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

The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.

Why Stress Is Bad for Your Brain

Sapolsky, Robert M.·1996·Science

Open this paper in CoChat — free account

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.

Integrity signals

Registry

Crossref · 10.1126/science.273.5276.749

Cites

12 of 12 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

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
Hippocampal atrophy in recurrent major depression
Sheline, Y. I., Wang, P. W., Gado, M. H., Csernansky, J. G., & Vannier, M. W. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.9.3908 · Cited by 1,932
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
Sapolsky, R., Uno, H., Rebert, C., & Finch, C. (1990) · The Journal of Neuroscience · doi:10.1523/jneurosci.10-09-02897.1990 · Cited by 1,103
Effect of Neonatal Handling on Age-Related Impairments Associated with the Hippocampus
Meaney, M. J., Aitken, D. H., van Berkel, C., Bhatnagar, S., & Sapolsky, R. M. (1988) · Science · doi:10.1126/science.3340858 · Cited by 1,074
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
Starkman, M. N., Gebarski, S. S., Berent, S., & Schteingart, D. E. (1992) · Biological Psychiatry · doi:10.1016/0006-3223(92)90079-f · Cited by 840
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

Flagged first, then by citations

Show all 12 references

Research works printed but not linked: 3

BREMNER J, IN PRESS BIOL PSYCHI .
GURVITS T, IN PRESS BIOL PSYCHI .
STARKMAN M, COMMUNICATION .

