High Risk For Autism Research Articles

Childhood anaesthesia and autism risk: population and murine study.

Early childhood exposure to general anaesthesia has been linked to potential changes in infant brain morphology and behaviour in preclinical studies, contributing to long-term behaviours associated with autism spectrum disorder. This study investigates the association between early childhood exposure to general anaesthesia and the risk of autism, using a population-based cohort study with matching for baseline characteristics and evaluates the effect of sevoflurane exposure on autism-like behaviour in mice, using the Taiwan Maternal and Child Health Database. Children aged 0-3 who received at least one exposure to general anaesthesia between 2004 and 2014 were matched 1:1 with children who were not exposed. Risk ratios and confidence intervals were used to assess the relationship between general anaesthesia and the occurrence of autism. Additionally, mice were exposed to sevoflurane for 2 h on postnatal days 5-7, and changes in behaviour related to autism were evaluated. Propensity score matching resulted in 7530 children in each group. The incidence rates (IRs) of autism were 11.26 and 6.05 per 100 000 person-years in the exposed and unexposed groups, respectively. The incidence ratio for autism following exposure to general anaesthesia was 1.86 (95% confidence interval, 1.34-2.59). In mice, sevoflurane exposure induced autism-like behaviours and led to the downregulation of high-risk autism genes, including ARID1B, GABRA5, GABRB3, GRIN2B, SHANK3 and SUV420H1. Early childhood exposure to general anaesthesia is associated with an increased risk of autism. Repeated exposure to sevoflurane in mice induces autism-like behaviours, suggesting a potential link between anaesthesia and the development of autism.

Ash1 l loss-of-function results in structural birth defects and altered cortical development

Abstract The histone methyltransferase ASH1L plays a crucial role in regulating gene expression across various organ systems during development, yet its role in brain development remains largely unexplored. Over 130 individuals with autism harbour heterozygous loss-of-function ASH1L variants, and population studies confirm it as a high-risk autism gene. Previous studies on Ash1 l deficient mice have reported autistic-like behaviours and provided insights into the underlying neuropathophysiology. In this study, we used mice with a cre-inducible deletion of Ash1 l exon 4, which results in a frame shift and premature stop codon (p.V1693Afs*2). Our investigation evaluated the impact of Ash1 l loss-of-function on survival and craniofacial skeletal development. Using a tamoxifen-inducible cre strain, we targeted Ash1 l knockout early in cortical development (Emx1-Cre-ERT2; e10.5). Immunohistochemistry was utilized to assess cortical lamination, while EdU incorporation aided in birthdating cortical neurons. Additionally, single-cell RNA sequencing was employed to compare cortical cell populations and identify genes with differential expression. At e18.5, the proportion of homozygous Ash1 l germline knockout embryos appeared normal; however, no live Ash1 l null pups were present at birth (e18.5: n = 77, P = 0.90; p0: n = 41, P = 0.00095). Notably, Ash1l-/- exhibited shortened nasal bones (n = 31, P = 0.017). In the cortical-specific knockout model, SATB2 neurons showed increased numbers (n = 6/genotype, P = 0.0001) and were distributed through the cortical plate. Birthdating revealed generation of ectopically placed deep layer neurons that express SATB2 (e13.5 injection: n = 4/genotype, P = 0.0126). Single cell RNA sequencing revealed significant differences in gene expression between control and mutant upper layer neurons, leading to distinct clustering. Pseudotime analysis indicated that the mutant cluster followed an altered cell differentiation trajectory. This study underscores the essential role of Ash1 l in postnatal survival and normal craniofacial development. In the cortex, ASH1L exerts broad effects on gene expression and is indispensable for determining the fate of upper layer cortical neurons. These findings provide valuable insights into the potential mechanisms of ASH1L neuropathology, shedding light on its significance in neurodevelopmental disorders like autism.

