Functioning Autism Spectrum Disorder Research Articles

Longitudinal changes in executive function in autism spectrum disorder: A systematic review and meta-analyses.

Individuals with an autism spectrum disorder (ASD) diagnosis show impairment in executive function (EF). However, findings are mixed regarding differences in the age effect on EF between autistic individuals and persons with typical development (TD). Questions remain regarding whether the age-related trajectories of EF in ASD are the same as or different from those in TD. To bridge this knowledge gap, we conducted a systematic review and meta-analyses of longitudinal studies that compared age-related changes in EF between ASD and TD groups (preregistration: osf.io/j5764). A literature search was conducted using PubMed, PsycINFO, and Web of Science on January 29, 2024. After screening by two independent reviewers, 14 longitudinal studies were included. Random-effects meta-analyses of studies involving a maximum total of 518 autistic and 3558 TD children and adolescents (mean baseline ages: 5.7-12.0 years) showed that ASD had significantly poorer EF than TD at both baseline and follow-up. However, there was no significant group difference in the age-related change in EF across domains, including working memory, inhibition, shifting, and planning. Robust Bayesian meta-analyses also provided substantial evidence in favor of the null hypothesis that ASD and TD groups showed similar changes over time for most EF processes. Limitations of the literature included the limited number of longitudinal studies and a narrow range of developmental stages and EF constructs analyzed across studies. Altogether, these findings suggest that autistic children and adolescents generally can improve in EF over time similarly to their neurotypical peers. This has important implications for parents and educators, encouraging appropriate EF training and intervention for autistic children and adolescents at an early stage.

The perception of emotional prosody between children with high functioning autism spectrum disorder and typically developing children

In this study, we compared the ability of children with high- functioning autism spectrum disorder and typically developing children to recognize emotions using recorded words and sentences, while they had to choose the image displaying the emotion and indicate the correct answer verbally. A descriptive analysis was performed and the results demonstrated that typically developing children had similar performance in recognizing the emotional state through image selection and in recognizing the emotional state and expressing it through verbal production. Also, these children performed better compared to children with autism. Children with high- functioning autism showed a reduced ability to recognize emotions as expressed by changes in the recordings compared to typically developing children. Children with high - functioning autism scored low scores on both tests, but performed better on the test where a response with an image selection was required. Therefore, the expression of the recognition of the emotional state of the speaker seemed to be assisted by some visual stimuli.

Hot Executive Function in Autism Spectrum Disorder: A Brief Narrative Review

Executive function (EF), encompassing high-order cognitive processes essential for goal-directed behavior, is often impaired in Autism Spectrum Disorder (ASD). This review addresses the problem of limited understanding regarding the distinction between “cool” and “hot” EF, their respective manifestations, and developmental trajectories in ASD. While cool EF in ASD has been widely investigated, the impairments and development of hot EF are less explored despite potentially also playing a role in ASD's socio-cognitive challenges. The purpose of this narrative review is to synthesize existing literature on hot EF and its development in ASD, particularly in relation to cool EF. Our approach involves a comprehensive examination of current studies to identify gaps and propose directions for future research. The review highlights the scarcity of studies on hot EF in ASD and concludes that targeted interventions should address both cool and hot EF deficits. Future research directions include longitudinal studies, neural investigations, and culturally diverse samples to further elucidate the role of hot EF in ASD. Understanding these distinctions can refine intervention strategies, ultimately enhancing support for individuals with ASD.

Neurofeedback training of executive function in autism spectrum disorder: distinct effects on brain activity levels and compensatory connectivity changes

