Tumor necrosis factor receptor 2: a potential target for antidepressant drug development

A large body of work implicates cytokines and their related pathways in the pathophysiologies of mood disorders. Much of the data on the role of cytokines in major depression and bipolar disorder suggest that pathways regulated by tumor necrosis factor (TNF)-α make a significant contribution to their pathophysiologies. In the present review, we contrast the well-established role of TNF-related pathways acting to mediate classic pro-inflammatory cytokine activity with growing evidence that such pathways have more diverse functions in the human central nervous system. Here, it will be argued that changes in levels of the TNF receptor type 2 in mood disorders would be consistent with a neuroprotective role for the receptor against the pathophysiologies of mood disorders. This hypothesis is of significance when considering how interventions that act to modulate TNF-regulated pathways can be used to treat the symptoms of mood disorders.