Prevalence of Autism risk among children undergoing regular Psychophysical Development Screening in Kazakhstan

BackgroundInformation about the situation with autism in Kazakhstan is extremely limited due to the lack of research on autism in both Kazakhstan and Central Asia. The prevalence of autism spectrum disorder risk among young children during routine screening was assessed using the M-CHAT-R/F tool. MethodsThis study took place in the offices of pediatric neurologists and family doctors in three primary healthcare organizations in the Karaganda, Kazakhstan. The researchers offered participation in the study and M-CHAT-R checklist completion during visits by parents and children to pediatric neurologists and family doctors for the purpose of screening for psychophysical development. Linear regression analysis was used to determine risk factors for the development of autism spectrum disorder. ResultsThe results of an analysis of 526 study participants showed the prevalence of high-risk autism spectrum disorders to be 27.4 %. Factors associated with a high risk of autism spectrum disorder in this study were child age, gender, parental age, and a diagnosis of developmental disorder. ConclusionsThe use of specific tools to screen for developmental disorders by primary care organizations is recommended. Primary care providers have regular contact with children before they reach school age and can provide family-centered, comprehensive, and coordinated care, including more comprehensive medical assessments.

Structural deviations of the posterior fossa and the cerebellum and their cognitive links in a neurodevelopmental deletion syndrome.

High-impact genetic variants associated with neurodevelopmental disorders provide biologically-defined entry points for mechanistic investigation. The 3q29 deletion (3q29Del) is one such variant, conferring a 40-100-fold increased risk for schizophrenia, as well as high risk for autism and intellectual disability. However, the mechanisms leading to neurodevelopmental disability remain largely unknown. Here, we report the first in vivo quantitative neuroimaging study in individuals with 3q29Del (N = 24) and neurotypical controls (N = 1608) using structural MRI. Given prior radiology reports of posterior fossa abnormalities in 3q29Del, we focused our investigation on the cerebellum and its tissue-types and lobules. Additionally, we compared the prevalence of cystic/cyst-like malformations of the posterior fossa between 3q29Del and controls and examined the association between neuroanatomical findings and quantitative traits to probe gene-brain-behavior relationships. 3q29Del participants had smaller cerebellar cortex volumes than controls, before and after correction for intracranial volume (ICV). An anterior-posterior gradient emerged in finer grained lobule-based and voxel-wise analyses. 3q29Del participants also had larger cerebellar white matter volumes than controls following ICV-correction and displayed elevated rates of posterior fossa arachnoid cysts and mega cisterna magna findings independent of cerebellar volume. Cerebellar white matter and subregional gray matter volumes were associated with visual-perception and visual-motor integration skills as well as IQ, while cystic/cyst-like malformations yielded no behavioral link. In summary, we find that abnormal development of cerebellar structures may represent neuroimaging-based biomarkers of cognitive and sensorimotor function in 3q29Del, adding to the growing evidence identifying cerebellar pathology as an intersection point between syndromic and idiopathic forms of neurodevelopmental disabilities.

Neuropsychiatric disorders in adults with atopic dermatitis: Apopulation-based cohort study.

Atopic dermatitis (AD) may be associated with an increased burden of neuropsychiatric outcomes such as anxiety and depression, but longitudinal data on the impact of AD severity is lacking, and a comprehensive assessment of neuropsychiatric disease in adults with AD is needed. Determine risk of incident neuropsychiatric disease among adults with AD by severity. A cohort study using electronic health records data from UK general practices from 1994 to 2015. Adults (≥18 years) with AD were matched on age, practice and index date to patients without AD. AD severity was categorized using treatments and dermatology referrals. Outcomes were incident anxiety, depression, bipolar disorder, schizophrenia, attention-deficit/hyperactivity disorder (ADHD), autism, obsessive-compulsive disorder (OCD), suicidality and completed suicide. Comparing 625,083 adults with AD to 2,678,888 adults without AD, AD was associated with higher risk of anxiety [HR 1.14 (1.13-1.15)], depression [1.14 (1.13-1.15)] and OCD [1.48 (1.38-1.58)] across all severities. Mild or moderate AD was also associated with higher risk of autism, ADHD, bipolar disorder and suicidality. Atopic dermatitis is associated with a higher risk of multiple neuropsychiatric conditions, but these risks differ by specific condition and AD severity. Clinicians should inquire about mental health in patients with AD.

