Autism Spectrum Disorder Population Research Articles

High-Functioning Autism and Virtual Reality Applications: A Scoping Review

In recent years, the number of applications of virtual reality (VR) for the Autism spectrum disorder (ASD) population has increased and has become one of the most suitable tools to address the psychological needs of these individuals. The present scoping review aims to provide a literature mapping of experimental studies that have used immersive and semi-immersive VR for assessments or interventions specifically addressing high-functioning autism. A total of 23 papers were included and analyzed following PRISMA guidelines. The identified studies concerned social skills (11 papers), eye gaze and joint attention (3 papers), motor learning (3 papers), job training (2 papers), and other aims or rationales (4 papers). The evidence shows that, despite the intellectual potential of high-functioning ASD individuals, little research has been conducted to provide interventions that offer concrete training to improve their adaptive functioning. In addition, the percentage of individuals below 18 years of age is representative of half of the included studies, so aiming future studies at the early stages of development might be an asset in preparing the next generation of young adults to cope with age-related challenges, as early assessments and interventions are more likely to produce major long-term effects.

Clinical and neuropsychological correlates of theta-band functional excitation-inhibition ratio in autism: an EEG study

ObjectiveHow abnormal brain signaling impacts cognition in autism spectrum disorder (ASD) remained elusive. This study aimed to investigate the local and global brain signaling in ASD indicated by theta-band functional excitation-inhibition (fE/I) ratio and explored psychophysiological relationships between fE/I, cognitive deficits, and ASD symptomatology. MethodsA total of 83 ASD and typically developing (TD) individuals participated in this study. Participants’ interference control and set-shifting abilities were assessed. Resting-state electroencephalography (EEG) was used for estimating theta-band fE/I ratio. ResultsASD individuals (n = 31 without visual EEG abnormality; n = 22 with visual EEG abnormality) generally performed slower in a cognitive task tapping interference control and set-maintenance abilities, but only ASD individuals with visually abnormal EEG performed significantly slower than their TD counterparts (Bonferroni-corrected ps < .001). Heightened theta-band fE/I ratios at the whole-head level, left and right hemispheres were observed in the ASD subgroup without visual EEG abnormality only (Bonferroni-corrected ps < .001), which remained highly significant when only data from medication-naïve participants were analyzed. In addition, higher left hemispheric fE/I ratios in ASD individuals without visual EEG abnormality were significantly correlated with faster interference control task performance, in turn faster reaction time was significantly associated with less severe restricted, repetitive behavior (Bonferroni-corrected ps ≤ .0017). ConclusionsDifferential theta-band fE/I within the ASD population. Heightened theta-band fE/I in ASD without visual EEG abnormality may be associated with more efficient filtering of distractors and a less severe ASD symptom manifestation. SignificanceBrain signaling, indicated by theta-band fE/I, was different in ASD subgroups. Only ASD with visually-normal EEG showed heightened theta-band fE/I, which was associated with faster processing of visual distractors during a cognitive task. More efficient distractor filtering was associated with less restricted, repetitive behaviors.

Early executive functioning predicts externalizing problems in neurodiverse preschoolers.

Children with autism spectrum disorder (ASD) often exhibit externalizing problems, which have been linked with increased anxiety and depression, peer rejection, and parental stress. Identification of early predictors of externalizing behaviors in autism will facilitate identification of vulnerable children and implementation of early preventative interventions. There is ample evidence that executive functioning, social functioning, and temperament are predictive of later externalizing problems in general populations, but less is known about these relations in ASD and other neurodiverse populations, particularly in the early preschool years. To address this gap, we assessed the relations between executive functioning, social functioning, and temperament at age 3 and externalizing problems at age 5 in a sample of neurodiverse children with ASD and other neurodevelopmental disorders and delays. Analyses revealed that severity of early executive functioning impairment predicted increased externalizing problems. Severity of social autism symptoms moderated this relationship such that the effect of executive functioning on externalizing problems decreased as autism symptoms increased. These findings suggest that executive functioning is an important target for identifying and developing interventions for vulnerable children and underscore the necessity of considering severity of autism symptoms when researching the development of externalizing problems in children with neurodevelopmental disorders.

