Early-Life Adversity, Emotional/Behavioural Regulation and Psychopathology

Leaders: Michel Boivin, Michael Meaney, Jean-Philippe Gouin

Negative life experience during early development including sexual and physical abuse as well as profound emotional neglect, are among the strongest predictors of psychiatric pathology, particularly depression, substance disorders and suicide. Such factors also influence clinical course, including early onset of illness, poor treatment response, increased comorbidity and chronic health care utilization. It is generally assumed that childhood adversity influences psychological development and induces patterns of behavioral responses, which in turn, associate with pervasive interpersonal difficulties and an enhanced reactivity to stress. These traits, in turn, increase the risk for depressive psychopathology, substance use and suicide. There is substantial theoretical and empirical research supporting the validity and strength of the association between childhood adversity and psychiatric illness. However, we are only now starting to understand how molecular mechanisms may account for such strong and long-lasting effects. How does adversity in early-life influence the risk for psychopathology over the lifespan?

Significant insight into this critical issue comes from studies of maternal care in rodents as well as from translational work supported by this Réseau. Researchers from our Réseau conducted groundbreaking work in the rat indicating that maternal care influences the epigenetic programming in the offspring of genes critical in the regulation of the HPA response to stress. Subsequent work using brain tissue from the BB has provided evidence that these findings translate to humans. More importantly, work supported by our Réseau has shown clear evidence that childhood adversity increases the risk of negative mental health outcomes through epigenetic processes acting at comparable genomic sites between species. This work, however, opened a number of important and relevant questions. In addition, there has been significant advance in our knowledge of epigenetic mechanisms over the last few years. The proposed strategic group on early-life adversity, emotional regulation and psychopathology will expand on the work supported previously and promote research investigating relevant and timely questions. For instance, what is the stability of DNA methylation changes associated with vulnerability of mood disorders and suicide? What other epigenetic mechanisms beyond DNA methylation mechanisms may play a role and account for susceptibility to mood disorders and suicide as a result of early-life adversity? What is the effect of substance use on methylation and other epigenetic marks? How do histone marks and other epigenetic factors change according to treatment and correlate with treatment response?

Other important questions relate to the development of risk. What behavioral mediators of increased risk of mood disorders and suicide result from epigenetic changes? What are other important contributing and mediating factors? Can behavioral and molecular factors associated with early-life adversity be modified? Do other traumatic events convey risk through similar mechanisms? Do they have cumulative effects? Important aims of this strategic group will be to encourage the development of trans-disciplinary work that facilitate and advance this type of study.