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
MUNCK, A., GUYRE, P. M., & HOLBROOK, N. J. (1984) · Endocrine Reviews · doi:10.1210/edrv-5-1-25 · Cited by 3,083
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MRI-based measurement of hippocampal volume in patients with combat- related posttraumatic stress disorder
(1995) · American Journal of Psychiatry · doi:10.1176/ajp.152.7.973 · Cited by 1,610
Hippocampal damage associated with prolonged glucocorticoid exposure in primates
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Effect of Neonatal Handling on Age-Related Impairments Associated with the Hippocampus
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Self-citation
Chronic Psychosocial Stress Causes Apical Dendritic Atrophy of Hippocampal CA3 Pyramidal Neurons in Subordinate Tree Shrews
Magariños, A. M., McEwen, B. S., Flügge, G., & Fuchs, E. (1996) · The Journal of Neuroscience · doi:10.1523/jneurosci.16-10-03534.1996 · Cited by 864
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
Uno, H., Tarara, R., Else, J., Suleman, M., & Sapolsky, R. (1989) · The Journal of Neuroscience · doi:10.1523/jneurosci.09-05-01705.1989 · Cited by 728
Hypothalamic-pituitary-adrenal activity in aged, cognitively impaired and cognitively unimpaired rats
Issa, A. M., Rowe, W. B., Gauthier, S. G., & Meaney, M. (1990) · Journal of Neuroscience · doi:10.1523/jneurosci.10-10-03247.1990 · Cited by 438
Neurological status of Vietnam veterans with chronic posttraumatic stress disorder
Gurvits, T. V., Lasko, N. B., Schachter, S. C., Kuhne, A., Orr, S. P., & Pitman, R. K. (1993) · Journal of Neuropsychiatry · doi:10.1176/jnp.5.2.183 · Cited by 109

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Background
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Background
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Background
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Background
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Background
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“[119–121].”
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Background
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“…models of psychological trauma, exposure to repeated stress causes dendritic atrophy of pyramidal neurons in the hippocampus (Adamec et al, 2012; McEwen and Magarinos, 1997; McEwen, 2007; Popoli et al, 2012; Sapolsky, 1996), and this is mediated partly by glutamate excitotoxicity (McEwen, 2007).”
Background
Lower Cortisol and Higher ACTH Levels in Individuals with Autism
Ćurin, J. M., Terzić, J., Petković, Z. B., Zekan, L., Marinovic‐Terzić, I., & Šušnjara, I. M. (2003) · Journal of Autism and Developmental Disorders · doi:10.1023/a:1025019030121 · Cited by 92
Frequent Blood–Brain Barrier Disruption in the Human Cerebral Cortex
Tomkins‐Netzer, O., Kaufer, D., Korn, A., Shelef, I., Golan, H., Reichenthal, E., Soreq, H., & Friedman, A. (2001) · Cellular and Molecular Neurobiology · doi:10.1023/a:1015147920283 · Cited by 92
“While our study points to stress as an important cause underlying prolonged BBB disruption in humans, future research will elucidate the association between such disruption and stress-related excitotoxic brain damage (Haley et al., 2000; Sapolsky, 1996).”
BackgroundResult
Parents’ education as a determinant of educational childcare time
Giménez-Nadal, J. I., & Molina, J. A. (2012) · Journal of Population Economics · doi:10.1007/s00148-012-0443-7 · Cited by 91
“1Previous research has shown a negative relationship between stress and brain development (e.g., Sapolsky 1996; Bremmer and Vermetten 2001; Teicher et al. 2002) and between physical/emotional neglect and children’s neurodevelopment and health (e.g., Anda et al. 2006; Dube et al. 2003; Edwards et…”
Background
Anticholinesterases induce multigenic transcriptional feedback response suppressing cholinergic neurotransmission
Kaufer, D., Friedman, A., Seidman, S., & Soreq, H. (1999) · Chemico-Biological Interactions · doi:10.1016/s0009-2797(99)00046-0 · Cited by 90
“Altogether, anti-ChE exposure may be perceived as an especially acute stress event, explaining the similar symptoms of anti-ChE exposure and post-traumatic stress disorder [35,36].”
Background
Clinical Perspectives on Neurobiological Effects of Psychological Trauma
Weber, D. A., & Reynolds, C. R. (2004) · Neuropsychology Review · doi:10.1023/b:nerv.0000028082.13778.14 · Cited by 89
“Other effects include a reduction in lymphocytes in the blood leading to a weaker immune system (Sapolsky, 1996) and neuronal death (Munck et al., 1984).”