National Survey on bladder and bowel dysfunctions in Autism Spectrum Disorder population.

To evaluate lower urinary tract symptoms (LUTS) and bowel disorders in a population of young subjects with autism spectrum disorder (ADS) by a national survey and to assess the relationship between the occurrence, frequency, and type of LUTS and the severity of behavioral and neuropsychiatric characteristics. A survey on LUTS and bowel disorders in the ASD population was sent by mail and social media through the main Italian Associations of ASD between February and September 2022. The correlation between LUTS and ASD severity was also assessed. The survey was completed by 502 subjects with a mean age of 16.6 years ± 10 years: male participants were 413 (mean age: 16.5 years ± 9.8 years), while female participants 89 (mean age: 17.2 years ± 10.9 years). ADS severity was found low in 29.9%, moderate in 27.1%, and severe in 43%. LUTS were reported by 77.1%, storage symptoms in 51.4%, and voiding symptoms in 60.6%. Urinary incontinence was reported by 12.5%. Enuresis was reported by 14.3% (72/502) of the respondents: primary enuresis in 70.8% (51/72), secondary in the remaining. Pads were used by 40 subjects with a median of 2.9 pads/day (range, 0-8). A toilet training program was performed by 61 of the respondents, with satisfactory results in 40/61 (65.6%). A significant correlation was found between greater ASD severity and higher LUTS rates. The mean VAS score on the impact of LUTS on family relationships was 2 ± 2.9. Regular bowel function was reported by 57.4% (288/502) of the respondents, while increased daily defecations were present in 11.2% (56/502), constipation in 31.5% (158/502), and fecal incontinence in 7.9% (40/502). This survey demonstrated that LUTS are very common in the young ASD population and that the prevalence of urinary symptoms is related to higher severity of the ASD condition. Bowel disorders are often associated with urinary symptoms and dysfunctions. Urologists should be aware of the frequent occurrence of urological disorders and symptoms in individuals with ASD and should be involved in their clinical management in a multidisciplinary team that cares for these people.

Exploratory focused pharmacogenetic testing reveals novel markers associated with risperidone pharmacokinetics in Saudi children with autism.

Background: Autism spectrum disorders (ASDs) encompass a broad range of phenotypes characterized by diverse neurological alterations. Genomic studies have revealed considerable overlap between the molecular mechanisms implicated in the etiology of ASD and genes involved in the pharmacokinetic (PK) and pharmacodynamic (PD) pathways of antipsychotic drugs employed in ASD management. Given the conflicting data originating from candidate PK or PD gene association studies in diverse ethnogeographic ASD populations, dosage individualization based on "actionable" pharmacogenetic (PGx) markers has limited application in clinical practice. Additionally, off-label use of different antipsychotics is an ongoing practice, which is justified given the shortage of approved cures, despite the lack of satisfactory evidence for its safety according to precision medicine. This exploratory study aimed to identify PGx markers predictive of risperidone (RIS) exposure in autistic Saudi children. Methods: This prospective cohort study enrolled 89 Saudi children with ASD treated with RIS-based antipsychotic therapy. Plasma levels of RIS and 9-OH-RIS were measured using a liquid chromatography-tandem mass spectrometry system. To enable focused exploratory testing, genotyping was performed with the Axiom PharmacoFocus Array, which included a collection of probe sets targeting PK/PD genes. A total of 720 PGx markers were included in the association analysis. Results: A total of 27 PGx variants were found to have a prominent impact on various RIS PK parameters; most were not located within the genes involved in the classical RIS PK pathway. Specifically, 8 markers in 7 genes were identified as the PGx markers with the strongest impact on RIS levels (p < 0.01). Four PGx variants in 3 genes were strongly associated with 9-OH-RIS levels, while 5 markers in 5 different genes explained the interindividual variability in the total active moiety. Notably, 6 CYP2D6 variants exhibited strong linkage disequilibrium; however, they significantly influenced only the metabolic ratio and had no considerable effects on the individual estimates of RIS, 9-OH-RIS, or the total active moiety. After correction for multiple testing, rs78998153 in UGT2B17 (which is highly expressed in the brain) remained the most significant PGx marker positively adjusting the metabolic ratio. For the first time, certain human leukocyte antigen (HLA) markers were found to enhance various RIS exposure parameters, which reinforces the gut-brain axis theory of ASD etiology and its suggested inflammatory impacts on drug bioavailability through modulation of the brain, gastrointestinal tract and/or hepatic expression of metabolizing enzymes and transporters. Conclusion: Our hypothesis-generating approach identified a broad spectrum of PGx markers that interactively influence RIS exposure in ASD children, which indicated the need for further validation in population PK modeling studies to define polygenic scores for antipsychotic efficacy and safety, which could facilitate personalized therapeutic decision-making in this complex neurodevelopmental condition.