Sorted by citations

Items 201–300 of 1,000

Inducible nitric oxide synthase expression in brain cortex after acute restraint stress is regulated by nuclear factor κB‐mediated mechanisms
Madrigal, J. L. M., Moro, M. A., Lizasoain, I., Lorenzo, P., Castrillo, A., Boscá, L., & Leza, J. C. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00108.x · Cited by 180
“…that long-lasting stress affects synaptic plasticity, dendritic morphology and neurogenesis in animals (reviewed in Kim and Yoon 1998) and induces both clinical and anatomical features of neurotoxic damage in humans (i.e. post-traumatic stress disorder) (Sapolsky 1996; Sheline et al. 1996).”
Background
Association between trauma exposure and delusional experiences in a large community-based sample
Scott, J. G., Chant, D. C., Andrews, G., Martin, G., & McGrath, J. J. (2007) · The British Journal of Psychiatry · doi:10.1192/bjp.bp.106.026708 · Cited by 183
A Historical Framework for Social Epidemiology
Berkman, L. F., & Kawachi, I. I. (2014) · Oxford University Press eBooks · doi:10.1093/med/9780195377903.003.0001 · Cited by 181
The Ginkgo biloba extract EGb 761 rescues the PC12 neuronal cells from β-amyloid-induced cell death by inhibiting the formation of β-amyloid-derived diffusible neurotoxic ligands
Yao, Z., Drieu, K., & Papadopoulos, V. (2001) · Brain Research · doi:10.1016/s0006-8993(00)03131-0 · Cited by 181
Cortisol, Learning, Memory, and Attention in Relation to Smaller Hippocampal Volume in Police Officers with Posttraumatic Stress Disorder
Lindauer, R., Olff, M., van Meijel, E. P. M., Carlier, I. V. E., & Gersons, B. P. R. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.06.033 · Cited by 188
Genetic dissection of glucocorticoid receptor function in mice
Tronche, F., Kellendonk, C., Reichardt, H. M., & Schütz, G. (1998) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(98)80007-5 · Cited by 177
Correlational relationship between shock intensity and corticosterone secretion on the establishment and subsequent expression of contextual fear conditioning.
Cordero, M. I., Merino, J. J., & Sandi, C. (1998) · Behavioral Neuroscience · doi:10.1037//0735-7044.112.4.885 · Cited by 206
Blast Injury from Explosive Munitions
Černak, I., Savić, J., Ignjatovic, D., & Jevtić, M. (1999) · doi:10.1097/00005373-199907000-00021 · Cited by 178
Child Maltreatment and Memory
Goodman, G. S., Quas, J. A., & Ogle, C. M. (2009) · Annual Review of Psychology · doi:10.1146/annurev.psych.093008.100403 · Cited by 190
Clarifying the Origin of Biological Abnormalities in PTSD Through the Study of Identical Twins Discordant for Combat Exposure
Pitman, R. K., Gilbertson, M. W., Gurvits, T. V., May, F. S., Lasko, N. B., Metzger, L. J., Shenton, M. E., Yehuda, R., Orr, S. P., & for the Harvard/VA PTSD Twin Study Investigators (2006) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1364.019 · Cited by 185
Neurobiology of Mice Selected for High Voluntary Wheel-running Activity
Rhodes, J. S. (2005) · Integrative and Comparative Biology · doi:10.1093/icb/45.3.438 · Cited by 173
“For example, the High-Runner mice have chronically elevated corticosterone levels, whether they are exercising or not (Girard and Garland, 2002), which can damage the body and brain (Sapolsky, 1996, 2000).”
Background
Differential Association of Concurrent, Baseline, and Average Depressive Symptoms With Cognitive Decline in Older Adults
Dotson, V. M., Resnick, S. M., & Zonderman, A. B. (2008) · American Journal of Geriatric Psychiatry · doi:10.1097/jgp.0b013e3181662a9c · Cited by 175
Acute stress and hippocampal histone H3 lysine 9 trimethylation, a retrotransposon silencing response
Hunter, R. G., Murakami, G., Dewell, S. B., Seligsohn, M., Baker, M. E. R., Datson, N. A., McEwen, B. S., & Pfaff, D. W. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1215810109 · Cited by 178
“Proc Natl Acad Sci USA 108(7):3035–3040.”
Salivary Cortisol as a Predictor of Socioemotional Adjustment during Kindergarten: A Prospective Study
Smider, N. A., Essex, M. J., Kalin, N. H., Buss, K. A., Klein, M. H., Davidson, R. J., & Goldsmith, H. H. (2002) · Child Development · doi:10.1111/1467-8624.00393 · Cited by 175
Salivary cortisol and DHEA: association with measures of cognition and well-being in normal older men, and effects of three months of DHEA supplementation.
van Niekerk, J. K., Huppert, F. A., & Herbert, J. (2001) · Psychoneuroendocrinology · doi:10.1016/s0306-4530(01)00014-2 · Cited by 171
“, 1997), hippocampal atrophy in rodents and humans (Sapolsky, 1996; Lupien et al., 1998), and impairment of episodic or event memory which is thought to be hippocampus dependent (Squire, 1992; Lupien et al.”
