Investigating the relationship between stress and the epigenome




Miller, Melissa P. H.

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Lifetime stress exposure has profound effects on neurobiology with lifelong implications for mental health. Epigenetic processes, such as DNA methylation, have been proposed as playing a role in shaping the trajectories of stress-related disorders such as major depression and posttraumatic stress disorder, yet the relationship between stress and DNA methylation has yet to be evaluated in depth. The research presented in this thesis aimed to evaluate 1) the factors associated with chronic biological stress, 2) the relationship between chronic biological stress and DNA methylation, 3) and the impact of acute psychological stress on DNA methylation. Chapters 3 and 4 of this thesis utilized human subjects to investigate the complexity of hair cortisol as a biomarker of chronic stress and its relationship with the epigenome. Results from these studies indicate that chronic biological stress is subtly influenced by both demographic and psychological factors, possibly in a sex-dependent manner. We also report many DNA methylation sites across the genome that are associated with chronic biological stress. Chapter 5 of this thesis aimed to determine the impact of acute stress on the epigenome in humans using a controlled laboratory experiment. For the first time in the literature, we test the influence of acute psychological stress on genome-wide DNA methylation and report novel sites related to stress and immune function that may be sensitive to acute stress, and that are implicated in chronic stress. Taken together, these studies link acute and chronic stress, support the notion that both short- and long-term stress have epigenetic impact, and inform the mechanism of psychopathology. The specific molecular processes by which different types of stress promote epigenetic changes across the lifespan and contribute to the differential susceptibility of males and females to psychiatric morbidity require further investigation.


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