Developmental associations between motor and communication outcomes in Fragile X syndrome: Variation in the context of co-occurring autism.

LAY ABSTRACT: Fragile X syndrome (FXS), the leading heritable cause of intellectual disability, has a co-occurrence rate of autism spectrum disorder (ASD) estimated at ~60%. Children with FXS experience delayed achievement and slower development of key motor abilities, which happens to an even greater extent for children with both FXS and ASD. A multitude of studies have demonstrated that motor abilities are foundational skills related to later communication outcomes in neurotypical development, as well as in the context of ASD. However, these associations remain unexamined in FXS, or FXS + ASD. In this study, we aimed to determine the associations between early motor skills and their rate of development on communication outcomes in FXS. Furthermore, we investigated whether these associations varied in the context of co-occurring FXS + ASD. Results revealed within-FXS variation in the context of co-occurring ASD between some aspects of motor development and communication outcomes, yet within-FXS consistency between others. Findings provide evidence for variability in developmental processes and outcomes in FXS in the context of co-occurring ASD and offer implications for intervention.

Similar Gap-Overlap Profiles in Children with Fragile X Syndrome and IQ-Matched Autism.

PURPOSE: Fragile X syndrome (FXS) is a single-gene disorder characterized by moderate to severe cognitive impairment and a high association with autism spectrum disorder (ASD) and Attention-Deficit/Hyperactivity Disorder (ADHD). Atypical visual attention is a feature of FXS, ASD, and ADHD. Thus, studying early attentional patterns in young children with FXS can offer insight into early emerging neurocognitive processes underlying challenges and contribute to our understanding of common and unique features of ASD and ADHD in FXS. METHODS: The present study examined visual attention indexed by the gap-overlap paradigm in children with FXS (n = 39) compared to children with ASD matched on intellectual ability and age (n = 40) and age-matched neurotypical controls (n = 34). The relationship between gap-overlap performance and intellectual ability, ASD, and ADHD across groups was characterized. Saccadic reaction times (RT) were collected across baseline, gap, and overlap conditions. RESULTS: Results indicate no group differences in RT for any conditions. However, RT of the ASD and NT groups became slower throughout the experiment whereas RT of the FXS group did not change, suggesting difficulties in habituation for the FXS group. There was no relationship between RT and intellectual ability, ADHD, or ASD symptoms in the FXS and ASD groups. In the NT group, slower RT was related to elevated ADHD symptoms only. CONCLUSION: Taken together, findings suggest that the social attention differences documented in FXS and ASD may be due to other cognitive factors, such as reward or motivation, rather than oculomotor control of visual attention.

Neural correlates of face processing among preschoolers with fragile X syndrome, autism spectrum disorder, autism siblings, and typical development.

The current study examined patterns of event-related potential (ERP) responses during a face processing task in groups of preschoolers uniquely impacted by autism spectrum disorder (ASD), including (1) children with ASD; (2) children with fragile X syndrome (FXS); (3) children with familial risk for ASD, but without a diagnosis (i.e., ASIBs); and (4) a low-risk control (LRC) group. Children with FXS have a high incidence of ASD diagnoses, but there have been no studies of the ERP response to faces in children with FXS and little work focused on children with ASD who have cognitive impairment. The current study examined children's ERP responses to faces and houses in four groups: LRC (N = 28, age = 5.2 years), ASIB (N = 23, age = 5.5 years), FXS (N = 19, age = 5.82 years), and ASD (N = 23, age = 5.5 years). The FXS and ASD groups were characterized by the presence of cognitive impairment. Pictures of upright and inverted faces and houses were presented while recording EEG with a 128-channel system. The N170 occurred at about 200 ms post stimulus onset, was largest on the posterior-lateral electrodes, and was larger for faces than houses. The P1 and N170 ERP components were larger for the FXS group than for the other three groups. The N170 ERP amplitude for the ASD and ASIB groups was smaller than both the LRC and FXS groups, and the LRC and FXS groups had the largest N170 responses on the right side. No difference was found in N170 latency between groups. The similarity of the ASD and ASIB responses suggest a common genetic or environmental origin of the reduced response. Although children with FXS have a high incidence of ASD outcomes, they differed from ASD and ASIB children in this study. Specifically, the children with FXS were hyperresponsive to all stimulus types while the ASD and ASIB groups showed attenuated responses for specific stimuli.