Background
Stress and hippocampal abnormalities in psychiatric disorders
Sala, M. (2004) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2003.12.005 · Cited by 174
“Hippocampal shrinkage in MDD may be due to repeated episodes of hypercortisolemia during depressive events (Sapolsky, 1996; Sheline, 2000) and seems to be prevented by antidepressants (Sheline et al.”
Background
Parasites affect song complexity and neural development in a songbird
Spencer, K. A., Buchanan, K. L., Leitner, S., Goldsmith, A. R., & Catchpole, C. K. (2005) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.2005.3188 · Cited by 171
“This does not preclude the potential role of stress hormones in the expression of such characters, as prolonged exposure to elevated stress hormones can have serious negative effects on neuronal growth and survival (McEwen & Sapolsky 1995; Sapolsky 1996; Buchanan 2000).”
Reduced Levels of Thyroid Hormones, Insulin, and Glucose, and Lower Body Core Temperature in the Growth Hormone Receptor/Binding Protein Knockout Mouse
Hauck, S., Hunter, W. S., Danilovich, N., Kopchick, J. J., & Bartke, A. (2001) · Experimental Biology and Medicine · doi:10.1177/153537020122600607 · Cited by 169
HPA system regulation and adult attachment anxiety: individual differences in reactive and awakening cortisol
Quirin, M., Pruessner, J. C., & Kuhl, J. (2008) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2008.01.013 · Cited by 167
“…parental care, can have enduring effects on stress reactivity, hypothalamus–pituitary–adrenal (HPA) system regulation, and neurodevelopment as evidenced by studies on rodents (e.g., Sapolsky, 1996; Sapolsky and Meaney, 1986; Meaney et al., 0306-4530/$ - see front matter & 2008 Elsevier Ltd.”
Background
Corticosteroid receptors and neuroplasticity
Sousa, N., Cerqueira, J., & Almeida, O. F. X. (2007) · Brain Research Reviews · doi:10.1016/j.brainresrev.2007.06.007 · Cited by 165
Perioperative cognitive trajectory in adults
Nadelson, M. R., Sanders, R. D., & Avidan, M. S. (2014) · British Journal of Anaesthesia · doi:10.1093/bja/aet420 · Cited by 168
Factors underlying cognitive decline in old age and Alzheimer’s disease: the role of the hippocampus
Jaroudi, W., Garami, J. K., Garrido, S., Hornberger, M., Kéri, S., & Moustafa, A. A. (2017) · Reviews in the Neurosciences · doi:10.1515/revneuro-2016-0086 · Cited by 172
Comorbidity of mild cognitive disorder and depression - a neuropsychological analysis
Reischies, F. M., & Neu, P. (2000) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s004060070023 · Cited by 169
High corticosterone levels in prenatally stressed rats predict persistent paradoxical sleep alterations
Dugovic, C., Maccari, S., Weibel, L., Turek, F. W., & Van Reeth, A. O. (1999) · The Journal of Neuroscience · doi:10.1523/jneurosci.19-19-08656.1999 · Cited by 166
“Significant correlations between sleep abnormalities and dysfunctions of the HPA axis have been shown in depressed patients (Poland et al., 1992; Hubain et al., 1998) and may result from a stress component (Sapolsky, 1996; Rosenwasser and WirzJustice, 1997).”
Background
Victimization and Substance Abuse among Women: Contributing Factors, Interventions, and Implications
Logan, T., Walker, R., Cole, J., & Leukefeld, C. G. (2002) · Review of General Psychology · doi:10.1037/1089-2680.6.4.325 · Cited by 170
Chronic mild stress impairs cognition in mice: From brain homeostasis to behavior
Li, S., Wang, C., Wang, W., Dong, H., Hou, P., & Tang, Y. (2008) · Life Sciences · doi:10.1016/j.lfs.2008.02.010 · Cited by 174
“For humans, psychosocial stress plays an important role in the development and maintenance of both mood disorders and cognitive impairments (Sapolsky, 1996; Simoens et al., 2007; Oei et al., 2006).”
Background
Stress and Brain Atrophy
Bremner, J. D. (2006) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/187152706778559309 · Cited by 165
Environmental Influences on Neural Plasticity, the Limbic System, Emotional Development and Attachment: A Review
Joseph, R. (1999) · Child Psychiatry & Human Development · doi:10.1023/a:1022660923605 · Cited by 160
Further Development and Validation of the Occupational Fatigue Exhaustion Recovery (OFER) Scale
Winwood, P. C., Lushington, K., & Winefield, A. H. (2006) · Journal of Occupational and Environmental Medicine · doi:10.1097/01.jom.0000194164.14081.06 · Cited by 160
“damage is associated with a number of maladaptive health outcomes, including the reported characteristics of chronic fatigue.(17,22) By comparison with acute fatigue, chronic fatigue is characterized by: “.”
Background
Neuroimaging in Posttraumatic Stress Disorder and Other Stress-Related Disorders
