AbstractPTSD is a debilitating mental disorder of which sleep disturbances (SD), insomnia and nightmares are commonly reported symptoms. These not only have a major impact on quality of life, they also serve to drive overall psychopathology severity. Recent literature has identified SDs as a risk factor serving to reduce resilience not only to PTSD, but also to depression and anxiety disorders. A comprehensive understanding of how sleep and PTSD are linked on a biological level is key to determine how they influence each other, and from this derive evidence-based solutions to increase resilience among those most at risk. The aims of the current thesis were to examine how SDs and PTSD relate to one another on a molecular biological level. Firstly, a systematic review identified three main molecular systems shared between PTSD and sleep; 1) inflammatory response, 2) HPA-axis stress response and 3) regulation of trophic factors. Following this, peripheral blood protein marker comparison between PTSD and controls identified cystatin C, PAI-1, tPA, IL-8, IFNγ, EGF, D-dimer, midkine, folic acid and homocysteine to have altered expression profiles. Follow up analysis specifically on the tPA/PAI-1 molecular cascade identified PAI-1 serves to act
as a homeostatic inhibitor to the function of tPA, by forming PAI-1/tPA complexes, and this relationship is altered in PTSD. Subsequent examination of peripheral protein marker expression identified elevated pro-inflammatory biomarkers and an increase in the expression of tPA and PAI-1/tPA was apparent in current insomnia. We proposed dysregulation of the BDNF/tPA/PAI-1 system serves a molecular cross-over point whereby active insomnia can increase vulnerability to developing PTSD. Finally, the current works identified both insomnia and psychopathology symptom severity are significantly decreased using a short sleep skills training programme. However, this work could not conclude improving sleep through this programme increases PTSD resilience by reducing PAI-1/tPA complex formation.
|Date of Award||Oct 2022|
|Sponsors||Randox Laboratories Ltd.|
|Supervisor||Tara Moore (Supervisor), Susan Lagdon (Supervisor) & Diego Cobice (Supervisor)|