Perinatal Brain Iron Deficiency Increases the Vulnerability of Rat Hippocampus to Hypoxic Ischemic Insult
Rao, R., de Ungria, M., Sullivan, D. J., Wu, P. W., Wobken, J. D., Nelson, C. A., & Georgieff, M. (1999) · Journal of Nutrition · doi:10.1093/jn/129.1.199 · Cited by 88
Knock-out and Knock-in Mice to Investigate the Role of Nicotinic Receptors in the Central Nervous System
Champtiaux, N., & Changeux, J. (2002) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1568007023339247 · Cited by 88
The Importance of Glucocorticoids in AlcoholDependence and Neurotoxicity
Rose, A. K., Shaw, S., Prendergast, M., & Little, H. J. (2010) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2010.01298.x · Cited by 92
“In view of the established neurotoxic effects of glucocorticoids (McEwen, 2000; Newcomer et al., 1999; Sapolsky, 1986; 1993; 1996a,b; 2000), it is likely that they play a major role in the cognitive deficits, as discussed below.”
Background
Magical Flight and Monstrous Stress: Technologies of Absorption and Mental Wellness in Azeroth
Snodgrass, J. G., Lacy, M. G., Dengah, H. J. F., Fagan, J. M., & Most, D. E. (2010) · Culture Medicine and Psychiatry · doi:10.1007/s11013-010-9197-4 · Cited by 104
Glucocorticoid Response to Forced Exercise in Laboratory House Mice (Mus domesticus)
Coleman, M. A., Garland, T., Marler, C. A., Newton, S. S., Swallow, J. G., & Carter, P. A. (1998) · Physiology & Behavior · doi:10.1016/s0031-9384(97)00441-1 · Cited by 89
Idiopathic Environmental Intolerance
Staudenmayer, H., Binkley, K. E., Leznoff, A., & Phillips, S. (2003) · Toxicological Reviews · doi:10.2165/00139709-200322040-00006 · Cited by 89
Atrophy of the hippocampus in posttraumatic stress disorder: How and when?
Sapolsky, R. M. (2001) · Hippocampus · doi:10.1002/hipo.1026 · Cited by 88
Stress response in school-age children who have been growth retarded since early childhood
Fernald, L. C. H., & Grantham‐McGregor, S. (1998) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/68.3.691 · Cited by 84
Long-Lasting Effects of Maternal Separation on an Animal Model of Post-Traumatic Stress Disorder: Effects on Memory and Hippocampal Oxidative Stress
Diehl, L. A., Alvares, L. D. O., Noschang, C. G., Engelke, D. S., Andreazza, A. C., Gonçalves, C. A., Quillfeldt, J. A., & Dalmaz, C. (2011) · Neurochemical Research · doi:10.1007/s11064-011-0660-6 · Cited by 85
“stress [50–55].”
The relationship between early life stress and microstructural integrity of the corpus callosum in a non-clinical population
Paul, R., Henry, L., Grieve, S., Guilmette, T., Niaura, R., Bryant, R., Bruce, S., Williams, L., Richard, C. C., Cohen, R., et al. (2008) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s1549 · Cited by 97
Childhood Adversity and the Endogenous Versus Nonendogenous Distinction in Women With Major Depression
Harkness, K. L., & Monroe, S. M. (2002) · American Journal of Psychiatry · doi:10.1176/appi.ajp.159.3.387 · Cited by 86
Structural Changes in the Brain in Depression and Relationship to Symptom Recurrence
Bremner, J. D. (2002) · CNS Spectrums · doi:10.1017/s1092852900017442 · Cited by 89
Chronic voluntary wheel running facilitates corticosterone response habituation to repeated audiogenic stress exposure in male rats
Sasse, S. K., Greenwood, B. N., Masini, C. V., Nyhuis, T. J., Fleshner, M., Day, H. E. W., & Campeau, S. (2008) · Stress · doi:10.1080/10253890801887453 · Cited by 85
A volumetric study of amygdala in cancer survivors with intrusive recollections
Matsuoka, Y., Yamawaki, S., Inagaki, M., Akechi, T., & Uchitomi, Y. (2003) · Biological Psychiatry · doi:10.1016/s0006-3223(02)01907-8 · Cited by 86
“Four recent volumetric studies have shown that chronic PTSD is associated with smaller hippocampal volume (Bremner et al 1995; Bremner et al 1997; Gurvits et al 1996; Stein et al 1997), and animal research has indicated that chronic stress can damage the hippocampus (McEwen and Magarinos 1997; Sapolsky 1996).”
Background
Effects of glucocorticoids on declarative memory function in major depression
Bremner, J. D., Vythilingam, M., Vermetten, E. H. G. J. M., Anderson, G. M., Newcomer, J. W., & Charney, D. S. (2004) · Biological Psychiatry · doi:10.1016/j.biopsych.2003.10.020 · Cited by 85
Implicit but Not Explicit Affectivity Predicts Circadian and Reactive Cortisol: Using the Implicit Positive and Negative Affect Test
Quirin, M., Kazén, M., Rohrmann, S., & Kühl, J. (2009) · Journal of Personality · doi:10.1111/j.1467-6494.2008.00552.x · Cited by 97
“(Sapolsky, 1996).”
