Neurotypical Boys Research Articles

Single-dose effects of methylphenidate and atomoxetine on functional connectivity during an n-back task in boys with ADHD

RationaleWorking memory deficits and associated neurofunctional abnormalities are frequently reported in attention-deficit/hyperactivity disorder (ADHD). Methylphenidate and atomoxetine improve working memory performance and increase activation of regions under-functioning in ADHD. Additionally, methylphenidate has been observed to modulate functional networks involved in working memory. No research, however, has examined the effects of atomoxetine or compared the two drugs.ObjectivesThis study aimed to test methylphenidate and atomoxetine effects on functional connectivity during working memory in boys with ADHD.MethodsWe tested comparative effects of methylphenidate and atomoxetine on functional connectivity during the n-back task in 19 medication-naïve boys with ADHD (10–15 years old) relative to placebo and assessed potential normalisation effects of brain dysfunctions under placebo relative to 20 age-matched neurotypical boys. Patients were scanned in a randomised, double-blind, cross-over design under single doses of methylphenidate, atomoxetine, and placebo. Controls were scanned once, unmedicated.ResultsPatients under placebo showed abnormally increased connectivity between right superior parietal gyrus (rSPG) and left central operculum/insula. This hyperconnectivity was not observed when patients were under methylphenidate or atomoxetine. Furthermore, under methylphenidate, patients showed increased connectivity relative to controls between right middle frontal gyrus (rMFG) and cingulo-temporo-parietal and striato-thalamic regions, and between rSPG and cingulo-parietal areas. Interrogating these networks within patients revealed increased connectivity between both rMFG and rSPG and right supramarginal gyrus under methylphenidate relative to placebo. Nonetheless, no differences across drug conditions were observed within patients at whole brain level. No drug effects on performance were observed.ConclusionsThis study shows shared modulating effects of methylphenidate and atomoxetine on parieto-insular connectivity but exclusive effects of methylphenidate on connectivity increases in fronto-temporo-parietal and fronto-striato-thalamic networks in ADHD.

Teachers’ relational competence: perceptions of teachers and students with and without ADHD and ASD

ABSTRACT This study examined whether teachers’ professional development of their relational competence with students with attention deficit hyperactivity disorder (ADHD) and/or autism spectrum disorder (ASD) modifies teachers’ and students’ perceptions of their teacher-student relationships (TSR). Participants comprised teachers (n = 33) and students (n = 232) from two elementary schools: one intervention school (InS) and one control school (CoS). InS teachers reported significant TSR improvements, regardless of student group or gender (p = .03). Among InS students, significant results were driven by female neurodiverse (ND) students and neurotypical (NT) male students (p = .03). Nevertheless, positive effects were solely observed among ND female students, while NT male students, conversely, reported decreased TSR during follow-up tests. No significant effects were found at the CoS irrespective of teacher or student ratings. The findings suggest that enhancing teachers’ understanding of relational competence concerning ND students will not only improve their own perceptions of their TSR but also those of ND female students. Nonetheless, directing teachers’ focus towards one student group (ND students) risks diminishing teachers’ attention towards other student groups, potentially explaining the poorer follow-up results among NT boys. The finding warrants further investigation, as it indicates a challenge for teachers to establish sufficient relational engagement with all students.

Analysis of salivary steroid hormones in boys with autism spectrum disorder

BackgroundAutism spectrum disorders (ASD) is a neurodevelopmental disorder with high incidence rate and difficult diagnosis. The purpose of this study was to explore whether salivary cortisol, dehydroepiandrosterone (DHEA) and pregnenolone can be used as biomarkers of ASD children.MethodsThe saliva samples of 55 boys with ASD were collected as the experimental group, and the saliva samples of 24 neurotypical boys were collected as the control group. The Child Behavior Checklist (CBCL), Autism Behavior Checklist (ABC), Social Responsiveness Scale (SRS), Repetitive Behavior Scale (RBS) were used to assess the severity of symptoms in boys with ASD. Cortisol, DHEA and pregnenolone concentrations in saliva were measured using an ABSSCIEX QTRAP® 6500 + LC/MS/MS system. SPSS 23.0 was used for statistical analysis. Comparisons between the two groups which conform to normal distribution were performed by T-test, and those which don’t conform to normal distribution were performed by Mann–Whitney U test. Correlation analysis between two variables was performed using Spearman's correlation analysis. Receiver operating characteristic curve (ROC) analysis was performed to evaluate the discriminatory sensitivity of each hormone between ASD and normal control groups. Logistic regression models were used to analyze whether DHEA and salivary pregnenolone can be used as a biomarker of ASD.ResultsThere were no significant differences in age, and weight between the ASD group and the normal control group. The ABC, SRS, RBS and CBCL scale scores in the ASD group were significantly higher than those in the normal control group. The salivary DHEA and pregnenolone concentrations in the ASD group were significantly higher than those in the normal control group, but there was no significant difference in cortisol. Spearman's correlation analysis showed that only pregnenolone associated with ABC. Logistic regression model analysis suggested that pregnenolone in saliva was an independent predictor of ASD. ROC analysis found that pregnenolone had good discrimination sensitivity between ASD and normal controls.ConclusionGave salivary preoperative a space for utilization as biomarker as number of cases are limited to this high expectation.