Single-cell brain organoid screening identifies developmental defects in autism

The development of the human brain involves unique processes (not observed in many other species) that can contribute to neurodevelopmental disorders1–4. Cerebral organoids enable the study of neurodevelopmental disorders in a human context. We have developed the CRISPR–human organoids–single-cell RNA sequencing (CHOOSE) system, which uses verified pairs of guide RNAs, inducible CRISPR–Cas9-based genetic disruption and single-cell transcriptomics for pooled loss-of-function screening in mosaic organoids. Here we show that perturbation of 36 high-risk autism spectrum disorder genes related to transcriptional regulation uncovers their effects on cell fate determination. We find that dorsal intermediate progenitors, ventral progenitors and upper-layer excitatory neurons are among the most vulnerable cell types. We construct a developmental gene regulatory network of cerebral organoids from single-cell transcriptomes and chromatin modalities and identify autism spectrum disorder-associated and perturbation-enriched regulatory modules. Perturbing members of the BRG1/BRM-associated factor (BAF) chromatin remodelling complex leads to enrichment of ventral telencephalon progenitors. Specifically, mutating the BAF subunit ARID1B affects the fate transition of progenitors to oligodendrocyte and interneuron precursor cells, a phenotype that we confirmed in patient-specific induced pluripotent stem cell-derived organoids. Our study paves the way for high-throughput phenotypic characterization of disease susceptibility genes in organoid models with cell state, molecular pathway and gene regulatory network readouts.

Positive screen on Modified Checklist for Autism in Toddlers (M-CHAT) born with very low birth weight and intrauterine growth restriction: a cross-sectional study

BACKGROUND: The aim of this study was to verify the Modified Checklist for Autism in Toddlers (M-CHAT) responses among children born with very low birth weight (VLBW) with and without (IUGR).METHODS: A cross-sectional study was carried out with toddlers born with VLBW, with and without IUGR. IUGR was based both on fetal ultrasound and birth weight for gestational age. M-CHAT was completed by the parents.RESULTS: Sixty-nine children completed the study and 30 (43.4%) screened positive for ASD. Analysis of children with positive and negative M-CHAT screens found no significant differences, except IUGR; 13 (43.3%) vs. 6 (15.3%), P=0.021. Multivariate analysis showed that IUGR remained significant; OR=5.3 (1.3-21.8), P=0.019.CONCLUSIONS: Toddlers born with very low birth weight associated with IUGR have a high risk for autism, according to the M-CHAT. Further studies are needed to confirm these results.

Is Breastfeeding Duration Associated with Risk of Developing ASD?

Background: There are few studies in the world on the duration of breastfeeding and the risk of autism. To our knowledge, no study has yet explained the association between breastfeeding duration and ASD in Iran. Aims: The present study evaluated the association between breastfeeding and the risk of ASD in offspring in the west of Iran. Methods: This case-control study was performed on 100 children aged 3-14 years who had a medical record in the Autism Spectrum Disorder Research Center and the Autism Association of Hamadan and were diagnosed with autism according to the Diagnostic and Statistical Manual of mental disorders [DSM-5] criteria. The control group included healthy children who had active family record in comprehensive health service centers. All analyzes were performed using Stata software version 14. The significance level was considered less than 0.05. Results: After adjusting for other variables, each increase in the month of breastfeeding was associated with a 5% decrease in odds of ASD [OR=0.95 [95% CI: 0.91, 0.99], P=0.03]. The odds of ASD in boys were significantly higher [OR=3.85 [95% CI: 1.91, 7.76], P<0.001]. Moreover, drug use [OR=0.01], history of autism [OR=6.62], history of psychiatry disorder [OR=7.2] were significantly associated with increased odds of ASD [P<0.05]. Conclusion: These findings showed that breastfeeding duration can be a protective factor for ASD. Therefore, policymakers and health staff can reduce the risk of autism by promoting increased breastfeeding duration, especially for children with high risk for autism.

