Cited by 1,306Stress Responses and CortisolMemory and Neural MechanismsNeuroscience and Neuropharmacology Research

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Why Stress Is Bad for Your Brain

Sapolsky, Robert M.·1996·Science

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Abstract

Several recent studies of humans correlate stress with atrophy of the hippocampus, an area of the brain required for memory and cognition. In his Perspective, Sapolsky argues that the underlying causal agent may be glucocorticoids secreted in abnormally high amounts under stressful conditions.

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Crossref · 10.1126/science.273.5276.749

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Physiological functions of glucocorticoids in stress and their relation to pharmacological actions
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Self-citation
Chronic Psychosocial Stress Causes Apical Dendritic Atrophy of Hippocampal CA3 Pyramidal Neurons in Subordinate Tree Shrews
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Hippocampal formation volume, memory dysfunction, and cortisol levels in patients with Cushing's syndrome
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Hippocampal damage associated with prolonged and fatal stress in primates
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“Second, stress/distress increases the activity of the hypothalamic-pituitary-adrenal axis and thus the levels of glucocorticoid hormones (22), which may cause structural and functional damage to the brain, especially in the medial temporal lobe (23,24).”
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Perspectives on Fatigue from the Study of Chronic Fatigue Syndrome and Related Conditions
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“Recent research suggests that although this system in humans has been highly adaptive throughout history, the stress response may be inappropriately triggered by a wide assortment of everyday occurrences that do not pose a real threat to survival, thus initiating the cascade of physiologic responses more frequently th…”
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Gender differences in response of hippocampus to chronic glucocorticoid stress: Role of glutamate receptors
Liu, H. H., Payne, H. R., Wang, B., & Brady, S. T. (2006) · Journal of Neuroscience Research · doi:10.1002/jnr.20782 · Cited by 42
Aging and Alzheimer’s Disease
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Glucocorticoids in Alzheimer??s Disease
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Depression: A Biopsychosocial, Integrative, and Evolutionary Approach
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Hormones and Hierarchies
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Cognitive Impairments in Occupational Burnout – Error Processing and Its Indices of Reactive and Proactive Control
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“Based on the assumption that burnout is a stress-related syndrome (Maslach et al., 2001), the research on the consequences of long-term stress on the brain and cognition is particularly interesting (Sapolsky, 1996; Buwalda et al., 2005; Marin et al., 2011).”
Background
Amygdala functional connectivity is reduced after the cold pressor task
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The prisoners of despair: right hemisphere deficiency and suicide
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“In particular, emotional trauma and other stressful events elevate levels of corticosteroids, which destroy the hippocampal cells [189,190,191] that are particularly sensitive to this substance [74].”
Background
Alcohol Withdrawal Syndrome
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HIV-1 Infection and its Impact on the HPA Axis, Cytokines, and Cognition
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“Moreover, glucocorticoids, the end product of the HPA axis, are considered to cause atrophy of the hippocampus (Sapolsky, 1996) and may exacerbate the destructive effects of other factors in the brain of HIV infected individuals.”
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The Moderating Effect of the APOE ɛ4 Allele on the Relationship Between Hippocampal Volume and Cognitive Decline in Older Depressed Patients
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“Sapolsky and colleagues (14) have proposed a glucocorticoid cascade hypothesis in which depression or chronic stressors lead to chronic, prolonged activation of the HypothalamicPituitary-Adrenal axis (HPA axis).”
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Chronic stress, cortical plasticity and neuroecology
Reser, J. E. (2016) · Behavioural Processes · doi:10.1016/j.beproc.2016.06.010 · Cited by 43
Stress, childhood trauma, and cognitive functions in functional neurologic disorders
