Grant: CIHR Fellowship

Around 6% of the population will experience post-traumatic stress disorder (PTSD) during their lifetimes. Individuals with PTSD are more likely to have poor physical health outcomes, as well as increased rates of other mental health problems including depression (MDD), which is estimated to co-occur with PTSD at rates above 50%. Unfortunately, PTSD can be difficult to treat with medication given the lack of any PTSD-specific drugs. Because PTSD only emerges after a given traumatizing event, we need to understand how trauma is biologically embedded into the brain. Epigenetic changes are considered a principal method by which the environment impacts cell function. Epigenetics are modifications to the genetics of a cell that do not affect the sequence of the DNA - in other words, they do not affect the actual genetic code, but they may affect how the code is read. This can occur by changing how hard it is to access specific genes or how DNA is packaged. However, we lack understanding of 1) the epigenetics of PTSD, 2) how this signature might vary across different brain cell types, as well as 3) the ability to distinguish the epigenetic signature of PTSD from that of MDD. Given the access to well characterized postmortem human brain samples from the Veteran's Affairs Brain Bank, we can compare the molecular profile of brain cells from individuals with PTSD, MDD, and no history of psychiatric illness as control subjects. Specifically, through various single cell assays, I plan to look at changes in the DNA accessibility, architecture, and gene expression (quantities at which genes are read out to produce a protein product) at each individual cell on its own, so that we can look at the different classes of cells and how they interact which each other. These findings can advance our understanding of the epigenetic underpinnings of disabling diseases such as PTSD and MDD, pave the way for new treatments, and eventually translate to better patient outcomes.