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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Self-citation
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BREMNER J, IN PRESS BIOL PSYCHI .
GURVITS T, IN PRESS BIOL PSYCHI .
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Zelazo, P. D., & Lyons, K. E. (2012) · Child Development Perspectives · doi:10.1111/j.1750-8606.2012.00241.x · Cited by 446
“…attitude that may directly attenuate influences that interfere with reflection (such as cortisol/stress; e.g., Pechtel & Pizzagalli, 2010; Sapolsky, 1996) and amplify influences that promote it (such as dopamine/approach-oriented emotions such as Child Development Perspectives, Volume 0,…”
Background
Magnetic resonance imaging (MRI) measurement of hippocampal volume in posttraumatic stress disorder: a meta-analysis
Kitayama, N., Vaccarino, V., Kutner, M., Weiss, P., & Bremner, J. D. (2005) · Journal of Affective Disorders · doi:10.1016/j.jad.2005.05.014 · Cited by 423
“Studies in animals suggest that stress results in structural changes in the hippocampus (McEwen et al., 1992; Sapolsky, 1996).”
Background
Executive function and the promotion of social–emotional competence
Riggs, N. R., Jahromi, L. B., Razza, R. A., Dilworth‐Bart, J. E., & Mueller, U. (2006) · Journal of Applied Developmental Psychology · doi:10.1016/j.appdev.2006.04.002 · Cited by 486
“…in the structure and function of the brain (Beers & De Bellis, 2002; Cicchetti & Tucker, 1994; Dawson et al., 2001; De Bellis, Keshavan, Spencer, & Hall, 2000; Fishbein, 2001; Ito, Teicher, Glod, & Ackerman, 1998; McEwen, 1997; Sapolsky, 1996; Stein, Koverola, Hanna, Torchia, & McCarty, 1997).”
Is depression a risk factor for dementia or cognitive decline?
Jorm, A. F. (2000) · Gerontology · doi:10.1159/000022163 · Cited by 416
Early life influences on life-long patterns of behavior and health
McEwen, B. S. (2003) · Mental Retardation and Developmental Disabilities Research Reviews · doi:10.1002/mrdd.10074 · Cited by 418
Allostasis and Allostatic Load
McEwen, B. S., & Wingfield, J. C. (2007) · Elsevier eBooks · doi:10.1016/b978-012373947-6.00025-8 · Cited by 418
MR-based in vivo hippocampal volumetrics: 2. Findings in neuropsychiatric disorders
Geuze, E., Vermetten, E., & Bremner, J. D. (2005) · Molecular Psychiatry · doi:10.1038/sj.mp.4001579 · Cited by 412
Maternal prenatal cortisol and infant cognitive development: moderation by infant–mother attachment
Bergman, K., Sarkar, P., Glover, V., & O'Connor, T. G. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.01.002 · Cited by 395
“Other evidence(25-26) that links cortisol exposure and impaired cognitive”
Antenatal Glucocorticoids and Programming of the Developing CNS
Matthews, S. G. (2000) · Pediatric Research · doi:10.1203/00006450-200003000-00003 · Cited by 400
Developing Sustainable Leaders Through Coaching and Compassion
Boyatzis, R. E., Smith, M. L., & Blaize, N. (2006) · Academy of Management Learning & Education · doi:10.5465/amle.2006.20388381 · Cited by 389
“neural tissue through normal neurogenesis (McEwen, 1998; Sapolsky, 1996; Sapolsky, 1999,”
Stress and development: Behavioral and biological consequences
Bremner, J. D., & Vermetten, E. H. G. J. M. (2001) · Development and Psychopathology · doi:10.1017/s0954579401003042 · Cited by 399
“(McEwen, 2000; Sapolsky, 1996, 2000; Sapolsky, Uno, Rebert, & Finch, 1990).”
Recurrent depressive symptoms and the incidence of dementia and mild cognitive impairment
Dotson, V. M., Beydoun, M. A., & Zonderman, A. B. (2010) · Neurology · doi:10.1212/wnl.0b013e3181e62124 · Cited by 385
Neonatal maternal separation reduces hippocampal mossy fiber density in adult Long Evans rats
Huot, R. L., Plotsky, P. M., Lenox, R. H., & McNamara, R. K. (2002) · Brain Research · doi:10.1016/s0006-8993(02)02985-2 · Cited by 392
“cortisol [12,13,54,85,89,90,97].”
BackgroundInfluential
Chronic widespread pain and fibromyalgia: what we know, and what we need to know
Clauw, D. J., & Crofford, L. J. (2003) · Best Practice & Research Clinical Rheumatology · doi:10.1016/s1521-6942(03)00035-4 · Cited by 386
Glutathione Depletion, Lipid Peroxidation and Mitochondrial Dysfunction Are Induced by Chronic Stress in Rat Brain
Madrigal, J. L. M. (2001) · Neuropsychopharmacology · doi:10.1016/s0893-133x(00)00208-6 · Cited by 381
Neurosteroids: Expression of Steroidogenic Enzymes and Regulation of Steroid Biosynthesis in the Central Nervous System
Mensah‐Nyagan, A. G., do Rego, J. L., Beaujean, D., Luu-The, V., Pelletier, G., & Vaudry, H. (1999) · Pharmacological Reviews · doi:10.1016/s0031-6997(24)01395-4 · Cited by 379
“Depending on their chemical nature and concentration, steroids can induce either protective or deleterious effects on nerve cells (Uno et al., 1989; Yu, 1989; Jones, 1993; Sapolsky, 1996; Green et al., 1997; Seckl, 1997; Kimonides et al., 1998).”
