A white paper on a neurodevelopmental framework for drug discovery in autism and other neurodevelopmental disorders.

In the last decade there has been a revolution in terms of genetic findings in neurodevelopmental disorders (NDDs), with many discoveries critical for understanding their aetiology and pathophysiology. Clinical trials in single-gene disorders such as fragile X syndrome highlight the challenges of investigating new drug targets in NDDs. Incorporating a developmental perspective into the process of drug development for NDDs could help to overcome some of the current difficulties in identifying and testing new treatments. This paper provides a summary of the proceedings of the 'New Frontiers Meeting' on neurodevelopmental disorders organised by the European College of Neuropsychopharmacology in conjunction with the Innovative Medicines Initiative-sponsored AIMS-2-TRIALS consortium. It brought together experts in developmental genetics, autism, NDDs, and clinical trials from academia and industry, regulators, patient and family associations, and other stakeholders. The meeting sought to provide a platform for focused communication on scientific insights, challenges, and methodologies that might be applicable to the development of CNS treatments from a neurodevelopmental perspective. Multidisciplinary translational consortia to develop basic and clinical research in parallel could be pivotal to advance knowledge in the field. Although implementation of clinical trials for NDDs in paediatric populations is widely acknowledged as essential, safety concerns should guide each aspect of their design. Industry and academia should join forces to improve knowledge of the biology of brain development, identify the optimal timing of interventions, and translate these findings into new drugs, allowing for the needs of users and families, with support from regulatory agencies.

Evaluating Sex and Age Differences in ADI-R and ADOS Scores in a Large European Multi-site Sample of Individuals with Autism Spectrum Disorder.

Research on sex-related differences in Autism Spectrum Disorder (ASD) has been impeded by small samples. We pooled 28 datasets from 18 sites across nine European countries to examine sex differences in the ASD phenotype on the ADI-R (376 females, 1763 males) and ADOS (233 females, 1187 males). On the ADI-R, early childhood restricted and repetitive behaviours were lower in females than males, alongside comparable levels of social interaction and communication difficulties in females and males. Current ADI-R and ADOS scores showed no sex differences for ASD severity. There were lower socio-communicative symptoms in older compared to younger individuals. This large European ASD sample adds to the literature on sex and age variations of ASD symptomatology.

Early interaction in autism spectrum disorder: Mothers' and children's behaviours during joint engagement.

BACKGROUND: More knowledge about the interaction between young children with autism spectrum disorder and their parents is one way to improve intervention. This study aims to investigate the behaviours of mothers and children with autism spectrum disorder during joint engagement, with a focus on pacing or rate (i.e., incidences per minute) of their behaviours when being in this state. METHOD: Video recordings of 10 min of free-play between 58 children (2-4 years) diagnosed with childhood autism and their mothers were used to examine rate of mothers' and children's behaviours (i.e., toy introduction, toy expansion, positive affect, and language) during joint engagement, the association between rate of mothers and children's behaviours, the relation between rate of mothers' behaviours and time in joint engagement, and how child factors might be associated with the latter. RESULTS: Mothers(m) and children(c) showed similar rate of positive affect (Mm  = 0.6/Mc  = 0.5) and toy expansion (Mm  = 0.7/Mc  = 0.7) per minute, whereas mothers talked almost three times more than their children (Mm  = 10.2/Mc  = 3.8). In contrast, mothers introduced fewer toys compared to the children (Mm  = 0.7/Mc  = 1.2). Rate of mothers' toy introduction, toy expansion, and positive affect was inversely related to time in joint engagement (Regression coefficient = -70.7 to -48.5, p = .006 to .024). Rates of mothers' and children's behaviours were associated (Spearman rank order coefficient = .53 to .29, p < .001 to .03), but neither rate of children's behaviours nor mental age was associated with the observed relation between rate of these maternal behaviours and time in joint engagement. CONCLUSION: Time in joint engagement was related to rate of mothers' behaviours and children's mental age but not to rate of children's behaviours in this study. Thus, intervention teaching parents of young children with autism strategies designed to increase time in joint engagement may be vital. The complex nature of the interaction between mother and child behaviours in promoting joint engagement warrants further elucidation.