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DEPRESSION

An opening for humor in melancholy

Nature Neuroscience volume 20, pages 1657–1658 (2017)Cite this article

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A leaky blood–brain barrier may contribute to neuropsychiatric disease. Chronic stress is shown to alter blood–brain barrier permeability, allowing an inflammatory response to penetrate the brain. The deficit is mostly around the nucleus accumbens, an area central to motivation. The affected animals exhibit features of depression.

In attempts to move beyond a strictly spiritual conceptualization of mental faculties, Hippocrates of Kos introduced the notion of circulating humors, which would act in concert to determine aspects of personality. Diseases of the mind would then reflect an imbalance between different humors. An excess of black bile, for example, was said to result in depression. The Greek ideas prevailed for over 2,000 years, until cellular hypotheses for pathogenesis of mental illness began to take center stage. More recently, circuit biology has dominated our attempts to understand depression. In this issue of Nature Neuroscience, Menard et al.1 evoke the ancient notions of bodily humors infiltrating the brain to contribute to depression in a study describing how the blood–brain barrier becomes compromised following exposure of mice to chronic stress. Their result—that a change in blood–brain barrier permeability occurs selectively in a brain circuit important for some aspects of depression—appears to integrate aspects of twenty-first-century circuit neuroscience with humorism from the fifth century bce.

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Fig. 1: Stress acts on Cldn5 to increase blood–brain barrier permeability and depression-related behaviors.

Debbie Maizels/Springer Nature.

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Authors and Affiliations

  1. Department of Psychiatry, Division of Integrative Neuroscience, Columbia University and the New York State Psychiatric Institute, New York, NY, USA

    E. David Leonardo & Alex Dranovsky

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  1. E. David Leonardo
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  2. Alex Dranovsky
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Correspondence to E. David Leonardo or Alex Dranovsky.

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The authors declare no competing financial interests.

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Leonardo, E.D., Dranovsky, A. An opening for humor in melancholy. Nat Neurosci 20, 1657–1658 (2017). https://doi.org/10.1038/s41593-017-0015-y

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