Abstract
Factors leading to stress-related disorders may be traced back to the prenatal environment. Mechanisms by which prenatal exposures operate to change biobehavioral stress mediators are not understood. Animal studies suggest that prenatal overexposure to glucocorticoids - as a consequence of exogenous exposures, e.g., carbenoxolone, or experimental manipulations, e.g. a low protein diet, which alters function of the feto-placental glucocorticoid barrier, may be a mechanistic factor.
This cross-disciplinary CRP utilizes the low protein rat model to determine early dietary effects on expression of genes known to be involved in stress pathways in the brain; explores novel genes differentially expressed in response to maternal diet in stress-sensitive brain areas; and examines potential mechanisms by which differences in gene expression occur by determining their methylation status. Similar experimental dietary manipulations in human pregnancy are not possible.
However, access to three unique European cohorts within this CRP provides us with excellent opportunities to address such mechanisms: the Dutch Hunger Winter Study focusing on maternal prenatal malnutrition, the Southampton Women’s Study focusing on normal variations in maternal diet, and a cohort of Finnish children exposed prenatally to varying levels of maternal glycyrrhizin in licorice. This CRP capitalizes on these natural experiments to explore biobehavioral and mental health consequences. It will test whether prenatal effects are mediated by known stress-related genes and/or novel susceptibility genes identified in the low protein rat experiment and a previous human genome-wide analysis. Finally, effects of childhood trauma (evacuations during WW II) and other adversities occurring over the life-course and their interaction with an individual’s genetic set-up on stress mediators, behavioral stress responses and psychiatric disorders will be determined using the Helsinki Birth Cohort.
This CRP therefore addresses fundamental questions central to the EuroStress program, providing novel mechanistic insight into how adverse early life experiences influence risk of subsequent stress-related disorders.
Project Leader
Professor Katri Räikköne
Faculty of Behavioral Sciences University of Helsinki , Finland
Principal Investigators
Dr. Tessa Roseboom
Academic Medical Center Amsterd, Netherlands
Professor Johan Eriksson
University of Helsinki, Finland
Associated Partners
Dr. Susan Ozanne
University of Cambridge, United Kingdom
Professor David Phillips
University of Southamptom, United Kingdom
Professor Leif Groop
University of Lund Malmö, Sweden
