Pre-existing Inflammation Produces Depression Following Spinal Cord Injury
Abstract
Major depressive disorder (MDD) is a significant, but understudied, consequence of spinal cord injury (SCI). Approximately 11-24% of SCI patients experience MDD, compared to 8% in the general population, yet there are no therapies specific for SCI patients. Previously, we have shown that one-third of spinally injured rats exhibit behavioral, physiological, and immunological correlates of depression. This is concomitant with the human population, and, moreover, indicates that a biological mechanism is responsible for the rise in depression after SCI. As increased inflammation is strongly associated with depression in both animal and human studies, it is likely that the immune activation inherent to SCI fosters future depression. To address this hypothesis, the experiments presented here explored the impact of inflammation on depression in a rat model of SCI. The first experiment evaluated the protective effects of minocycline, an anti-inflammatory drug, on the development of depression. The results indicated that inflammation after injury may not influence depression, but that higher inflammatory profiles before injury predicted depressive outcomes. The next experiment explored the sufficiency of pre-existing inflammation for the development of depression after injury. Pre-treatment with the pro-inflammatory cytokine IL-6 produced a significant elevation in incidence of depression following SCI. Finally, I investigated the hypothesis that pre-existing inflammation may lead to glucocorticoid resistance, dysregulation of the immune response after injury, and subsequent depression. Refuting this hypothesis, I found that subjects with pre-existing inflammation did not have higher corticosterone levels post-injury, although they did have elevated depression-like behaviors. Together, the findings here suggest that pre-existing inflammation predicts susceptibility to depression following a major stressor, such as SCI. These results underscore the importance of a deeper understanding of the relationship between stress and inflammation, and the impact of pre-existing differences on psychiatric health care.
Subject
DepressionInflammation
Spinal Cord Injury
Glucocorticoid receptor
Interleukin-6
Minocycline
Citation
Brakel, Kiralyn (2020). Pre-existing Inflammation Produces Depression Following Spinal Cord Injury. Doctoral dissertation, Texas A&M University. Available electronically from https : / /hdl .handle .net /1969 .1 /192196.