The Relationship of Steroid Hormones, Genes Related to Testosterone Metabolism and Behavior in Boys With Autism in Slovakia.

ObjectivePurpose of the study was to identify the relationship among actual plasmatic levels of steroid hormones and behavioral manifestations in boys with autism and to assess the genetic contribution to these manifestations. Methods172 boys with autism under 10 years of age and 135 neurotypical boys attended the study. ADI-R and ADOS-2 were used to evaluate the core symptom severities. Problem behavior was assessed using BPI-01 questionnaire. Levels of testosterone, estradiol, dehydroepiandrosterone, dehydroepiandrosterone-sulfate and sex hormone binding globulin (SHBG) were measured in plasma of autistic boys. Three SNPs (in ESR1, SHBG, SRD5A2 genes) and one STR in AR gene (number of CAG repeats in first exon) were assessed. Hormonal levels and number of CAG repeats in AR gene were used for correlation analysis with behavioral measures. Genotype and allelic frequencies were compared among autistic and neurotypical boys. ResultsWe found negative relationship among SHBG levels and restricted, repetitive behaviors (measured by ADOS-2) and positive relationship among actual testosterone levels and frequency of stereotyped behavior (measured by BPI-01). ConclusionActual levels of SHBG and testosterone are related to severities of restricted and repetitive behaviors in boys with autism. Mechanisms of action of these hormones in brain require further investigation.

DNA methylation and behavioral dysfunction in males with 47,XXY and 49,XXXXY: a pilot study

BackgroundEqual dosage of X-linked genes between males and females is maintained by the X-inactivation of the second X chromosome in females through epigenetic mechanisms. Boys with aneuploidy of the X chromosome exhibit a host of symptoms such as low fertility, musculoskeletal anomalies, and cognitive and behavioral deficits that are presumed to be caused by the abnormal dosage of these genes. The objective of this pilot study is to assess the relationship between CpG methylation, an epigenetic modification, at several genes on the X chromosome and behavioral dysfunction in boys with supernumerary X chromosomes.ResultsTwo parental questionnaires, the Behavior Rating Inventory of Executive Function (BRIEF) and Child Behavior Checklist (CBCL), were analyzed, and they showed expected differences in both internal and external behaviors between neurotypical (46,XY) boys and boys with 49,XXXXY. There were several CpGs in AR and MAOA of boys with 49,XXXXY whose methylation levels were skewed from levels predicted from having one active (Xa) and three inactive (Xi) X chromosomes. Further, methylation levels of multiple CpGs in MAOA showed nominally significant association with externalizing behavior on the CBCL, and the methylation level of one CpG in AR showed nominally significant association with the BRIEF Regulation Index.ConclusionsBoys with 49,XXXXY displayed higher levels of CpG methylation at regulatory intronic regions in X-linked genes encoding the androgen receptor (AR) and monoamine oxidase A (MAOA), compared to that in boys with 47,XXY and neurotypical boys. Our pilot study results suggest a link between CpG methylation levels and behavior in boys with 49,XXXXY.

Theory of Mind and Moral Decision-Making in the Context of Autism Spectrum Disorder.

Social impairment in Autism Spectrum Disorder (ASD) has been linked to Theory of Mind (ToM) deficits. However, little research has investigated the relationship between ToM and moral decision-making in children with ASD. This study compared moral decision-making and ToM between aggregate-matched ASD and neurotypical boys (n = 38 per group; aged 6-12). In a third-party resource allocation task manipulating recipient merit, wealth, and health, neurotypical children allocated significantly more resources to the morally deserving recipient, suggesting equitable allocation. A comparatively larger portion of the ASD group allocated equally. ToM emerged as a predictor of moral decision-making. We suggest that ToM (cognitive empathy) deficits may underly atypical moral decision-making in ASD by limiting the integration of empathic arousal (affective empathy) with moral information.

