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Autism sibling recurrence in prospective infant family history studies is ~20% at 3 years but systematic follow-up to mid-childhood is rare. In population and clinical cohorts autism is not recognized in some children until school-age or later. One hundred and fifty-nine infants with an older sibling with autism underwent research diagnostic assessments at 3 years and mid-childhood (6 to 12 years (mean 9)). We report the autism sibling recurrence rate in mid-childhood and compare developmental and behavioral profiles at mid-childhood and 3 years in those with earlier versus later recognized autism, and those who had, or had not, received a community autism diagnosis. The autism recurrence rate in this sample in mid-childhood was 37.1%, 95% CI [29.9%, 44.9%] and higher in boys than girls. Around half of those diagnosed with autism in mid-childhood had not received a diagnosis at 3 years. Later, diagnosis was more common in girls than boys. While some had sub-threshold symptoms at 3, in others late diagnosis followed a largely typical early presentation. Sibling recurrence based on community clinical diagnosis was 24.5%, 95% CI [18.4%, 31.9%]. Those who also had a community diagnosis tended to be older, have lower adaptive function and higher autism and inattention symptoms. Notwithstanding limitations of a single site study, modest sample size and limits to generalisability, autism sibling recurrence in family history infants may be higher in mid-childhood than in studies reporting diagnostic outcome at 3 years. Findings have implications for families and clinical services, and for prospective family history studies.

Background: There are very few mechanistic studies of the long-term impact of psychosocial interventions in childhood. The parent-mediated Paediatric Autism Communication Therapy (PACT) RCT showed sustained effects on autistic child outcomes from pre-school to mid-childhood. We investigated the mechanism by which the PACT intervention achieved these effects. Methods: Of 152 children randomised to receive PACT or treatment as usual between 2 and 5 years of age, 121 (79.6%) were followed 5–6 years after the endpoint at a mean age of 10.5 years. Assessors, blind to the intervention group, measured Autism Diagnostic Observation Scale Calibrated Severity Score (ADOS CSS) for child autistic behaviours and Teacher Vineland (TVABS) for adaptive behaviour in school. Hypothesised mediators were child communication initiations with caregivers in a standard play observation (Dyadic Communication Measure for Autism, DCMA). Hypothesised moderators of mediation were baseline child non-verbal age equivalent scores (AE), communication and symbolic development (CSBS) and ‘insistence on sameness’ (IS). Structural equation modelling was used in a repeated measures mediation design. Results: Good model fits were obtained. The treatment effect on child dyadic initiation with the caregiver was sustained through the follow-up period. Increased child initiation at treatment midpoint mediated the majority (73%) of the treatment effect on follow-up ADOS CSS. A combination of partial mediation from midpoint child initiations and the direct effect of treatment also contributed to a near-significant total effect on follow-up TVABS. No moderation of this mediation was found for AE, CSBS or IS. Conclusions: Early sustained increase in an autistic child's communication initiation with their caregiver is largely responsible for the long-term effects from PACT therapy on autistic and adaptive behaviour outcomes. This supports the theoretical logic model of PACT therapy but also illuminates fundamenta

It was suggested that children's referent selection may not lay memory traces sufficiently strong to lead to retention of new word-object mappings. If this was the case we expect incorrect selections to be easily rectified through feedback. Previous work suggested this to be the case in toddlers at typical likelihood (TL) but not in those at elevated likelihood (EL) for autism spectrum disorder (ASD) (Bedford et al.2013). Yet group differences in lexical knowledge may have confounded these findings. Here, TL (N = 29) and EL toddlers (N = 75) chose one of two unfamiliar objects as a referent for a new word. Both groups retained the word-referent mapping above chance when their choices were immediately reinforced but were at chance after corrective feedback. The same pattern of results was obtained when children observed another experimenter make the initial referent choice. Thus, children's referent choices lay memory traces that compete with subsequent correction; these strong word-object associations are not a result of children actively choosing potential referents for new words.