Diffusion tensor imaging analysis of the corpus callosum in children with high-risk autism spectrum disorder.

Autism spectrum disorder (ASD) is a severe neurodevelopmental disorder that begins in early infancy and childhood and is characterized by impaired social communication and repetitive stereotyped behaviors. The purpose of this study was to examine the development of the corpus callosum and its relationship to neurobehavior in young children with high-risk (HR) ASD using magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). Twenty-one children with HR-ASD who visited Anhui Children's Hospital between January 2020 and December 2021 were selected as the study group, while 19 matched children with normal development during the same time were adopted as the control group. Cranial MRI+DTI were performed for all of the enrolled children and fractional anisotropy (FA) measurements were taken in each region of the corpus callosum. The FA values in all regions of the corpus callosum were higher in the study group than in the control group (0.417 ± 0.016 vs. 0.412 ± 0.02 in the corpus callosum knee, 0.439 ± 0.018 vs. 0.431 ± 0.023 in the corpus callosum body, and 0.446 ± 0.017 vs. 0.434 ± 0.019 in the splenium of corpus callosum [SCC]), where the difference in the FA in the SCC was statistically significant between the two groups (P< 0.05). There was a positive correlation between the FA in the corpus callosum knee and speech scores in the neuropsychological development of the study group (P< 0.05). There was a premature development tendency for corpus callosum myelination in young children with HR-ASD, and the developmental tendency was visible in the SCC. There was also a positive relationship between corpus callosum knee development and language function.

Prenatal exposure to ambient air pollution and autism spectrum disorders: Results from a family-based case-control study.

Autism prevalence has increased considerably, but its etiology is still poorly understood. While there have been suggestions regarding associations between air pollution exposure and neurodevelopmental disorders, several studies have looked at the effect of air pollution exposure on autism. However, the results are inconsistent. The possible role of unknown confounders is mainly blamed for this inconsistency. To minimize confounding effects, we evaluated the impact of air pollution exposure on autism using a family-based case-control study. Cases were individuals with a diagnosis of autism born between 2009 and 2012 in Isfahan city, Iran. The controls did not have a previous history of autism and were cousins of the case person. The controls were matched with the autistic cases in terms of residential location and age range. For each trimester of pregnancy, carbon monoxide (CO), nitrogen dioxide (NO2), ozone (O3), sulfur dioxide (SO2), and PM10 exposure were estimated using the inverse distance weighted method. The analysis indicates a significant association between CO exposure and autism in the second trimester (OR=1.59; p=0.046, 95% CI: 1.01-2.51) and entire pregnancy (OR=2.02; p=0.049, 95% CI: 1.01-2.95). Likewise, exposure to NO2 during the second trimester (OR=1.17; p=0.006, 95% CI: 1.04-1.31), third trimester (OR=1.11; p=0.046, 95% CI: 1.01-1.24), and entire pregnancy (OR=1.27; p=0.007, 95% CI: 1.07-1.51) were found to be associated with increased risk of autism. Overall, our study found higher exposure to CO and NO2, particularly during the second and third trimesters of pregnancy, was significantly associated with a higher risk of autism.

The causal association between iron status and the risk of autism: A Mendelian randomization study.

Emerging evidence indicates a connection between serum iron levels and autism, but the underlying causal association is yet unclear. Thus, we performed two-sample Mendelian randomization (MR) analysis to evaluate the causal link between iron status on autism, using genetic instruments (p < 5E-08) strongly associated with iron status (N = 48,972), including serum iron, ferritin, transferrin levels, and transferrin saturation. Summary statistics of autism was obtained from two independent studies conducted by Psychiatric Genomics Consortium (PGC, Ncases = 5,305, Ncontrols = 5,305) and FinnGen Consortium (FC, Round six, Ncases = 344, Ncontrols = 258,095), respectively. Using the inverse-variance weighted (IVW) method, the combined results of PGC and FC demonstrated that genetically determined serum transferrin level was significantly associated with an increased risk of autism [odds ratio (OR) = 1.16, 95% CI: 1.03-1.30, p = 0.013]. There was no significant causal effect of serum iron (OR = 0.99, 95% CI: 0.72-1.37, p = 0.951), ferritin (OR = 0.88, 95% CI: 0.47-1.64, p = 0.676), and transferrin saturation (OR = 0.89, 95% CI: 0.72-1.09, p = 0.252) on autism. No obvious pleiotropy was found in this MR study. Taken together, our findings highlight that elevation of serum transferrin level might be associated with a high risk of autism, suggesting a potential role of iron deficiency in autism development. Future studies are warranted to clarify the underlying mechanism, which will pave a new path for the prevention and treatment of autism.