BackgroundDeficits in executive function (EF) are consistently reported in autism spectrum disorders (ASD). Tailored cognitive training tools, such as neurofeedback, focused on executive function enhancement might have a significant impact on the daily life functioning of individuals with ASD. We report the first real-time fMRI neurofeedback (rt-fMRI NF) study targeting the left dorsolateral prefrontal cortex (DLPFC) in ASD.MethodsThirteen individuals with autism without intellectual disability and seventeen neurotypical individuals completed a rt-fMRI working memory NF paradigm, consisting of subvocal backward recitation of self-generated numeric sequences. We performed a region-of-interest analysis of the DLPFC, whole-brain comparisons between groups and, DLPFC-based functional connectivity.ResultsThe ASD and control groups were able to modulate DLPFC activity in 84% and 98% of the runs. Activity in the target region was persistently lower in the ASD group, particularly in runs without neurofeedback. Moreover, the ASD group showed lower activity in premotor/motor areas during pre-neurofeedback run than controls, but not in transfer runs, where it was seemingly balanced by higher connectivity between the DLPFC and the motor cortex. Group comparison in the transfer run also showed significant differences in DLPFC-based connectivity between groups, including higher connectivity with areas integrated into the multidemand network (MDN) and the visual cortex.ConclusionsNeurofeedback seems to induce a higher between-group similarity of the whole-brain activity levels (including the target ROI) which might be promoted by changes in connectivity between the DLPFC and both high and low-level areas, including motor, visual and MDN regions.

Statistical analysis of methylation reveals epigenetic biomarkers for high- functioning autism spectrum disorder

Autism spectrum disorder (ASD) is a neurological disorder that affects social behavior and learning ability. Although studies have identified certain regions of the genome (22q13.33) linked to the increased risk of ASD, there is no clear etiology, which is why psychologists theorize that ASD is a complex interaction between genetic and environmental factors. The current study was designed to identify genes with a positive correlation toward the diagnosis of high-function autism spectrum disorder (HF-ASD). Samples were obtained from National Center for Biotechnology Information (NCBI) containing 450K CpG methylation from 69 subjects diagnosed as HF-ASD or typically developing (TD). We applied Principal Component Analysis (PCA) and further utilized two sample Kolmogorov-Smirnov test (KS-test) to obtain the p-values for each patient. False Discovery Rate (FDR Correction) is computed by Benjamini-Hochberg Procedure. Based on the output of the FDR method, we identified the top ten genes that have CpGs with statistically differentially methylated. Such potential epigenetic biomarker includes WBP11, LDHB, DHX29, NUB1, C2orf67, SNAI2, MTOR, CLCN3, SYNJ2BP, and TTK. Two sample KS test and FDR Correction code is available at: https://www.kaggle.com/code/aaravsharma123/gse109905-fdr-pvalues/notebook.

Effects of transcutaneous auricular vagus nerve stimulation and exploration of brain network mechanisms in children with high-functioning autism spectrum disorder: study protocol for a randomized controlled trial.

Autism Spectrum Disorders (ASD) are a collection of neurodevelopmental diseases characterized by poor social interaction and communication, a limited range of interests, and stereotyped behavior. High-functioning autism (HFA) indicates a subgroup of individuals with autism who possess cognitive and/or language skills that are within the average to above-normal range for their age. Transcutaneous auricular vagus nerve stimulation (taVNS) holds promise in children with HFA. However, few studies have used randomized controlled trials to validate the effectiveness of taVNS. Therefore, in this study, we intend to provide a study protocol to examine the therapeutic effects of taVNS in individuals diagnosed with HFA and to investigate the process of brain network remodeling in individuals with ASD using functional imaging techniques to observe alterations in large-scale neural networks. We planned to employ a randomized, double-blind experimental design, including 40 children receiving sham stimulation and 40 children receiving real stimulation. We will assess clinical scales and perform functional imaging examinations before and after the stimulation. Additionally, we will include age- and gender-matched healthy children as controls and conduct functional imaging examinations. We plan first to observe the therapeutic effects of taVNS. Furthermore, we will observe the impact of taVNS stimulation on the brain network. taVNS was a low-risk, easy-to-administer, low-cost, and portable option to modulate the vagus system. taVNS may improve the social performance of HFA. Changes in the network properties of the large-scale brain network may be related to the efficacy of taVNS. http://www.chictr.org.cn, identifier ChiCTR2300074035.