Internalising problems are common within Autism Spectrum Disorder (ASD); early intervention to support those with emerging signs may be warranted. One promising signal lies in how individual differences in temperament are shaped by parenting. Our longitudinal study of infants with and without an older sibling with ASD investigated how parenting associates with infant behavioural inhibition (8–14 months) and later effortful control (24 months) in relation to 3-year internalising symptoms. Mediation analyses suggest nondirective parenting (8 months) was related to fewer internalising problems through an increase in effortful control. Parenting did not moderate the stable predictive relation of behavioural inhibition on later internalising. We discuss the potential for parenting to strengthen protective factors against internalising in infants from an ASD-enriched cohort.

It was suggested that children's referent selection may not lay memory traces sufficiently strong to lead to retention of new word-object mappings. If this was the case we expect incorrect selections to be easily rectified through feedback. Previous work suggested this to be the case in toddlers at typical likelihood (TL) but not in those at elevated likelihood (EL) for autism spectrum disorder (ASD) (Bedford et al.2013). Yet group differences in lexical knowledge may have confounded these findings. Here, TL (N = 29) and EL toddlers (N = 75) chose one of two unfamiliar objects as a referent for a new word. Both groups retained the word-referent mapping above chance when their choices were immediately reinforced but were at chance after corrective feedback. The same pattern of results was obtained when children observed another experimenter make the initial referent choice. Thus, children's referent choices lay memory traces that compete with subsequent correction; these strong word-object associations are not a result of children actively choosing potential referents for new words.

Internalising problems are common within Autism Spectrum Disorder (ASD); early intervention to support those with emerging signs may be warranted. One promising signal lies in how individual differences in temperament are shaped by parenting. Our longitudinal study of infants with and without an older sibling with ASD investigated how parenting associates with infant behavioural inhibition (8–14 months) and later effortful control (24 months) in relation to 3-year internalising symptoms. Mediation analyses suggest nondirective parenting (8 months) was related to fewer internalising problems through an increase in effortful control. Parenting did not moderate the stable predictive relation of behavioural inhibition on later internalising. We discuss the potential for parenting to strengthen protective factors against internalising in infants from an ASD-enriched cohort.

Theta oscillations (spectral power and connectivity) are sensitive to the social content of an experience in typically developing infants, providing a possible marker of early social brain development. Autism is a neurodevelopmental condition affecting early social behaviour, but links to underlying social brain function remain unclear. We explored whether modulations of theta spectral power and connectivity by naturalistic social content in infancy are related to family history for autism. Fourteen-month-old infants with (family history; FH; N = 75) and without (no family history; NFH; N = 26) a first-degree relative with autism watched social and non-social videos during EEG recording. We calculated theta (4–5 Hz) spectral power and connectivity modulations (social–non-social) and associated them with outcomes at 36 months. We replicated previous findings of increased theta power and connectivity during social compared to non-social videos. Theta modulations with social content were similar between groups, for both power and connectivity. Together, these findings suggest that neural responses to naturalistic social stimuli may not be strongly altered in 14-month-old infants with family history of autism.

Preliminary evidence suggests that changes in DNA methylation, a widely studied epigenetic mechanism, contribute to the etiology of Autism Spectrum Disorder (ASD). However, data is primarily derived from post-mortem brain samples or peripheral tissue from adults. Deep-phenotyped longitudinal infant cohorts are essential to understand how epigenetic modifications relate to early developmental trajectories and emergence of ASD symptoms. We present a proof-of-principle study designed to evaluate the potential of prospective epigenetic studies of infant siblings of children with ASD. Illumina genome-wide 450 K DNA methylation data from buccal swabs was generated for 63 male infants at multiple time-points from 8 months to 2 years of age (total N = 107 samples). 11 of those infants received a diagnosis of ASD at 3 years. We conducted a series of analyses to characterize DNA methylation signatures associated with categorical outcome and neurocognitive measures from parent-report questionnaire, eye-tracking and electro-encephalography. Effects observed across the entire genome (epigenome-wide association analyses) suggest that collecting DNA methylation samples within infant-sibling designs allows for the detection of meaningful signals with smaller sample sizes than previously estimated. Mapping networks of co-methylated probes associated with neural correlates of social attention implicated enrichment of pathways involved in brain development. Longitudinal modelling found covariation between phenotypic traits and DNA methylation levels in the proximity of genes previously associated with cognitive development, although larger samples and more complete datasets are needed to obtain generalizable results. In conclusion, assessment of DNA methylation profiles at multiple time-points in infant-sibling designs is a promising avenue to comprehend developmental origins and mechanisms of ASD.