Early Motor Signs in Autism Spectrum Disorder.

A growing number of literature data suggest the presence of early impairments in the motor development of children with autism spectrum disorder, which could be often recognized even before the appearance of the classical social communication deficits of autism. In this narrative review, we aimed at performing an update about the available data on the early motor function in children with autism spectrum disorder. Early motor impairment in these children can manifest itself both as a mere delay of motor development and as the presence of atypicalities of motor function, such as a higher rate and a larger inventory, of stereotyped movements both with and without objects. In the perspective of a timely diagnosis, the presence of early motor signs can be an important clue, especially in an individual considered at high risk for autism. Motor and communication (both verbal and non-verbal) skills are connected and a pathogenetic role of early motor dysfunctions in the development of autism can be hypothesized. From this, derives the importance of an early enabling intervention aimed at improving motor skills, which could also have favorable effects on other aspects of development.

Interference with prenatal, perinatal, and neonatal brain development is associated with a high risk for autism and attention‐deficit/hyperactivity disorder

This commentary is on the original article by Påhlman et al. on pages 63–69 of this issue.

Abnormal visual attention to simple social stimuli in 4-month-old infants at high risk for Autism

Despite an increasing interest in detecting early signs of Autism Spectrum Disorders (ASD), the pathogenesis of the social impairments characterizing ASD is still largely unknown. Atypical visual attention to social stimuli is a potential early marker of the social and communicative deficits of ASD. Some authors hypothesized that such impairments are present from birth, leading to a decline in the subsequent typical functioning of the learning-mechanisms. Others suggested that these early deficits emerge during the transition from subcortically to cortically mediated mechanisms, happening around 2–3 months of age. The present study aimed to provide additional evidence on the origin of the early visual attention disturbance that seems to characterize infants at high risk (HR) for ASD. Four visual preference tasks were used to investigate social attention in 4-month-old HR, compared to low-risk (LR) infants of the same age. Visual attention differences between HR and LR infants emerged only for stimuli depicting a direct eye-gaze, compared to an adverted eye-gaze. Specifically, HR infants showed a significant visual preference for the direct eye-gaze stimulus compared to LR infants, which may indicate a delayed development of the visual preferences normally observed at birth in typically developing infants. No other differences were found between groups. Results are discussed in the light of the hypotheses on the origins of early social visual attention impairments in infants at risk for ASD.

Gene-Environment Interactions in Developmental Neurotoxicity: a Case Study of Synergy between Chlorpyrifos and CHD8 Knockout in Human BrainSpheres.