Comparison of gut microbiota in autism spectrum disorders and neurotypical boys in China: A case-control study

BackgroundAutism spectrum disorders (ASDs) are a set of complex neurobiological disorders. Growing evidence has shown that the microbiota that resides in the gut can modulate brain development via the gut–brain axis. However, direct clinical evidence of the role of the microbiota–gut–brain axis in ASD is relatively limited. MethodsA case-control study of 71 boys with ASD and 18 neurotypical controls was conducted at China-Japan Friendship Hospital. Demographic information and fecal samples were collected, and the gut microbiome was evaluated and compared by 16S ribosomal RNA gene sequencing and metagenomic sequencing. ResultsA higher abundance of operational taxonomic units (OTUs) based on fecal bacterial profiling was observed in the ASD group. Significantly different microbiome profiles were observed between the two groups. At the genus level, we observed a decrease in the relative abundance of Escherichia, Shigella, Veillonella, Akkermansia, Provindencia, Dialister, Bifidobacterium, Streptococcus, Ruminococcaceae UCG_002, Megasphaera, Eubacterium_coprostanol, Citrobacter, Ruminiclostridium_5, and Ruminiclostridium_6 in the ASD cohort, while Eisenbergiella, Klebsiella, Faecalibacterium, and Blautia were significantly increased. Ten bacterial strains were selected for clinical discrimination between those with ASD and the neurotypical controls. The highest AUC value of the model was 0.947. ConclusionSignificant differences were observed in the composition of the gut microbiome between boys with ASD and neurotypical controls. These findings contribute to the knowledge of the alteration of the gut microbiome in ASD patients, which opens the possibility for early identification of this disease.

Alteration of the steroidogenesis in boys with autism spectrum disorders

The etiology of autism spectrum disorders (ASD) remains unknown, but associations between prenatal hormonal changes and ASD risk were found. The consequences of these changes on the steroidogenesis during a postnatal development are not yet well known. The aim of this study was to analyze the steroid metabolic pathway in prepubertal ASD and neurotypical boys. Plasma samples were collected from 62 prepubertal ASD boys and 24 age and sex-matched controls (CTRL). Eighty-two biomarkers of steroidogenesis were detected using gas-chromatography tandem-mass spectrometry. We observed changes across the whole alternative backdoor pathway of androgens synthesis toward lower level in ASD group. Our data indicate suppressed production of pregnenolone sulfate at augmented activities of CYP17A1 and SULT2A1 and reduced HSD3B2 activity in ASD group which is partly consistent with the results reported in older children, in whom the adrenal zona reticularis significantly influences the steroid levels. Furthermore, we detected the suppressed activity of CYP7B1 enzyme readily metabolizing the precursors of sex hormones on one hand but increased anti-glucocorticoid effect of 7α-hydroxy-DHEA via competition with cortisone for HSD11B1 on the other. The multivariate model found significant correlations between behavioral indices and circulating steroids. From dependent variables, the best correlation was found for the social interaction (28.5%). Observed changes give a space for their utilization as biomarkers while reveal the etiopathogenesis of ASD. The aforementioned data indicate a direction of the future research with a focus on the expression and functioning of genes associated with important steroidogenic enzymes in ASD patients from early childhood to adrenarche.

60 Precision Medicine in Developmental Pediatrics: Image-based Classification of Children with Autism Spectrum Disorder using Deep Learning