We conducted a replication study of our prior report that increased alpha EEG connectivity at 14-months associates with later autism spectrum disorder (ASD) diagnosis, and dimensional variation in restricted interests/repetitive behaviours. 143 infants at high and low familial risk for ASD watched dynamic videos of spinning toys and women singing nursery rhymes while high-density EEG was recorded. Alpha functional connectivity (7–8 Hz) was calculated using the debiased weighted phase lag index. The final sample with clean data included low-risk infants (N = 20), and high-risk infants who at 36 months showed either typical development (N = 47), atypical development (N = 21), or met criteria for ASD (N = 13). While we did not replicate the finding that global EEG connectivity associated with ASD diagnosis, we did replicate the association between higher functional connectivity at 14 months and greater severity of restricted and repetitive behaviours at 36 months in infants who met criteria for ASD. We further showed that this association is strongest for the circumscribed interests subdomain. We propose that structural and/or functional abnormalities in frontal-striatal circuits underlie the observed association. This is the first replicated infant neural predictor of dimensional variation in later ASD symptoms.

Parents participating in a prospective longitudinal study of infants with older siblings with autism completed an autism screening questionnaire and were asked about any concerns relating to their child’s development, and children were administered an interactive assessment conducted by a researcher at 14 months. Scores on the parent questionnaire were highest for children later diagnosed with autism. Parental concerns and scores from the examiner-led assessment distinguished children with later developmental difficulties (both autism and other developmental atypicalities) from those who were developing typically. Children about whom parents expressed concern scored higher on both the questionnaire and the interactive assessment than those without concerns. There were no significant associations between total or individual item scores from the questionnaire and interactive assessment.

Background: Autism spectrum disorder (ASD) is characterised by persisting difficulties in everyday functioning. Adaptive behaviour is heterogeneous across individuals with ASD, and it is not clear to what extent early development of adaptive behaviour relates to ASD outcome in toddlerhood. This study aims to identify subgroups of infants based on early development of adaptive skills and investigate their association with later ASD outcome. Methods: Adaptive behaviour was assessed on infants at high (n = 166) and low (n = 74) familial risk for ASD between 8 and 36 months using the Vineland Adaptive Behavior Scales (VABS-II). The four domains of VABS-II were modelled in parallel using growth mixture modelling to identify distinct classes of infants based on adaptive behaviour. Then, we associated class membership with clinical outcome and ASD symptoms at 36 months and longitudinal measures of cognitive development. Results: We observed three classes characterised by decreasing trajectories below age-appropriate norms (8.3%), stable trajectories around age-appropriate norms (73.8%), and increasing trajectories reaching average scores by age 2 (17.9%). Infants with declining adaptive behaviour had a higher risk (odds ratio (OR) = 4.40; confidence interval (CI) 1.90; 12.98) for ASD and higher parent-reported symptoms in the social, communication, and repetitive behaviour domains at 36 months. Furthermore, there was a discrepancy between adaptive and cognitive functioning as the class with improving adaptive skills showed stable cognitive development around average scores. Conclusions: Findings confirm the heterogeneity of trajectories of adaptive functioning in infancy, with a higher risk for ASD in toddlerhood linked to a plateau in the development of adaptive functioning after the first year of life.