Background:Autism spectrum disorder (ASD) is a major public health concern caused by complex genetic and environmental components. Mechanisms of gene–environment () interactions and reliable biomarkers associated with ASD are mostly unknown or controversial. Induced pluripotent stem cells (iPSCs) from patients or with clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9 (CRISPR/Cas9)-introduced mutations in candidate ASD genes provide an opportunity to study () interactions.Objectives:In this study, we aimed to identify a potential synergy between mutation in the high-risk autism gene encoding chromodomain helicase DNA binding protein 8 (CHD8) and environmental exposure to an organophosphate pesticide (chlorpyrifos; CPF) in an iPSC-derived human three-dimensional (3D) brain model.Methods:This study employed human iPSC-derived 3D brain organoids (BrainSpheres) carrying a heterozygote CRISPR/Cas9-introduced inactivating mutation in CHD8 and exposed to CPF or its oxon-metabolite (CPO). Neural differentiation, viability, oxidative stress, and neurite outgrowth were assessed, and levels of main neurotransmitters and selected metabolites were validated against human data on ASD metabolic derangements.Results:Expression of CHD8 protein was significantly lower in CHD8 heterozygous knockout () BrainSpheres compared with ones. Exposure to CPF/CPO treatment further reduced CHD8 protein levels, showing the potential () interaction synergy. A novel approach for validation of the model was chosen: from the literature, we identified a panel of metabolic biomarkers in patients and assessed them by targeted metabolomics in vitro. A synergistic effect was observed on the cholinergic system, S-adenosylmethionine, S-adenosylhomocysteine, lactic acid, tryptophan, kynurenic acid, and acid levels. Neurite outgrowth was perturbed by CPF/CPO exposure. Heterozygous knockout of CHD8 in BrainSpheres led to an imbalance of excitatory/inhibitory neurotransmitters and lower levels of dopamine.Discussion:This study pioneered () interaction in iPSC-derived organoids. The experimental strategy enables biomonitoring and environmental risk assessment for ASD. Our findings reflected some metabolic perturbations and disruption of neurotransmitter systems involved in ASD. The increased susceptibility of BrainSpheres to chemical insult establishes a possibly broader role of () interaction in ASD. https://doi.org/10.1289/EHP8580

Aberrant auditory system and its developmental implications for autism

Most infants who are later diagnosed with autism show delayed speech and language and/or atypical language profile. There is a large body of research on abnormal speech and language in children with autism. However, auditory development has been relatively under-investigated in autism research, despite its inextricable relationship with language development and despite researchers' ability to detect abnormalities in brain development and behavior in early infancy. In this review, we synthesize research on auditory processing in the prenatal period through infancy and childhood in typically developing children, children at high risk for autism, and children diagnosed with autism. We conclude that there are clear neurobiological and behavioral links between abnormal auditory development and the deficits in social communication seen in autism. We then offer perspectives on the need for a systematic characterization of early auditory development in autism, and identified questions to be addressed in future research on the development of autism.

Lack of neural evidence for implicit language learning in 9-month-old infants at high risk for autism.

Word segmentation is a fundamental aspect of language learning, since identification of word boundaries in continuous speech must occur before the acquisition of word meanings can take place. We previously used functional magnetic resonance imaging (fMRI) to show that youth with autism spectrum disorder (ASD) are less sensitive to statistical and speech cues that guide implicit word segmentation. However, little is known about the neural mechanisms underlying this process during infancy and how this may be associated with ASD risk. Here, we examined early neural signatures of language-related learning in 9-month-old infants at high (HR) and low familial risk (LR) for ASD. During natural sleep, infants underwent fMRI while passively listening to three speech streams containing strong statistical and prosodic cues, strong statistical cues only, or minimal statistical cues to word boundaries. Compared to HR infants, LR infants showed greater activity in the left amygdala for the speech stream containing statistical and prosodic cues. While listening to this same speech stream, LR infants also showed more learning-related signal increases in left temporal regions as well as increasing functional connectivity between bilateral primary auditory cortex and right anterior insula. Importantly, learning-related signal increases at 9 months positively correlated with expressive language outcome at 36 months in both groups. In the HR group, greater signal increases were additionally associated with less severe ASD symptomatology at 36 months. These findings suggest that early differences in the neural networks underlying language learning may predict subsequent language development and altered trajectories associated with ASD risk.

Different Ways of Making a Point: A Study of Gestural Communication in Typical and Atypical Early Development.