Increased risk of acute stress disorder and post-traumatic stress disorder in children and adolescents with autism spectrum disorder: a nation-wide cohort study in Taiwan.

Children and adolescents with autism spectrum disorder (ASD) may be particularly vulnerable to the impact of traumatic events, yet the association between ASD and the risk of developing acute stress disorder and post-traumatic stress disorder (PTSD) remains uncertain. This study aims to investigate this association, addressing the gap in large-scale evidence on the subject. Conducted as a retrospective and matched cohort study, data was sourced from the National Health Insurance Research Database (NHIRD) in Taiwan, spanning from January 1, 2000, to December 31, 2015. The study included patients aged 18 years or under newly diagnosed with ASD (n=15,200) and compared them with a matched control group (n=45,600). The Cox proportional regression model was employed to assess the risk of acute stress disorder and PTSD. Over the 15-year follow-up period, a total of 132 participants developed either acute stress disorder or PTSD. Among them, 105 cases (0.691% or 64.90 per 100,000 person-years) were in the ASD group, while 27 cases (0.059% or 5.38 per 100,000 person-years) were in the control group. The adjusted hazard ratio for the ASD group was significantly higher compared to the control group (25.661 with 95% CI = 15.913-41.232; P < .001). This study provides compelling evidence that individuals with ASD face an elevated risk of developing acute stress disorder and PTSD. The findings underscore the importance of clinicians recognizing and addressing this vulnerability in ASD individuals exposed to traumatic events. This emphasizes the need for heightened attention to the risk of PTSD and acute stress disorder in the ASD population.

Autism Spectrum Disorder with Epilepsy: A Research Protocol for a Clinical and Genetic Study.

Autism spectrum disorder (ASD) is a common neurodevelopmental condition affecting ~1% of people worldwide. Core ASD features present with impaired social communication abilities, repetitive and stereotyped behaviors, and atypical sensory responses and are often associated with a series of comorbidities. Among these, epilepsy is frequently observed. The co-occurrence of ASD and epilepsy is currently thought to result from common abnormal neurodevelopmental pathways, including an imbalanced excitation/inhibition ratio. However, the pathological mechanisms involved in ASD-epilepsy co-morbidity are still largely unknown. Here, we propose a research protocol aiming to investigate electrophysiological and genetic features in subjects with ASD and epilepsy. This study will include a detailed electroencephalographic (EEG) and blood transcriptomic characterization of subjects with ASD with and without epilepsy. The combined approach of EEG and transcriptomic studies in the same subjects will contribute to a novel stratification paradigm of the heterogeneous ASD population based on quantitative gene expression and neurophysiological biomarkers. In addition, our protocol has the potential to indicate new therapeutic options, thus amending the current condition of absence of data and guidelines for the treatment of ASD with epilepsy.

Oral Health Statuses of Children and Young Adults with Autism Spectrum Disorder: An Umbrella Review.