Background: Difficulties with executive functioning (EF) are common in individuals with a range of developmental disorders, including autism spectrum disorder (ASD). Interventions that target underlying mechanisms of EF early in development could be broadly beneficial, but require infant markers of such mechanisms in order to be feasible. Prospective studies of infants at high familial risk (HR) for ASD have revealed a surprising tendency for HR toddlers to show longer epochs of attention to faces than low-risk (LR) controls. In typical development, decreases in look durations towards the end of the first year of life are driven by the development of executive attention - a foundational component of EF. Here, we test the hypothesis that prolonged attention to visual stimuli (including faces) in HR toddlers reflects early differences in the development of executive attention. Methods: In a longitudinal prospective study, we used eye-tracking to record HR and LR infants' looking behaviour to social and non-social visual stimuli at ages 9 and 15 months. At age 3 years, we assessed children with a battery of clinical research measures and collected parental report of effortful control (EC) - a temperament trait closely associated with EF and similarly contingent on executive attention. Results: Consistent with previous studies, we found an attenuated reduction in peak look durations to faces between 9 and 15 months for the HR group compared with the LR group, and lower EC amongst the HR-ASD group. In line with our hypothesis, change in peak look duration to faces between 9 and 15 months was negatively associated with EC at age 3. Conclusions: We suggest that for HR toddlers, disruption to the early development of executive attention results in an attenuated reduction in looking time to faces. Effects may be more apparent for faces due to early biases to orient towards them; further, attention difficulties may interact with earlier emerging differences in social informat

We integrated multiple behavioural and developmental measures from multiple time-points using machine learning to improve early prediction of individual Autism Spectrum Disorder (ASD) outcome. We examined Mullen Scales of Early Learning, Vineland Adaptive Behavior Scales, and early ASD symptoms between 8 and 36 months in high-risk siblings (HR; n = 161) and low-risk controls (LR; n = 71). Longitudinally, LR and HR-Typical showed higher developmental level and functioning, and fewer ASD symptoms than HR-Atypical and HR-ASD. At 8 months, machine learning classified HR-ASD at chance level, and broader atypical development with 69.2% Area Under the Curve (AUC). At 14 months, ASD and broader atypical development were classified with approximately 71% AUC. Thus, prediction of ASD was only possible with moderate accuracy at 14 months.

Several accounts have been proposed to explain difficulties with social interaction in autism spectrum disorder (ASD), amongst which atypical social orienting, decreased social motivation or difficulties with understanding the regularities driving social interaction. This study uses gaze-contingent eye-tracking to tease apart these accounts by measuring reward related behaviours in response to different social videos. Toddlers at high or low familial risk for ASD took part in this study at age 2 and were categorised at age 3 as low risk controls (LR), high-risk with no ASD diagnosis (HR-no ASD), or with a diagnosis of ASD (HR-ASD). When the on-demand social interaction was predictable, all groups, including the HR-ASD group, looked longer and smiled more towards a person greeting them compared to a mechanical Toy (Condition 1) and also smiled more towards a communicative over a non-communicative person (Condition 2). However, all groups, except the HR-ASD group, selectively oriented towards a person addressing the child in different ways over an invariant social interaction (Condition 3). These findings suggest that social interaction is intrinsically rewarding for individuals with ASD, but the extent to which it is sought may be modulated by the specific variability of naturalistic social interaction.

Superior visual search is one of the most common findings in the autism spectrum disorder (ASD) literature. Here, we ascertain how generalizable these findings are across task and participant characteristics, in light of recent replication failures. We tested 106 3-year-old children at familial risk for ASD, a sample that presents high ASD and ADHD symptoms, and 25 control participants, in three multi-target search conditions: easy exemplar search (look for cats amongst artefacts), difficult exemplar search (look for dogs amongst chairs/tables perceptually similar to dogs), and categorical search (look for animals amongst artefacts). Performance was related to dimensional measures of ASD and ADHD, in agreement with current research domain criteria (RDoC). We found that ASD symptom severity did not associate with enhanced performance in search, but did associate with poorer categorical search in particular, consistent with literature describing impairments in categorical knowledge in ASD. Furthermore, ASD and ADHD symptoms were both associated with more disorganized search paths across all conditions. Thus, ASD traits do not always convey an advantage in visual search; on the contrary, ASD traits may be associated with difficulties in search depending upon the nature of the stimuli (e.g., exemplar vs. categorical search) and the presence of co-occurring symptoms.

