The effect of prenatal stress on HPA-axis function and neurodevelopment: a gene-environment interaction study (PELS)


Animal studies have shown that early life stress at moments when critical developmental processes are taking place in parts of the nervous system or neuronal circuits involved in HPA-axis functioning (e.g., hippocampus, amygdala, prefrontal cortex), may induce epigenetic changes that alter later function of the HPA axis and cause more anxiety, enhanced stress sensitivity and impaired cognitive and emotional development, especially in genetically susceptible individuals. Although there is now good evidence that prenatal stress can have a long lasting effect in human’s also, there have been no studies of any interaction with underlying genetic factors, which may explain why some subjects are more sensitive or resilient than others.

The main goal of our CRP is to delineate specific risk factors associated with prenatal stress exposure that can result in adverse neurodevelopment of the child. We have designed two collaborative studies one of which involves recruiting a new cohort in which each of the four countries will follow an identical protocol and the second of which involves collecting DNA and new questionnaire data in our existing cohorts. A key feature of the first study is that we examine stress in early and late pregnancy to identify critical periods of risk and their associated outcomes. In the second study we maximize the value of existing samples within each country to examine differences in exposure and outcomes at various child ages.

The primary aims of the CRP are:

1) to determine the contribution of various types of antenatal maternal stress, including work stress and antenatal maternal cortisol level, for offspring birth outcomes and neurodevelopment in early childhood

2) to determine whether prenatal stress exposure interacts with measures of genetic susceptibility (i.e. specific candidate genes related to HPA-axis functioning), in predicting offspring neurodevelopmental outcome Results of our CRP may lead to prevention and intervention strategies focusing on minimizing the risks prenatal stress bears for later mental health.

Project Leader

Professor Bea Van Den Bergh
Faculty of Social and Behavioural Sciences Tilburg, Netherlands

Principal Investigators

Professor Stephan Claes
University of Leuven Group Biomedical Sciences Leuven, Belgium

Professor Vivette Glover
Faculty of Medicine, Institute of Reproductive and Developmental Biology Imperial College London, United Kingdom

Associated Partner

Dr. Alina Rodriguez
Psychologie, Uppsala University, Sweden