Date of Award
Doctor of Philosophy
John G. Orme, Shandra Forrest-Bank, Matthew Cooper, Alicia K. Smith
Trauma and early-life stress have been linked to poor mental and physical health outcomes. In fact, research has identified trauma and stress can influence epigenetic marks on genes that can alter gene activity. It is suspected that epigenetically altered gene activity is involved in behavior and mental health. This may help explain why some individuals don’t experience great benefit from treatment for the effects of stress, and severe mental health symptoms can be chronic for decades or a lifetime. Moreover, some trauma-related mental health symptoms have shown generational patterns that appear linked to epigenetic marks. Therefore, this study sought to investigate the potential inter-generational influence of mother’s trauma history and mental health on her offspring’s DNA methylation and gene expression in umbilical cord blood.
Standardized measures were used to assess mother’s trauma history and cumulative experienced fear (TLEQ), as well as mother’s mental health status during pregnancy (BSI). Genome-wide and candidate gene analyses were conducted after standard quality control data cleaning procedures. Batch and chip adjustments were made using the Combat package in R software, and the False Discovery Rate was employed to control for multiple comparisons.
Results indicate mother’s exposure to trauma in childhood predicts DNA methylation and gene expression in offspring. Additionally, mother’s mental health status during pregnancy significantly predicts differential gene expression on 245 genes in males only. Finally, mother’s fear completely mediates the influence of trauma on her mental health functioning. In conclusion, a mother’s traumatic experience has potential to influence gene regulation in her offspring. Most importantly, mother’s mental health during pregnancy appears to exert a great influence on gene regulation in males compared to female offspring.
Pilkay, Stefanie Renee, "Mediation and Moderation of Intergenerational Epigenetic Effects of Trauma. " PhD diss., University of Tennessee, 2017.