An enhanced ability to detect visual targets amongst distractors, known as visual search (VS), has often been documented in Autism Spectrum Disorders (ASD). Yet, it is unclear when this behaviour emerges in development and if it is specific to ASD. We followed up infants at high and low familial risk for ASD to investigate how early VS abilities links to later ASD diagnosis, the potential underlying mechanisms of this association and the specificity of superior VS to ASD. Clinical diagnosis of ASD as well as dimensional measures of ASD, attention-deficit/hyperactivity disorder (ADHD) and anxiety symptoms were ascertained at 3 years. At 9 and 15 months, but not at age 2 years, high-risk children who later met clinical criteria for ASD (HR-ASD) had better VS performance than those without later diagnosis and low-risk controls. Although HR-ASD children were also more attentive to the task at 9 months, this did not explain search performance. Superior VS specifically predicted 3 year-old ASD but not ADHD or anxiety symptoms. Our results demonstrate that atypical perception and core ASD symptoms of social interaction and communication are closely and selectively associated during early development, and suggest causal links between perceptual and social features of ASD.

Autism spectrum disorder (ASD) is a common, highly heritable, developmental disorder and later-born siblings of diagnosed children are at higher risk of developing ASD than the general population. Although the emergence of behavioural symptoms of ASD in toddlerhood is well characterized, far less is known about development during the first months of life of infants at familial risk. In a prospective longitudinal study of infants at familial risk followed to 36 months, we measured functional near-infrared spectroscopy (fNIRS) brain responses to social videos of people (i.e. peek-a-boo) compared to non-social images (vehicles) and human vocalizations compared to non-vocal sounds. At 4–6 months, infants who went on to develop ASD at 3 years (N = 5) evidenced-reduced activation to visual social stimuli relative to low-risk infants (N = 16) across inferior frontal (IFG) and posterior temporal (pSTS-TPJ) regions of the cortex. Furthermore, these infants also showed reduced activation to vocal sounds and enhanced activation to non-vocal sounds within left lateralized temporal (aMTG-STG/pSTS-TPJ) regions compared with low-risk infants and high-risk infants who did not develop ASD (N = 15). The degree of activation to both the visual and auditory stimuli correlated with parent-reported ASD symptomology in toddlerhood. These preliminary findings are consistent with later atypical social brain responses seen in children and adults with ASD, and highlight the need for further work interrogating atypical processing in early infancy and how it may relate to later social interaction and communication difficulties characteristic of ASD.

Autism spectrum disorder (ASD) is a common neurodevelopmental condition, and infant siblings of children with ASD are at a higher risk of developing autistic traits or an ASD diagnosis, when compared to those with typically developing siblings. Reports of differences in brain anatomy and function in high-risk infants which predict later autistic behaviors are emerging, but although cerebellar and subcortical brain regions have been frequently implicated in ASD, no high-risk study has examined these regions. Therefore, in this study, we compared regional MRI volumes across the whole brain in 4-6-month-old infants with (high-risk, n = 24) and without (low-risk, n = 26) a sibling with ASD. Within the high-risk group, we also examined whether any regional differences observed were associated with autistic behaviors at 36 months. We found that high-risk infants had significantly larger cerebellar and subcortical volumes at 4-6-months of age, relative to low-risk infants; and that larger volumes in high-risk infants were linked to more repetitive behaviors at 36 months. Our preliminary observations require replication in longitudinal studies of larger samples. If correct, they suggest that the early subcortex and cerebellum volumes may be predictive biomarkers for childhood repetitive behaviors. Autism Res 2019, 12: 614-627. (c) 2019 The Authors. Autism Research published by International Society for Autism Research published byWiley Periodicals, Inc.

There is a lack of measures that reflect the intervention priorities of parents of children with autism spectrum disorder (ASD) and that assess the impact of interventions on family experience and quality of life. The Autism Family Experience Questionnaire (AFEQ) was developed through focus groups and online consultation with parents, and reflected parental priorities. It was then administered to the parents of children enrolled in the Pre-school Autism Communication Trial and its 6-year follow-up study. The AFEQ showed good convergent validity with well-established measures of child adaptive functioning, parental mental health and parental wellbeing. It was sensitive to change in response to a parent-mediated intervention for young children with autism, showing treatment effect at treatment endpoint which increased at six-year follow-up