Bremner, J. D. (2007) · Neuroimaging Clinics of North America · doi:10.1016/j.nic.2007.07.003 · Cited by 174
Ketamine plus imipramine treatment induces antidepressant-like behavior and increases CREB and BDNF protein levels and PKA and PKC phosphorylation in rat brain
Réus, G. Z., Stringari, R. B., Ribeiro, K. F., Ferraro, A. K., Vitto, M. F., Cesconetto, P. A., de Souza, C. T., & Quevedo, J. (2011) · Behavioural Brain Research · doi:10.1016/j.bbr.2011.02.024 · Cited by 161
Disconnection and reconnection: The morphological basis of (mal)adaptation to stress
Sousa, N., & Almeida, O. F. X. (2012) · Trends in Neurosciences · doi:10.1016/j.tins.2012.08.006 · Cited by 159
Annual Research Review: Rethinking childhood trauma‐new research directions for measurement, study design and analytical strategies
Danese, A. (2019) · Journal of Child Psychology and Psychiatry · doi:10.1111/jcpp.13160 · Cited by 171
Variation in hypothalamic-pituitary-adrenal axis activity among bullied and non-bullied children
Vaillancourt, T., Duku, E., Decatanzaro, D., Macmillan, H., Muir, C., & Schmidt, L. A. (2008) · Aggressive Behavior · doi:10.1002/ab.20240 · Cited by 158
Involvement of hippocampal serotonin and neuropeptide Y in depression induced by chronic unpredicted mild stress
Luo, D. D., An, S. C., & Zhang, X. (2008) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2008.05.010 · Cited by 155
Effect of chronic high-dose exogenous cortisol on hippocampal neuronal number in aged nonhuman primates
Leverenz, J. B., Wilkinson, C. W., Wamble, M., Corbin, S., Grabber, J. E., Raskind, M. A., & Peskind, E. R. (1999) · The Journal of Neuroscience · doi:10.1523/jneurosci.19-06-02356.1999 · Cited by 154
“Based on these observations, concern has been raised that prolonged elevation of endogenous GCs caused by chronic stress or pharmacological doses of GCs commonly administered to humans with inflammatory or bronchospastic diseases might produce hippocampal neuronal loss and resultant cognitive impairment, particularly…”
Background
Neural correlates of memories of abandonment in women with and without borderline personality disorder.
Schmahl, C., Elzinga, B., Vermetten, E., Sanislow, C., McGlashan, T., & Bremner, J. (2003) · Biological Psychiatry · doi:10.1016/s0006-3223(02)01720-1 · Cited by 148
“Stress results in damage to hippocampal neurons with associated deficits in memory (McEwen and Magarinos 2001; Sapolsky 1996).”
Precarious employment experiences and their health consequences: Towards a theoretical framework
Tompa, E., Scott-Marshall, H. K., Dolinschi, R., Trevithick, S., & Bhattacharyya, S. (2007) · Work · doi:10.3233/wor-2007-00611 · Cited by 154
“Overexposure to glucocorticoids also causes atrophy of neurons (nerve cells) in the hippocampus, an area of the brain which is vital to memory and learning [111].”
Background
Enriched environment experience overcomes the memory deficits and depressive-like behavior induced by early life stress.
Cui, M., Yang, Y., Yang, J., Zhang, J., Han, H., Ma, W., Li, H., Mao, R., Xu, L., Hao, W., et al. (2006) · Neuroscience Letters · doi:10.1016/j.neulet.2006.05.048 · Cited by 153
Increased CSF cortisol in AD is a function of APOE genotype
Peskind, E. R., Wilkinson, C. W., Petrie, E. C., Schellenberg, G. D., & Raskind, M. A. (2001) · Neurology · doi:10.1212/wnl.56.8.1094 · Cited by 153
Serotonin Modulation of Sensory Inputs to the Lateral Amygdala: Dependency on Corticosterone
Stutzmann, G. E., McEwen, B. S., & LeDoux, J. E. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-22-09529.1998 · Cited by 151
“(McEwen et al., 1986; Herman et al., 1989; Sapolsky, 1996 ).”
Does professional development reduce the influence of teacher stress on teacher–child interactions in pre-kindergarten classrooms?
Sandilos, L. E., Goble, P., Rimm‐Kaufman, S. E., & Pianta, R. C. (2017) · Early Childhood Research Quarterly · doi:10.1016/j.ecresq.2017.10.009 · Cited by 152
Neonatal sex hormones have `organizational' effects on the hypothalamic-pituitary-adrenal axis of male rats
McCormick, C. M., Furey, B. F., Child, M., Sawyer, M. J., & Donohue, S. M. (1998) · Developmental Brain Research · doi:10.1016/s0165-3806(97)00155-7 · Cited by 150
Cognitive Flexibility and Theory of Mind Outcomes Among Foster Children: Preschool Follow-Up Results of a Randomized Clinical Trial
Lewis‐Morrarty, E., Dozier, M., Bernard, K., Terracciano, S., & Moore, S. V. (2012) · Journal of Adolescent Health · doi:10.1016/j.jadohealth.2012.05.005 · Cited by 168
Childhood Living Conditions, Socioeconomic Position in Adulthood, and Cognition in Later Life: Exploring the Associations
