Investigating associations between birth order and autism diagnostic phenotypes.

BACKGROUND: Birth order effects have been linked to variability in intelligence, educational attainment and sexual orientation. First- and later-born children have been linked to an increased likelihood of an Autism Spectrum Disorder (ASD) diagnosis, with a smaller body of evidence implicating decreases in cognitive functioning with increased birth order. The present study investigated the potential association between birth order and ASD diagnostic phenotypes in a large and representative population sample. METHODS: Data were obtained from an ongoing prospective diagnostic registry, collected between 1999 and 2017, including children (1-18 years of age, n = 5,404) diagnosed with ASD in the state of Western Australia. Children with ASD were ranked relative to sibling's birth to establish birth order within families at time of ASD diagnosis. Information reported to the registry by health professionals at the time of diagnostic evaluation included demographic and family characteristics, functional abilities and intellectual capacity. RESULTS: Adaptive functioning and intelligence scores decreased with increasing birth order, with later-born children more likely to have an intellectual disability. Compared to first-born children with siblings, first-born children without siblings at the time of diagnosis also exhibited decreased cognitive functioning. CONCLUSIONS: These findings demonstrate for the first time an association between increasing birth order and variability in ASD clinical phenotypes at diagnosis, with potential evidence of reproductive curtailment in children without siblings. Taken together, these findings have significant implications for advancing understanding about the potential mechanisms that contribute to heterogeneity in ASD clinical presentations as a function of birth order and family size.

Deconstructing the repetitive behaviour phenotype in autism spectrum disorder through a large population-based analysis.

OBJECTIVE: Restricted and repetitive pattern of behaviours and interests (RRB) are a cardinal feature of autism spectrum disorder (ASD), but there remains uncertainty about how these diverse behaviours vary according to individual characteristics. This study provided the largest exploration to date of the relationship between Repetitive Motor Behaviours, Rigidity/Insistence on Sameness and Circumscribed Interests with other individual characteristics in newly diagnosed individuals with ASD. METHOD: Participants (N = 3,647; 17.7% females; Mage = 6.6 years [SD = 4.7]) were part of the Western Australian (WA) Register for ASD, an independent, prospective collection of demographic and diagnostic data of newly diagnosed cases of ASD in WA. Diagnosticians rated each of the DSM-IV-TR criteria on a 4-point Likert severity scale, and here we focused on the Repetitive Motor Behaviours, Insistence on Sameness and Circumscribed Interests symptoms. RESULTS: The associations between RRB domains, indexed by Kendall's Tau, were weak, ranging from non-significant for both Circumscribed Interests and Repetitive Motor Behaviours to significant (.20) for Insistence on Sameness and Repetitive Motor Behaviours. Older age at diagnosis was significantly associated with lower Circumscribed Interests and significantly associated with higher Insistence on Sameness and Repetitive Motor Behaviours. Male sex was significantly associated with higher Repetitive Motor Behaviours but not Insistence on Sameness or Circumscribed Interests. CONCLUSIONS: The pattern of associations identified in this study provides suggestive evidence for the distinctiveness of Repetitive Motor Behaviours, Insistence on Sameness and Circumscribed Interests, highlighting the potential utility of RRB domains for stratifying the larger ASD population into smaller, more phenotypically homogeneous subgroups that can help to facilitate efforts to understand diverse ASD aetiology and inform design of future interventions.

Empathy for others' pain is disrupted at the neurophysiological level in schizophrenia.

OBJECTIVE: Previous research has shown that empathy for pain is disrupted at the neural level in people with schizophrenia. However, many of these studies have failed to assess key background contextual variables that have previously been linked to neurophysiological responding. Moreover, no study to date has examined the potential influence of schizotypal characteristics on neurophysiological responding in non-clinical individuals. METHODS: People with schizophrenia (N = 17) were compared to demographically matched controls (N = 19) on an event-related potential (ERP) empathy for pain paradigm. The control group also completed a measure of schizotypal personality traits. RESULTS: People with schizophrenia exhibited atypical neural responding at early, emotion-sharing (frontal N110), and late, cognitive (central late positive potential [LPP]) processing stages of pain empathy, relative to controls. In the control group, positive schizotypy traits were significantly negatively related to reduced ERP amplitude in the late, cognitive (central LPP) processing stage of empathy. CONCLUSIONS: These data cross-validate previous studies that have shown that schizophrenia is associated with atypicalities in bottom-up automatic resonance processes that likely contribute to empathic and socio-emotional processing deficits, and indicate that these findings cannot be easily attributed to background contextual differences between the two groups. The results also point to a potential relationship between positive schizotypal characteristics and neurophysiological responding. Implications for simulation theories of empathy and social functioning in schizophrenia are discussed. PRACTITIONER POINTS: Empathic processing has been consistently linked to well-being and mental health in many groups, including people with schizophrenia. Previous research has shown that, relative to controls, people with schizophrenia exhibit abnormalities in their neurophysiological empathic response, but in these prior studies, the two groups also differed in a number of potentially important background contextual variables. The current study shows that, when closely matched on background contextual variables, abnormal neural responding is still evident. These data suggest that empathy for pain is disrupted at the neurophysiological level in schizophrenia.