Background: Prospective studies of infants at familial risk for autism spectrum disorder (ASD) have yielded insights into the earliest signs of the disorder but represent heterogeneous samples of unclear aetiology. Complementing this approach by studying cohorts of infants with monogenic syndromes associated with high rates of ASD offers the opportunity to elucidate the factors that lead to ASD. Methods: We present the first report from a prospective study of ten 10-month-old infants with neurofibromatosis type 1 (NF1), a monogenic disorder with high prevalence of ASD or ASD symptomatology. We compared data from infants with NF1 to a large cohort of infants at familial risk for ASD, separated by outcome at age 3 of ASD (n = 34), atypical development (n = 44), or typical development (n = 89), and low-risk controls (n = 75). Domains assessed at 10 months by parent report and examiner observation include cognitive and adaptive function, sensory processing, social engagement, and temperament. Results: Infants with NF1 showed striking impairments in motor functioning relative to low-risk infants; this pattern was seen in infants with later ASD from the familial cohort (HR-ASD). Both infants with NF1 and the HR-ASD group showed communication delays relative to low-risk infants. Conclusions: Ten-month-old infants with NF1 show a range of developmental difficulties that were particularly striking in motor and communication domains. As with HR-ASD infants, social skills at this age were not notably impaired. This is some of the first information on early neurodevelopment in NF1. Strong inferences are limited by the sample size, but the findings suggest implications for early comparative developmental science and highlight motor functioning as an important domain to inform the development of relevant animal models. The findings have clinical implications in indicating an important focus for early surveillance and remediation in this early diagnosed genetic disorder.

Background: There has been increasing interest in the potential for pre-emptive interventions in the prodrome of autism, but little investigation as to their effect. Methods: A two-site, two-arm assessor-blinded randomised controlled trial (RCT) of a 12-session parent-mediated social communication intervention delivered between 9 and 14 months of age (Intervention in the British Autism Study of Infant Siblings-Video Interaction for Promoting Positive Parenting), against no intervention. Fifty-four infants (28 intervention, 26 nonintervention) at familial risk of autism but not otherwise selected for developmental atypicality were assessed at 9-month baseline, 15-month treatment endpoint, and 27- and 39-month follow-up. Primary outcome: severity of autism prodromal symptoms, blind-rated on Autism Observation Schedule for Infants or Autism Diagnostic Observation Schedule 2nd Edition across the four assessment points. Secondary outcomes: blind-rated parent–child interaction and child language; nonblind parent-rated communication and socialisation. Prespecified intention-to-treat analysis combined estimates from repeated measures within correlated regressions to estimate the overall effect of the infancy intervention over time. Results: Effect estimates in favour of intervention on autism prodromal symptoms, maximal at 27 months, had confidence intervals (CIs) at each separate time point including the null, but showed a significant overall effect over the course of the intervention and follow-up period (effect size [ES] = 0.32; 95% CI 0.04, 0.60; p =.026). Effects on proximal intervention targets of parent nondirectiveness/synchrony (ES = 0.33; CI 0.04, 0.63; p =.013) and child attentiveness/communication initiation (ES = 0.36; 95% CI 0.04, 0.68; p =.015) showed similar results. There was no effect on categorical diagnostic outcome or formal language measures. Conclusions: Follow-up to 3 years of the first RCT of a very early social communication intervention for infant