Business-nonprofit hybrid organizing: a dynamic approach to balancing benefits and costs.

Introduction: Efforts to address complex public health challenges can benefit from cross-sector collaboration, while also fostering growing business sector engagement in promoting health equity. What form business-nonprofit collaboration should take, however, is a difficult question for managers and leaders. Hybrid organizational forms, which combine for-profit and nonprofit elements within a single organization in unconventional ways, offer an innovative and potentially promising approach. Yet, while existing typologies of cross-sector collaboration have identified hybrid forms at one end of a continuum of possible forms of collaboration, these typologies do not differentiate the diversity such hybrid forms may take, and the costs and benefits of these innovative hybrid forms are poorly understood. This leaves managers interested in promoting public health through business-nonprofit hybrid organizing with limited guidance about how to maximize potential merits while mitigating drawbacks. Methods: We performed a qualitative comparative case study of three examples of business-nonprofit hybrid organizing. Data collection included 113 interviews with representatives from 42 organizations and observation of case study activities. We used thematic analysis within and across cases to characterize the form of hybrid organizing in each case and to examine benefits and costs of different forms for supporting initiatives. Results: We identified two hybrid, collaborative forms - Appended and Blended forms. Each form had benefits and costs, the significance of which shifted over time contingent on changing strategic priorities and operating environments. Benefits and costs of particular forms become more or less important for establishing and sustaining initiatives under different conditions, requiring a dynamic view. Discussion: No particular form of business-nonprofit hybrid organizing is inherently better than another. Optimizing hybrid organizing and ensuring resilient collaborations may mean allowing collaborative forms to evolve. Practitioners can manage tradeoffs between benefits and costs through an ongoing process of assessing the fit between a given collaborative form, strategic priorities, and relevant features of the operating environment. This dynamic view offers important insights for ensuring the resilience of business-nonprofit collaborative efforts to enhance public health.

Negative affect and respiratory sinus arrhythmia are differentially related to social anxiety and autism features in autistic preschoolers contrasted to fragile X syndrome.

Introduction: Autism spectrum disorder (ASD) is a highly heterogeneous and complex disorder with co-occurring disorders commonplace. This presents tremendous diagnostic challenges given the phenotypic overlap between autism and other diagnoses, including social anxiety, as well as variance in specific genetic disorders like fragile X syndrome (FXS). Biobehavioral measurement approaches integrate behavioral and biological data, and by so doing have the potential to address diagnostic challenges and shed light on the mechanisms underlying social impairments. Methods: The present study utilized a biobehavioral approach to evaluate how biologically based indices of baseline respiratory sinus arrhythmia (RSA) and temperamental negative affect differ and predict autism and anxiety in a sample of 120 preschoolers with non-syndromic autism (nsASD) with co-occurring intellectual impairment, FXS, and neurotypical (NT) development. Results: Results indicated that children with nsASD display elevated negative affect compared to both FXS and NT controls which did not differ from each other and females exhibited more negative affect relative to males. Interestingly, elevated negative affect predicted social anxiety, but not ASD in FXS. Baseline RSA did not differ across the groups; however, reduced RSA predicted elevated autism severity for the nsASD group but not those with FXS or NT development. Discussion: Taken together, biobehavioral markers differentiated the groups in discrete ways that advance our understanding of autism and promote improved diagnostic clarity using objective measurement.

Predictors, Parental Views, and Concordance Across Diagnostic Sources of Autism in Male Youth with Fragile X Syndrome: Clinical Best Estimate and Community Diagnoses.

Persons with fragile X syndrome (FXS) with cooccurring autism spectrum disorder (ASD) are at risk for poorer educational, medical, employment, and independent living outcomes. Thus, the identification of ASD in those with FXS is fundamental to ensuring access to appropriate supports to achieve good quality of life. Yet, optimal diagnostic methods and the exact rate of ASD comorbidity remains controversial, and description of ASD identification in the community in FXS has been limited. This study characterized ASD in a sample of 49 male youth with FXS across multiple diagnostic sources: parent-reported community diagnoses, classification derived from ADOS-2 and ADI-R thresholds, and clinical best-estimate classifications from an expert multidisciplinary team. High concordance was found between ADOS-2/ADI-R and clinical best estimate classifications, with both methods supporting ASD in ~ 75% of male youth with FXS. In contrast, 31% had a community diagnosis. Findings supported gross under-identification of ASD in male youth with FXS in community settings; 60% of those who met clinical best estimate criteria for ASD had not received a diagnosis in the community. Moreover, community diagnoses were poorly aligned with the presence of ASD symptoms as perceived by parents and professionals and, unlike clinical best estimate diagnoses, were not associated with cognitive, behavioral, or language features. Findings highlight under-identification of ASD in community settings as a significant barrier to service access for male youth with FXS. Clinical recommendations should emphasize the benefits of seeking a professional ASD evaluation for children with FXS who are noted to display key ASD symptoms.

