Longitudinal Analyses of Epigenetic Correlates of Externalizing and Internalizing Disorders

Statement of Problem: In the field of developmental psychopathology, there has been a historical debate colloquially referred to as “nature versus nurture” in the continued pursuit of understanding the genetic and environmental origins of mental illness. The emergent field of behavioral epigenetics has posited that the underlying dichotomy and conceptual separation between gene and environment influences itself is false. Epigenetic processes show that environmental influences act on genes mechanistically as environmental inputs biologically influence the expression of key genes in vital systems. In translating technological advances in epigenetics from the biomedical world, developmental psychopathologists have largely contextualized psychological phenotypes within the same biomedical disease model. However, psychological phenotypes are not automatically amenable to the same methodological framework, as they are uniquely complex in their classification and measurement and are best understood to be calibrated in early life during crucial periods of development. Methods and Procedures: Therefore, the central aim of this thesis was to apply epigenetic theory, methodology, and technology to clinically relevant psychological phenotypes in methodologically novel ways that take into account phenotypic complexity and developmental context. Using a longitudinal design from the Avon Longitudinal Study of Parents and Children (ALSPAC), this thesis explored the epigenetic underpinnings (i.e. DNA methylation) of risk and resilience for internalizing and externalizing disorders during sensitive periods of development. Results: Study 1, published in Development and Psychopathology in 2017, used a candidate gene approach examining epigenetic changes in the oxytocin receptor gene (OXTR) to study resilience to prenatal stress. Results showed that children who were resilient in the conduct problem domain only had differential DNA methylation profiles at birth than those who were not resilient. Study 2 used an epigenome-wide approach to explore potential novel epigenetic correlates of depression trajectories in adolescence with follow-up bioinformatic analyses. Results did not show any fetal programming effects when assessing DNA methylation at birth, but several novel genes were identified when DNA methylation was measured in adolescence. Conclusion: Because these epigenetic changes are heritable and potentially reversible, insights from epigenetic research have profound implications in the classification, identification, and treatment of mental illness