Background It is not known whether early intervention can improve long-term autism symptom outcomes. We aimed to follow-up the Preschool Autism Communication Trial (PACT), to investigate whether the PACT intervention had a long-term effect on autism symptoms and continued effects on parent and child social interaction. Methods PACT was a randomised controlled trial of a parent-mediated social communication intervention for children aged 2–4 years with core autism. Follow-up ascertainment was done at three specialised clinical services centres in the UK (London, Manchester, and Newcastle) at a median of 5·75 years (IQR 5·42–5·92) from the original trial endpoint. The main blinded outcomes were the comparative severity score (CSS) from the Autism Diagnostic Observation Schedule (ADOS), the Dyadic Communication Assessment Measure (DCMA) of the proportion of child initiatiations when interacting with the parent, and an expressive-receptive language composite. All analyses followed the intention-to-treat principle. PACT is registered with the ISRCTN registry, number ISRCTN58133827. Findings 121 (80%) of the 152 trial participants (59 [77%] of 77 assigned to PACT intervention vs 62 [83%] of 75 assigned to treatment as usual) were traced and consented to be assessed between July, 2013, and September, 2014. Mean age at follow-up was 10·5 years (SD 0·8). Group difference in favour of the PACT intervention based on ADOS CSS of log-odds effect size (ES) was 0·64 (95% CI 0·07 to 1·20) at treatment endpoint and ES 0·70 (95% CI −0·05 to 1·47) at follow-up, giving an overall reduction in symptom severity over the course of the whole trial and follow-up period (ES 0·55, 95% CI 0·14 to 0·91, p=0·004). Group difference in DCMA child initiations at follow-up showed a Cohen's d ES of 0·29 (95% CI −0.02 to 0.57) and was significant over the course of the study (ES 0·33, 95% CI 0·11 to 0·57, p=0·004). There were no group differences in the language composite at follow-up (ES 0·15, 95% CI, Background It is not known whether early intervention can improve long-term autism symptom outcomes. We aimed to follow-up the Preschool Autism Communication Trial (PACT), to investigate whether the PACT intervention had a long-term effect on autism symptoms and continued effects on parent and child social interaction. Methods PACT was a randomised controlled trial of a parent-mediated social communication intervention for children aged 2–4 years with core autism. Follow-up ascertainment was done at three specialised clinical services centres in the UK (London, Manchester, and Newcastle) at a median of 5·75 years (IQR 5·42–5·92) from the original trial endpoint. The main blinded outcomes were the comparative severity score (CSS) from the Autism Diagnostic Observation Schedule (ADOS), the Dyadic Communication Assessment Measure (DCMA) of the proportion of child initiatiations when interacting with the parent, and an expressive-receptive language composite. All analyses followed the intention-to-treat principle. PACT is registered with the ISRCTN registry, number ISRCTN58133827. Findings 121 (80%) of the 152 trial participants (59 [77%] of 77 assigned to PACT intervention vs 62 [83%] of 75 assigned to treatment as usual) were traced and consented to be assessed between July, 2013, and September, 2014. Mean age at follow-up was 10·5 years (SD 0·8). Group difference in favour of the PACT intervention based on ADOS CSS of log-odds effect size (ES) was 0·64 (95% CI 0·07 to 1·20) at treatment endpoint and ES 0·70 (95% CI −0·05 to 1·47) at follow-up, giving an overall reduction in symptom severity over the course of the whole trial and follow-up period (ES 0·55, 95% CI 0·14 to 0·91, p=0·004). Group difference in DCMA child initiations at follow-up showed a Cohen's d ES of 0·29 (95% CI −0.02 to 0.57) and was significant over the course of the study (ES 0·33, 95% CI 0·11 to 0·57, p=0·004). There were no group differences in the language composite at follow-up (ES 0·15, 95% CI

In addition to core symptoms, i.e., social interaction and communication difficulties and restricted and repetitive behaviors, autism is also characterized by aspects of superior perception [1]. One well-replicated finding is that of superior performance in visual search tasks, in which participants have to indicate the presence of an odd-one-out element among a number of foils [2-5]. Whether these aspects of superior perception contribute to the emergence of core autism symptoms remains debated [4, 6]. Perceptual and social interaction atypicalities could reflect co-expressed but biologically independent pathologies, as suggested by a "fractionable" phenotype model of autism [7]. A developmental test of this hypothesis is now made possible by longitudinal cohorts of infants at high risk, such as of younger siblings of children with autism spectrum disorder (ASD). Around 20% of younger siblings are diagnosed with autism themselves [8], and up to another 30% manifest elevated levels of autism symptoms [9]. We used eye tracking to measure spontaneous orienting to letter targets (O, S, V, and +) presented among distractors (the letter X; Figure 1). At 9 and 15 months, emerging autism symptoms were assessed using the Autism Observation Scale for Infants (AOSI; [10]), and at 2 years of age, they were assessed using the Autism Diagnostic Observation Schedule (ADOS; [11]). Enhanced visual search performance at 9 months predicted a higher level of autism symptoms at 15 months and at 2 years. Infant perceptual atypicalities are thus intrinsically linked to the emerging autism phenotype.