Distinct social attention profiles in preschoolers with autism contrasted to fragile X syndrome.

Social attention is a critical skill for learning and development. Social attention difficulties are present in both non-syndromic autism spectrum disorder (nsASD) and fragile X syndrome (FXS), and our understanding of these difficulties is complicated by heterogeneity in both disorders, including co-occurring diagnoses like intellectual disability and social anxiety. Existing research largely utilizes a single index of social attention and rarely includes children with intellectual impairment or uses a cross-syndrome approach. This study investigated whether multi-trait social attention profiles including naturalistic initial eye contact, facial attention, and social scene attention differ in preschool children with nsASD and FXS matched on developmental ability (DQ) and contrasted to neurotypical (NT) controls. The relationship between DQ, ASD severity, and social anxiety and social attention profiles was also examined. Initial eye contact related to social scene attention, implicating that naturalistic social attention is consistent with responses during experimental conditions. Reduced eye contact and lower social scene attention characterized nsASD and FXS. Children with nsASD displayed less facial attention than FXS and NT children, who did not differ. Lower DQ and elevated ASD severity associated with decreased eye contact in nsASD and FXS, and lower DQ was associated with lower social scene attention in FXS. Sex, social anxiety, and age were not associated with social attention. These findings suggest social attention profiles of children with nsASD are highly similar to, yet distinct from, children with FXS. Children with nsASD may present with a global social attention deficit whereas FXS profiles may reflect context-dependent social avoidance.

ADHD and ASD symptoms in young males with fragile X syndrome: associations with early trajectories of inhibitory control.

Inhibitory control (IC), the ability to suppress inappropriate responses, emerges late in the first year of life and improves across typical development, concurrent with brain maturation. The development of IC is critical to various social-emotional and behavioral functions, with IC difficulties being linked to numerous neurodevelopmental disorders, including attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Fragile X syndrome (FXS) is a single-gene disorder characterized by IC difficulties, and elevated rates of ADHD and ASD, making it a useful model for understanding the early development and consequences of IC. In this longitudinal study, we characterized IC trajectories across multiple time points between 16 and 71 months of age in young males with FXS (n = 79) relative to neurotypical (NT) controls (n=49). To explore the association between behavioral outcomes and IC, we identified a subsample of 50 children with longitudinal IC data and an outcome assessment for ADHD and ASD symptoms at age 5 (FXS: n = 26, NT: n = 24). Results indicated that, compared to their NT peers, young males with FXS exhibit differences in IC as early as 24 months, with group differences increasing through age 5. Additionally, we determined that lower IC levels at 24 months were associated with later ADHD symptoms and a decreasing slope in IC over time was associated with later ASD symptoms in male children with FXS. These findings help refine early developmental phenotypes of FXS and highlight IC as a potential target for early detection and intervention of ASD and ADHD symptoms in male children with FXS.

Cortical Source Analysis of the Face Sensitive N290 ERP Component in Infants at High Risk for Autism.

Appropriate head models for cortical source analysis were investigated and applied to source analyses examining the neural bases of the face-sensitive N290 event-related potential (ERP) component in infants at high risk for autism spectrum disorder (ASD). This included infant siblings of children with ASD (ASIBs) and infants with fragile X syndrome (FXS). First, alternative head models for use with ASIBs and FXS were investigated. Head models created from the infant's own MRI were examined in relation to five head models based on average MRI templates. The results of the head model comparison identified group-specific (i.e., ASIB or FXS) head models created from a large collection of structural MRIs as the best substitution for the head model created from the participant's own structural MRI. Second, the cortical source analysis was completed on N290 data collected from a previous study to investigate brain areas associated with face sensitive ERP responses. Participants' own MRIs were used for head models when available, and the group-specific head model was used when the participants' own MRIs were not available. The results provide evidence for unique patterns of neural activation during face processing across infants at high and low risk for ASD and across etiologically distinct high-risk groups. All infants demonstrated greater activation to faces than toys in brain areas most associated with specialized face processing. Infants with FXS displayed higher levels of activation to faces across all areas analyzed, while ASIBs show more muted levels of activation. Overall, the results of the current study demonstrate the importance of group-specific head models for accurate cortical source analysis in infants at high risk for ASD. This also allows for further research on early distinctions in brain function based on risk status.

