Depression is a leading cause of disability. To date, researchers are still finding ways to better understand and treat depression. One hypothesis suggests that a disordered inflammatory system contributes to depression. This thesis will delve into whether specific inflammatory insults are associated with depression and whether depression treatment is immunomodulatory in nature.
The first chapter examined the relationship between depression and episodes of infection and injury, and the relationship between depression and the use of anti-inflammatory agents, using biodata from a large population database and hospital-linked records. The second chapter examined whether the treatment of depression with ketamine was associated with immunomodulatory changes and whether α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors attenuated ketamine’s antidepressant effect.
Hospitalisation for infection and injury were associated with higher odds of recurrent depression. Fish oil supplementation was associated with lower odds of recurrent depression, but non-steroidal anti-inflammatory drug use was associated with higher odds of recurrent depression. In rodents, ketamine treatment altered the morphology of microglia and ribonucleic acid expressions of microglial activity. AMPA receptors were found to be crucial to ketamine’s antidepressant effect.
Key findings support the immunoinflammatory hypothesis of depression. Future research could focus on novel treatment approaches that target the inflammation signalling pathway.