Mitochondrial DNA Haplogroup K Is Protective Against Autism Spectrum Disorder Risk in Populations of European Ancestry

Accumulative evidence indicates a critical role of mitochondrial function in autism spectrum disorders (ASD), implying that ASD risk may be linked to mitochondrial dysfunction due to DNA (mtDNA) variations. Although a few studies have explored the association between mtDNA variations and ASD, the role of mtDNA in ASD is still unclear. Here, we aimed to investigate whether mitochondrial DNA haplogroups are associated with the risk of ASD. Two European cohorts and an Ashkenazi Jewish (AJ) cohort were analyzed, including 2,062 ASD patients in comparison with 4,632 healthy controls. DNA samples were genotyped using Illumina HumanHap550/610 and Illumina 1M arrays, inclusive of mitochondrial markers. Mitochondrial DNA (mtDNA) haplogroups were identified from genotyping data using HaploGrep2. A mitochondrial genome imputation pipeline was established to detect mtDNA variants. We conducted a case-control study to investigate potential associations of mtDNA haplogroups and variants with the susceptibility to ASD. We observed that the ancient adaptive mtDNA haplogroup K was significantly associated with decreased risk of ASD by the investigation of 2 European cohorts including a total of 2,006 cases and 4,435 controls (odds ratio= 0.64, P=1.79× 10-5), and we replicated this association in an Ashkenazi Jewish (AJ) cohort including 56 cases and 197 controls (odds ratio= 0.35, P= 9.46× 10-3). Moreover, we demonstrate that the mtDNA variants rs28358571, rs28358584, and rs28358280 are significantly associated with ASD risk. Further expression quantitative trait loci (eQTLs) analysis indicated that the rs28358584 and rs28358280 genotypes are associated with expression levels of nearby genes in brain tissues, suggesting those mtDNA variants may confer risk for ASD via regulation of expression levels of genes encoded by the mitochondrial genome. This study helps to shed light on the contribution of mitochondria in ASD and provides new insights into the genetic mechanism underlying ASD, suggesting the potential involvement of mtDNA-encoded proteins in the development of ASD. Increasing evidence indicates that mitochondrial dysfunction may be linked to autism spectrum disorder (ASD). This study investigated potential associations of mitochondrial DNA (mtDNA) variants in 2 European and Ashkenazi Jewish cohorts including 2,062 individuals with ASD and 4,632 healthy controls. Researchers found that the ancient mtDNA haplogroup K was linked to a reduced risk of ASD in both European and Ashkenazi Jewish populations. Additionally, specific mtDNA variants were associated with ASD risk and were shown to influence the expression of nearby genes in the brain. These findings highlight the potential involvement of mtDNA in ASD development, offering new insights into the genetic mechanisms underlying the disorder.

The mediators for the link between autism and real-world executive functions in adolescence and young adulthood.

Childhood factors that predict real-world executive function in autism spectrum disorder during the transition into adulthood are largely unknown. This study aimed to identify the predictors for the behavioral and cognitive aspects of real-world executive function in late adolescent and young adult autistic populations. We followed up 289 autistic youth (mean age 11.6 years) and 203 non-autistic controls (10.7 years) to their ages of 16.9 and 15.8, respectively. The Behavior Rating Inventory of Executive Function scale was used to measure the real-world executive function at late adolescence and young adulthood at follow-up. Potential predictors such as autistic symptoms, inattention or hyperactivity symptoms, peer relationship, emotional symptoms, and parenting styles were assessed in childhood at first enrollment. The results showed that childhood inattention, withdrawn behaviors, social communication difficulties, and child-reported emotion and inattention/hyperactivity may predict real-world lower executive function in late adolescence and young adults with autism. When separating executive function into behavioral and cognitive aspects, we found that oppositional behaviors and peer problems were specific predictors for behavioral regulation and cognitive function, respectively. Our findings suggested that treating common predictors in childhood, such as inattention, may potentially improve real-world executive function in autism during the transition into adulthood.

Effects of prefrontal transcranial direct current stimulation on social functioning in autism spectrum disorder: A randomized clinical trial.

Currently available pharmacological and behavioral interventions for adolescents and young adults with autism spectrum disorder (ASD) yield only modest effect in alleviating their core behavioral and cognitive symptoms, and some of these treatment options are associated with undesirable side effects. Hence, developing effective treatment protocols is urgently needed. Given emerging evidence shows that the abnormal connections of the frontal brain regions contribute to the manifestations of ASD behavioral and cognitive impairments, noninvasive treatment modalities that are capable in modulating brain connections, such as transcranial direct current stimulation (tDCS), have been postulated to be potentially promising for alleviating core symptoms in ASD. However, whether tDCS can reduce behavioral symptoms and enhance cognitive performance in ASD remains unclear. This randomized controlled trial involving 105 adolescents and young adults with ASD showed that multiple sessions of a tDCS protocol, which was paired up with computerized cognitive training, was effective in improving social functioning in adolescents and young adults with ASD. No prolonged and serious side effects were observed. With more future studies conducted in different clinical settings that recruit participants from a wider age range, this tDCS protocol may be potentially beneficial to a broad spectrum of individuals with autism.

