Inflammation-related Epigenetic Risk, Neurocognitive Function and Child and Adolescent Externalising and Internalising Problems

• In Event: 2-038 - New Directions in Research on (Epi)Gene-Environment Interplay in the Development of Psychopathology

Integrative Statement

Background: Children who experience adversities are at risk of developing persisting stress-related psychiatric disorders that can span externalising and internalising problems. Research has examined multiple possible mediating mechanisms for these associations; stress physiology has received the bulk of this attention. In the current study we consider an alternative mechanism, namely, inflammation. The “hidden wounds” hypothesis proposes that early psychosocial adversity translates into biological risk for mental illness by affecting the regulation of the immune system at sensitive stages of brain development. Recent evidence suggests that DNA methylation, a type of epigenetic modification that regulates gene expression, may be a biological mechanism by which adversity can result in low-grade inflammation. However, little is known about how adversity in different developmental periods may affect immune-related DNA methylation which could affect neurodevelopmental and mental health problems. This study examines the concerted influences of pre- and postnatal adversity, an immune-related DNA methylation biomarker, and cognitive function on the development of mental health problems from childhood to adolescence.
Method/Results: In 785 mother-child (50% male) pairs from a longitudinal epidemiological birth cohort, we investigated associations between inflammation-related epigenetic polygenic risk scores (i-ePGS), environmental exposures, cognitive function and child and adolescent internalising and externalising problems. We examined prenatal and postnatal effects (see Figure 1). For externalising problems, one prenatal effect was found: i-ePGS at birth associated with higher externalising problems (ages 7-15) indirectly through lower cognitive function (age 7). For internalising problems, we identified two effects. For a prenatal effect, i-ePGS at birth associated with higher internalising symptoms via continuity in i-ePGS at age 7. For a postnatal effect, higher postnatal adversity exposure (birth through age 7) associated with higher internalising problems (ages 7-15) via higher i-ePGS (age 7).
Discussion: Externalising problems were related mainly to prenatal effects involving lower cognitive function, whereas internalising problems appeared related to both prenatal and postnatal effects. We note, however, that the internalising pathway may be better measured by sensitivity to rewards and reward-related brain function. Future research may want to examine dampened reward sensitivity as a risk for future internalizing problems.

Authors

• Edward Dylan Barker, King's College London
  Presenting Author

• Cecil Charlotte, King's College London
  Non-Presenting Author

• Esther Walton, University of Bristol
  Non-Presenting Author

• Sara Jaffee, University of Pennsylvania
  Non-Presenting Author

• Thomas O'Connor, University of Rochester
  Non-Presenting Author