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Sex differences and stress across the lifespan
Open accessAbstract
Sex differences in stress responses can be found at all stages of life and are related to both the organizational and activational effects of gonadal hormones and to genes on the sex chromosomes. As stress dysregulation is the most common feature across neuropsychiatric diseases, sex differences in how these pathways develop and mature may predict sex-specific periods of vulnerability to disruption and increased disease risk or resilience across the lifespan. The aging brain is also at risk to the effects of stress, where the rapid decline of gonadal hormones in women combined with cellular aging processes promote sex biases in stress dysregulation. In this Review, we discuss potential underlying mechanisms driving sex differences in stress responses and their relevance to disease. Although stress is involved in a much broader range of diseases than neuropsychiatric ones, we highlight here this area and its examples across the lifespan.
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“the mechanisms to cope with stressors differ between males and females”
From Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity (2017) · cites this paper as Bale & Epperson, 2015
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“Both adolescence and the perinatal period are times of increased risk of the emergence of mental health problems.92”
From The transition to parenthood in obstetrics: enhancing prenatal care for 2-generation impact (2022) · cites this paper as [92]
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Metadata
- Authors
- Bale, T. L., & Epperson, C. N.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Bale, Tracy L
- Venue
- Nature Neuroscience
- Published
- 2015-09-25
- Volume
- 18
- Issue
- 10
- Pages
- 1413-1420
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC4620712
- OpenAlex
- W1734948187
- Cited by
- 751
- References
- 150
- Citations by year
- 2026: 70 · 2025: 89 · 2024: 61 · 2023: 52 · 2022: 74 · 2021: 91 · 2020: 70 · 2019: 72 · 2018: 81 · 2017: 46 · 2016: 44
- FWCI
- 4.55
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5r01mh091258-05)
- National Institute on Aging (R01AG048839, AG048839)
- National Institute of Mental Health (P50MH099910, R37MH108286, MH087597, MH 104184, MH 091258, MH099910, R01MH073030, MH 073030, R33MH104184, MH 108286, R01 MH-091258, R21MH104184, R01MH087597)
- National Institute on Drug Abuse (R01DA037289, DA030301, K24DA030301)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- sex differences, stress, stress dysregulation, lifespan development, gonadal hormones, organizational effects, activational effects, sex chromosomes, neuropsychiatric disorders, resilience, brain aging, cellular aging
- MeSH terms
- Aging, Animals, Brain, Female, Humans, Longevity, Male, Sex Characteristics, Stress, Psychological
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