The aim of this study is to investigate the influence of maternal risk factors before and/or during pregnancy on the development of social communication deficits and hyperactivity in children during later life. At the extreme end of each phenotypic spectrum, characterised by Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder (ADHD) respectively, considerable comorbidity has been reported 1. 20-50% of children with ADHD meet diagnostic criteria for ASD, and 30-80% of ASD children meet diagnostic criteria for ADHD1. Both conditions, ASD and ADHD, share variance at a behavioural level (e.g.2,3), and the identification of shared structural brain abnormalities (e.g. 4) and genetic risk factors (e.g. 5) implies the presence of some underlying shared disease aetiology (e.g. 6).

The overlap in characteristics between ADHD and ASD, both at a behavioural and at a neural level, raises the question of whether environmental or familial exposures that have previously been associated with ASD(e.g. 7,8,9) also confer risk of ADHD symptoms (specifically, hyperactivity in this context). Are those risks found in children with ASD who lack ADHD symptoms? Establishing differences in environmental risk factor profiles is an important step towards the identification of the role of specific environmental risk within GxE interactions (as proposed in B954) and the detection of critical time windows during child development where environmental or familial exposures may exacerbate genetically mediated risk.

Using the phenotypic richness and power of the ALSPAC cohort, we will focus on the investigation of broad ASD and ADHD phenotypes during the course of child and adolescent development. Specifically,we will model individual and joint trajectories for the development of social communication deficits (mother-reported SCDC measurements: 91, 128, 166, 198 mns) and hyperactive behaviour (mother-reported SDQ scores: 47, 81, 97, 115, 140, 157, 198 mns). We will examine risk of the child following one or other trajectory in relation to reports of maternalsubstance use (smoking, marijuana use and alcohol use) during and before pregnancy, maternal infections (influenza) during and before pregnancy and a maternal history of psychiatric disorders.

We will also investigate whether these trajectories, and any associated risk, are moderated by parenting influences, such as parental warmth 10 (aggregated parenting measure at 8 months and 33 months derived by Andrea Waylen and Sarah Stewart-Brown)

Using structural equation modelling, weseek to identify risk factors that are unique with respect to the expression of the individualbroad ASD and ADHD phenotypesand, if possible, to distinguish them from risk factors that are shared, and likely to indicate a common aetiology.