The Speedometer of Life
Almeida, D. M., Piazza, J. R., Stawski, R. S., & Klein, L. C. (2010) · Elsevier eBooks · doi:10.1016/b978-0-12-380882-0.00012-7 · Cited by 87
Volume measurement with magnetic resonance imaging of hippocampus-amygdala formation in patients with anorexia nervosa
Giordano, G. D., Renzetti, P., Parodi, R. C., Foppiani, L., Zandrino, F., Giordano, G. D., & Sardanelli, F. (2001) · Journal of Endocrinological Investigation · doi:10.1007/bf03343884 · Cited by 83
Psycho-biological factors associated with underground spaces: What can the new era of cognitive neuroscience offer to their study?
Roberts, A. C., Christopoulos, G. I., Car, J., Soh, C. K., & Lü, M. (2016) · Tunnelling and Underground Space Technology · doi:10.1016/j.tust.2015.12.016 · Cited by 87
Increased neurogenesis and brain‐derived neurotrophic factor in neurokinin‐1 receptor gene knockout mice
Morcuende, S., Gadd, C. A., Peters, M., Moss, A., Harris, E., Sheasby, A., Fisher, A. S., Felipe, C. D., Mantyh, P. W., Rupniak, N. M. J., et al. (2003) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2003.02911.x · Cited by 83
Does Caregiving Stress Affect Cognitive Function in Older Women?
Lee, S., Kawachi, I. I., & Grodstein, F. (2003) · The Journal of Nervous and Mental Disease · doi:10.1097/01.nmd.0000106000.02232.30 · Cited by 82
“Studies with MRI have shown that stress-related disorders such as recurrent depressive illness and posttraumatic stress disorder are all associated with atrophy of the hippocampus (McEwen and Magarinos, 1997; Sapolsky, 1996).”
Background
Absence of hippocampal volume differences in survivors of the Nazi Holocaust with and without posttraumatic stress disorder
Golier, J. A., Yehuda, R., De Santi, S., Segal, S., Dolan, S., & de Leon, M. J. (2005) · Psychiatry Research: Neuroimaging · doi:10.1016/j.pscychresns.2005.02.007 · Cited by 105
“The possibility that stress induces hippocampal atrophy in the human brain is captivating since it could explain the link between stress exposure and the subsequent development of neuropsychiatric disorders and cognitive impairment (Sapolsky, 1996); however, the links between stress, hypothalamic–pituitary– adrenal ax…”
Background
Two different putative genetic animal models of childhood depression—A review
Malkesman, O., & Weller, A. (2009) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2009.03.003 · Cited by 81
“From the results it seems that prepubertal FSL and WKY rats are both genetic animal models of childhood depression, exhibiting lower levels of BDNF in the hippocampus (at least in one region) as has been found in several human studies (Chen et al., 2001; Sapolsky, 1996; Sheline et al., 1996; Hashimoto et al., 2004) an…”
Indicators of Job Strain at Midlife and Cognitive Functioning in Advanced Old Age
Andel, R., Crowe, M. G., Kåreholt, I., Wastesson, J. W., & Parker, M. G. (2011) · The Journals of Gerontology Series B · doi:10.1093/geronb/gbq105 · Cited by 86
“287 Received May 21, 2010; Accepted December 16, 2010 Decision Editor: Robert West, PhD CHRONIC stress may lead to neural degeneration (Radley & Morrison, 2005; Sapolsky, 1996) and contribute to cognitive aging (Wilson et al., 2003).”
Background
Evolutionary Approaches to Psychopathology and Cognitive Therapy
Gilbert, P. (2002) · Journal of Cognitive Psychotherapy · doi:10.1891/jcop.16.3.263.52515 · Cited by 78
“There is now good evidence that a stress hormone called cortisol is useful for short-term defensive behavior but can actually damage the immune system and the brain if it is elevated for too long (Sapolsky, 1996, 2000).”
Background
Testosterone in utero and at birth dictates how stressful experience will affect learning in adulthood
Shors, T. J., & Miesegaes, G. R. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.202199999 · Cited by 78
Postnatal Touch Stimulation Acutely Alters Corticosterone Levels and Glucocorticoid Receptor Gene Expression in the Neonatal Rat
Jutapakdeegul, N., Casalotti, S. O., Govitrapong, P., & Kotchabhakdi, N. (2003) · Developmental Neuroscience · doi:10.1159/000071465 · Cited by 79
Glucocorticoids: Protectors of the Brain during Innate Immune Responses
Glezer, I., & Rivest, S. (2004) · The Neuroscientist · doi:10.1177/1073858404263494 · Cited by 79
“One known outcome of high GC levels in stressed individuals is the exacerbation of neuronal death during aging (Sapolsky 1996).”
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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Why Stress Is Bad for Your Brain

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