RCN: Identifying Causal Risk Factors and Treatments for Depression, Anxiety, and ADHD in Young People

Context: Depression, anxiety, and attention deficit hyperactivity disorder (ADHD) are common mental health conditions that occur from childhood to adolescence and have major impacts on young people’s well-being, development, and educational and economic outcomes.
The Challenge
Discovering effective interventions to mitigate the adverse consequences of these conditions requires reliable causal evidence. However, limitations of existing evidence include:

Limited evidence from RCTs: There are relatively few randomised trials of young people and those that do have small sample sizes, limited follow-up, and do not record critical outcomes of interest to patients and the public.
Observational studies can be unreliable because controlling all pre-existing differences between individuals (confounding), reverse causation, and differentiating familial factors is challenging.
Conventional Mendelian randomization using population-based summary data can be unreliable because it does not differentiate societal and familial factors from causation.

This project aims to leverage large-scale genetic data to better understand the causes of these conditions and inform the development of effective interventions to improve young people's mental health. It will use a novel Mendelian randomization phenome-wide association study (MR-PheWAS) within family Mendelian randomization and drug-target Mendelian randomization analyses.
Aims and approaches
Aim: To provide reliable causal evidence of mechanisms that affect young people’s mental health.
This project will develop reliable evidence of causal mechanisms and potential intervention targets and strategies to improve outcomes for young people with 1) depression and anxiety and 2) ADHD using three approaches:

Approach 1: Discover when the earliest symptoms of depression, anxiety and ADHD emerge and evaluate the direction of causation for risk factors.

Approach 2: Investigate how familial factors affect young people’s mental...