Backgrounds and Trainings in Cannabis Therapeutics of Dispensary Personnel.

PURPOSE: A growing body of scientific research indicates that oncology teams tend to offer individuals with cancer little clinical advice regarding medicinal cannabis (MC) and that individuals with cancer instead turn to cannabis dispensaries for MC guidance. Our objective was to investigate dispensary personnel's backgrounds and trainings in MC advising. METHODS: The study design was semistructured interviews across 13 states with cannabis dispensary personnel in managerial or client-facing positions. Of 38 recruited, 26 (68%) completed interview. The primary outcome was training in MC advising. Researchers targeted thematic saturation and adhered to Consolidated Criteria for Reporting Qualitative Research. RESULTS: Of 26 participants, 54% were female, with an average age of 40 (range: 22-64) years. Half worked in client-facing roles; half worked in managerial ones. Study participants endorsed passionate commitment to their profession, often motivated by personal experience with MC therapeutics. Cannabis dispensaries often privileged sales skills over cannabis therapeutics knowledge when hiring, resulting in uneven baseline levels of cannabis therapeutics expertise among staff. Most participants reported workplace cannabis therapeutics training to be unstandardized and weak. They described dispensary personnel as resourceful in pursuing cannabis knowledge, self-financing learning in off-hours, sampling dispensary products, and exchanging knowledge. Nearly half the participants called for quality, standardized cannabis therapeutics training for dispensary personnel. CONCLUSION: The many oncology teams who defer to dispensary personnel regarding MC advising rely on a workforce who views themselves as unevenly trained. Further research should include a national survey of cannabis dispensary personnel to learn whether these findings hold true in a larger sample. If so, the oncology community must determine the best approach to clinically advising individuals with cancer about MC.

Attention/Deficit Hyperactivity Disorder in Adolescent and Young Adult Males With Fragile X Syndrome.

This study characterized the rates of attention-deficit/hyperactivity disorder (ADHD) in adolescent and young adult males with fragile X syndrome (FXS) using a multi-method approach integrating a DSM-based parent interview (Children's Interview for Psychiatric Syndromes; P-ChIPS, Fristad et al., 1998) and a parent rating scale (Child Behavior Checklist; CBCL, Achenbach, 2001). Thirty-one males with FXS, aged 16-24 years, participated. Forty-two percent met DSM-5 criteria for ADHD and 35% exceeded the CBCL cut-offs. Agreement between the two classification methods was fair (κ = 0.38). Autism symptom severity and nonverbal cognitive ability did not predict ADHD diagnoses/symptoms. Results show high rates of ADHD in males with FXS during late adolescence and young adulthood, which are not accounted for by impaired nonverbal cognitive skills or autism symptom severity. DSM-based ADHD-specific scales are recommended over broadband symptom scales to improve accurate identification.

Daily Living Skills in Adolescent and Young Adult Males With Fragile X Syndrome.

By adulthood, most males with fragile X syndrome (FXS) require support to navigate day-to-day settings. The present study cross-sectionally: (1) characterized the profile of daily living skills in males with FXS and (2) examined associated participant characteristics (i.e., fragile X mental retardation protein [FMRP] expression, nonverbal cognition, language, autism symptomatology, and anxiety symptomatology) using the Waisman-Activities of Daily Living questionnaire. Males with FXS (n = 57, ages 15-23 years) needed more help/support in the areas of domestic and community daily livings skills, than in the area of personal daily living skills. Significant associations were observed between reduced daily living skills and lower nonverbal cognition, receptive language, expressive language, and increased autism symptomatology. Receptive language emerged as the strongest unique predictor of daily living skill performance.

