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Stress and the brain: individual variability and the inverted-U

Nature Neuroscience volume 18, pages 1344–1346 (2015)Cite this article

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It is a truism that the brain influences the body and that peripheral physiology influences the brain. Never is this clearer than during stress, where the subtlest emotions or the most abstract thoughts can initiate stress responses, with consequences throughout the body, and the endocrine transducers of stress alter cognition, affect and behavior. For a fervent materialist, few things in life bring more pleasure than contemplating the neurobiology of stress.

The early years of the field of stress biology were dominated by the first half of the neuroendocrine loop, namely the ability of the brain to initiate the body's stress response. Stress physiology was born early in the last century, in the Paleolithic era of Walter Cannon implicating the sympathetic nervous system in the 'fight or flight' response, and in Hans Selye identifying glucocorticoids as the other main mediator of the stress response. These foundational findings took the field in many directions. One was the revolutionary work of Geoffrey Harris, Roger Guillemin and Andrew Schally showing that the brain is an endocrine gland, secreting releasing and inhibiting hormones into the hypothalamic-pituitary portal system; in many ways, the decades-long arc of that revolution was bracketed by stress research, in that corticotropin-releasing hormone was the first of the principal hypothalamic hormones whose existence was inferred physiologically and the last to be isolated and biochemically characterized.

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Figure 1: Conceptualization of the inverted-U in the context of the benefits and costs of stress.

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  1. Robert M. Sapolsky is in the Departments of Biological Sciences, Neurology and Neurosurgery, Stanford University, Stanford, California, USA.,

    Robert M Sapolsky

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  1. Robert M Sapolsky
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Correspondence to Robert M Sapolsky.

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Sapolsky, R. Stress and the brain: individual variability and the inverted-U. Nat Neurosci 18, 1344–1346 (2015). https://doi.org/10.1038/nn.4109

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