Does stochastic resonance improve performance for individuals with higher autism-spectrum quotient?

While noise is generally believed to impair performance, the detection of weak stimuli can sometimes be enhanced by introducing optimum noise levels. This phenomenon is termed 'Stochastic Resonance' (SR). Past evidence suggests that autistic individuals exhibit higher neural noise than neurotypical individuals. It has been proposed that the enhanced performance in Autism Spectrum Disorder (ASD) on some tasks could be due to SR. Here we present a computational model, lab-based, and online visual identification experiments to find corroborating evidence for this hypothesis in individuals without a formal ASD diagnosis. Our modeling predicts that artificially increasing noise results in SR for individuals with low internal noise (e.g., neurotypical), however not for those with higher internal noise (e.g., autistic, or neurotypical individuals with higher autistic traits). It also predicts that at low stimulus noise, individuals with higher internal noise outperform those with lower internal noise. We tested these predictions using visual identification tasks among participants from the general population with autistic traits measured by the Autism-Spectrum Quotient (AQ). While all participants showed SR in the lab-based experiment, this did not support our model strongly. In the online experiment, significant SR was not found, however participants with higher AQ scores outperformed those with lower AQ scores at low stimulus noise levels, which is consistent with our modeling. In conclusion, our study is the first to investigate the link between SR and superior performance by those with ASD-related traits, and reports limited evidence to support the high neural noise/SR hypothesis.

New insights from the last decade of research in psychiatric genetics: discoveries, challenges and clinical implications.

Psychiatric genetics has made substantial progress in the last decade, providing new insights into the genetic etiology of psychiatric disorders, and paving the way for precision psychiatry, in which individual genetic profiles may be used to personalize risk assessment and inform clinical decision-making. Long recognized to be heritable, recent evidence shows that psychiatric disorders are influenced by thousands of genetic variants acting together. Most of these variants are commonly occurring, meaning that every individual has a genetic risk to each psychiatric disorder, from low to high. A series of large-scale genetic studies have discovered an increasing number of common and rare genetic variants robustly associated with major psychiatric disorders. The most convincing biological interpretation of the genetic findings implicates altered synaptic function in autism spectrum disorder and schizophrenia. However, the mechanistic understanding is still incomplete. In line with their extensive clinical and epidemiological overlap, psychiatric disorders appear to exist on genetic continua and share a large degree of genetic risk with one another. This provides further support to the notion that current psychiatric diagnoses do not represent distinct pathogenic entities, which may inform ongoing attempts to reconceptualize psychiatric nosology. Psychiatric disorders also share genetic influences with a range of behavioral and somatic traits and diseases, including brain structures, cognitive function, immunological phenotypes and cardiovascular disease, suggesting shared genetic etiology of potential clinical importance. Current polygenic risk score tools, which predict individual genetic susceptibility to illness, do not yet provide clinically actionable information. However, their precision is likely to improve in the coming years, and they may eventually become part of clinical practice, stressing the need to educate clinicians and patients about their potential use and misuse. This review discusses key recent insights from psychiatric genetics and their possible clinical applications, and suggests future directions.