This study aimed to comprehensively evaluate the oral health statuses of children and adults within the autism spectrum disorder (ASD) population through an umbrella review approach. The prevalence of dental caries, periodontal disease, and associated variables were investigated across selected studies. A systematic search was conducted across databases including PubMed, Scopus, EMBASE, Science Citation Index, Science Direct, Web of Science, MEDLINE, and Wiley Online Library to identify relevant studies. The assessed variables included dental caries prevalence, periodontal disease prevalence, oral hygiene indicators, and the necessity of dental treatment. The pooled prevalence rates, odds ratios, and standardized mean differences were calculated where applicable. The pooled prevalence of dental caries among ASD individuals ranged from 60.6% to 67.3%, while the periodontal disease prevalence ranged from 59.8% to 69.4%. High rates of dental treatment under general anesthesia were reported. Heterogeneous dental caries and periodontal disease prevalence rates were identified, highlighting the need for collaboration and preventive care. Several studies also reported higher prevalence rates of dental trauma and self-inflicted oral injuries among individuals with ASD. However, the review also identified significant methodological limitations in the included studies, including inconsistency in oral health assessment methods and potential bias. The necessity for targeted policies due to high prevalence rates and the requirement for integrated care systems in high DMFT regions were also observed. The umbrella review synthesized diverse findings, revealing variations in dental caries and periodontal disease prevalence among ASD individuals. This review underscores the need for tailored interventions and policies to address oral health disparities. It highlights the necessity of integrated care systems, methodological improvements, and longitudinal studies to comprehensively address the multifaceted oral health challenges within the ASD population.

Enhancing autism spectrum disorder classification in children through the integration of traditional statistics and classical machine learning techniques in EEG analysis

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder hallmarked by challenges in social communication, limited interests, and repetitive, stereotyped movements and behaviors. Numerous research efforts have indicated that individuals with ASD exhibit distinct brain connectivity patterns compared to control groups. However, these investigations, often constrained by small sample sizes, have led to inconsistent results, suggesting both heightened and diminished long-range connectivity within ASD populations. To bolster our analysis and enhance their reliability, we conducted a retrospective study using two different connectivity metrics and employed both traditional statistical methods and machine learning techniques. The concurrent use of statistical analysis and classical machine learning techniques advanced our understanding of model predictions derived from the spectral or connectivity attributes of a subject's EEG signal, while also verifying these predictions. Significantly, the utilization of machine learning methodologies empowered us to identify a unique subgroup of correctly classified children with ASD, defined by the analyzed EEG features. This improved approach is expected to contribute significantly to the existing body of knowledge on ASD and potentially guide personalized treatment strategies.

Expression of miRNAs in Pre-Schoolers with Autism Spectrum Disorders Compared with Typically Developing Peers and Its Effects after Probiotic Supplementation.

Alteration of the microbiota-gut-brain axis has been recently recognized as a possible contributor to the physiopathology of autism spectrum disorder (ASD). In this context, microRNA (miRNAs) dysfunction, implicated both in several neuropathological conditions including ASD and in different gastrointestinal disorders (GIDs), could represent an important modulating factor. In this contextual framework, we studied the transcriptional profile of specific circulating miRNAs associated with both ASD (miR-197-5p, miR-424-5p, miR-500a-5p, miR-664a-5p) and GID (miR-21-5p, miR-320a-5p, miR-31-5p, miR-223-5p) in a group of pre-schoolers with ASD and in typically developing (TD) peers. In the ASD group, we also assessed the same miRNAs after a 6-month supplementation with probiotics and their correlation with plasma levels of zonulin and lactoferrin. At baseline, the expression of miRNAs involved in ASD were significantly reduced in ASD pre-schoolers vs. TD controls. Regarding the miRNAs involved in GID, the expression levels of miR-320-5p, miR-31-5p, and miR-223-5p were significantly higher in ASD than in TD subjects, whereas miR-21-5p showed significantly reduced expression in the ASD group vs. TD group. Supplementation with probiotics did not significantly change the expression of miRNAs in the ASD population. We found a significative negative correlation between zonulin and miR-197-5p and miR-21-5p at baseline, as well as between lactoferrin and miR-223-5p after 6 months of probiotic supplementation. Our study confirms the presence of an altered profile of the miRNAs investigated in ASD versus TD peers that was not modified by supplementation with probiotics.