A developmental neuroscience approach to the search for biomarkers in autism spectrum disorder.

PURPOSE OF REVIEW: The delineation of biomarkers in autism spectrum disorder (ASD) offers a promising approach to inform precision-medicine-based approaches to ASD diagnosis and treatment and to move toward a mechanistic description of the disorder. However, biomarkers with sufficient sensitivity or specificity for clinical application in ASD are yet to be realized. Here, we review recent evidence for early, low-level alterations in brain and behavior development that may offer promising avenues for biomarker development in ASD. RECENT FINDINGS: Accumulating evidence suggests that signs associated with ASD may unfold in a manner that maps onto the hierarchical organization of brain development. Genetic and neuroimaging evidence points towards perturbations in brain development early in life, and emerging evidence indicates that sensorimotor development may be among the earliest emerging signs associated with ASD, preceding social and cognitive impairment. SUMMARY: The search for biomarkers of risk, prediction and stratification in ASD may be advanced through a developmental neuroscience approach that looks outside of the core signs of ASD and considers the bottom-up nature of brain development alongside the dynamic nature of development over time. We provide examples of assays that could be incorporated in studies to target low-level circuits.

Feasibility of a 2-minute eye-tracking protocol to support the early identification of autism.

We tested the potential for Gazefinder eye-tracking to support early autism identification, including feasible use with infants, and preliminary concurrent validity of trial-level gaze data against clinical assessment scores. We embedded the ~ 2-min 'Scene 1S4' protocol within a comprehensive clinical assessment for 54 consecutively-referred, clinically-indicated infants (prematurity-corrected age 9-14 months). Alongside % tracking rate as a broad indicator of feasible assessment/data capture, we report infant gaze data to pre-specified regions of interest (ROI) across four trial types and associations with scores on established clinical/behavioural tools. Most infants tolerated Gazefinder eye-tracking well, returning high overall % tracking rate. As a group, infants directed more gaze towards social vs. non-social (or more vs. less socially-salient) ROIs within trials. Behavioural autism features were correlated with increased gaze towards non-social/geometry (vs. social/people) scenes. No associations were found for gaze directed to ROIs within other stimulus types. Notably, there were no associations between developmental/cognitive ability or adaptive behaviour with gaze towards any ROI. Gazefinder assessment seems highly feasible with clinically-indicated infants, and the people vs. geometry stimuli show concurrent predictive validity for behavioural autism features. Aggregating data across the ~ 2-min autism identification protocol might plausibly offer greater utility than stimulus-level analysis alone.

Non-pharmacological interventions for autistic children: An umbrella review.

LAY ABSTRACT: What is already known about the topic?The delivery of evidence-based interventions is an important part of the clinical pathway for many autistic children and their families. However, parents, practitioners, and policymakers face challenges making evidence informed decisions, due to the wide variety of interventions available and the large, and often inconsistent, body of evidence regarding their effectiveness.What this paper adds?This is a comprehensive umbrella review, also known as a 'review of reviews', which examined the range of interventions available, the evidence for their effectiveness, and whether effects were influenced by factors relating to individual children (e.g. chronological age, core autism characteristics, and related skills) or the ways interventions were delivered (by whom and in what setting, format, mode, and amount). There was evidence for positive therapeutic effects for some, but not all, interventions. No single intervention had a positive effect for all child and family outcomes of interest. The influence of child and delivery characteristics on effects was unclear.Implications for practice, research, and policyThe findings provide parents, practitioners, and policymakers with a synthesis of the research evidence to inform decision-making and highlight the importance of individualised approaches in the absence of clear and consistent evidence. The findings also highlight the need to improve consistency and completeness in reporting of research studies, so that the same questions may be answered more comprehensively in the future.