Here’s the story: Narrative ability and executive function in autism spectrum disorder

BackgroundDifficulties with narrative have been reported in individuals diagnosed with autism spectrum disorder (ASD), but the role of executive function on narrative ability has not been examined in ASD. In this study, we aimed to (1) examine whether narrative abilities of ASD children differed from neurotypical (NT) children who did not differ in age, sex, and IQ; and (2) investigate relations between executive function and narrative ability in ASD children. MethodNarratives were elicited from 64 ASD children and 26 NT children using a wordless picture book and coded to derive several aspects of narrative ability such as propositions, evaluative devices, and self-repairs. Executive functions (specifically, inhibition and working memory) were measured using both experimenter-administered assessment and parent-report measures. ResultsCompared to NT children, ASD children produced fewer propositions but did not differ in their use of evaluative devices and self-repairs during narrative production. Greater inhibitory challenges related to more self-repairs involving repetition of story elements, whereas working memory did not relate to any of the measures of narrative ability among ASD children. ConclusionsThis study revealed that narratives by verbally fluent ASD children were shorter and less complex than those by NT children but did not differ in the specific features of narratives. Furthermore, although ASD children did not make more self-repairs than NT children, difficulty with inhibition was related to more self-repairs, indicating more dysfluent narrative production in ASD children, which has implications for intervention.

Children with autism spectrum disorder present glymphatic system dysfunction evidenced by diffusion tensor imaging along the perivascular space

This study used diffusion tensor imaging (DTI) along the perivascular space (DTI-ALPS) to assess glymphatic system function in autism spectrum disorder (ASD) compared to healthy controls. Patients with ASD may have glymphatic system dysfunction, which is related to age. We retrospectively included 30 children with ASD and 25 healthy controls in this study. 3T magnetic resonance imaging scanner was used to perform DTI magnetic resonance imaging on all participants, and the DTI-ALPS index was calculated from the DTI data. Additionally, we evaluated how the DTI-ALPS index differed between the 2 groups. Moreover, we examined the relationships between the bilateral DTI-ALPS index and the age of the participants. The DTI-ALPS index considerably differed between groups. In the left index (1.02 ± 0.12 vs. 1.27 ± 0.25, P < .001) and in the right index (1.03 ± 0.12 vs. 1.32 ± 0.20, P < .001), the DTI-ALPS in ASD patients was significantly lower than that in healthy controls. Furthermore, the DTI-ALPS index was strongly and positively associated with age. In patients with ASD, there is a glymphatic system dysfunction. This is intimately correlated to age. Our findings suggest the importance of the DTI-ALPS approach in assessing the function of the glymphatic system in ASD.

Neural correlates of eye contact and social function in autism spectrum disorder.

Reluctance to make eye contact during natural interactions is a central diagnostic criterion for autism spectrum disorder (ASD). However, the underlying neural correlates for eye contacts in ASD are unknown, and diagnostic biomarkers are active areas of investigation. Here, neuroimaging, eye-tracking, and pupillometry data were acquired simultaneously using two-person functional near-infrared spectroscopy (fNIRS) during live "in-person" eye-to-eye contact and eye-gaze at a video face for typically-developed (TD) and participants with ASD to identify the neural correlates of live eye-to-eye contact in both groups. Comparisons between ASD and TD showed decreased right dorsal-parietal activity and increased right ventral temporal-parietal activity for ASD during live eye-to-eye contact (p≤0.05, FDR-corrected) and reduced cross-brain coherence consistent with atypical neural systems for live eye contact. Hypoactivity of right dorsal-parietal regions during eye contact in ASD was further associated with gold standard measures of social performance by the correlation of neural responses and individual measures of: ADOS-2, Autism Diagnostic Observation Schedule, 2nd Edition (r = -0.76, -0.92 and -0.77); and SRS-2, Social Responsiveness Scale, Second Edition (r = -0.58). The findings indicate that as categorized social ability decreases, neural responses to real eye-contact in the right dorsal parietal region also decrease consistent with a neural correlate for social characteristics in ASD.

Quantitative trait locus analysis for endophenotypes reveals genetic substrates of core symptom domains and neurocognitive function in autism spectrum disorder

