Impact of inflammation on neurotransmitter changes in major depression: An insight into the action of antidepressants

This review summarises the evidence that chronic low grade inflammation plays an important role in the pathology of depression. Evidence is provided that pro-inflammatory cytokines, together with dysfunctional endocrine and neurotransmitter systems, provide a network of changes that underlie depression and may ultimately contribute to the neurodegenerative changes that characterise depression in the elderly. Antidepressants attenuate the inflammatory changes and hypercortisolaemia by reducing the release of the pro-inflammatory cytokines from activated microglia, and by sensitizing the glucocorticoids receptors in the HPA axis. These effects correlate with an improvement in monoamine neurotransmitter function. The possible mechanisms whereby this cascade of changes occurs are outlined. In conclusion, the mechanisms whereby antidepressants act should now consider the involvement of the immune and endocrine systems in addition to the central neurotransmitters. This may open up possibilities for a new generation of antidepressants in the future.