44 Functional Connectivity In The Default Mode Network Of ASD and ADHD

Objective:Autism Spectrum Disorders (ASD) and Attention Deficit Hyperactivity Disorder (ADHD) are neurodevelopmental disorders with overlapping symptomatology and shared genetic makeup. Numerous previous studies have investigated ASD and ADHD using resting state functional networks. One functional network of particular interest is the Default Mode Network (DMN), as it has been shown to be abnormal in several mental disorders. Previous studies have investigated the DMN in ASD and ADHD separately but reported mixed trends of increased and decreased functional connectivity (FC) in the DMN in ASD and increased FC in ADHD. Additionally, little studies have investigated executive and attentional network dysfunction in the DMN for ASD and ADHD populations. To better understand the shared characteristics between ASD and ADHD, this study analyzed the DMN FC in children with ASD and ADHD.Participants and Methods:Archival datasets from Autism Brain Imaging Data Exchange (ABIDE)-I and ADHD-200 datasets were used, with 33 ADHD, 35 ASD, and 32 typically developing (TD) males (ages = 7-17 years). After applying a standard pre-processing pipeline, 11 regions of interest (ROIs) from the Dosenbach-160 atlas were examined with 55 ROI pairs generated for the 100 subjects.Results:Significant differences were noted between ASD-ADHD groups in attentional networks and executive functioning networks. Specifically, significant Group x VIQ interactions were noted for FC between the following pairs of regions: medial prefrontal cortex - ventromedial prefrontal cortex, anterior cingulate cortex -ventromedial prefrontal cortex, inferior temporal lobe - ventromedial prefrontal cortex, angular -ventromedial prefrontal cortex, angular -anterior cingulate cortex, inferior temporal lobe -ventrolateral prefrontal cortex, angular -superior frontal lobe, and intraparietal sulcus -superior frontal lobe. In the above FC pairs, FC in ADHD was negatively correlated with VIQ, with no correlation for ASD and positive correlation for TD. Previous literature has indicated that ADHD individuals demonstrate increased executive functioning deficits compared to ASD individuals. This study provides evidence at a neural level for these findings by demonstrating decreased FC trends in ADHD in attentional and executive functioning networks compared to ASD individuals. Group and VIQ main effects demonstrated mixed patterns across the three groups, as well as shared decreased FC in attention/executive networks for both ASD and ADHD groups.Conclusions:In summary, this study found similar findings from previous studies regarding mixed connectivity patterns, as well as shared dysfunction between ASD and ADHD groups. These results help in solidifying the theory that ASD and ADHD share clinical and neural patterns which need to be examined further. Future directions include utilizing more ASD+ADHD comorbid individuals in studies comparing ASD and ADHD FC trends as well as seeking to further understand the neuropsychological and neuroimaging profiles in ASD and ADHD.

Pharmacogenetics May Prevent Psychotropic Adverse Events in Autism Spectrum Disorder: An Observational Pilot Study.

Up to 73% of individuals with autism spectrum disorder (ASD) and intellectual disability (ID) currently have prescriptions for psychotropic drugs. This is explained by a higher prevalence of medical and psychiatric chronic comorbidities, which favors polypharmacy, increasing the probability of the appearance of adverse events (AEs). These could be a preventable cause of harm to patients with ASD and an unnecessary waste of healthcare resources. To study the impact of pharmacogenetic markers on the prevention of AE appearance in a population with ASD and ID. This is a cross-sectional, observational study (n = 118, 72 participants completed all information) in the ASD population. Sociodemographic and pharmacological data were gathered. The Udvalg for Kliniske Undersøgelser Scale (UKU Scale) was used to identify AEs related to the use of psychotropic medication. Polymorphisms of DOP2, ABCB1, and COMT were genotyped and correlated with the AE to find candidate genes. Furthermore, a review of all medications assessed in a clinical trial for adults with autism was performed to enrich the search for potential pharmacogenetic markers, keeping in mind the usual medications. The majority of the study population were men (75%) with multiple comorbidities and polypharmacy, the most frequently prescribed drugs were antipsychotics (69%); 21% of the participants had four or more AEs related to psychotropic drugs. The most common were "Neurological" and" Psychiatric" (both 41%). Statistical analysis results suggested a significant correlation between the neurological symptoms and the DOP2 genotype, given that they are not equally distributed among its allelic variants. The final review considered 19 manuscripts of medications for adults with ASD, and the confirmed genetic markers for those medications were consulted in databases. A possible correlation between neurologic AEs and polymorphisms of DOP2 was observed; therefore, studying this gene could contribute to the safety of this population's prescriptions. The following studies are underway to maximize statistical power and have a better representation of the population.