Autism spectrum disorder (ASD) represents a heterogeneous group of neurodevelopmental disorders and is largely attributable to genetic risk factors. Phenotypic and genetic heterogeneity of ASD have been well-recognized; however, genetic substrates for endophenotypes that constitute phenotypic heterogeneity are not yet known. In the present study, we compiled data from the Autism Genetic Resource Exchange, which contains the demographic and detailed phenotype information of 11,961 individuals. Notably, the whole-genome sequencing data available from MSSNG and iHART for 3833 individuals in this dataset was used to perform an endophenotype-wide association study. Using a linear mixed model, genome-wide association analyses were performed for 29 endophenotype scores and 0.58 million common variants with variant allele frequency ≥ 5%. We discovered significant associations between 9 genetic variants and 6 endophenotype scores comprising neurocognitive development and severity scores for core symptoms of ASD at a significance threshold of p < 5 × 10–7. Of note, the Stereotyped Behaviors and Restricted Interests total score in Autism Diagnostic Observation Schedule Module 3 was significantly associated with multiple variants in the VPS13B gene, a causal gene for Cohen syndrome and a candidate gene for syndromic ASD. Our findings yielded loci with small effect sizes due to the moderate sample size and, thus, require validation in another cohort. Nonetheless, our endophenotype-wide association analysis extends previous candidate gene discovery in the context of genotype and endophenotype association. As a result, these candidate genes may be responsible for specific traits that constitute core symptoms and neurocognitive function of ASD rather than the disorder itself.

Neuropsychological profile of executive functions in autism spectrum disorder and schizophrenia spectrum disorders: a comparative group study in adults

As assessed by numerous neuropsychological tasks, individuals with autism spectrum disorder (ASD) and schizophrenia spectrum disorders (SSDs) have similar impairments related to executive functions (EFs). The neuropsychological profile of these two conditions was examined using the three-component EFs’ framework of Miyake and Friedman (Cogn Psychol 41(1):49-100, 2000). This approach assesses Inhibition (suppression of unwanted and irrelevant information/responses), Updating (use and control of contents of working memory), and Shifting (disengagement between activities or mental tasks) using nine different tasks. In line with previous research, we expected greater performance deficits in ASD in all three components compared to SSD, as well as faster responses for the SSD group. A self-paced task format allowed us to examine whether unlimited time given for a task would lead to better performance. The sample was constituted by the control group (N = 25), ASD group (N = 24), and SSD group (N = 12). Groups did not differ on Inhibition performance. In Updating, individuals with SSD performed poorer than the other groups. As for Shifting, both groups demonstrated poorer performance compared to controls, with the SSD group presenting the greatest difficulties. In terms of reaction time (RT), SSD participants’ RT were the slowest on Inhibition and Shifting tasks. There was a positive correlation between performance and time spent on Inhibition and Shifting only for the SSD group, which demonstrates that their performance improves when there are no time constraints. Our work provides a better understanding of spared and impaired EFs, which could be useful for designing strategies aimed at improving specific EFs in each group.

Odor identification impairment in autism spectrum disorder might be associated with mitochondrial dysfunction.

Deficits in olfactory function in autism spectrum disorder (ASD) have already been reported. However, the results of previous studies are not consistent, and the pathophysiological mechanisms of olfactory dysfunction in ASD are not clear. Fifty-three male ASD children or teenagers aged 9-16 years were recruited for the study. The identification and discrimination portion of the Sniffin' Sticks test (SST) was used to assess the olfactory function of the enrolled subjects. The severity of ASD core symptoms and the intelligence quotient (IQ) of participants were assessed. In addition, to explore the potential mechanism underlying olfactory dysfunction, a series of plasma biochemical indicators of oxidative stress, mitochondrial function and inflammation were measured. The mean raw scores on the SST identification and discrimination test of the study subjects were significantly lower than those of typically developing subjects reported in normative data studies. After adjusting for IQ, the odor identification score was not significantly associated with any ASD symptoms. Odor identification was found to be significantly associated with the ratio of L-lactate (L)/pyruvate (P) but not with other measured indicators. The current study validates the impairment of odor identification and discrimination in Chinese ASD children. Odor identification dysfunction may be an independent clinical symptom of ASD. The plasma L/P ratio was found to be significantly associated with odor identification performance, which suggests that mitochondrial dysfunction may be a potential mechanism underlying odor identification impairment in ASD.

Gaze and social functioning associations in autism spectrum disorder: A systematic review and meta-analysis.