Deictic pointing is among the most impaired gestures in children with autism. Research on typical development demonstrates that contact with the referent and handshape when pointing, are associated with different communicative intentions and developmental stages. Despite their importance, the morphological features of pointing remain largely unexplored in autism. The aim of the present study was to map out pointing production in autism with a focus on handshape and contact with the referent. Participants (age range = 1–6 years old) with ASD (n = 16), at high risk for autism (n = 13) and typically developing children (n = 18) interacted with their caregivers in a gesture elicitation task. Results showed that children with ASD produced fewer pointing gestures overall and fewer index finger pointing without contact with the referent compared to the typically developing children.Lay SummaryChildren with autism produce less gestures than typical children, and pointing gestures appear to be more affected than other gesture types. Whether children point using their index finger or the palm, and whether they touch or not the referent is crucial for understanding communicative intentions. This is the first study to document experimentally exactly how pointing gestures differ in autism in comparison to typical development. We found important qualitative differences in the communicative patterns of children with autism and at risk for autism, that may serve to identify potential new markers for early diagnosis. Autism Res 2021, 14: 984–996. © 2020 The Authors. Autism Research published by International Society for Autism Research and Wiley Periodicals LLC.

Attentional bias to fearful faces in infants at high risk for autism spectrum disorder.

Individuals with autism spectrum disorder (ASD) and their first-degree relatives show differences from neurotypical individuals in emotional face processing. Prospective studies of infant siblings of children with ASD, a group at high risk for autism (HRA), allow researchers to examine the early emergence of these differences. This study used eye tracking to examine disengagement of attention from emotional faces (fearful, happy, neutral) at 6, 9, and 12 months in low-risk control infants (LRC) and HRA infants who received a subsequent clinical judgment of ASD (HRA+) or non-ASD (HRA-). Infants saw centrally presented faces followed by a peripheral distractor (with face remaining present). For each emotion, latency to shift to the distractor and percentage of trials with no shift were calculated. Results showed increased saccadic latency and a greater percentage of no-shift trials for fearful faces. No between-group differences were present for emotion; however, there was an interaction between age and group for disengagement latency, with HRA+ infants slower to shift at 12 months compared with the other 2 groups. Exploratory correlational analyses looking at shift biases to fearful faces alongside measures of social behavior at 12 and 18 months (from the Communication and Symbolic Behavior Scales) revealed that for HRA+ infants, 9- and 12-month fear biases were significantly related to 12- and 18-month social abilities, respectively. This work suggests that both low- and high-risk infants show biases to threat-relevant faces, and that for HRA+, differences in attention shifting emerge with age, and a stronger fear bias could potentially relate to less social difficulty. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Application of the Still-Face Paradigm in Early Screening for High-Risk Autism Spectrum Disorder in Infants and Toddlers.

Background: Although autism spectrum disorder (ASD) can currently be diagnosed at the age of 2 years, age at ASD diagnosis is still 40 months or even later. In order to early screening for ASD with more objective method, behavioral videos were used in a number of studies in recent years.Method: The still-face paradigm (SFP) was adopted to measure the frequency and duration of non-social smiling, protest behavior, eye contact, social smiling, and active social engagement in high-risk ASD group (HR) and typical development group (TD) (HR: n = 45; TD: n = 43). The HR group was follow-up until they were 2 years old to confirm final diagnosis. Machine learning methods were used to establish models for early screening of ASD.Results: During the face-to-face interaction (FF) episode of the SFP, there were statistically significant differences in the duration and frequency of eye contact, social smiling, and active social engagement between the two groups. During the still-face (SF) episode, there were statistically significant differences in the duration and frequency of eye contact and active social engagement between the two groups. The 45 children in the HR group were reclassified into two groups after follow-up: five children in the N-ASD group who were not meet the criterion of ASD and 40 children in the ASD group. The results showed that the accuracy of Support Vector Machine (SVM) classification was 83.35% for the SF episode.Conclusion: The use of the social behavior indicator of the SFP for a child with HR before 2 years old can effectively predict the clinical diagnosis of the child at the age of 2 years. The screening model constructed using SVM based on the SF episode of the SFP was the best. This also proves that the SFP has certain value in high-risk autism spectrum disorder screening. In addition, because of its convenient, it can provide a self-screening mode for use at home.Trial registration: Chinese Clinical Trial Registry, ChiCTR-OPC-17011995.