A multi-task learning model with reinforcement optimization for ASD comorbidity discrimination

How to discriminate the comorbidities in autism spectrum disorder (ASD) population has long been an intriguing and challenging issue in neuroscience and neurology practices. Taking attention deficit hyperactivity disorder (ADHD) for example, electroencephalogram (EEG) analysis has alleviated the problem caused by the task of evaluation of similar behaviors of subjects with ASD, ADHD and ASD+ADHD, which requires a very high expertise to reach any concrete conclusions. However, the performance of ASD comorbidity discrimination is still limited by two major difficulties 1) crucial EEG features regarding ASD and ASD+ADHD largely overlap, and 2) reliable data for model training are routinely insufficient.This study proposes a multi-task learning method with “reinforcement optimization” (namely RO-MLT) working in a two-fold manner: 1)Modeling for Discrimination: a multi-task CNN model maintains the target discrimination task (ASD vs. ASD+ADHD) with the aid of the auxiliary task (ASD vs. Typically Developed (TD)), which is designed to mitigate the aforementioned difficulties on model training; and 2) Reinforcement Optimization: a reinforcement learning algorithm enhances the model's feature extraction and fusion capabilities by optimizing its shared structure.Experimental results based on resting-state EEG that collected from 150 ASD, ASD+ADHD or TD children with the RO-MLT method against the state-of-the-art counterparts indicate that RO-MLT is far superior in terms of all performance indicators (e.g., accuracy). Ablation experiments also show that introduction of multi-task learning and reinforcement optimization can achieve a performance boost-up by 11.07%, a gain even higher than the sums of introduction of two individual techniques to the model design.

B - 24 Neuropsychological Profile of a Child with ASD, ADHD, and Psychotic Features.

Autism Spectrum Disorder (ASD), Attention Deficit-Hyperactivity Disorder (ADHD), and psychotic traits, although highly comorbid, have rarely been studied in children. Existing research indicates that impulsivity, comprehension difficulties, and inflexibility are overlapping symptoms within the ASD and ADHD populations. Adult research shows high comorbidity estimates between ASD and psychosis. Here we describe the neuropsychological profile of a 14-year-old boy with diagnoses of ASD and ADHD with psychotic features. We highlight the value of comprehensive and flexible neuropsychological assessment while integrating detailed testing, behavioral observations, and collateral report. Medical history of this child included late-term and breech birth with his first Apgar score at expected level and his second score falling below expected level. Delayed acquisition of developmental milestones, learning difficulties, speech difficulties, anxiety, and hyperactivity, were reported. Auditory hallucinations triggered by stress were observed during evaluation. Comprehensive neuropsychological evaluation requires nonstandard exploration of cognitive domains and time-limited testing sessions to acquire robust estimates of functioning. Overall cognitive abilities were in the borderline range with highly variable academic performances (extremely low to average). All performances were grossly below age level and were significantly impacted by auditory hallucinations but were consistent with the diagnoses of ASD and ADHD. This case of a boy with ASD, ADHD, and auditory hallucinations demonstrates the diagnostic overlap among these conditions and the necessity for flexible neuropsychological testing, detailed behavioral observations and caregiver report in the assessment of overlapping clinical features. Multiple sources of data are required to identify patterns in symptomatology to inform differential diagnosis and comorbidities.

Using Augmented Reality Toward Improving Social Skills: Scoping Review.

