Causal analysis of maternal substance use during pregnancy and offspring psychopathology

Rationale
Genetic and environmental effects contribute to the aetiology of schizophrenia, autism, and other neurodevelopmental disorders. A number of studies have shown that children who are exposed to adverse environments in-utero have an increased risk of developing these outcomes later in life. For example we, and others, have shown that maternal smoking and alcohol use during pregnancy are associated with increased risk of psychosis during adolescence. However, whether any observed associations are due to causal effects of these substances on brain pathology is unclear. Confounding by other factors such as maternal stress during pregnancy and socioeconomic factors may be an alternative explanation. Traditional epidemiological approaches are not able to establish whether such associations are causal and novel approaches are required to address this uncertainty.

Aims & Objectives
Aim: To establish whether maternal substance use has causal effects on offspring psychopathology
The objectives are to:
1) Examine whether maternal smoking, alcohol, or cannabis use during pregnancy are associated with offspring schizophrenia, autism, or other neurodevelopmental outcomes in large population-based cohorts
2) Use causal analysis methods including negative controls, exposure-discordant siblings, and Mendelian Randomisation to establish if associations are causal

Methods
1. Review the background literature relevant to this project

2. Define appropriate exposure/outcome measures and covariates and agree an analysis plan with supervisors

3. Learn appropriate techniques for analysis of data. Epidemiological approaches will include use of negative controls (for example comparing associations of maternal substance use during pregnancy with those for pre/post pregnancy, or with those for paternal substance use during pregnancy, or use of exposure-discordant siblings), and use of Mendelian Randomisation

4. Conduct statistical analyses

5. Publish research, present at inter/national conference, and write up thesis

This project will involve use of a number of datasets including the ALSPAC birth cohort and Swedish registry-linkage data. There will be opportunities for the student to spend time at the Karolinska Institute in Stockholm.