Neural Correlates of Infant Face Processing and Later Emerging Autism Symptoms in Fragile X Syndrome.

Fragile X syndrome (FXS) is the leading known genetic cause of autism spectrum disorder (ASD) with 60-74% of males with FXS meeting diagnostic criteria for ASD. Infants with FXS have demonstrated atypical neural responses during face processing that are unique from both typically developing, low-risk infants and infants at high familial risk for ASD (i.e., infants siblings of children with ASD). In the current study, event-related potential (ERP) responses during face processing measured at 12 months of age were examined in relation to ASD symptoms measured at ~48 months of age in participants with FXS, as well as siblings of children with ASD and low-risk control participants. Results revealed that greater amplitude N290 responses in infancy were associated with more severe ASD symptoms in childhood in FXS and in siblings of children with ASD. This pattern of results was not observed for low-risk control participants. Reduced Nc amplitude was associated with more severe ASD symptoms in participants with FXS but was not observed in the other groups. This is the first study to examine ASD symptoms in childhood in relation to infant ERP responses in FXS. Results indicate that infant ERP responses may be predictive of later symptoms of ASD in FXS and the presence of both common and unique pathways to ASD in etiologically-distinct high-risk groups is supported (i.e., syndromic risk vs. familial risk).

A single-session behavioral protocol for successful event-related potential recording in children with neurodevelopmental disorders.

Event-related potentials (ERPs) are an ideal tool for measuring neural responses in a wide range of participants, including children diagnosed with neurodevelopmental disorders (NDDs). However, due to perceived barriers regarding participant compliance, much of this work has excluded children with low IQ and/or reduced adaptive functioning, significant anxiety symptoms, and/or sensory processing difficulties, including heterogeneous samples of children with autism spectrum disorder (ASD) and children with fragile X syndrome (FXS). We have developed a behavioral support protocol designed to obtain high-quality ERP data from children in a single session. Using this approach, ERP data were successfully collected from participants with ASD, FXS, and typical development (TD). Higher success rates were observed for children with ASD and TD than children with FXS. Unique clinical-behavioral characteristics were associated with successful data collection across these groups. Higher chronological age, nonverbal mental age, and receptive language skills were associated with a greater number of valid trials completed in children with ASD. In contrast, higher language ability, lower autism severity, increased anxiety, and increased sensory hyperresponsivity were associated with a greater number of valid trials completed in children with FXS. This work indicates that a "one-size-fits-all" approach cannot be taken to ERP research on children with NDDs, but that a single-session paradigm is feasible and is intended to promote increased representation of children with NDDs in neuroscience research through development of ERP methods that support inclusion of diverse and representative samples.

Motor Influences on Communication: Comparisons Between Down Syndrome and Fragile X Syndrome.

Motor skills, an important foundation for language and communication, are considerably delayed in children with Down syndrome (DS) and fragile X syndrome (FXS). However, the impact of these impairments on expressive and receptive communication and the phenotypic specificity of these associations remains unknown. Participants included 37 with DS and 37 age and developmentally matched children with FXS. Syndrome-specific motor and communication profiles emerged, with higher communication scores seen in the DS versus FXS on, but lower gross motor scores. Significant associations between domains of motor and communication were identified for both groups with additional phenotype-specific patterns. Findings demonstrate the importance of early motor abilities for communication in DS and FXS. Implications for phenotypic specificity and targeted intervention are discussed.

Emergence of Developmental Delay in Infants and Toddlers With an FMR1 Mutation.

BACKGROUND: Children with FMR1 gene expansions are known to experience a range of developmental challenges, including fragile X syndrome. However, little is known about early development and symptom onset, information that is critical to guide earlier identification, more accurate prognoses, and improved treatment options. METHODS: Data from 8 unique studies that used the Mullen Scales of Early Learning to assess children with an FMR1 gene expansion were combined to create a data set of 1178 observations of >500 young children. Linear mixed modeling was used to explore developmental trajectories, symptom onset, and unique developmental profiles of children <5 years of age. RESULTS: Boys with an FMR1 gene full mutation showed delays in early learning, motor skills, and language development as young as 6 months of age, and both sexes with a full mutation were delayed on all developmental domains by their second birthday. Boys with a full mutation continued to gain skills over early childhood at around half the rate of their typically developing peers; girls with a full mutation showed growth at around three-quarters of the rate of their typically developing peers. Although children with a premutation were mostly typical in their developmental profiles and trajectories, mild but significant delays in fine motor skills by 18 months were detected. CONCLUSIONS: Children with the FMR1 gene full mutation demonstrate significant developmental challenges within the first 2 years of life, suggesting that earlier identification is needed to facilitate earlier implementation of interventions and therapeutics to maximize effectiveness.