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Effects of social adversity and HIV on subcortical shape and neurocognitive function
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“Disruption of the HPA-axis has been associated with loss of neuronal connections and smaller hippocampal volume (Rao et al. 2010; Sapolsky 1996;Woon and Hedges 2008) and altered amygdala connectivity (Thomason et al. 2015).”
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Mental health status and its predictors among call center employees: A cross‐sectional study
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Assessment of astrocytes as a mediator of memory and learning in rodents
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“…cognitive processes and memory (Oitzl and de Kloet, 1992; Sandi and Rose, 1994, 1997; Roozendaal et al., 1996; Sandi, 1997), chronic stress is generally detri- mental to the memory process (Sapolsky et al., 1985; Sapolsky, 1996; Stranahan et al., 2008; Karatsoreos et al., 2010; Yun et al., 2010).”
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Prenatal Cocaine Exposure and Infant Cortisol Reactivity
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Treatment for traumatic memories
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“Importantly, excessive cortisol release following an aversive or stressful experience can cause hippocampal neurons to atrophy (McEwen, 1995; Sapolsky, 1996; Yehuda & Sapolsky, 1997) and may impair subsequent hippocampal functioning related to learning and memory (Jacobs & Nadel, 1985).”
Background
The Psychobiology of Posttraumatic Stress Disorder: An Overview
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Electroconvulsive stimulations prevent stress-induced morphological changes in the hippocampus
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Variations in response to trauma and hippocampal subfield changes
Postel, C., Mary, A., Dayan, J., Fraisse, F., Vallée, T., Guillery‐Girard, B., Viader, F., Sayette, V. D. L., Peschanski, D., Eustache, F., et al. (2021) · Neurobiology of Stress · doi:10.1016/j.ynstr.2021.100346 · Cited by 44
“…following the trauma, owing to either prolonged activation of the hypothalamic-pituitary-adrenal axis and release of glucocorticoid stress hormones (Sapolsky, 1996; Steudte-Schmiedgen et al., 2016) or hypersensitivity of glucocorticoid receptors (Szeszko et al., 2018), may cause different types of…”
BackgroundInfluential
Relationship between stress and pain in work‐related upper extremity disorders: The hidden role of chronic multisymptom illnesses*
Clauw, D. J., & Williams, D. A. (2002) · American Journal of Industrial Medicine · doi:10.1002/ajim.10068 · Cited by 40
Maternal responsiveness moderates the relationship between allostatic load and working memory
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“Consistent with this theoretical perspective, individuals who are thought to suffer from prolonged stress exposure, such as those suffering from chronic depression or posttraumatic stress syndrome, have working memory deficits as well as morphological changes in the hippocampus (McEwen et al., 1997; Sapolsky, 1996).”
Background
Applying animal learning theory: training captive animals to comply with veterinary and husbandry procedures
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Larger dentate gyrus volume as predisposing resilience factor for the development of trauma-related symptoms
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Biomedical models of fibromyalgia
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“Studies in rodents have demonstrated that exposure to endotoxin, trauma, or separation in the neonatal period all lead to permanent changes in the subsequent biological response to stress, extending throughout the life of the animal [45,46].”
Background

Authors: Sapolsky, R. M.
Affiliations: Stanford University (US)
Corresponding author: Sapolsky, Robert M.
ORCID: Sapolsky, Robert M.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 1996-08-09
Volume: 273
Issue: 5276
Pages: 749-750
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.273.5276.749
OpenAlex: W1994048221
Cited by: 1,306
References: 12
Citations by year: 2026: 10 · 2025: 13 · 2024: 12 · 2023: 17 · 2022: 27 · 2021: 36 · 2020: 37 · 2019: 24 · 2018: 27 · 2017: 32 · 2016: 35 · 2015: 45 · 2014: 49 · 2013: 43 · 2012: 51
FWCI: 24.94
Type: journal article
Language: en
Open access: closed
Locations: Science (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: stress, hippocampal atrophy, glucocorticoids, memory, cognition, neurodegeneration, stress hormones
MeSH terms: Animals, Atrophy, Brain, Cushing Syndrome, Depressive Disorder, Female, Glucocorticoids, Hippocampus, Humans, Magnetic Resonance Imaging, Male, Stress, Physiological, Stress Disorders, Post-Traumatic, Causality

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