Fors, S., Lennartsson, C., & Lundberg, O. (2009) · The Journals of Gerontology Series B · doi:10.1093/geronb/gbp029 · Cited by 152
Psychic trauma causing grossly reduced brain metabolism and cognitive deterioration
Markowitsch, H. J., Kessler, J., van der Ven, C., Weber‐Luxenburger, G., Albers, M., & Heiss, W. (1998) · Neuropsychologia · doi:10.1016/s0028-3932(97)00093-6 · Cited by 147
Psychoendocrine antecedents of persistent first-episode major depression in adolescents: a community-based longitudinal enquiry
GOODYER, I. M., HERBERT, J., & TAMPLIN, A. (2003) · Psychological Medicine · doi:10.1017/s0033291702007286 · Cited by 146
“For example, DHEA has neuroprotective properties and diminishes the deleterious effects of cortisol in the hippocampus (Sapolsky, 1996; Kimonides et al. 1998; Mao & Barger, 1998; Gubba et al. 2000).”
Background
Fortnightly review: Stress, the brain, and mental illness
Herbert, J. (1997) · BMJ · doi:10.1136/bmj.315.7107.530 · Cited by 146
Interface of physical and emotional stress regulation through the endogenous opioid system and μ-opioid receptors
Ribeiro, S. C. M., Kennedy, S. E., Smith, Y. R., Stohler, C. S., & Zubieta, J. (2005) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2005.08.011 · Cited by 152
“…disrupted state, results in an imbalance of the primary mediators and in widespread physiological and anatomical changes and damages resulting from mechanisms evolutionarily well adapted to deal with physical, acute stressful situations (Sapolsky, 1996; McEwen, 2004; Korte et al., 2005).”
Background
Introduction: Protective and damaging effects of stress mediators: The good and bad sides of the response to stress
McEwen, B. S. (2002) · Metabolism · doi:10.1053/meta.2002.33183 · Cited by 143
Chronic AMPA receptor potentiator (LY451646) treatment increases cell proliferation in adult rat hippocampus
Bai, F., Bergeron, M., & Nelson, D. L. (2003) · Neuropharmacology · doi:10.1016/s0028-3908(03)00104-7 · Cited by 144
The role of hippocampus in the pathophysiology of bipolar disorder
Frey, B. N., Andreazza, A. C., Nery, F. G., Martins, M. R., Quevedo, J., Soares, J. C., & Kapczinski, F. (2007) · Behavioural Pharmacology · doi:10.1097/fbp.0b013e3282df3cde · Cited by 162
“Conversely, the hippocampus is particularly vulnerable to damage after repeated stress (Sapolsky, 1996), and glucocorticoid-induced impairment in declarative memory is associated with decreased activation of the parahippocampus (De Quervain et al., 2003).”
Background
ALL OUR SONS: THE DEVELOPMENTAL NEUROBIOLOGY AND NEUROENDOCRINOLOGY OF BOYS AT RISK
Schore, A. N. (2017) · Infant Mental Health Journal · doi:10.1002/imhj.21616 · Cited by 153
Memory beyond the hippocampus
Tulving, E., & Markowitsch, H. J. (1997) · Current Opinion in Neurobiology · doi:10.1016/s0959-4388(97)80009-8 · Cited by 142
Stress risk factors and stress-related pathology: Neuroplasticity, epigenetics and endophenotypes
Radley, J. J., Kabbaj, M., Jacobson, L., Heydendael, W., Yehuda, R., & Herman, J. P. (2011) · Stress · doi:10.3109/10253890.2011.604751 · Cited by 147
“…of HPA axis hyperactivity in depressive illness (see Jacobson, this article) raises the prospect that clarifying the mechanisms of stress neuroendocrine systems in animal studies may help to understand the pathophysiology of this disorder (Carroll et al. 1976; Sapolsky 1996; Sheline et al. 1996).”
Background
Anxious personality predicts an increased risk of Parkinson's disease
Bower, J. H., Grossardt, B. R., Maraganore, D. M., Ahlskog, J. E., Colligan, R. C., Geda, Y. E., Therneau, T. M., & Rocca, W. A. (2010) · Movement Disorders · doi:10.1002/mds.23230 · Cited by 141
Cortisol, Dehydroepiandrosterone, and Estradiol Measured Over 24 Hours in Women With Childhood Sexual Abuse-Related Posttraumatic Stress Disorder
Bremner, J. D., Vermetten, E. H. G. J. M., & Kelley, M. E. (2007) · The Journal of Nervous and Mental Disease · doi:10.1097/nmd.0b013e3181594ca0 · Cited by 146
“, 1997), and alterations in the hippocampus (Sapolsky, 1996).”
Background
Voluntary exercise and palatable high-fat diet both improve behavioural profile and stress responses in male rats exposed to early life stress: Role of hippocampus
Maniam, J., & Morris, M. J. (2010) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2010.05.012 · Cited by 149
“Longterm exposure to corticosterone is detrimental to hippocampal neuron survival and leads to hippocampal atrophy (Sapolsky, 1996).”
Evolutionary functions of early social modulation of hypothalamic–pituitary–adrenal axis development in humans
Flinn, M. V., Nepomnaschy, P. A., Muehlenbein, M. P., & Ponzi, D. (2011) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2011.01.005 · Cited by 125