Augmented reality (AR) has emerged as a promising technology in educational settings owing to its engaging nature. However, apart from applications aimed at the autism spectrum disorder population, the potential of AR in social-emotional learning has received less attention. This scoping review aims to map the range of AR applications that improve social skills and map the characteristics of such applications. In total, 2 independent researchers screened 2748 records derived from 3 databases in December 2021-PubMed, IEEE Xplore, and ACM Guide to Computing Literature. In addition, the reference lists of all the included records and existing reviews were screened. Records that had developed a prototype with the main outcome of improving social skills were included in the scoping review. Included records were narratively described for their content regarding AR and social skills, their target populations, and their outcomes. Evaluation studies were assessed for methodological quality. A total of 17 records met the inclusion criteria for this study. Overall, 10 records describe applications for children with autism, primarily teaching about reading emotions in facial expressions; 7 records describe applications for a general population, targeting both children and adults, with a diverse range of outcome goals. The methodological quality of evaluation studies was found to be weak. Most applications are designed to be used alone, although AR is well suited to facilitating real-world interactions during a digital experience, including interactions with other people. Therefore, future AR applications could endorse social skills in a general population in more complex group settings.

Interpersonal matching of autistic trait levels in typically developed individuals is associated with spontaneous gaze following and initiation during face-to-face social interaction.

People with autism spectrum disorders (ASD) usually exhibit typical behaviours and thoughts that are called autistic traits. Autistic traits are widely and continuously distributed among typically developed (TD) and ASD populations. Previous studies have found that people with ASD have difficulty in following the eye gaze of social peers. However, it remains unknown whether TD adults with high or low autistic traits also differ in spontaneous gaze following and initiation in face-to-face social interactions. To fill this gap, this study used a novel and naturalistic gaze-cueing paradigm to examine this research question. A 4 (group: high-high, high-low, low-high or low-low autistic traits) × 3 (congruency: congruent, neutral, or incongruent) mixed-measures design was used. Typically developed adults who were high or low in autistic traits completed a visual search task while a confederate who was high or low in autistic traits sat facing them. Critically, the match of autistic traits within a participant-confederate pair was manipulated. The confederate gazed at (congruent) or away from (incongruent) the location of the target prior to the appearance of the target. Participants were not explicitly instructed to follow the confederate's gaze. Autistic traits were associated with spontaneous gaze following and initiation in face-to-face social interactions. Specifically, only when both the participant and confederate were low in autistic traits did the incongruent gaze cues of confederates interfere with the participants' responses. Autistic traits impeded gaze following and initiation by TD adults. This study has theoretical and practical implications regarding autistic trait-induced social deficits and indicates a new approach for social skill interventions.

A Potential Biomarker of Brain Activity in Autism Spectrum Disorders: A Pilot fNIRS Study in Female Preschoolers

Autism spectrum disorder (ASD) refers to a neurodevelopmental condition whose detection still remains challenging in young females due to the heterogeneity of the behavioral phenotype and the capacity of camouflage. The availability of quantitative biomarkers to assess brain function may support in the assessment of ASD. Functional Near-infrared Spectroscopy (fNIRS) is a non-invasive and flexible tool that quantifies cortical hemodynamic responses (HDR) that can be easily employed to describe brain activity. Since the study of the visual phenotype is a paradigmatic model to evaluate cerebral processing in many neurodevelopmental conditions, we hypothesized that visually-evoked HDR (vHDR) might represent a potential biomarker in ASD females. We performed a case-control study comparing vHDR in a cohort of high-functioning preschooler females with ASD (fASD) and sex/age matched peers. We demonstrated the feasibility of visual fNIRS measurements in fASD, and the possibility to discriminate between fASD and typical subjects using different signal features, such as the amplitude and lateralization of vHDR. Moreover, the level of response lateralization was correlated to the severity of autistic traits. These results corroborate the cruciality of sensory symptoms in ASD, paving the way for the validation of the fNIRS analytical tool for diagnosis and treatment outcome monitoring in the ASD population.

16 - Survey on bladder and bowel dysfunctions in a young autism spectrum disorder population

16 - Survey on bladder and bowel dysfunctions in a young autism spectrum disorder population

Contributions to auditory system conduction velocity: insights with multi-modal neuroimaging and machine learning in children with ASD and XYY syndrome.

