![]() ![]() ![]() The pivotal role of psychosocial stress in the modern world are then examined, highlighting inflammasome activation and immune cell trafficking as novel mechanisms by which stress-induced inflammatory signals can be transmitted to the brain. We first consider the origins of this notion from an evolutionary perspective, examining the advantages of depressive behaviours in the context of host immune responses to pathogens, predators and conspecifics in ancestral environments. In this Review, we outline emerging data that point to the immune system - and, in particular, the inflammatory response - as a potentially important contributor to the pathophysiology of depression. Accordingly, there is a pressing need for new conceptual frameworks for understanding the development of depression to develop better treatments. Although effective treatments are available, approximately one third of all patients with depression fail to respond to conventional antidepressant therapies 2, further contributing to the global burden of the disease. Depression is a devastating disorder, afflicting up to 10% of the adult population in the United States and representing one of the leading causes of disability worldwide 1.
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