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Why Stress Is Bad for Your Brain
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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“Cumulative exposure to high levels of cortisol over the lifetime is known to be related to hippocampal atrophy.”
From Self-esteem, locus of control, hippocampal volume, and cortisol regulation in young and old adulthood (2005) · cites this paper as Sapolsky, 1996
In the citing paper
“Documented effects of stress include impairment and damage to specific brain structures via the action of neurotoxic glucocorticoids (Sapolsky, 1996;Watanabe et al., 1992;Woolley et al., 1990).”
From Self-esteem, locus of control, hippocampal volume, and cortisol regulation in young and old adulthood (2005) · cites this paper as Sapolsky, 1996
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“Chronic states of stress essentially lead to heightened levels of glucocorticoids, which cause the death of cells associated with new memory and learning in the hippocampus [ 19 ].”
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Jelícic, M., & Merckelbach, H. L. G. J. (2004) · The Journal of Nervous and Mental Disease · doi:10.1097/01.nmd.0000135494.20416.59 · Cited by 37
“METHODOLOGICAL ISSUES At first sight, most studies cited above seem to yield evidence for the hypothesis that traumatic stress may lead to hippocampal damage and memory deficits (Bremner, 1999, 2002; Sapolsky, 1996).”
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“…impairs episodic memory (Burt et al., 1995; Zakzanis et al., 1998), and the dominant hypothesis is that stress-induced changes in the hippocampus are responsible (Sapolsky, 1996, 2000; Sheline et al., 1999; MacQueen et al., 2003; MacQueen and Frodl, 2011; Huang et al., 2013; Travis et al., 2014).”
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“…depletion within the CNS, and reduced hippocampal volume, are compatible with those of the chronic stress response [see Yehuda, 2001; see also Sapolsky, 1996; Lupien et al., 1998], one might suspect that EGb 761, which has stress-alleviating activity, might be of some value in treating this…”
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“In turn glucocorticoids can cause loss of neurons, particularly in the hippocampus, a key brain structure for memory (Sapolsky 1996).”
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“In addition, depression is associated with activity of the hypothalamic-pituitary-axis (HPA) (Nemeroff & Vale, 2005; Sapolsky, 2001) and increases in glucocorticoid hydrocortisone which may contribute to damage in the hippocampus and reduced hippocampal volumes (Sapolsky, 1996).”
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“Similar results have been reported by many researchers [3—10].”
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“…of the HPA axis; chronic activation of which is linked to depression, heart disease, bone demineralization, loss of muscle mass, increased abdominal fat, and decreased hippocampal volume (Ader 2001; Heim et al. 2000; McEwen 1998; McEwen and Sapolsky 1995; Repetti et al. 2002; Sapolsky 1996).”
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“In addition to gonadal steroids, glucocorticoids (stress hormones) likewise affect the volume of some neuronal regions such as the hippocampus [reviewed by Sapolsky, 1996].”
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“…well established that stress precipitates or exacerbates several physical and psychological disorders (Brown and Harris, 1987; Pasternac and Talajic, 1991; Hammen et al., 1992; Stratakis and Chrousos, 1995; Sapolsky, 1996; Arborelius et al., 1999, 2004; hology and Neuroscienc (T.J. Nyhuis). er B.V.”
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“…changes (e.g., low levels of cortisol and ACTH/corticotrophin; Heim et al. 2004; Huether 1998), which in turn has been found to be associated with decreased hippocampal volume and impaired memory and decision making (Carrion et al. 2001; Kitayama et al. 2006; Nelson and Carver 1998; Sapolsky 1996).”
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“Further, it is hypothesized to heighten levels of glucocorticoid hormones in the blood, which could cause damage to the hippocampus (Bremner, 2006; Lupien et al., 1999; Sapolsky, 1996) and, possibly, increase buildup of beta-amyloid (Aβ) peptide and tauprotein in the brain (both of which are involved in the developmen…”
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“…that stress, through an increase in glucocorticoid levels, induces neurotoxic effects, and with evidence that elevated glucocorticoid levels are associated with memory impairment and hippocampal atrophy (Squire, 1992 ; Lupien et al. 1994, 1998 ; Sapolsky, 1996 ; León-Carrión et al. 2009).”
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“In both human (Sapolsky 1996;Sapolsky et al 1986), and non-human primates (Uno et al 1989) elevated levels of stress hormones such as catecholamines and cortisol can affect brain growth by accelerating loss of neurons (Swaab et al 2005) or by delaying myelination (Dunlop 1997).”
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“Pronounced HPA activation has also been associated with depression (Sapolsky, 1996).”
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“…this paper motivates the design and evaluation of interfaces using principles from research on stress given its long history of scholarly study [14] (reviewed in [7]) and demonstrated effects on the brain [12], long-term recall [13], cardiovascular system [6], and cognitive performance [6].”
BackgroundNoorafshan, A., Abdollahifar, M., Asadi-Golshan, R., Rashidiani-Rashidabadi, A., & Saied (2014) · Acta Neurobiologiae Experimentalis · doi:10.55782/ane-2014-1971 · Cited by 27
“© 2014 by Polish Neuroscience Society - PTBUN, Nencki Institute of Experimental Biology INTRODUCTION Chronic stress is a risk factor for many psychopathological conditions, including depression and anxiety disorders (Kendler et al. 1995, Sapolsky 1996, Shelton 2004).”
