Environment-Mediated Genetics: The Power of Biological Non-Determinism for Mental Health

Introduction

Mental health problems are associated with variation in the brain and genome. The mechanisms underlying these associations are extremely hard to discern because they are subtly distributed across thousands of genes and not specific to neural processes. Meanwhile, a focus on biology tends to induce feelings of helplessness among those affected by mental health problems, as biology is typically seen as deterministic.

Proposal Overview

I propose that both our mechanistic understanding and the sense of personal agency will leap forward if we consider modifiable, heritable social and lifestyle factors (i.e. "environment") centrally within the causal chain from genes to brain to mental health.

Environmental Factors

Environmental factors are known to be heritable, yet a bottom-up gene-brain causal model prevails due to its intuitive and practical appeal. Standard methods are limited to pairwise associations between the many relevant genetic, brain, and environmental variables.

1. The heritable environment is thus hard to account for.
2. It is challenging to embrace it as an opportunity.

Method Development

We developed a new multivariate method that can identify patterns of shared genetic effects across thousands of variables. By combining this method with genetically informed causal models and family designs, we will:

• Reveal the overall explanatory power and pervasiveness of environment-mediated genetic influences on brain and mental health.
• Further characterize these to identify which environmental factors are potential mediators of genetic influences on brain and mental health.
• Investigate when these factors emerge and if and how they are personally modifiable.

Project Goal

The goal of EM-POWER is to lay empirical foundations for a new non-deterministic biological paradigm that leads to new mechanistic insights of environment-mediated biological mechanisms, within this project and beyond.

Future Outcome

The future outcome is that people will know the potential of personal control over biological factors and can break causal chains from genetic vulnerability to mental health problems.