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Viewpoints

Revisiting the Stress Concept: Implications for Affective Disorders

Bruce S. McEwen and Huda Akil
Journal of Neuroscience 2 January 2020, 40 (1) 12-21; DOI: https://doi.org/10.1523/JNEUROSCI.0733-19.2019
Bruce S. McEwen
1The Rockefeller University, New York, New York 10065, and
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Huda Akil
2University of Michigan Medical School, Ann Arbor, Michigan 48109
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Abstract

Over the last 50 years, the concept of stress has evolved significantly, and our understanding of the underlying neurobiology has expanded dramatically. Rather than consider stress biology to be relevant only under unusual and threatening conditions, we conceive of it as an ongoing, adaptive process of assessing the environment, coping with it, and enabling the individual to anticipate and deal with future challenges. Though much remains to be discovered, the fundamental neurocircuitry that underlies these processes has been broadly delineated, key molecular players have been identified, and the impact of this system on neuroplasticity has been well established. More recently, we have come to appreciate the critical interaction between the brain and the rest of the body as it pertains to stress responsiveness. Importantly, this system can become overloaded due to ongoing environmental demands on the individual, be they physical, physiological, or psychosocial. The impact of this overload is deleterious to brain health, and it results in vulnerability to a range of brain disorders, including major depression and cognitive deficits. Thus, stress biology is one of the best understood systems in affective neuroscience and is an ideal target for addressing the pathophysiology of many brain-related diseases. The story we present began with the discovery of glucocorticoid receptors in hippocampus and has extended to other brain regions in both animal models and the human brain with the further discovery of structural and functional adaptive plasticity in response to stressful and other experiences.

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The Journal of Neuroscience: 40 (1)
Journal of Neuroscience
Vol. 40, Issue 1
2 Jan 2020
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Revisiting the Stress Concept: Implications for Affective Disorders
Bruce S. McEwen, Huda Akil
Journal of Neuroscience 2 January 2020, 40 (1) 12-21; DOI: 10.1523/JNEUROSCI.0733-19.2019

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Revisiting the Stress Concept: Implications for Affective Disorders
Bruce S. McEwen, Huda Akil
Journal of Neuroscience 2 January 2020, 40 (1) 12-21; DOI: 10.1523/JNEUROSCI.0733-19.2019
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  • Article
    • Abstract
    • Introduction
    • The major neural and molecular elements of the stress system
    • How brain and body systems continually interact for brain health and disease
    • Experience and the epigenetic life course
    • The central role of glucocorticoids and their receptors
    • Stress and affective disorders: reverse translation to animal models
    • Brain health and the broader social context
    • Future directions: the neurobiology of stress as the basic science of affective disorders
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  • RE: Bruce McEwen passing
    Pat Levitt
    Published on: 03 January 2020
  • In Memory of Bruce McEwen
    Huda Akil
    Published on: 02 January 2020
  • Published on: (3 January 2020)
    Page navigation anchor for RE: Bruce McEwen passing
    RE: Bruce McEwen passing
    • Pat Levitt, Professor - Pediatrics, Children's Hospital Los Angeles and the University of Southern California

    Driving to work early this morning in LA, after receiving the news from Michael Meaney regarding the death of Bruce McEwen, I was numb. My mind wandered, realizing how much we take for granted, in science and medicine, being touched by greatness. Maybe we know at the time, but we don’t take a deep breath and appreciate the profoundness of our colleagues and friends – the impact that they have on our values, the very high bar that they help set for us – and the acknowledgement that we are all in this to make a difference, no matter how small, no matter how large. Bruce was all of that and more to the field of neuroscience and biomedicine, to the Academies that he loved so much, to the National Scientific Council on the Developing Child, whose members he adored and who adored him, and to me personally, for being so supportive of whatever crazy ideas I expressed to him regarding the biological impact of early life stress on children and the enduring effects across their lifespan; no one was more encyclopedic and no one was more caring about children and families who he hoped would benefit from the research in which we engage.

    I will miss him deeply.

    Competing Interests: None declared.
  • Published on: (2 January 2020)
    Page navigation anchor for In Memory of Bruce McEwen
    In Memory of Bruce McEwen
    • Huda Akil, Professor, University of Michigan Medical School

    On January 2, 2020, on the same day that this Viewpoint paper was published, Bruce McEwen passed away. His death marks the end of an era in affective neuroscience. Fifty-two years ago, Bruce brought the brain to the study of stress biology by demonstrating the existence of glucocorticoid binding sites in the hippocampus. This was but the start of a breathtaking sequence of foundational discoveries that Bruce and his colleagues have made over the decades, entirely re-framing our thinking about this most basic of functions- coping with our environment.
    Many of the concepts we currently take for granted arose from his work, including the effects of steroid hormones on neural structure and neuroplasticity, the concept of allostatic load, the differentiation between “good” and “bad” stress, and the impact of general health on stress vulnerability and resilience. Bruce also thought deeply about the importance of social context on stress biology and brain health. His vision ranged from the molecular and mechanistic to the societal and humanistic. This review gives a flavor of that thinking but barely touches on the breadth and depth of his influence.
    Beyond being an intellectual giant, Bruce was a remarkable human. A love of knowledge, a passion for science, a prodigious memory blended miraculously with unassailable integrity, a generous and generative spirit, exemplary mentorship and the capacity for limitless kindness and friendship. I have never met a more civilize...

    Show More

    On January 2, 2020, on the same day that this Viewpoint paper was published, Bruce McEwen passed away. His death marks the end of an era in affective neuroscience. Fifty-two years ago, Bruce brought the brain to the study of stress biology by demonstrating the existence of glucocorticoid binding sites in the hippocampus. This was but the start of a breathtaking sequence of foundational discoveries that Bruce and his colleagues have made over the decades, entirely re-framing our thinking about this most basic of functions- coping with our environment.
    Many of the concepts we currently take for granted arose from his work, including the effects of steroid hormones on neural structure and neuroplasticity, the concept of allostatic load, the differentiation between “good” and “bad” stress, and the impact of general health on stress vulnerability and resilience. Bruce also thought deeply about the importance of social context on stress biology and brain health. His vision ranged from the molecular and mechanistic to the societal and humanistic. This review gives a flavor of that thinking but barely touches on the breadth and depth of his influence.
    Beyond being an intellectual giant, Bruce was a remarkable human. A love of knowledge, a passion for science, a prodigious memory blended miraculously with unassailable integrity, a generous and generative spirit, exemplary mentorship and the capacity for limitless kindness and friendship. I have never met a more civilized man. It has been one of the greatest honors of my life to know him, to collaborate with him, to learn from him, and to be his friend.

    Show Less
    Competing Interests: None declared.

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