Child maltreatment and HPA axis dysregulation: relationship to major depressive disorder and post traumatic stress disorder in females
Shea, A., Walsh, C., MacMillan, H., & Steiner, M. (2005) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2004.07.001 · Cited by 378
“the potential negative effects of long-term exposure of glucorticoids on the brain (Sapolsky, 1996).”
Background
Repeated stress alters dendritic spine morphology in the rat medial prefrontal cortex
Radley, J. J., Rocher, A. B., Rodriguez, A., Ehlenberger, D. B., Dammann, M., McEwen, B. S., Morrison, J. H., Wearne, S. L., & Hof, P. R. (2007) · The Journal of Comparative Neurology · doi:10.1002/cne.21588 · Cited by 393
“…to play a critical role in the etiology of numerous psychiatric illnesses, such as depression, posttraumatic stress disorder, and anxiety (Sapolsky, 1996; Heim et al., 1997; McEwen, 1998; Newport and Nemeroff, 2000; Caspi et al., 2003), and in other instances it may precipitate the…”
Background
A systematic review and meta-analysis of magnetic resonance imaging measurement of structural volumes in posttraumatic stress disorder
O'Doherty, D. C. M., Chitty, K. M., Saddiqui, S., Bennett, M. R., & Lagopoulos, J. (2015) · Psychiatry Research: Neuroimaging · doi:10.1016/j.pscychresns.2015.01.002 · Cited by 375
“Animal studies on rodents (McEwen et al., 1992; Sunanda et al., 1995; Magarinos et al., 1996; Sapolsky, 1996; Gould et al., 1998; McEwen, 2000b; Stewart et al., 2005) and primates (Sapolsky et al.”
Background
Serotonergic vulnerability and depression: assumptions, experimental evidence and implications
Jans, L. A. W., Riedel, W. J., Markus, C. R., & Blokland, A. (2006) · Molecular Psychiatry · doi:10.1038/sj.mp.4001920 · Cited by 382
Increase in Urinary Cortisol Excretion and Memory Declines: MacArthur Studies of Successful Aging
Seeman, T. E., McEwen, B. S., Singer, B. H., Albert, M., & Rowe, J. W. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.82.8.4173 · Cited by 383
Structural and functional plasticity of the human brain in posttraumatic stress disorder
Bremner, J. D., Elzinga, B. M., Schmahl, C. G., & Vermetten, E. H. G. J. M. (2007) · Progress in brain research · doi:10.1016/s0079-6123(07)67012-5 · Cited by 379
Neuroprotective effects of Ginkgo biloba extract
Ahlemeyer, B., & Krieglstein, J. (2003) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-003-3080-1 · Cited by 368
Evidence for Acquired Pregenual Anterior Cingulate Gray Matter Loss from a Twin Study of Combat-Related Posttraumatic Stress Disorder
Kasai, K., Yamasue, H., Gilbertson, M. W., Shenton, M. E., Rauch, S. L., & Pitman, R. K. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.06.022 · Cited by 377
Hippocampal Volume in Patients With Alcohol Dependence
Agartz, I., Momenan, R., Rawlings, R. R., Kerich, M. J., & Hommer, D. W. (1999) · Archives of General Psychiatry · doi:10.1001/archpsyc.56.4.356 · Cited by 359
“The hippocampus is rich in glucocorticoid receptors and considered particularly vulnerable.(13) Thus, the human hippocampus may be more affected than other brain structures by alcohol’s neurotoxic effects.”
Background
Structural roles of acetylcholinesterase variants in biology and pathology
Grisaru, D., Sternfeld, M., Eldor, A., Glick, D., & Soreq, H. (1999) · European Journal of Biochemistry · doi:10.1046/j.1432-1327.1999.00693.x · Cited by 359
Diseases Among Men 20 Years After Exposure to Severe Stress
Boscarino, J. A. (1997) · Psychosomatic Medicine · doi:10.1097/00006842-199711000-00008 · Cited by 352
Fibromyalgia: an overview
Clauw, D. J. (2009) · The American Journal of Medicine · doi:10.1016/j.amjmed.2009.09.006 · Cited by 350
Early Intervention and the Development of Self-Regulation
Fonagy, P., & Target, M. (2002) · Psychoanalytic Inquiry · doi:10.1080/07351692209348990 · Cited by 391
Origins of depression in later life
BLAZER, D. G., & HYBELS, C. F. (2005) · Psychological Medicine · doi:10.1017/s0033291705004411 · Cited by 347
“cortisol which in turn causes loss of pre-existing hippocampal neurons (Sapolsky, 1996), a loss that may be prevented in part by use of antidepressant medications (Czeh et al.”
Background
Song as an honest signal of developmental stress in the zebra finch (Taeniopygia guttata)
Spencer, K. A., Buchanan, K. L., Goldsmith, A. R., & Catchpole, C. K. (2003) · Hormones and Behavior · doi:10.1016/s0018-506x(03)00124-7 · Cited by 345
Higher cortisol levels following exposure to traumatic reminders in abuse-related PTSD
Elzinga, B. M., Schmahl, C. G., Vermetten, E., van Dyck, R., & Bremner, J. D. (2003) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300226 · Cited by 341
“Studies in animals show that high levels of GCs may have a long-term inhibitory effect on memory function with GC-mediated hippocampal toxicity and memory dysfunction with stress (McEwen et al, 1992; Sapolsky, 1996; Arbel et al, 1994; Conrad et al, 1996; Luine et al, 1994; Ohl et al, 2000).”
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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