Autism spectrum disorder (ASD) is characterized by significant social functioning impairments, including (but not limited to) emotion recognition, mentalizing, and joint attention. Despite extensive investigation into the correlates of social functioning in ASD, only recently has there been focus on the role of low‐level sensory input, particularly visual processing. Extensive gaze deficits have been described in ASD, from basic saccadic function through to social attention and the processing of complex biological motion. Given that social functioning often relies on accurately processing visual information, inefficient visual processing may contribute to the emergence and sustainment of social functioning difficulties in ASD. To explore the association between measures of gaze and social functioning in ASD, a systematic review and meta‐analysis was conducted. A total of 95 studies were identified from a search of CINAHL Plus, Embase, OVID Medline, and psycINFO databases in July 2021. Findings support associations between increased gaze to the face/head and eye regions with improved social functioning and reduced autism symptom severity. However, gaze allocation to the mouth appears dependent on social and emotional content of scenes and the cognitive profile of participants. This review supports the investigation of gaze variables as potential biomarkers of ASD, although future longitudinal studies are required to investigate the developmental progression of this relationship and to explore the influence of heterogeneity in ASD clinical characteristics.Lay SummaryThis review explored how eye gaze (e.g., where a person looks when watching a movie) is associated with social functioning in autism spectrum disorder (ASD). We found evidence that better social functioning in ASD was associated with increased eye gaze toward faces/head and eye regions. Individual characteristics (e.g., intelligence) and the complexity of the social scene also influenced eye gaze. Future research including large longitudinal studies and studies investigating the influence of differing presentations of ASD are recommended.

Differences in social brain function in autism spectrum disorder are linked to the serotonin transporter: A randomised placebo-controlled single-dose crossover trial

Alterations in the serotonergic control of brain pathways responsible for facial emotion processing in people with autism spectrum disorder (ASD) may be a target for intervention. However, the molecular underpinnings of autistic-neurotypical serotonergic differences are challenging to access in vivo. Receptor-Enriched Analysis of functional Connectivity by Targets (REACT) has helped define molecular-enriched functional magnetic resonance imaging (fMRI) brain networks based on a priori information about the spatial distribution of neurochemical systems from available PET templates. We used REACT to estimate the dominant fMRI signal related to the serotonin (5-HT) transporter (SERT) distribution during processing of aversive facial emotion in adults with and without ASD. We first predicted a group difference in baseline (placebo) functioning of this system. We next used a single 20 mg oral dose of citalopram, a serotonin reuptake inhibitor, to test the hypothesis that network activity in people with and without ASD would respond differently to inhibition of SERT. To confirm the specificity of our findings, we also repeated the analysis with 5-HT1A, 5-HT1B, 5-HT2A and 5-HT4 receptor maps. Using REACT with the SERT map, we found a baseline group difference in the SERT-enriched response to faces in the ventromedial prefrontal cortex. A single oral dose of citalopram 'shifted' the response in the ASD group towards the neurotypical baseline but did not alter response in the control group. Similar differences in SERT-enriched response were observed after controlling for other 5-HT maps. Our findings suggest that the SERT-enriched functional network is dynamically different in ASD during processing of socially relevant stimuli. Whether this acute neurobiological response to citalopram in ASD translates to a clinical target will be an important next step.

Impaired odor identification ability and olfactory hedonic capacity in children with elevated autistic traits

AbstractAtypical olfactory function in autism spectrum disorder has been documented in numerous studies, but little is known about its occurrence in individuals with autistic traits. The aim of the current study was to investigate odor identification ability and olfactory hedonic capacity in children with autistic traits. We recruited 415 children and measured their autistic traits by the Short Autism Spectrum Quotient. The Universal Sniff (U‐Sniff) test was used to measure odor identification ability and olfactory hedonic capacity. Olfactory hedonic capacity was also measured using the children's version of the Chemosensory Pleasure Scale (CPS‐C). Odor identification and olfactory hedonic capacity measured by CPS‐C were negatively correlated with autistic traits. Children with higher autistic traits exhibited poorer odor identification ability and olfactory trait hedonic capacity measured by CPS‐C but intact olfactory state hedonic capacity measured by odor pleasantness. These results pertaining to odor identification and olfactory hedonic capacity may be the endophenotypic markers for autism spectrum disorder.Practical ApplicationsOur study extends the knowledge on children with high autistic traits and provides a new perspective on olfactory identification ability and olfactory hedonic capacity in children with high autistic traits. In addition, our findings suggest olfactory testing may provide a new approach for detecting and understanding autism.