Personality Predicts Cognitive Function Over 7 Years in Older Persons
Chapman, B. P., Duberstein, P. R., Tindle, H. A., Sink, K. M., Robbins, J. A., Tancredi, D. J., & Franks, P. J. (2011) · American Journal of Geriatric Psychiatry · doi:10.1097/jgp.0b013e31822cc9cb · Cited by 139
The Role of the Hypothalamus–Pituitary–Adrenal (HPA) Axis in Test-Induced Anxiety: Assessments, Physiological Responses, and Molecular Details
Hinds, J. A., & Sánchez, E. R. (2022) · Stresses · doi:10.3390/stresses2010011 · Cited by 165
“If the overproduction of GCs lasts for several weeks, it can cause atrophy of hippocampal dendrites and permanent loss of hippocampal neurons [33].”
Dual Monoamine Modulation for Improved Treatment of Major Depressive Disorder
Trân, P. V., Bymaster, F. P., McNamara, R. K., & Potter, W. Z. (2003) · Journal of Clinical Psychopharmacology · doi:10.1097/00004714-200302000-00011 · Cited by 134
Hypotheses and controversies related to effects of stress on the hippocampus: An argument for stress‐induced damage to the hippocampus in patients with posttraumatic stress disorder
Bremner, J. D. (2001) · Hippocampus · doi:10.1002/hipo.1023 · Cited by 140
Long-term moderate elevation of corticosterone facilitates avian food-caching behaviour and enhances spatial memory
Витальевич, П. В. (2003) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.2003.2551 · Cited by 138
“It is widely believed that long-term chronic stress and associated long-term elevation of glucocorticoid hormone levels have negative effects on the cognitive abilities of animals by causing neuronal cell death and reducing neurogenesis ( Sapolsky 1992, 1996; McEwen & Sapolsky 1995; McEwen 2000).”
Background
Daily stressors and memory failures in a naturalistic setting: Findings from the va normative aging study.
Neupert, S. D., Almeida, D. M., Mroczek, D. K., & Spiro, A. (2006) · Psychology and Aging · doi:10.1037/0882-7974.21.2.424 · Cited by 151
Transgenerational effects of prenatal nutrient restriction on cardiovascular and hypothalamic‐pituitary‐adrenal function
Bertram, C. E., Khan, O., Ohri, S. K., Phillips, D. I., Matthews, S. G., & Hanson, M. A. (2008) · The Journal of Physiology · doi:10.1113/jphysiol.2007.147967 · Cited by 135
“Chronic elevation of glucocorticoids can result in a reduction in hippocampal volume in the rat and human (Sapolsky, 1999; Lupien & Lepage, 2001; Roy & Sapolsky, 2003).”
Background
Social and environmental stressors in the home and childhood asthma
Suglia, S. F., Duarte, C. S., Sandel, M. T., & Wright, R. J. (2009) · Journal of Epidemiology & Community Health · doi:10.1136/jech.2008.082842 · Cited by 139
“A second interpretation is that housing quality is a direct source of stress and thus a contributor to the stress pathway, and as such influences the risk of asthma. When environmental demands are found to be taxing or threatening, and coping resources are viewed to be inadequate, individuals perceive themselves as be…”
Background
Measures of Prefrontal System Dysfunction in Posttraumatic Stress Disorder
Koenen, K. C., Driver, K. L., Oscar‐Berman, M., Wolfe, J., Folsom, S., Huang, M. T., & Schlesinger, L. (2001) · Brain and Cognition · doi:10.1006/brcg.2000.1256 · Cited by 137
A longitudinal study of differences in late- and early-onset geriatric depression: Depressive symptoms and psychosocial, cognitive, and neurological functioning
Sachs‐Ericsson, N., Corsentino, E. A., Moxley, J. H., Hames, J. L., Rushing, N. C., Sawyer, K., Joiner, T. E., Selby, E. A., Zarit, S. H., Gotlib, I. H., et al. (2012) · Aging & Mental Health · doi:10.1080/13607863.2012.717253 · Cited by 140
“First, in earlyonset depression (EOD), repeated depressive episodes over an individual’s lifetime are posited to lead to damage to the hippocampus (Sapolsky, 1996).”
Influential
Circadian rhythms and depression: effects of exercise in an animal model
Solberg, L. C., Horton, T. H., & Turek, F. W. (1999) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1999.276.1.r152 · Cited by 134
The psychobiology of anxiolytic drugs
Sandford, J. J., Argyropoulos, S. V., & Nutt, D. (2000) · Pharmacology & Therapeutics · doi:10.1016/s0163-7258(00)00082-6 · Cited by 137
Stress Impact on Resting State Brain Networks
Soares, J. M., Sampaio, A., Ferreira, L. M., Santos, N. C., Marques, P., Marques, F., Palha, J. A., Cerqueira, J., & Sousa, N. (2013) · PLoS ONE · doi:10.1371/journal.pone.0066500 · Cited by 137
“However, when the homeostatic mechanisms are disrupted, namely through prolonged stress exposure, maladaptive responses take place and trigger inappropriate functional responses with behavioral consequences, including deficits in attention control [2–5].”
Background