BackgroundSalivary cortisol is associated with cognitive changes in patients with fibromyalgia
Lin, Y.-J., Ko, Y., Chow, L., Hsiao, F., Liu, H., Wang, P., & Chen, W. (2021) · Scientific Reports · doi:10.1038/s41598-020-79349-0 · Cited by 27
Ng, A., Wei, B., Jain, J., Ward, E. A., Tandon, S. D., Moskowitz, J. T., Krogh‐Jespersen, S., Wakschlag, L. S., & Alshurafa, N. I. (2022) · JMIR mhealth and uhealth · doi:10.2196/33850 · Cited by 29
“Physiological stress that persists from one day to the next, or residual stress, can be most damaging to neurovascular health and lead to chronic diseases [27,28].”
BackgroundThe HPA Axis in HIV-1 Infection
Kumar, M., Kumar, A. M., Waldrop, D. G., Antoni, M. H., Schneiderman, N., & Eisdorfer, C. (2002) · JAIDS Journal of Acquired Immune Deficiency Syndromes · doi:10.1097/00126334-200210012-00010 · Cited by 27
How does epidermal pathology interact with mental state?
Denda, M., Takei, K., & Denda, S. (2012) · Medical Hypotheses · doi:10.1016/j.mehy.2012.11.027 · Cited by 28
Stixrud, W. R. (2012) · Organizational Behavior Teaching Review · doi:10.1177/1052562911430317 · Cited by 28
Adolescents with Anorexia Nervosa: The Impact of the Disorder on Bones and Brains
Katzman, D. K., & Zipursky, R. B. (1997) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1997.tb48202.x · Cited by 27
Bremner, J. D. (2007) · Cambridge University Press eBooks · doi:10.1017/cbo9780511500008.010 · Cited by 28
Inverse relation between cortisol and anger and their relation to performance and explicit memory
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“In the case of a social evaluative threat, the hypothalamic-pituitaryadrenal (HPA) axis is activated and stress hormones, including cortisol, are released to supply the organism with additional energy to respond to the stressor (Dickerson and Kemeny, 2004; Sapolsky, 1992, 1996).”
BackgroundMajor Hypercorticism Is an Endocrine Feature of Ewes with Naturally Occurring Scrapie
Gayrard, V., Picard‐Hagen, N., Grino, M., Sauze, N., Grandjean, C., Galea, J., Andréoletti, O., Schelcher, F., & Toutain, P. (2000) · Endocrinology · doi:10.1210/endo.141.3.7345 · Cited by 27
Nankova, B. B., Fuchs, S. Y., Serova, L. I., Ronai, Z. A., Wild, D., & Sabban, E. L. (1998) · Stress · doi:10.3109/10253899809167293 · Cited by 27
Newer treatments for fibromyalgia syndrome
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“In the Vitton and colleagues (2004) study evaluating milnacipran, statistically signifi cant differences were noted in overall improvement, physical functioning, level of fatigue and degree of reported physical impairment. In the Arnold and colleagues (2004b) trial of duloxetine compared to placebo, participants treat…”
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Masini, C. V., Nyhuis, T. J., Sasse, S. K., Day, H. E. W., & Campeau, S. (2011) · Stress · doi:10.3109/10253890.2010.548013 · Cited by 25
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Ambulatory assessed implicit affect is associated with salivary cortisol
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“…been linked to psychological and physiological problems such as chronic fatigue, cardiovascular disease, depression, abdominal obesity as well as specific neuronal changes in the prefrontal cortex, hippocampus, and amygdala (Sapolsky, 1996; Smyth et al., 1998; Rosengren et al., 2004; McEwen, 2005).”
BackgroundInfluentialStress Effects on the Developing Brain
Gunnar, M. R. (2007) · Oxford University Press eBooks · doi:10.1093/acprof:oso/9780195306255.003.0006 · Cited by 26
Stress, Depression, Resilience and Ageing: A Role for the LPA-LPA1 Pathway
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“Taken together, a comprehensive understanding of neurobiological mechanisms of the reduction of hippocampal volume and the atrophy observed in certain brain areas after intense and long-lasting stressing situations [76] requires the consideration of numerous interdependent factors.”
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The magic that binds us: Magical thinking and inclusive fitness.
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Assessment of stress in non-human primates: application of the neutrophil activation test
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The Role of Early Experience in Infant Development
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Contemporary work characteristics, stress, and ill health
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The role of hepcidin in chronic mild stress-induced depression
Farajdokht, F., Soleimani, M., Mehrpouya, S., Barati, M., & Nahavandi, A. (2015) · Neuroscience Letters · doi:10.1016/j.neulet.2015.01.008 · Cited by 26
Metadata
- Authors
- Sapolsky, R. M.
- Affiliations
- Stanford University (US)
- Corresponding author
- Sapolsky, Robert M.
- ORCID
- Sapolsky, Robert M.
- Venue
- Science
- Published
- 1996-08-09
- Volume
- 273
- Issue
- 5276
- Pages
- 749-750
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- 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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