Attention Bias and Prodromal Anxiety Symptoms in Toddlers With Fragile X Syndrome and Down Syndrome.

Early identification of behavioral risk markers for anxiety is essential to optimize long-term outcomes in children with neurodevelopmental disorders. This study analyzed attentional avoidance and its relation to anxiety and autism spectrum disorder (ASD) symptomatology during social and nonsocial fear conditions in toddlers with fragile X syndrome (FXS) and Down syndrome (DS). Toddlers with FXS and DS exhibited increased nonsocial attentional avoidance relative to typically developing (TD) toddlers. Attentional avoidance was not related to anxiety symptom severity in any group; however, higher ASD symptom severity was related to more social attentional avoidance in the FXS and TD groups. Findings suggest that there may be different underlying mechanisms driving attentional avoidance across neurodevelopmental disorders.

Early behavioral and physiological markers of social anxiety in infants with fragile X syndrome.

BACKGROUND: Social anxiety is highly prevalent in neurotypical children and children with fragile X syndrome (FXS). FXS is a genetic syndrome that is characterized by intellectual disability and an increased risk for autism spectrum disorder. If social anxiety is left untreated, negative outcomes are highly prevalent later in life. However, early detection of social anxiety is challenging as symptoms are often subtle or absent very early in life. Given the prevalence and impairment associated with childhood social anxiety, efforts have accelerated to identify risk markers of anxiety. A cluster of early features of anxiety have been identified including elevated behavioral inhibition, attentional biases, and physiological dysregulation that index early emerging markers of social anxiety. Infants with FXS provide a unique opportunity to study the earlier predictors of social anxiety. The current study utilized a multi-method approach to investigate early markers of social anxiety in 12-month-old infants with FXS. METHOD: Participants included 32 infants with FXS and 41 low-risk controls, all approximately 12 months old. Parent-reported social behavioral inhibition was recorded from the Infant Behavior Questionnaire (IBQ-R). Direct observations of behavioral inhibition and attention were measured during a stranger approach task with respiratory sinus arrhythmia collected simultaneously. RESULTS: Parent-reported social behavioral inhibition was not significantly different between groups. In contrast, direct observations suggested that infants with FXS displayed elevated behavioral inhibition, increased attention towards the stranger, and a blunted respiratory sinus arrhythmia response. CONCLUSIONS: Findings suggest that infants with FXS show both behavioral and physiological markers of social anxiety at 12 months old using a biobehavioral approach with multiple sources of input. Results highlight the importance of a multi-method approach to understanding the complex early emergent characteristics of anxiety in infants with FXS.

Emergence and rate of autism in fragile X syndrome across the first years of life.

Prospective longitudinal studies of idiopathic autism spectrum disorder (ASD) have provided insights into early symptoms and predictors of ASD during infancy, well before ASD can be diagnosed at age 2-3 years. However, research on the emergence of ASD in disorders with a known genetic etiology, contextualized in a developmental framework, is currently lacking. Using a biobehavioral multimethod approach, we (a) determined the rate of ASD in N = 51 preschoolers with fragile X syndrome (FXS) using a clinical best estimate (CBE) procedure with differential diagnoses of comorbid psychiatric disorders and (b) investigated trajectories of ASD symptoms and physiological arousal across infancy as predictors of ASD in preschoolers with FXS. ASD was not diagnosed if intellectual ability or psychiatric disorders better accounted for the symptoms. Our results determined that 60.7% of preschoolers with FXS met the Diagnostic and Statistical Manual of Mental Disorders (fifth edition) (DSM-5) criteria for ASD using the CBE procedure. In addition, 92% of these preschoolers presented with developmental delay and 45.4% also met criteria for psychiatric disorders, either anxiety, ADHD, or both. ASD diagnoses in preschoolers with FXS were predicted by elevated scores on traditional ASD screeners in addition to elevated autonomic arousal and avoidant eye contact from infancy.