Disturbances of the stress response: the role of the HPA axis during alcohol withdrawal and abstinence.
Adinoff, B. H., Iranmanesh, A., Veldhuis, J. D., & Fisher, L. (1998) · Europe PMC (PubMed Central) · Cited by 134
Epigenetic control of neurobehavioural plasticity: the role of neurotrophins
Branchi, I., Francia, N., & Alleva, E. (2004) · Behavioural Pharmacology · doi:10.1097/00008877-200409000-00006 · Cited by 133
“Stress exerts a detrimental action on hippocampal structure and function (Sapolsky, 1996, 2003), and it has been hypothesised that decreased BDNF levels represent one of the molecular mechanisms of this process (Thoenen, 1995).”
Background
Peripheral and central kynurenine pathway abnormalities in major depression
Paul, E. R., Schwieler, L., Erhardt, S., Boda, S., Trepci, A., Kämpe, R., Asratian, A., Holm, L., Yngve, A., Dantzer, R., et al. (2022) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2022.01.002 · Cited by 134
“While connections between stressrelated, melancholic MDD and neural-level dysfunction have been identified and widely discussed (Sapolsky, 1996), the present findings could help bridge the gap between a putative metabolic-inflammatory subtype and abnormal brain function.”
A Longitudinal Magnetic Resonance Imaging Study of Brain Changes in Adolescents With Anorexia Nervosa
Katzman, D. K. (1997) · Archives of Pediatrics and Adolescent Medicine · doi:10.1001/archpedi.1997.02170450043006 · Cited by 133
Prevention of chronic stress-induced depression-like behavior by inducible nitric oxide inhibitor
Wang, D., An, S. C., & Zhang, X. (2008) · Neuroscience Letters · doi:10.1016/j.neulet.2007.12.041 · Cited by 131
Favourable prognostic factors with infantile spasms
Riikonen, R. (2009) · European Journal of Paediatric Neurology · doi:10.1016/j.ejpn.2009.03.004 · Cited by 131
Long-Term Unpredictable Foraging Conditions and Physiological Stress Response in Mountain Chickadees (Poecile gambeli)
Витальевич, П. В., Kitaysky, A. S., Wingfield, J. C., & Clayton, N. S. (2001) · General and Comparative Endocrinology · doi:10.1006/gcen.2001.7684 · Cited by 131
“Prolonged, elevated levels of coricosterone resulting from long-term stress have been uggested to cause muscular atrophy, structural damge to the brain, and cognitive impairments (McEwen nd Sapolsky, 1995; Sapolsky, 1996).”
Background
Excess “read-through” acetylcholinesterase attenuates but the “synaptic” variant intensifies neurodeterioration correlates
Sternfeld, M., Shoham, S., Klein, O., Flores‐Flores, C., Evron, T., Idelson, G. H., Kitsberg, D., Patrick, J. W., & Soreq, H. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.140004597 · Cited by 130
Specifying the Neuropsychology of Affective Disorders: Clinical, Demographic and Neurobiological Factors
Beblo, T., Sinnamon, G., & Baune, B. T. (2011) · Neuropsychology Review · doi:10.1007/s11065-011-9171-0 · Cited by 128
“It is suggested from experimental research in highly stressed animals that cortisol can damage the hippocampus (Sapolsky 1996).”
Background
Abnormal Fear Memory as a Model for Posttraumatic Stress Disorder
Desmedt, A., Marighetto, A., & Piazza, P. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.06.017 · Cited by 140
Neuroimaging and emerging psychotic disorders: The Melbourne ultra-high risk studies
Pantelis, C., Velakoulis, D., Wood, S. J., Yücel, M., Yung, A. R., Phillips, L., Sun, D.-Q., & McGorry, P. D. (2007) · International Review of Psychiatry · doi:10.1080/09540260701512079 · Cited by 128
“Stress hormones, such as cortisol, or HPA-axis dysregulation have been associated with structural damage to medial temporal regions (Bremner, 1999; Sapolsky, 1996; Yehuda, 2001) and an explanation for the findings in high-risk populations from our study and from the EHRS, is that they result from…”
Background
Seeing the unexpected: How sex differences in stress responses may provide a new perspective on the manifestation of psychiatric disorders
Klein, L. C., & Corwin, E. J. (2002) · Current Psychiatry Reports · doi:10.1007/s11920-002-0072-z · Cited by 128
Selective Blockade of the Mineralocorticoid Receptor Impairs Hypothalamic‐Pituitary‐Adrenal Axis Expression of Habituation
Cole, M. A., Kalman, B. A., Pace, T. W. W., Topczewski, F., Lowrey, M. J., & Spencer, R. L. (2000) · Journal of Neuroendocrinology · doi:10.1046/j.1365-2826.2000.00555.x · Cited by 128
Translocator protein-mediated pharmacology of cholesterol transport and steroidogenesis
Papadopoulos, V., Aghazadeh, Y., Fan, J., Campioli, E., Zirkin, B. R., & Midzak, A. S. (2015) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2015.03.014 · Cited by 141
