The role of inflammation in depression: from evolutionary imperative to modern treatment target

In this Review, the authors relate the growing appreciation of the neuroimmune circuits that link inflammatory and immune responses with depressive behaviours. They explore the evolutionary basis of this neuroimmune link and discuss how a better understanding of these pathways may lead to new therapies that treat depression by targeting the immune system. Crosstalk between inflammatory pathways and neurocircuits in the brain can lead to behavioural responses, such as avoidance and alarm, that are likely to have provided early humans with an evolutionary advantage in their interactions with pathogens and predators. However, in modern times, such interactions between inflammation and the brain appear to drive the development of depression and may contribute to non-responsiveness to current antidepressant therapies. Recent data have elucidated the mechanisms by which the innate and adaptive immune systems interact with neurotransmitters and neurocircuits to influence the risk for depression. Here, we detail our current understanding of these pathways and discuss the therapeutic potential of targeting the immune system to treat depression.