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Effects of stress throughout the lifespan on the brain, behaviour and cognition

Key Points

  • During stress there is activation of the hypothalamic-pituitary-adrenal (HPA) axis, culminating in the production of glucocorticoids. Glucocorticoids can easily access the brain, where they bind to receptors and influence the brain and behaviour.

  • Different outcomes result from exposure to stress at different periods of an individual's life.

  • Exposure to stress in the prenatal period leads to programming effects, as evidenced by increased reactivity to stress later in life and reduced hippocampal volume in adulthood.

  • Exposure to prenatal stress has been associated with learning impairments, enhanced sensitivity to drugs of abuse, and increases in anxiety and depression-related behaviours in adulthood.

  • Maternal separation is a potent stressor in the postnatal period, and it leads to increased secretion of glucocorticoids that can extend into adulthood. By contrast, exposure to severe abuse during infancy is associated with lower levels of glucocorticoids in both primates and humans.

  • Stress during adolescence has more important effects on the HPA axis than a similar stress exposure during adulthood. Moreover, the effects of stress during adolescence can incubate until adulthood, at which time they will become apparent.

  • The effects of stress exposure on the brain and behaviour in adulthood are similar to those that are observed in childhood and adolescence. However, unlike these latter effects, the former effects are reversible; that is, they usually disappear after cessation of the stressor.

  • In adulthood, chronic exposure to high levels of glucocorticoids has been associated with depressive disorder. By contrast, patients with post-traumatic stress disorder present lower levels of glucocorticoids.

  • The effects of stress during aging are associated with both memory impairments and reduced hippocampal volumes.

  • The life cycle model of stress explains why different disorders emerge in populations exposed to stress at different stages of their lives.

Abstract

Chronic exposure to stress hormones, whether it occurs during the prenatal period, infancy, childhood, adolescence, adulthood or aging, has an impact on brain structures involved in cognition and mental health. However, the specific effects on the brain, behaviour and cognition emerge as a function of the timing and the duration of the exposure, and some also depend on the interaction between gene effects and previous exposure to environmental adversity. Advances in animal and human studies have made it possible to synthesize these findings, and in this Review a model is developed to explain why different disorders emerge in individuals exposed to stress at different times in their lives.

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Figure 1: The stress system.
Figure 2: The life cycle model of stress.

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Acknowledgements

Sonia Lupien holds a Research Chair on Gender and Mental Health by the Canadian Institutes of Health Research.

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Glossary

Programming

When an environmental factor that acts during a sensitive developmental period affects the structure and function of tissues, leading to effects that persist throughout life.

Mineralocorticoid receptor

A receptor that is activated by mineralocorticoids, such as aldosterone and deoxycorticosterone, as well as glucocorticoids, such as cortisol and cortisone. It also responds to progestins.

Glucocorticoid receptor

A receptor that is activated by cortisol, corticosterone and other glucocorticoids and is expressed in almost every cell in the body. It regulates genes controlling development, metabolism and the immune response.

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Lupien, S., McEwen, B., Gunnar, M. et al. Effects of stress throughout the lifespan on the brain, behaviour and cognition. Nat Rev Neurosci 10, 434–445 (2009). https://doi.org/10.1038/nrn2639

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