This review summarizes evidence that chronic low grade inflammation plays an important role in the pathology of depression. Pro-inflammatory cytokines, together with dysfunctional endocrine and neurotransmitter systems, appear to provide a network of changes that underlie depression and may ultimately contribute to the neurodegenerative changes characterizing 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 glucocorticoid receptors in the HPA axis. These effects correlate with an improvement in monoamine neurotransmitter function. Possible mechanisms whereby this cascade of changes occurs are outlined. In conclusion, Dr. Leonard suggests that 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.
Leonard BE: Impact of inflammation on neurotransmitter changes in major depression: An insight into the action of antidepressants. Prog. Neuropsychopharmacol. Biol. Psychiatry 48: 261-267 (2014).