SummaryBackgroundResults of small trials suggest that early interventions for social communication are effective for the treatment of autism in children. We therefore investigated the efficacy of such an intervention in a larger trial.MethodsChildren with core autism (aged 2 years to 4 years and 11 months) were randomly assigned in a one-to-one ratio to a parent-mediated communication-focused (Preschool Autism Communication Trial [PACT]) intervention or treatment as usual at three specialist centres in the UK. Those assigned to PACT were also given treatment as usual. Randomisation was by use of minimisation of probability in the marginal distribution of treatment centre, age (≤42 months or >42 months), and autism severity (Autism Diagnostic Observation Schedule-Generic [ADOS-G] algorithm score 12–17 or 18–24). Primary outcome was severity of autism symptoms (a total score of social communication algorithm items from ADOS-G, higher score indicating greater severity) at 13 months. Complementary secondary outcomes were measures of parent-child interaction, child language, and adaptive functioning in school. Analysis was by intention to treat. This study is registered as an , number ISRCTN58133827.Results152 children were recruited. 77 were assigned to PACT (London [n=26], Manchester [n=26], and Newcastle [n=25]); and 75 to treatment as usual (London [n=26], Manchester [n=26], and Newcastle [n=23]). At the 13-month endpoint, the severity of symptoms was reduced by 3·9 points (SD 4·7) on the ADOS-G algorithm in the group assigned to PACT, and 2·9 (3·9) in the group assigned to treatment as usual, representing a between-group effect size of −0·24 (95% CI −0·59 to 0·11), after adjustment for centre, sex, socioeconomic status, age, and verbal and non-verbal abilities. Treatment effect was positive for parental synchronous response to child (1·22, 0·85 to 1·59), child initiations with parent (0·41, 0·08 to 0·74), and for parent-child shared attention (0·33, −0·02 to 0·68). Effects on directly assessed language and adaptive functioning in school were small.InterpretationOn the basis of our findings, we cannot recommend the addition of the PACT intervention to treatment as usual for the reduction of autism symptoms; however, a clear benefit was noted for parent-child dyadic social communication.FundingUK Medical Research Council, and UK Department for Children, Schools and Families.

Autism spectrum disorders (ASDs) are common, heritable neurodevelopmental conditions. The genetic architecture of ASDs is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASDs by using Affymetrix 10K SNP arrays and 1,181 [corrected] families with at least two affected individuals, performing the largest linkage scan to date while also analyzing copy number variation in these families. Linkage and copy number variation analyses implicate chromosome 11p12-p13 and neurexins, respectively, among other candidate loci. Neurexins team with previously implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for contributing to ASDs.

SummaryBackgroundIt 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.MethodsPACT 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.Findings121 (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 −0·23 to 0·53).InterpretationThe results are the first to show long-term symptom reduction after a randomised controlled trial of early intervention in autism spectrum disorder. They support the clinical value of the PACT intervention and have implications for developmental theory.FundingMedical Research Council.

A Randomised Treatment Trial design of this kind in classical autism is feasible and acceptable to patients. This pilot study suggests significant additional treatment benefits following a targeted (but relatively non-intensive) dyadic social communication treatment, when compared with routine care. The study needs replication on larger and independent samples. It should encourage further RCT designs in this area.

Recognition of the marked receptive language impairment relative to expressive language, found to affect at least one-third of preschoolers with autism in this sample, has important implications for interacting with these children and for informing appropriate targets in language and communication intervention.