Temperamental markers in toddlers with autism spectrum disorder.
ABSTRACT: BACKGROUND:Although temperament has been recognized as an important contributor to childhood psychopathology, its role in emergent autism spectrum phenotypes is not well understood. This study examined whether toddlers with autism spectrum disorder (ASD) display temperamental vulnerabilities compared to toddlers with other developmental challenges, whether these characteristics are distinct from core autism symptoms, if they are stable over time, and if they contribute to social outcomes in preschool. METHODS:Parents of 165 toddlers with ASD, 58 nonverbal ability- and chronological age- (CA) matched developmentally delayed (DD) toddlers, and 92 CA-matched typically developing (TD) toddlers completed the Toddler Behavior Assessment Questionnaire-Supplemental (TBAQ-S) at 26 months (SD = 6; Time 1). TBAQ-S data were also available for a subset of toddlers with ASD (n = 126) at 43 months (SD = 9; Time 2). RESULTS:Compared to the DD and TD groups, toddlers with ASD exhibited vulnerabilities within the Effortful Control domain as well as the Surgency domain. They also displayed greater Negative Emotionality compared to TD peers. In the ASD group, temperamental characteristics were not concurrently related to autism severity or developmental level and individual differences were highly stable over time. Changes in Perceptual Sensitivity, Inhibitory Control, and Low-Intensity Pleasure from age 2 to 3.5 uniquely predicted autism symptom severity and adaptive social skill level at Time 2. CONCLUSIONS:Temperamental vulnerabilities in toddlers with ASD are stable over time and involve attentional and behavioral control as well as affective reactivity. They contribute uniquely to social outcomes in preschool and are likely to signal risk for developing later maladaptive attentional, affective, and behavioral symptoms. Considering biologically based dimensions may shed light on noncore facets of the early ASD phenotype that are potentially relevant to the emergence of comorbid conditions later in childhood.
Project description:Multiple eye-tracking studies have highlighted the "atypical" nature of social attention in autism. However, it is unclear how "atypical" or "typical" should be quantified.We developed a method for identifying moments when members of a group looked at similar places (High-Cohesion Time Frames; HCTFs). We defined typicality as the proximity of gaze points to typically developing (TD) gaze points during TD HCTFs. Comparing toddlers with ASD (n?= 112) to developmentally delayed (DD, n?= 36) and TD (n?= 163) toddlers during a video with Dyadic Bid, Sandwich-Making, Joint Attention, and Animated Toys conditions, we examined (a) individual typicality scores, (b) the relationship between typicality and symptom severity, and (c) HCTF distributions associated with each diagnostic group.The ASD group had lower gaze typicality scores compared to the TD and DD groups in the Dyadic Bid and Sandwich-Making conditions but not during Animated Toys. The DD and TD groups did not differ in any condition. Correlational analyses indicated that higher typicality scores were associated with increased looking at pre-planned locations of the scene indexed by each experimental condition. In the ASD group, lower gaze typicality was associated with more severe autism symptoms. Examining ASD HCTFs, the gaze of toddlers with ASD was least cohesive during Dyadic Bid and most cohesive during Animated Toys.In contrast to non-ASD groups, toddlers with ASD show high cohesion during salient nonsocial events, suggesting that consistency in looking strategies may depend more on perceptual features. These findings are consequential for understanding individual differences in visual attention in ASD and for the design of more sensitive biomarker tasks for stratification, between-group differentiation, and measuring response to treatment.
Project description:OBJECTIVE:There is a prevailing notion that children with autism spectrum disorder (ASD) exhibit intense negative and attenuated positive emotions, although the empirical evidence regarding their emotional expressiveness (EE) is limited. Given the importance of emotions in shaping social and cognitive development, we examined intensity and valence of EE and links between EE and autism severity and parent-reported temperament in ASD. METHOD:Toddlers (aged 21.2 months) with ASD (n = 43), developmental delay (DD, n = 16), and typical development (TD, n = 40) underwent standardized probes designed to induce anger, joy, and fear. Intensity of EE through facial and vocal channels were coded offline. Autism severity and temperament were quantified using the Autism Diagnostic Observation Schedule-2 (ADOS-2) and Early Childhood Behavior Questionnaire (ECBQ). RESULTS:The ASD group exhibited less intense fear compared to both the DD and TD groups, more intense anger than DD but not TD, with no differences in joy intensity. All groups showed similar levels of incongruous negative EE. Intensity of fear and anger were not associated with severity of autism symptoms, but lower intensity of joy was related to greater autism severity. Expressed fear and joy were associated with temperament. CONCLUSION:The study provides no support for a negative emotionality bias in ASD. Instead, toddlers with ASD display a muted response to threat and an accentuated response to goal blockage, whereas the ability to express positive emotions appears intact. Negative emotionality and social disability dimensions are independent. The study demonstrates the complexity of EE in ASD and motivates investigations into underlying mechanisms as well as its role in shaping complex phenotypes of affected children.
Project description:Importance:Enhanced selective attention toward nonsocial objects and impaired attention to social stimuli constitute key clinical features of autism spectrum disorder (ASD). Yet, the mechanisms associated with atypical selective attention in ASD are poorly understood, which limits the development of more effective interventions. In typically developing individuals, selective attention to social and nonsocial stimuli is associated with the informational value of the stimuli, which is typically learned over the course of repeated interactions with the stimuli. Objective:To examine value learning (VL) of social and nonsocial stimuli and its association with selective attention in preschoolers with and without ASD. Design, Setting, and Participants:This case-control study compared children with ASD vs children with developmental delay (DD) and children with typical development (TD) recruited between March 3, 2017, and June 13, 2018, at a university-based research laboratory. Participants were preschoolers with ASD, DD, or TD. Main Outcomes and Measures:Procedure consisted of an eye-tracking gaze-contingent VL task involving social (faces) and nonsocial (fractals) stimuli and consisting of baseline, training, and choice test phases. Outcome measures were preferential attention to stimuli reinforced (high value) vs not reinforced (low value) during training. The hypotheses were stated before data collection. Results:Included were 115 preschoolers with ASD (n?=?48; mean [SD] age, 38.30 [15.55] months; 37 [77%] boys), DD (n?=?31; mean [SD] age, 45.73 [19.49] months; 19 [61%] boys), or TD (n?=?36; mean [SD] age, 36.53 [12.39] months; 22 [61%] boys). The groups did not differ in sex distribution; participants with ASD or TD had similar chronological age; and participants with ASD or DD had similar verbal IQ and nonverbal IQ. After training, the ASD group showed preference for the high-value nonsocial stimuli (mean proportion, 0.61 [95% CI, 0.56-0.65]; P?<?.001) but not for the high-value social stimuli (mean proportion, 0.51 [95% CI, 0.46-0.56]; P?=?.58). In contrast, the DD and TD groups demonstrated preference for the high-value social stimuli (DD mean proportion, 0.59 [95% CI, 0.54-0.64]; P?=?.001 and TD mean proportion, 0.57 [95% CI, 0.53-0.61]; P?=?.002) but not for the high-value nonsocial stimuli (DD mean proportion, 0.52 [95% CI, 0.44-0.59]; P?=?.64 and TD mean proportion, 0.50 [95% CI, 0.44-0.57]; P?=?.91). Controlling for age and nonverbal IQ, autism severity was positively correlated with enhanced learning in the nonsocial domain (r?=?0.22; P?=?.03) and with poorer learning in the social domain (r?=?-0.26; P?=?.01). Conclusions and Relevance:Increased attention to objects in preschoolers with ASD may be associated with enhanced VL in the nonsocial domain. When paired with poor VL in the social domain, enhanced value-driven attention to objects may play a formative role in the emergence of autism symptoms by altering attentional priorities and thus learning opportunities in affected children.
Project description:OBJECTIVE:Clinical diagnosis of autism spectrum disorder (ASD) relies on time-consuming subjective assessments. The primary purpose of this study was to investigate the utility of salivary microRNAs for differentiating children with ASD from peers with typical development (TD) and non-autism developmental delay (DD). The secondary purpose was to explore microRNA patterns among ASD phenotypes. METHOD:This multicenter, prospective, case-control study enrolled 443 children (2-6 years old). ASD diagnoses were based on DSM-5 criteria. Children with ASD or DD were assessed with the Autism Diagnostic Observation Schedule II and Vineland Adaptive Behavior Scales II. MicroRNAs were measured with high-throughput sequencing. Differential expression of microRNAs was compared among the ASD (n = 187), TD (n = 125), and DD (n = 69) groups in the training set (n = 381). Multivariate logistic regression defined a panel of microRNAs that differentiated children with ASD and those without ASD. The algorithm was tested in a prospectively collected naïve set of 62 samples (ASD, n = 37; TD, n = 8; DD, n = 17). Relations between microRNA levels and ASD phenotypes were explored. RESULT:Fourteen microRNAs displayed differential expression (false discovery rate < 0.05) among ASD, TD, and DD groups. A panel of 4 microRNAs (controlling for medical/demographic covariates) best differentiated children with ASD from children without ASD in training (area under the curve = 0.725) and validation (area under the curve = 0.694) sets. Eight microRNAs were associated (R > 0.25, false discovery rate < 0.05) with social affect, and 10 microRNAs were associated with restricted/repetitive behavior. CONCLUSION:Salivary microRNAs are "altered" in children with ASD and associated with levels of ASD behaviors. Salivary microRNA collection is noninvasive, identifying ASD-status with moderate accuracy. A multi-"omic" approach using additional RNA families could improve accuracy, leading to clinical application. CLINICAL TRIAL REGISTRATION INFORMATION:A Salivary miRNA Diagnostic Test for Autism; https://clinicaltrials.gov/; NCT02832557.
Project description:There are several studies on oxidative stress of Autism Spectrum Disorder (ASD), but in these cases there is no study to measure oxidative stress and antioxidant capacity at the same time or studies considering childhood development. Therefore, this study comprehensively assessed the level of oxidative stress in ASD children by simultaneously measuring reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP). The subjects were Japanese, 77 typical development (TD) children, 98 ASD children, samples were plasma. The subjects were divided into age groups: toddlers/preschool age (2-6 years) and school age (7-15 years), to compare the relationships among the d-ROMs levels and BAP/d-ROMs ratios. Furthermore, the correlations between the Parent-interview ASD Rating Scales (PARS) scores and the measured values were analyzed. The levels of d-ROMs were significantly higher in the ASD (7-15 years) than in TD (7-15 years). The PARS scores were significantly higher in the ASD and were significantly correlated with d-ROMs levels. These results suggested that d-ROMs and BAP/d-ROMs ratios could be objective, measured indicators that could be used in clinical practice to assess stress in ASD children.
Project description:To compare gastrointestinal (GI) problems among children with: (1) autism spectrum disorder (ASD), (2) developmental delay (DD) and (3) typical development (TD), GI symptom frequencies were obtained for 960 children from the CHildhood Autism Risks from Genetics and Environment (CHARGE) study. We also examined scores on five Aberrant Behavior Checklist (ABC) subscales comparing ASD children with high versus low frequency GI symptoms. Compared to TD children, those with ASD [aOR 7.92 (4.89-12.85)] and DD [aOR 4.55 (2.51-8.24)] were more likely to have at least one frequent GI symptom. Restricting to ASD children, those with frequent abdominal pain, gaseousness, diarrhea, constipation or pain on stooling scored worse on irritability, social withdrawal, stereotypy, and hyperactivity compared with children having no frequent GI symptoms. Frequent GI problems affect young children with ASD and DD more commonly than those with TD. Maladaptive behaviors correlate with GI problems, suggesting these comorbidities require attention.
Project description:Temperament atypicalities have been documented in infancy and early development in children who develop autism spectrum disorders (ASD). The current study investigates whether there are differences in developmental trajectories of temperament between infants and toddlers with and without ASD. Parents of infant siblings of children with autism completed the Carey Temperament Scales about their child at 6, 12, 18, 24, and 36 months of age. Temperament trajectories of children with ASD reflected increases over time in activity level, and decreasing adaptability and approach behaviors relative to high-risk typically developing (TD) children. This study is the first to compare temperament trajectories between high-risk TD infants and infants subsequently diagnosed with ASD in the developmental window when overt symptoms of ASD first emerge.
Project description:Further understanding of the longitudinal changes in visual pattern of toddlers with autism spectrum disorders (ASDs) is needed. We examined twelve 19 to 33-month-old toddlers at their first diagnosis (mean age: 25.1 months) and after six months (mean age: 31.7 months) during two initiating joint attention (IJA) tasks using eye tracking. Results were compared with the performance of age-matched typically developing (TD) toddlers evaluated at a single time-point. Autistic toddlers showed longitudinal changes in the visual sensory processing of the IJA tasks, approaching TD performance with an improvement in the ability to disengage and to explore the global space. Findings suggest the use of eye tracking technology as an objective, non-intrusive, adjunctive tool to measure outcomes in toddlers with ASD.
Project description:Increasing evidence suggests that autism spectrum disorder (ASD) and many forms of developmental delay (DD) originate during fetal development. Preeclampsia may trigger aberrant neurodevelopment through placental, maternal, and fetal physiologic mechanisms.To determine whether preeclampsia is associated with ASD and/or DD.The Childhood Autism Risks from Genetics and the Environment (CHARGE) study is a population-based, case-control investigation of ASD and/or DD origins. Children from 20 California counties aged 24 to 60 months at the time of recruitment and living in catchment areas with a biological parent fluent in English or Spanish were enrolled from January 29, 2003, through April 7, 2011. Children with ASD (n?=?517) and DD (n?=?194) were recruited through the California Department of Developmental Services, the Medical Investigation of Neurodevelopmental Disorders (MIND) Institute, and referrals. Controls with typical development (TD) (n?=?350) were randomly selected from birth records and frequency matched on age, sex, and broad geographic region. Physicians diagnosing preeclampsia were masked to neurodevelopmental outcome, and those assessing neurodevelopmental function were masked to preeclampsia status.Preeclampsia and placental insufficiency were self-reported and abstracted from medical records.The Autism Diagnostic Observation Schedule and Autism Diagnostic Interview-Revised were used to confirm ASD, whereas children with DD and TD were confirmed by Mullen Scales of Early Learning and Vineland Adaptive Behavior Scales and were free of autistic symptoms. Hypotheses were formulated before data collection.Children with ASD were twice as likely to have been exposed in utero to preeclampsia as controls with TD after adjustment for maternal educational level, parity, and prepregnancy obesity (adjusted odds ratio, 2.36; 95% CI, 1.18-4.68); risk increased with greater preeclampsia severity (test for trend, P?=?.02). Placental insufficiency appeared responsible for the increase in DD risk associated with severe preeclampsia (adjusted odds ratio, 5.49; 95% CI, 2.06-14.64).Preeclampsia, particularly severe disease, is associated with ASD and DD. Faulty placentation manifests in the mother as preeclampsia with vascular damage, enhanced systemic inflammation, and insulin resistance; in the placenta as oxygen and nutrient transfer restriction and oxidative stress; and in the fetus as growth restriction and progressive hypoxemia. All are potential mechanisms for neurodevelopmental compromise.
Project description:Evidence suggests that differences in motor function are an early feature of autism spectrum disorder (ASD). One aspect of motor ability that develops during childhood is postural control, reflected in the ability to maintain a steady head and body position without excessive sway. Observational studies have documented differences in postural control in older children with ASD. The present study used computer vision analysis to assess midline head postural control, as reflected in the rate of spontaneous head movements during states of active attention, in 104 toddlers between 16-31 months of age (Mean?=?22 months), 22 of whom were diagnosed with ASD. Time-series data revealed robust group differences in the rate of head movements while the toddlers watched movies depicting social and nonsocial stimuli. Toddlers with ASD exhibited a significantly higher rate of head movement as compared to non-ASD toddlers, suggesting difficulties in maintaining midline position of the head while engaging attentional systems. The use of digital phenotyping approaches, such as computer vision analysis, to quantify variation in early motor behaviors will allow for more precise, objective, and quantitative characterization of early motor signatures and potentially provide new automated methods for early autism risk identification.