Prospective reports of chronic life stress predict decreased grey matter volume in the hippocampus
Open accessAbstract
Chronic stress in non-human animals decreases the volume of the hippocampus, a brain region that supports learning and memory and that regulates neuroendocrine activity. In humans with stress-related psychiatric syndromes characterized by impaired learning and memory and dysregulated neuroendocrine activity, surrogate and retrospective indicators of chronic stress are also associated with decreased hippocampal volume. However, it is unknown whether chronic stress is associated with decreased hippocampal volume in those without a clinical syndrome. We tested whether reports of life stress obtained prospectively over an approximate 20-year period predicted later hippocampal grey matter volume in 48 healthy postmenopausal women. Women completed the Perceived Stress Scale repeatedly from 1985 to 2004; in 2005 and 2006, their hippocampal grey matter volume was quantified by voxel-based morphometry. Higher Perceived Stress Scale scores from 1985 to 2004 - an indicator of more chronic life stress - predicted decreased grey matter volume in the right orbitofrontal cortex and right hippocampus. These relationships persisted after accounting for age, total grey matter volume, time since menopause, use of hormone therapy, subclinical depressive symptoms, and other potentially confounding behavioral and age-related cerebrovascular risk factors. The relationship between chronic life stress and regional grey matter volume - particularly in the hippocampus and orbitofrontal cortex - appears to span a continuum that extends to otherwise healthy individuals. Consistent with animal and human clinical evidence, we speculate that chronic-stress-related variations in brain morphology are reciprocally and functionally related to adaptive and maladaptive changes in cognition, neuroendocrine activity, and psychiatric vulnerability.
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In a prospective cohort study of postmenopausal women, higher scores on perceived stress, averaged over nearly two decades, predicted smaller hippocampal grey matter.
“In a prospective cohort study of postmenopausal women, higher scores on perceived stress, averaged over nearly two decades, predicted smaller hippocampal grey matter (Gianaros et al., 2007).”
From More than a feeling: A unified view of stress measurement for population science (2018) · cites this paper as Gianaros et al., 2007
Voxel-based morphometry has uncovered a relationship between shrinkage of grey matter volume in the hippocampus and orbitofrontal cortex and prospective reports of chronic life stress over a 20 year period.
“Another study, using voxel-based morphometry, has uncovered a relationship between shrinkage of grey matter volume in the hippocampus and orbitofrontal cortex and prospective reports of chronic life stress over a 20 year period (Gianaros et al., 2007).”
From Central effects of stress hormones in health and disease: understanding the protective and damaging effects of stress and stress mediators (2008) · cites this paper as Gianaros et al., 2007
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- Authors
- Gianaros, P. J., Jennings, J. R., Sheu, L. K., Greer, P. J., Kuller, L. H., & Matthews, K. A.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- Gianaros, Peter J.
- Venue
- NeuroImage
- Publisher
- Elsevier BV
- Published
- 2007-04
- Volume
- 35
- Issue
- 2
- Pages
- 795-803
- ISSN
- 1053-8119 (ISSN-L)
- PMC
- PMC1868546
- OpenAlex
- W1984959581
- Cited by
- 324
- References
- 76
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 15 · 2023: 12 · 2022: 21 · 2021: 25 · 2020: 19 · 2019: 15 · 2018: 17 · 2017: 21 · 2016: 19 · 2015: 11 · 2014: 24 · 2013: 24 · 2012: 22
- FWCI
- 6.49
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- NeuroImage (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Public Health Service (K01-070616-01)
- National Heart, Lung, and Blood Institute (HL076852=076858, R24HL076852)
- National Institute of Mental Health (K01MH070616)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Keywords
- orbitofrontal cortex, perceived stress, postmenopausal women, brain structure, neuroendocrine activity, cognitive impairment, hormone therapy
- MeSH terms
- Aged, Chronic Disease, Female, Hippocampus, Humans, Organ Size, Prospective Studies, Stress, Psychological
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