Early Life Stress: A Translational Study of Affective and Behavioral Outcomes and Genetic Modulation.

This translational and cross-disciplinary project explores the relationships between adverse early life experiences and the development of risk or resilience to later life stress, with a focus on behavioural changes and genetic modulation. In humans, abu se, parental neglect and other traumatic experiences are quite prevalent in our society. These experiences are frequently associated with lifelong mental health issues and several other problems. Clearly not all individuals subjected to these experiences develop difficulties. The project aims to conduct a longitudinal study with high number of respondents of sexual abused victims in childhood, where the severity of different symptoms (e.g. affective disorders, sleep and circadian disturbances) will be ass essed together with how perceived social support moderate the relationship between early life stressor and the severity of the different symptoms. Using an established animal model for early and later life stress which presents an epigenetic regulation as sociated with childhood abuse in humans, we will go deeper into the mechanisms of individual differences in outcomes. Beyond an assessment of endophenotypes, we aim to characterize brain region specific changes in the animal model. We predict that the cho sen stress paradigms will manifest lasting changes in gene expression profiles. Changes in genome-wide gene expression profiles will be investigated by microarrays and will be followed-up by a gene-set based functional classification of biological systems /processes. Candidate genes will be mined into whole genome association studies on cognition, the human study on sexual abused victims in childhood and various psychiatric disorders. Most experimental work in this field has used males only, despite the fa ct that studies in both animals and humans report sex differences in response to stress. Present studies will also include gender aspects. Such step is critical to develop new more effective clinical interventions