively for patterns, and Chi-square cross tabs used to compare sensory processing and participation (categorical variables) between the two groups.Results186 parents (93 children with autism and 93 typically developing children) participated. In the autism group, 77.4 percent (n=72) were males, or 4:1 male to female ratio. Children with autism compared with typical group experienced- a) higher sensory processing difficulties and b) less participation in childhood occupation (except basic activities like eating and sleep). Sensory processing difficulties in the autism children is lower compared to developed countries, but, the prevalence of sensory processing difficulties in the ‘typical’ children (21.5 percent) was higher than data from USA and Israel (9-15%). There were significant differences in sensory processing difficulties between the two group (p<0.05), except for movement sensitivity (p=0.28). Auditory filtering section were most affected in children with autism.ConclusionDifferences were found in the sensory processing difficulties (especially auditory filtering) and lower participation in autism group compared to ‘normal’ group. A higher percentage of sensory processing difficulties was also found in the ‘normal/ typically developing children’, which may be attributed to cultural or geographical factors (living in high rise flats with less playing space). More studies are needed comparing rural and urban children.

Gray matter covariations and core symptoms of autism. The EU-AIMS Longitudinal European Autism Project

BackgroundVoxel-based Morphometry (VBM) studies in Autism Spectrum Disorder (autism) have yielded diverging results. This might partly be attributed to structural alterations being associating with the combined influence of several regions rather than with a single region. Further, these structural covariation differences may relate to continuous measures of autism rather than with categorical case-control contrasts. The current study aimed to identify structural covariation alterations in autism, and assessed canonical correlations between brain covariation patterns and core autism symptoms.MethodsWe studied 347 individuals with autism and 252 typically developing individuals, aged between 6 and 30 years, who have been deeply phenotyped in the Longitudinal European Autism Project (LEAP). All participants’ VBM maps were decomposed into spatially independent components using Independent Component Analysis. A Generalized Linear Model (GLM) was used to examine case-control differences. Next, Canonical Correlation Analysis (CCA) was performed to separately explore the integrated effects between all the brain sources of gray matter variation and two sets of core autism symptoms.ResultsGLM analyses showed significant case-control differences for two independent components. The first component was primarily associated with decreased density of bilateral insula, inferior frontal gyrus, orbitofrontal cortex, and increased density of caudate nucleus in the autism group relative to typically developing individuals. The second component was related to decreased densities of the bilateral amygdala, hippocampus, and parahippocampal gyrus in the autism group relative to typically developing individuals. The CCA results showed significant correlations between components that involved variation of thalamus, putamen, precentral gyrus, frontal, parietal, and occipital lobes, and the cerebellum, and repetitive, rigid and stereotyped behaviors and abnormal sensory behaviors in autism individuals.LimitationsOnly 55.9% of the participants with autism had complete questionnaire data on continuous parent-reported symptom measures.ConclusionsCovaried areas associated with autism diagnosis and/or symptoms are scattered across the whole brain and include the limbic system, basal ganglia, thalamus, cerebellum, precentral gyrus, and parts of the frontal, parietal, and occipital lobes. Some of these areas potentially subserve social-communicative behavior whereas others may underpin sensory processing and integration, and motor behavior.