“Because of the well-known pathogenic potential of glucocorticoid excess on the hippocampus (McEwen, 1994; Sapolsky, 1996), we examined whether EGb 761 and its bioactive terpene trilactones ginkgolides A and B (GKA, GKB) exert their beneficial effect by regulating glucocorticoid levels.”
Background
Effects of Traumatic Stress on Brain Structure and Function: Relevance to Early Responses to Trauma
Bremner, J. D. (2005) · Journal of Trauma & Dissociation · doi:10.1300/j229v06n02_06 · Cited by 132
“Although cortisol released during the time of the life-threatening danger is one of the most important factors that helps survival, it may have long-term negative effects on several organ systems (Sapolsky, 1996).”
BackgroundInfluential
Interrelated and interdependent
Diamond, A. D. (2006) · Developmental Science · doi:10.1111/j.1467-7687.2007.00578.x · Cited by 137
The Influence of Depression on Cognitive Decline in Community-Dwelling Elderly Persons
Sachs‐Ericsson, N., Joiner, T. E., Plant, E. A., & Blazer, D. G. (2005) · American Journal of Geriatric Psychiatry · doi:10.1097/00019442-200505000-00009 · Cited by 126
Food deprivation modulates chronic stress effects on object recognition in male rats: role of monoamines and amino acids
Beck, K. D., & Luine, V. N. (1999) · Brain Research · doi:10.1016/s0006-8993(99)01380-3 · Cited by 127
Follow-up Care of High-Risk Infants
(2004) · PEDIATRICS · doi:10.1542/peds.2004-0866 · Cited by 127
Short-term stress experienced at time of immunization induces a long-lasting increase in immunologic memory
Dhabhar, F. S., & Viswanathan, K. (2005) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00145.2005 · Cited by 126
“It is often overlooked that an acute (lasting for minutes to hours) stress response has salubrious effects in the short run (12, 16, 32, 42), although chronic stress can be harmful (4, 14, 33, 37, 41).”
Glucocorticoids are necessary for enhancing the acquisition of associative memories after acute stressful experience
Beylin, A. V., & Shors, T. J. (2003) · Hormones and Behavior · doi:10.1016/s0018-506x(02)00025-9 · Cited by 126
Memory Mechanisms in Posttraumatic Stress Disorder
Layton, B. S., & Krikorian, R. (2002) · Journal of Neuropsychiatry · doi:10.1176/jnp.14.3.254 · Cited by 130
“LeDoux(3) speculated that peritraumatic amnesia might result from amygdalar activation of the hypothalamic-pituitary-adrenal axis, a neuroendocrinological mechanism that results in hippocampal dysfunction as a result of chronic stress.(22) However, as LeDoux himself indicated, the neuroendocrinological mechanism is im…”
Background
The relationship between potency of oxidative stress and severity of depression
Yanık, M., Erel, Ö., & Katı, M. (2004) · Acta Neuropsychiatrica · doi:10.1111/j.0924-2708.2004.00090.x · Cited by 126
“It was reported that oxidative stress, which is one of the mechanisms, causes the destruction of cells by reducing the volume in hippocampus (5,20,21).”
Background
Memory for traumatic experiences in early childhood
Cordón, I. M., Pipe, M.-E., Sayfan, L., Melinder, A., & Goodman, G. S. (2004) · Developmental Review · doi:10.1016/j.dr.2003.09.003 · Cited by 124
“Animal models, for instance, indicate that high levels of glucocorticoids released during times of stress leads to hippocampal damage (e.g., McEwen et al., 1992; Sapolsky, 1996).”
Background
Studies of hormone action in the hippocampal formation
McEwen, B. S., Magariños, A. M., & Reagan, L. P. (2002) · Journal of Psychosomatic Research · doi:10.1016/s0022-3999(02)00307-0 · Cited by 124
“[21,24] for review).”
Urban social stress – Risk factor for mental disorders. The case of schizophrenia
Lederbogen, F., Haddad, L., & Meyer‐Lindenberg, A. (2013) · Environmental Pollution · doi:10.1016/j.envpol.2013.05.046 · Cited by 130
“Chronic stress was also found to be associated with a decrease in volume in of the hippocampus, a structure central to memory storage and retrieval (Sapolsky, 1996).”
Background
Action of Glucocorticoids on Survival of Nerve Cells: Promoting Neurodegeneration or Neuroprotection?1
Ábrahám, I. M., Harkany, T., Horvath, K. M., & Luiten, P. G. M. (2001) · Journal of Neuroendocrinology · doi:10.1046/j.1365-2826.2001.00705.x · Cited by 125
Cognitive and motor development of children with and without congenital adrenal hyperplasia after early-prenatal dexamethasone
Meyer-Bahlburg, H. F. L., Dolezal, C., Baker, S. W., Carlson, A. D., Obeid, J. S., & New, M. I. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-021129 · Cited by 123

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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Why Stress Is Bad for Your Brain

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks