The goal of this study is to examine whether alterations to the immune system, specifically inflammatory processes, explain how exposure to early life stressors continue to impact adolescent brain development after the stressors have subsided. Children's early experiences lay the groundwork for long-term brain development. This is particularly clear in the context of early life stress (ELS), which alters neural circuits involved in learning and self-regulation during adolescence. Identifying biological sequelae that follow ELS exposure and contribute to neurodevelopmental outcomes is a pressing scientific priority given that ELS exposure poses significant risks to cognitive and emotional development. The immune system presents itself as a promising biological mechanism by which ELS impacts long-term neurodevelopment because it is highly sensitive to early experiences and has strong bidirectional connections with the brain.
The Psychoneuroimmunological Effects of Early Life Stress Study will test for links between ELS exposure, inflammatory processes, and neurodevelopment across a 2-year period in adolescence. This project will use blood samples to assess pro-inflammatory gene expression. It will employ functional magnetic resonance imaging to evaluate the development of two distinct prefrontal-subcortical circuits involved in learning about threats and self-regulation. Longitudinal data will be collected from a group of adopted adolescents who experienced institutional orphanage care as infants--a severe form of ELS--as well as a group of never-institutionalized adolescents. The researcher will test the hypothesis that inflammatory processes promote brain development relevant for learning about threats and disrupt brain development relevant for regulating emotional responses to threats in ELS-exposed adolescents. Pro-inflammatory gene expression will be tested as a mediator between ELS and (a) increased prefrontal-subcortical connectivity during threat learning, and (b) diminished prefrontal-subcortical connectivity during self-regulation. Establishing this stress-immune-brain chain will inform basic models of neurodevelopment and may help explain why ELS deleteriously affects psychosocial and cognitive outcomes.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