The M50 electrophysiological auditory evoked response time can be measured at the superior temporal gyrus with magnetoencephalography (MEG) and its latency is related to the conduction velocity of auditory input passing from ear to auditory cortex. In children with autism spectrum disorder (ASD) and certain genetic disorders such as XYY syndrome, the auditory M50 latency has been observed to be elongated (slowed). The goal of this study is to use neuroimaging (diffusion MR and GABA MRS) measures to predict auditory conduction velocity in typically developing (TD) children and children with autism ASD and XYY syndrome. Non-linear TD support vector regression modeling methods accounted for considerably more M50 latency variance than linear models, likely due to the non-linear dependence on neuroimaging factors such as GABA MRS. While SVR models accounted for ~80% of the M50 latency variance in TD and the genetically homogenous XYY syndrome, a similar approach only accounted for ~20% of the M50 latency variance in ASD, implicating the insufficiency of diffusion MR, GABA MRS, and age factors alone. Biologically based stratification of ASD was performed by assessing the conformance of the ASD population to the TD SVR model and identifying a sub-population of children with unexpectedly long M50 latency. Multimodal integration of neuroimaging data can help build a mechanistic understanding of brain connectivity. The unexplained M50 latency variance in ASD motivates future hypothesis generation and testing of other contributing biological factors.

Neonatal immune signatures differ by sex regardless of neurodevelopmental disorder status: Macrophage migration inhibitory factor (MIF) alone reveals a sex by diagnosis interaction effect

Immune dysregulation, including aberrant peripheral cytokine/chemokine levels, is implicated in neurodevelopmental disorders (NDD) such as autism spectrum disorder (ASD). While the diagnosis of ASD is more common in males compared to females, sex effects in immune dysregulation related to neurodevelopment remain understudied. The aim of this exploratory study was to determine whether there are sex-specific effects in neonatal immune dysregulation with respect to an ASD or delayed development (DD) diagnosis. We utilized the data from the Early Markers for Autism study, a population based case-control study of prenatal and neonatal biomarkers of ASD. The immune profile of newborns later diagnosed with ASD (n = 482, 91 females), DD (n = 140, 61 females) and sex-matched general population controls (GP; n = 378, 67 females) were analyzed using neonatal bloodspots (NBS) via 42-plex multiplex assay. Multiple linear regression analysis was performed to identify whether sex was associated with differences in cytokine/chemokine levels of children with ASD, DD, and GP. A sex by diagnosis interaction effect was observed only for the chemokine macrophage migration inhibitory factor (MIF), with males displaying higher levels of NBS MIF than females in the GP control group (p = 0.02), but not in ASD (p = 0.52) or DD (p = 0.29) groups. We found that regardless of child diagnosis, newborn bloodspot eluates from females had a significantly higher concentration than males with the same diagnosis of the chemokines granulocyte chemotactic protein 2 (GCP-2; p < 0.0001), macrophage inflammatory protein 2-alpha (GROβ; p = 0.002), interferon-inducible t-cell alpha chemoattractant (I-TAC; p < 0.0001), stromal cell-derived factor 1 alpha and beta (SDF-1α-β; p = 0.03), innate inflammatory chemokines interferon-gamma induced protein 10 (IP-10; p = 0.02), macrophage inflammatory protein 1-alpha (MIP-1α; p = 0.02), and Th1-related pro-inflammatory cytokine interleukin-12 active heterodimer (IL-12p70; p = 0.002). In contrast, males had a higher concentration than females of secondary lymphoid-tissue chemokine (6CKINE; p = 0.02), monocyte chemotactic protein 1 (MCP-1; p = 0.005) and myeloid progenitor inhibitory factor 1 (MPIF-1; p = 0.03). Results were similar when analyses were restricted to NBS from DD and ASD further classified as ASD with intellectual disability (ID), ASD without ID, and DD (GCP-2, p = 0.007; I-TAC, p = 0.001; IP-10, p = 0.005; IL-12p70, p = 0.03 higher in females; MPIF-1, p = 0.03 higher in male). This study is the first to examine sex differences in neonatal cytokine/chemokine concentrations, and whether these differences are associated with neurodevelopmental outcomes. Results highlight the importance of considering sex as a critical factor in understanding the immune system as it relates to child development.