Abstract Introduction/Background Autism spectrum disorder (ASD) is a neurodevelopmental disorder resulting in challenges with social communication, sensory differences, and repetitive and restricted patterns of behavior. ASD affects approximately 1 in 66 children in North America, with boys being affected four times more frequently than girls. Currently, diagnosis is made primarily based on clinical features and no robust biomarker for ASD diagnosis has been identified. Potential image-based biomarkers to aid ASD diagnosis may include structural properties of deep gray matter regions in the brain. Objectives The primary objective of this work was to investigate if children with ASD show micro- and macrostructural alterations in deep gray matter structures compared to neurotypical children, and if these biomarkers can be used for an automatic ASD classification using deep learning. Design/Methods Quantitative apparent diffusion coefficient (ADC) magnetic resonance imaging data was obtained from 23 boys with ASD ages 0.8 – 19.6 years (mean 7.6 years) and 39 neurotypical boys ages 0.3 – 17.75 years (mean 7.6 years). An atlas-based method was used for volumetric analysis and extraction of median ADC values for each subject within the cerebral cortex, hippocampus, thalamus, caudate, putamen, globus pallidus, amygdala, and nucleus accumbens. The extracted quantitative regional volumetric and median ADC values were then used for the development and evaluation of an automatic classification method using an artificial neural network. Results The classification model was evaluated using 10-fold cross validation resulting in an overall accuracy of 76%, which is considerably better than chance level (62%). Specifically, 33 neurotypical boys were correctly classified, whereas 6 neurotypical boys were incorrectly classified. For the ASD group, 14 boys were correctly classified, while 9 boys were incorrectly classified. This translates to a precision of 70% for the children with ASD and 79% for neurotypical boys. Conclusion To the best of our knowledge, this is the first method to classify children with ASD using micro- and macrostructural properties of deep gray matter structures in the brain. The first results of the proposed deep learning method to identify children with ASD using image-based biomarkers are promising and could serve as the platform to create a more accurate and robust deep learning model for clinical application.

Neurogenetic Profiles of Risk and Resilience in Female Autism

Understanding sex differences in brain function and genetics is critical to delineating the systems biology of autism spectrum disorder (ASD), but female ASD is understudied. We integrate imaging and genetic data in a sex-balanced sample of ASD and neurotypical youth to evaluate the hypothesis that there are female-specific pathways of ASD risk and resilience. FMRI data reveal a neurofunctional profile of female ASD characterized by motor, striatal, and frontal involvement not observed in male ASD. Further, we observe greater recruitment of salience and executive control networks among neurotypical girls versus neurotypical boys and autistic girls, suggesting neural correlates of the “Female Protective Effect.” Larger copy number variants containing gene(s) expressed in striatal cortex in autistic girls versus boys suggest a female-specific etiological role for potential impacts to this brain region. Our findings advocate caution in drawing conclusions regarding autistic girls based on male-predominant samples.

'It's different for girls': Gender differences in the friendships and conflict of autistic and neurotypical adolescents.

This mixed-methods study examined gender differences in the friendships and conflict experiences of autistic girls and boys relative to their neurotypical peers. In total, 102 adolescents (27 autistic girls, 26 autistic boys, 26 neurotypical girls, and 23 neurotypical boys), aged between 11 and 18 years completed the Friendship Qualities Scale, the Revised Peer Experiences Questionnaire and were interviewed about their friendships. Results demonstrated that in many ways, the friendships and social experiences of autistic girls are similar to those of neurotypical girls. Autistic girls, however, have significantly more social challenges than their neurotypical peers, experiencing more conflict and finding that conflict harder to manage successfully. Autistic boys showed quantitatively different friendship patterns to all other groups. There were consistent gender differences in the type of conflict which boys and girls experienced, regardless of diagnostic status. These findings suggest that gender, rather than diagnosis per se, plays a critical role in the way that autistic adolescents perceive and experience their social relationships.

Perceptual integration and visual object recognition in children with high functioning autism

Background: Although defects in social and communicative functioning are the most obvious features in autistic children, there is evidence suggesting that unusual perceptual processing is at least a concomitant and possible cause of many of the behavioral signs and symptoms of autism spectrum. In the present study, the perceptual integration of autistic children was studied. These processes require perceptual coherence in visual structure in a holistic manner. Methods: 25 high-functioning autistic and 25 neuro-typical boys were assessed in term of visual perceptual processing. Visual stimuli included fragmented (incomplete) and complete object images that were presented in a monitor. The subject’s task was rapid and accurate naming of images that were seen. Responses were compared by independent t-test. Also, the effect of completeness factor and group type on the samples’ visual processing was analyzed by repeated measure analysis of variance. Results: The autistic children had lower function in naming the fragmented picture, however, both groups were equivalent in recognition of the complete image. On the other hand, all subjects in this study performed better in naming the complete images compared with the fragmented images. Also, the interaction effect of image type and group on visual processing was significant. Conclusion: Defect in recognition of fragmented images can be indicative of disturbance of processes related to visual perceptual integration in individuals with autism. Detection of these images in autistic children was significantly different from that of normal children, that indicates weakness of processes related to visual completion and perceptual integration.