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The molecular and cellular mechanisms of depression: a focus on reward circuitry

Molecular Psychiatry volume 24, pages 1798–1815 (2019)Cite this article

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Abstract

Depression is a complex disorder that takes an enormous toll on individual health. As affected individuals display a wide variation in their clinical symptoms, the precise neural mechanisms underlying the development of depression remain elusive. Although it is impossible to phenocopy every symptom of human depression in rodents, the preclinical field has had great success in modeling some of the core affective and neurovegetative depressive symptoms, including social withdrawal, anhedonia, and weight loss. Adaptations in select cell populations may underlie these individual depressive symptoms and new tools have expanded our ability to monitor and manipulate specific cell types. This review outlines some of the most recent preclinical discoveries on the molecular and neurophysiological mechanisms in reward circuitry that underlie the expression of behavioral constructs relevant to depressive symptoms.

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Acknowledgements

We acknowledge Drs CA Calarco, JF Cheer, and DP Covey for instructive comments on this manuscript. MKL is supported by NIH R01DA038613, R01MH106500, and R01DA047843. MEF is supported by NIH F32MH116574.

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    Megan E. Fox & Mary Kay Lobo

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Fox, M.E., Lobo, M.K. The molecular and cellular mechanisms of depression: a focus on reward circuitry. Mol Psychiatry 24, 1798–1815 (2019). https://doi.org/10.1038/s41380-019-0415-3

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