60 YEARS OF NEUROENDOCRINOLOGY: Redefining neuroendocrinology: stress, sex and cognitive and emotional regulation
Open accessAbstract
The discovery of steroid hormone receptors in brain regions that mediate every aspect of brain function has broadened the definition of ‘neuroendocrinology’ to include the reciprocal communication between the brain and the body via hormonal and neural pathways. The brain is the central organ of stress and adaptation to stress because it perceives and determines what is threatening, as well as the behavioral and physiological responses to the stressor. The adult and developing brain possess remarkable structural and functional plasticity in response to stress, including neuronal replacement, dendritic remodeling, and synapse turnover. Stress causes an imbalance of neural circuitry subserving cognition, decision-making, anxiety and mood that can alter expression of those behaviors and behavioral states. This imbalance, in turn, affects systemic physiology via neuroendocrine, autonomic, immune and metabolic mediators. In the short term, as for increased fearful vigilance and anxiety in a threatening environment, these changes may be adaptive. But, if the danger passes and the behavioral state persists along with the changes in neural circuitry, such maladaptation may need intervention with a combination of pharmacological and behavioral therapies, as is the case for chronic anxiety and depression. There are important sex differences in the brain responses to stressors that are in urgent need of further exploration. Moreover, adverse early-life experience, interacting with alleles of certain genes, produce lasting effects on brain and body over the life-course via epigenetic mechanisms. While prevention is most important, the plasticity of the brain gives hope for therapies that take into consideration brain–body interactions.
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Most findings on childhood trauma and alcohol outcomes come from adult population-based data with retrospective reports of childhood trauma.
“However, most findings are from adult population-based data with retrospective reports of CT (8,9).”
From Impact of Childhood Trauma on Executive Function in Adolescence—Mediating Functional Brain Networks and Prediction of High-Risk Drinking (2020) · cites this paper as [9]
Prior literature suggests childhood trauma sets off a cascade of neurobiological events that produce lasting alterations in susceptible people, including neurohumoral and proinflammatory responses to severe chronic stress and changes in brain development, network architecture, and circuits.
“Previous literature suggests that CT triggers a cascade of neurobiological events that lead to enduring alterations in susceptible individuals.”
From Impact of Childhood Trauma on Executive Function in Adolescence—Mediating Functional Brain Networks and Prediction of High-Risk Drinking (2020) · cites this paper as [9]
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Self-citationEffects of estrogen in the CNS
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Estrogen Promotes Stress Sensitivity in a Prefrontal Cortex-Amygdala Pathway
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Self-citationSpatial memory retention is enhanced by acute and continuous estradiol replacement
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Stress and the dynamic genome: Steroids, epigenetics, and the transposome
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Self-citationCan Posttraumatic Stress Disorder Be Prevented with Glucocorticoids?
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Pereira, A. C., Lambert, H. K., Grossman, Y. S., Dumitriu, D., Waldman, R., Jannetty, S. K., Calakos, K., Janssen, W. G., McEwen, B. S., & Morrison, J. H. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1421285111 · Cited by 116 · see citing works
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Localization of the Glucocorticoid Receptor in Rat Brain Mitochondria
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Self-citationCellular and molecular mechanisms of hippocampal activation by acute stress are age-dependent
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Environment complexity stimulates visual cortex neurogenesis: death of a dogma and a research career
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New Interneurons in the Adult Neocortex: Small, Sparse, but Significant?
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Estrogen and the aging brain: an elixir for the weary cortical network
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Self-citationEstradiol Facilitates the Release of Neuropeptide Y to Suppress Hippocampus-Dependent Seizures
Ledoux, V. A., Smejkalová, T., May, R. M., Cooke, B. M., & Woolley, C. S. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.4688-08.2009 · Cited by 85 · see citing works
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Seasonal and sex differences in the hippocampus of a wild rodent
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Association of 3H Corticosterone-1,2 with Macromolecules extracted from Brain Cell Nuclei
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Self-citationInfant temperament predicts life span in female rats that develop spontaneous tumors
Cavigelli, S. A., Yee, J. R., & McClintock, M. K. (2006) · Hormones and Behavior · doi:10.1016/j.yhbeh.2006.06.001 · Cited by 55 · see citing works
Akers, K. G., Yang, Z., DelVecchio, D. P., Reeb, B. C., Romeo, R. D., McEwen, B. S., & Tang, A. C. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002840 · Cited by 54 · see citing works
Self-citationStress-Induced Lipocalin-2 Controls Dendritic Spine Formation and Neuronal Activity in the Amygdala
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Miller, M. M., Morrison, J. H., & McEwen, B. S. (2012) · Behavioural Brain Research · doi:10.1016/j.bbr.2012.01.029 · Cited by 46 · see citing works
Self-citationRomeo, R. D., Staub, D. R., Jasnow, A. M., Karatsoreos, I. N., Thornton, J. E., & McEwen, B. S. (2005) · Endocrinology · doi:10.1210/en.2004-0886 · Cited by 46 · see citing works
Self-citationBloss, E. B., Hunter, R. G., Waters, E. M., Muñoz, C., Bernard, K., & McEwen, B. S. (2007) · Experimental Neurology · doi:10.1016/j.expneurol.2007.10.007 · Cited by 43 · see citing works
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Next generation antidepressants
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Antidepressant epigenetic action
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- Authors
- McEwen, B. S., Gray, J. D., & Nasca, C.
- Affiliations
- Rockefeller University (US)
- Corresponding author
- McEwen, Bruce S
- Venue
- Journal of Endocrinology
- Publisher
- Bioscientifica
- Published
- 2015-05-01
- Volume
- 226
- Issue
- 2
- Pages
- T67-T83
- ISSN
- 0022-0795 (ISSN-L)
- 1479-6805
- PMC
- PMC4515381
- OpenAlex
- W2264087504
- Cited by
- 253
- References
- 150
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 10 · 2023: 22 · 2022: 20 · 2021: 37 · 2020: 17 · 2019: 25 · 2018: 27 · 2017: 33 · 2016: 36 · 2015: 9
- FWCI
- 2.72
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- American Foundation for Suicide Prevention
- Hope for Depression Research Foundation
- National Institutes of Health (MH41256)
- National Institute of Mental Health (R37MH041256, F32MH102065, R01MH041256)
- National Institute of Neurological Disorders and Stroke (R01NS007080)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- neuroendocrinology, stress, sex differences, steroid hormone receptors, neuroplasticity, anxiety, depression, cognitive regulation, emotion regulation, childhood adversity, epigenetics, gene-environment interaction, brain-body interaction, neuroendocrine pathways
- MeSH terms
- Brain, Cognition, Emotions, Humans, Hydrocortisone, Hypothalamo-Hypophyseal System, Pituitary-Adrenal System, Sex Characteristics, Stress, Physiological, Stress, Psychological, Epigenesis, Genetic
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