Continuity of temperament subgroup classifications from infancy to toddlerhood in the context of early autism traits.

Our previous cross-sectional investigation (Chetcuti et al., 2020) showed that infants with autism traits could be divided into distinct subgroups based on temperament. This longitudinal study builds on this existing work by exploring the continuity of temperament subgroup classifications and their associations with behavioral/clinical phenotypic features from infancy to toddlerhood. 103 infants (68% male) showing early signs of autism were referred to the study by community healthcare professionals and seen for assessments when aged around 12-months (Time 1), 18-months (Time 2), and 24-months (Time 3). Latent profile analysis revealed inhibited/low positive, active/negative reactive, and sociable/well-regulated subgroups at each timepoint, and a unique reactive/regulated subgroup at Time 3. Cross-tabulations indicated a significant likelihood of children having a recurrent subgroup classification from one timepoint to the next, and no apparent patterns to the movement of children who did change from one subgroup to another over time. Temperament subgroups were associated with concurrent child social-emotional functioning and autism traits, but unrelated to child age, sex, or developmental level. These findings suggest that temperament subgroup classifications might represent a reliable and very early indicator of autism characteristics and social-emotional functioning among infants/toddlers with autism traits.

Caregiver sensitivity predicts infant language use, and infant language complexity predicts caregiver language complexity, in the context of possible emerging autism.

While theory supports bidirectional effects between caregiver sensitivity and language use, and infant language acquisition-both caregiver-to-infant and also infant-to-caregiver effects-empirical research has chiefly explored the former unidirectional path. In the context of infants showing early signs of autism, we investigated prospective bidirectional associations with 6-min free-play interaction samples collected for 103 caregivers and their infants (mean age 12-months; and followed up 6-months later). We anticipated that measures of caregiver sensitivity/language input and infant language would show within-domain temporal stability/continuity, but also that there would be predictive associations from earlier caregiver input to subsequent child language, and vice versa. Caregiver sensitive responsiveness (from the Manchester Assessment of Caregiver-Infant interaction [MACI]) predicted subsequent infant word tokens (i.e., amount of language, coded following the Systematic Analysis of Language Transcripts [SALT]). Further, earlier infant Mean Length of Utterance (MLU; reflecting language complexity, also derived from SALT coding) predicted later caregiver MLU, even when controlling for variability in infant ages and clear within-domain temporal stability/continuity in key measures (i.e., caregiver sensitive responsiveness and infant word tokens; and infant and caregiver MLU). These data add empirical support to theorization on how caregiver input can be both supportive of, and potentially influenced by, infant capacities, when infants have social-communication differences and/or communication/language delays suggestive of possible emerging autism.

Parent-Child Interactions May Help to Explain Relations Between Parent Characteristics and Clinically Observed Child Autistic Behaviours.

The importance of supporting parent-child interactions has been noted in the context of prodromal autism, but little consideration has been given to the possible contributing role of parental characteristics, such as psychological distress. This cross-sectional study tested models in which parent-child interaction variables mediated relations between parent characteristics and child autistic behaviour in a sample of families whose infant demonstrated early signs of autism (N = 103). The findings suggest that associations between parent characteristics (psychological distress; aloofness) and child autistic behaviours may be mediated by the child's inattentiveness or negative affect during interactions. These findings have important implications in developing and implementing interventions in infancy which target the synchrony of parent-child interaction with the goal to support children's social communication development.

Estimated Therapy Costs and Downstream Cost Consequences of iBASIS-Video Interaction to Promote Positive Parenting Intervention vs Usual Care Among Children Displaying Early Behavioral Signs of Autism in Australia.

Importance: The growing global prevalence of autism spectrum disorder (ASD) is associated with increasing costs for support services. Ascertaining the effects of a successful preemptive intervention for infants showing early behavioral signs of autism on human services budgets is highly policy relevant. Objective: To estimate the net cost impact of the iBASIS-Video Interaction to Promote Positive Parenting (iBASIS-VIPP) intervention on the Australian government. Design, Setting, and Participants: Infants (aged 12 months) showing early behavioral indicators of autism were recruited through community settings into the multicenter Australian iBASIS-VIPP randomized clinical trial (RCT), a 5- to 6-month preemptive parent-mediated intervention, between June 9, 2016, and March 30, 2018, and were followed up for 18 months to age 3 years. This economic evaluation, including cost analysis (intervention and cost consequences) and cost-effectiveness analyses of iBASIS-VIPP compared with usual care (treatment as usual [TAU]), modeled outcomes observed at age 3 through to 12 years (13th birthday) and was conducted from April 1, 2021, to January 30, 2023. Data analysis was conducted from July 1, 2021, to January 29, 2023. Exposures: iBASIS-VIPP intervention. Main Outcomes and Measures: To project the diagnostic trajectory and associated disability support costs drawing on the Australian National Disability Insurance Scheme (NDIS), the main outcome was the differential treatment cost of iBASIS-VIPP plus TAU vs TAU and disability-related government costs modeled to age 12 years, using a clinical diagnosis of ASD and developmental delay (with autism traits) at 3 years. Costs were calculated in Australian dollars and converted to US dollars. Economic performance was measured through the following: (1) differential net present value (NPV) cost (iBASIS-VIPP less TAU), (2) investment return (dollars saved for each dollar invested, taking a third-party payer perspective), (3) break-even age when treatment cost was offset by downstream cost savings, and (4) cost-effectiveness in terms of the differential treatment cost per differential ASD diagnosis at age 3 years. Alternate values of key parameters were modeled in 1-way and probabilistic sensitivity analysis, the latter identifying the likelihood of an NPV cost savings. Results: Of the 103 infants enrolled in the iBASIS-VIPP RCT, 70 (68.0%) were boys. Follow-up data at age 3 years were available for 89 children who received TAU (44 [49.4%]) or iBASIS-VIPP (45 [50.6%]) and were included in this analysis. The estimated mean differential treatment cost was A $5131 (US $3607) per child for iBASIS-VIPP less TAU. The best estimate of NPV cost savings was A $10 695 (US $7519) per child (discounted at 3% per annum). For each dollar invested in treatment, a savings of A $3.08 (US $3.08) was estimated; the break-even cost occurred at age 5.3 years (approximately 4 years after intervention delivery). The mean differential treatment cost per lower incident case of ASD was A $37 181 (US $26 138). We estimated that there was an 88.9% chance that iBASIS-VIPP would deliver a cost savings for the NDIS, the dominant third-party payer. Conclusions and Relevance: The results of this study suggest that iBASIS-VIPP represents a likely good-value societal investment for supporting neurodivergent children. The estimated net cost savings were considered conservative, as they covered only third-party payer costs incurred by the NDIS and outcomes were modeled to just age 12 years. These findings further suggest that preemptive interventions may be a feasible, effective, and efficient new clinical pathway for ASD, reducing disability and the costs of support services. Long-term follow-up of children receiving preemptive intervention is needed to confirm the modeled results.

The Utility of Natural Language Samples for Assessing Communication and Language in Infants Referred with Early Signs of Autism.

Natural Language Sampling (NLS) offers clear potential for communication and language assessment, where other data might be difficult to interpret. We leveraged existing primary data for 18-month-olds showing early signs of autism, to examine the reliability and concurrent construct validity of NLS-derived measures coded from video-of child language, parent linguistic input, and dyadic balance of communicative interaction-against standardised assessment scores. Using Systematic Analysis of Language Transcripts (SALT) software and coding conventions, masked coders achieved good-to-excellent inter-rater agreement across all measures. Associations across concurrent measures of analogous constructs suggested strong validity of NLS applied to 6-min video clips. NLS offers benefits of feasibility and adaptability for validly quantifying emerging skills, and potential for standardisation for clinical use and rigorous research design.

Occurrence of psychosis and bipolar disorder in adults with autism: A systematic review and meta-analysis.

OBJECTIVE: Evidence suggests that individuals with autism spectrum disorder have increased rates of co-occurring psychosis and/or bipolar disorder. Considering the peak age of onset for psychosis and bipolar disorder occurs in adulthood, we investigated the co-occurrence of these disorders in adults with autism. METHODS: We conducted a systematic review and meta-analysis (PROSPERO Registration Number: CRD42018104600) to (1) examine the prevalence of psychosis and bipolar disorder in adults with autism, and (2) review potential risk factors associated with their co-occurrence. RESULTS: Fifty-three studies were included. The pooled prevalence for the co-occurrence of psychosis in adults with autism was 9.4 % (N = 63,657, 95 %CI = 7.52, 11.72). The pooled prevalence for the co-occurrence of bipolar disorders in adults with autism was 7.5 % (N = 31,739, 95 %CI = 5.79, 9.53). CONCLUSIONS: Psychosis and bipolar disorder occur at a substantially higher prevalence in adults with autism compared to general population estimates. While there is an overall dearth of research examining risk factors for these disorders in autism, males had increased likelihood of co-occurring psychosis, and females of co-occurring bipolar disorder. These results highlight the need for ongoing assessment and monitoring of these disorders in adults with autism.

A systematic review of the biological, social, and environmental determinants of intellectual disability in children and adolescents.

Aim: This systematic review aimed to identify the most important social, environmental, biological, and/or genetic risk factors for intellectual disability (ID). Methods: Eligible were published prospective or retrospective comparative studies investigating risk factors for ID in children 4-18 years. Exclusions were single group studies with no comparator without ID and a sample size <100. Electronic databases (Medline, Cochrane Library, EMBASE, PsycInfo, Campbell Collaboration, and CINAHL) were searched for eligible publications from 1980 to 2020. Joanna Briggs Institute critical appraisal instruments, appropriate for study type, were used to assess study quality and risk of bias. Descriptive characteristics and individual study results were presented followed by the synthesis for individual risk factors, also assessed using GRADE. Results: Fifty-eight individual eligible studies were grouped into six exposure topics: sociodemographic; antenatal and perinatal; maternal physical health; maternal mental health; environmental; genetic or biological studies. There were few eligible genetic studies. For half the topics, the certainty of evidence (GRADE) was moderate or high. Conclusion: Multiple studies have examined individual potential determinants of ID, but few have investigated holistically to identify those populations most at risk. Our review would indicate that there are vulnerable groups where risk factors we identified, such as low socioeconomic status, minority ethnicity, teenage motherhood, maternal mental illness, and alcohol abuse, may cluster, highlighting a target for preventive strategies. At-risk populations need to be identified and monitored so that interventions can be implemented when appropriate, at preconception, during pregnancy, or after birth. This could reduce the likelihood of ID and provide optimal opportunities for vulnerable infants. Systematic review registration: [https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=120032], identifier [CRD42019120032].

An evidence-based framework for determining the optimal amount of intervention for autistic children.

The provision of timely, effective, and socially valid non-pharmacological intervention is at the core of efforts to support the development of young autistic children. These efforts are intended to support children to develop skills, empower their caregivers, and lay the foundation for optimal choice, independence, and quality of life into adulthood. But what is the optimal amount of intervention? In this Viewpoint, we review current guidelines and consider evidence from an umbrella review of non-pharmacological interventions for autistic children aged up to 12 years. We show the lack of consensus on the issue, identify factors that might be relevant to consider, and present an evidence-based framework for determining the optimal amount of intervention for each child, along with recommendations for future research.

Caregiver Psychological Distress Predicts Temperament and Social-Emotional Outcomes in Infants with Autism Traits.

Child temperament and caregiver psychological distress have been independently associated with social-emotional difficulties among individuals with autism. However, the interrelationship among these risk factors has rarely been investigated. We explored the reciprocal interplay between child temperament (surgency, negative affectivity, and self-regulation) and caregiver psychological distress in the development of child internalizing and externalizing symptoms, in a cohort of 103 infants showing early autism traits. Caregivers completed questionnaires when children were aged around 12-months (Time 1 [T1]), 18-months (Time 2 [T2]), and 24-months (Time 3 [T3]). Cross-lagged path models revealed a significant pathway from T1 caregiver psychological distress through lower T2 child self-regulation to subsequently greater T3 child internalizing symptoms. No such caregiver-driven pathway was evident through T2 child negative affectivity or in the prediction of T3 child externalizing symptoms. Further, no support was found for temperament-driven pathways through caregiver psychological distress to child social-emotional difficulties. Child surgency was mostly unrelated to caregiver psychological distress and social-emotional difficulties. These findings implicate the need to support the mental health of caregivers with an infant with autism traits in order to enhance the emotion regulation and social-emotional development of their infants.

The course and prognostic capability of motor difficulties in infants showing early signs of autism.

Delays within the motor domain are often overlooked as an early surveillance marker for autism. The present study evaluated motor difficulties and its potential as an early predictive marker for later autism likelihood in a cohort of infants (N = 96) showing early behavioral signs of autism aged 9-14 months. The motor domain was evaluated using the motor subscales of the Mullen Scales of Early Learning at baseline, and at a 6-month follow-up. The Autism Diagnostic Observation Schedule - Toddler Module (ADOS-T) was completed at follow-up as a measure of autism likelihood. Motor difficulties were common at baseline, with 63/96 (65.6%) infants scoring very low or below average in the gross motor domain and 29/96 (30.2%) in the fine motor domain. At follow-up, gross motor difficulties had resolved for many, with 23/63 (36.5%) infants maintaining these difficulties. Fine motor difficulties resolved in fewer infants, with 20/29 (69.0%) continuing to present with fine motor delays at follow-up. Adjusted linear regression models suggested that fine motor scores at baseline (ß = -0.12, SE = 0.04) and follow-up (ß = -0.17, SE = 0.05) were associated with higher ADOS-T scores; with difficulties across both timepoints (ß = 5.60, SE = 1.35) the strongest (largest in magnitude) association with ADOS-T scores of the predictors examined. Motor difficulties are prominent in children displaying emerging signs of autism, with persistent fine motor difficulties predictive of the developing autism phenotype. The findings indicate the potential clinical value of including evaluation of motor skills within early autism surveillance measures. LAY SUMMARY: This prospective study evaluated motor development over a 6-month period in infants showing early behavioral signs of autism. Atypical motor development was a common feature of infants showing early signs of autism and persistent fine motor difficulties were predictive of the emerging autism phenotype.

Performance of the Autism Observation Scale for Infants with community-ascertained infants showing early signs of autism.

LAY ABSTRACT: We investigated whether a commonly used research assessment - the Autism Observation Scale for Infants (AOSI) - accurately measures autism behaviours among infants showing early signs of autism identified within the community. The AOSI is often included in studies tracking the development of infants at increased likelihood of autism, such as the infant siblings of diagnosed children. However, the suitability of this measure has not previously been tested with community-referred infants. We administered the AOSI with infants when aged 9 to 14 months and again 6 months later. Our researchers - independent of the AOSI development team and newly trained on this measure - were able to administer the brief interactive assessment and score it accurately. The infants' AOSI scores were linked to their scores on other established and validated clinical assessments, particularly at the second visit when average age was 18 months. Stronger correspondence of AOSI and other scores at this second visit suggests early autism behaviours are better established and more consistent by 18 months of age, even though these infants showed clear enough signs of possible autism to prompt referral to our study around 12 months of age. However, the moderate association of AOSI scores over time suggests that, like infant siblings - who mostly do not develop autism - community-identified infants showing early signs may also have variable developmental pathways in early life.

Effect of Preemptive Intervention on Developmental Outcomes Among Infants Showing Early Signs of Autism: A Randomized Clinical Trial of Outcomes to Diagnosis.

Importance: Intervention for individuals with autism spectrum disorder (ASD) typically commences after diagnosis. No trial of an intervention administered to infants before diagnosis has shown an effect on diagnostic outcomes to date. Objective: To determine the efficacy of a preemptive intervention for ASD beginning during the prodromal period. Design, Setting, and Participants: This 2-site, single rater-blinded randomized clinical trial of a preemptive intervention vs usual care was conducted at 2 Australian research centers (Perth, Melbourne). Community sampling was used to recruit 104 infants aged 9 to 14 months showing early behaviors associated with later ASD, as measured by the Social Attention and Communication Surveillance-Revised. Recruitment occurred from June 9, 2016, to March 30, 2018. Final follow-up data were collected on April 15, 2020. Interventions: Infants were randomized on a 1:1 ratio to receive either a preemptive intervention plus usual care or usual care only over a 5-month period. The preemptive intervention group received a 10-session social communication intervention, iBASIS-Video Interaction to Promote Positive Parenting (iBASIS-VIPP). Usual care comprised services delivered by community clinicians. Main Outcomes and Measures: Infants were assessed at baseline (approximate age, 12 months), treatment end point (approximate age, 18 months), age 2 years, and age 3 years. Primary outcome was the combined blinded measure of ASD behavior severity (the Autism Observation Scale for Infants and the Autism Diagnostic Observation Schedule, second edition) across the 4 assessment points. Secondary outcomes were an independent blinded clinical ASD diagnosis at age 3 years and measures of child development. Analyses were preregistered and comprised 1-tailed tests with an α level of .05. Results: Of 171 infants assessed for eligibility, 104 were randomized; 50 infants (mean [SD] chronological age, 12.40 [1.93] months; 38 boys [76.0%]) received the iBASIS-VIPP preemptive intervention plus usual care (1 infant was excluded after randomization), and 53 infants (mean [SD] age, 12.38 [2.02] months; 32 boys [60.4%]) received usual care only. A total of 89 participants (45 in the iBASIS-VIPP group and 44 in the usual care group) were reassessed at age 3 years. The iBASIS-VIPP intervention led to a reduction in ASD symptom severity (area between curves, -5.53; 95% CI, -∞ to -0.28; P = .04). Reduced odds of ASD classification at age 3 years was found in the iBASIS-VIPP group (3 of 45 participants [6.7%]) vs the usual care group (9 of 44 participants [20.5%]; odds ratio, 0.18; 95% CI, 0-0.68; P = .02). Number needed to treat to reduce ASD classification was 7.2 participants. Improvements in caregiver responsiveness and language outcomes were also observed in the iBASIS-VIPP group. Conclusions and Relevance: Receipt of a preemptive intervention for ASD from age 9 months among a sample of infants showing early signs of ASD led to reduced ASD symptom severity across early childhood and reduced the odds of an ASD diagnosis at age 3 years. Trial Registration: http://anzctr.org.au identifier: ACTRN12616000819426.

Empathic deficits in schizophrenia: the potential role of rapid facial mimicry.

Emotional facial expressions evoke rapid, involuntary, and covert facial reactions in the perceiver that are consistent with the emotional valence of the observed expression. These responses are believed to be an important low-level mechanism contributing to the experience of empathy, which some have argued rely on a simulation mechanism subserved by the human mirror neuron system (MNS). Because schizophrenia is associated with pervasive social cognitive difficulties which have been linked to structural abnormalities in the MNS network, the aim of the present study was to provide the first assessment of how rapid facial mimicry reactions (within 1000 ms poststimulus onset) are affected in schizophrenia. Activity in the corrugator supercilii and zygomaticus major muscle regions was quantified using electromyography while individuals with schizophrenia (n = 25) and controls (n = 25) viewed images of happy and angry facial expressions. In contrast to controls, individuals with schizophrenia demonstrated atypical facial mimicry reactions which were not associated with any clinical features of the disorder. These data provide evidence for a low-level disruption that may be contributing to empathizing deficits in schizophrenia and are discussed in relation to neuropsychological models of empathy and schizophrenia.

Subgroups of Temperament Associated with Social-Emotional Difficulties in Infants with Early Signs of Autism.

Links between temperament and social-emotional difficulties are well-established in normative child development but remain poorly characterized in autism. We sought to characterize distinct temperament subgroups and their associations with concurrent internalizing and externalizing symptoms in a sample of 103 infants (Mage = 12.39 months, SD = 1.97; 68% male) showing early signs of autism. Latent profile analysis was used to identify subgroups of infants with distinct temperament trait configurations on the Infant Behavior Questionnaire-Revised. Derived subgroups were then compared in terms of internalizing and externalizing symptoms on the Infant-Toddler Social and Emotional Assessment. Three distinct temperament subgroups were identified: (a) inhibited/low positive (n = 22), characterized by low Smiling and Laughter, low High-Intensity Pleasure, low Vocal Reactivity, and low Approach; (b) active/negative reactive (n = 23), characterized by high Activity Level, high Distress to Limitations, high Sadness, high Fear, and low Falling Reactivity; and (c) well-regulated (n = 51), characterized by high Cuddliness, high Soothability, and high Low-Intensity Pleasure. There were no differences in infant sex ratio, mean age or developmental/cognitive ability. Inhibited/low-positive infants had significantly more behavioral autism signs than active/negative reactive and well-regulated infants, who did not differ. Inhibited/low-positive and active/negative reactive infants had higher internalizing symptoms, relative to well-regulated infants, and active/negative reactive infants also had higher externalizing symptoms. These findings align closely with those garnered in the context of normative child development, and point to child temperament as a putative target for internalizing and externalizing interventions. LAY SUMMARY: This study explored whether infants with early signs of autism could be grouped according to temperament characteristics (i.e., emotional, behavioral, and attentional traits). Three subgroups were identified that differed with respect to emotional and behavioral difficulties. Specifically, "inhibited/low-positive" infants had high emotional difficulties, "active/negative reactive" infants had high emotional and behavioral difficulties, while "well-regulated" infants had the lowest difficulties.