Evidence from several fields of research indicates that the adaptation of the stress response system is a key feature of many complex disease states with a psychiatric component. The mechanistic functioning of the hypothalamic-pituitary-adrenal (HPA; stress) axis is highly conserved across vertebrate taxa, underscoring the importance of optimal management of circulating stress hormones such as glucocorticoids. This mechanism plays two principal roles: 1) maintaining homeostatic balance and 2) moderating physiological and behavioural responses to environmental challenges. Thus, the stress response system has the potential to mediate the link between environmental variability, variation in behaviour, and health. Our overall research objective is to understand the molecular mechanisms governing long-term changes in biological systems underlying the response to stress and related signaling pathways involved in stress-related behaviour. We are examining epigenetics as candidate biological mechanisms of gene x environment interactions. Epigenetic mechanisms can modify the expression of genes without a change nucleotide sequence. Using rodent models, we are examining the impact of maternal overnutrition and maternal behaviour on neural mechanisms of stress and anxiety behaviour. In humans, our recent multi-disciplinary CIHR-funded research aims to identify the influence of maternal prenatal stress on infant stress biology and health and the impact of interventions on epigenetic mechanisms. Finally, we are investigating the impact of HPA dysfunction in Chronic Fatigue Syndrome on epigenetic signaling in patients and healthy controls. These studies will help identify mechanisms by which environmental factors, particularly early in life, can be biologically embedded, leading to chronic dysfunctional mental health outcomes.
Epigenetic Mechanisms Mediating the Impact of the Environment on the Stress Response System and Behaviour