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Neuroimmune mechanisms of depression

Abstract

Current diagnosis of depression is based solely on behavioral symptomatology. The available US Food and Drug Administration–approved treatments for depression have come from serendipitous discovery and are ineffective in nearly 30–50% of patients, which is thought to reflect a lack of specificity in targeting underlying pathophysiological mechanisms. Recent evidence has identified depression-related disruptions in a neuroimmune axis that interfaces the immune system and CNS to control behavior. This Review examines the evidence in patients and in animal models of depression that demonstrates how the peripheral immune system acts on the brain to alter an individual's response to stress, ultimately contributing to their vulnerability to mood disorders.

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Figure 1: Circuits of the neuroimmune axis.
Figure 2: Inflammation and the brain.

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Acknowledgements

This research was supported by US National Institute of Mental Health grants RO1 MH090264 (to S.J.R.) and RO1 MH104559 (to S.J.R. and M.M.), the Johnson & Johnson International Mental Health Research Organization Rising Star Award (to S.J.R.), an Irma T. Hirschl/Monique Weill-Caulier Trust Research Award (to S.J.R.), a Brain and Behavior Research Foundation Young Investigator Award (G.E.H.) and a Swiss National Science Foundation Early Postdoc Mobility fellowship (to V.K.).

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Correspondence to Scott J Russo.

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Our previous work on IL-6 and depression was supported in part by a research grant from Janssen Pharmaceuticals.

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Hodes, G., Kana, V., Menard, C. et al. Neuroimmune mechanisms of depression. Nat Neurosci 18, 1386–1393 (2015). https://doi.org/10.1038/nn.4113

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