Negative life stress and longitudinal hippocampal volume changes in older adults with and without depression
Open accessAbstract
Major depressive disorder is associated with smaller hippocampal volumes but the mechanisms underlying this relationship are unclear. To examine the effect of environmental influences, we examined the relationship between self-reported stressors and two-year change in hippocampal volume. Seventy elderly nondepressed subjects and eighty-nine elderly depressed subjects were followed for two years. The number of negative stressful life events (nSLE), perceived stress levels, and cranial MRI were obtained at baseline and at the two-year assessment. For secondary analyses, subjects provided blood for 5-HTTLPR polymorphism genotyping. After controlling for covariates including presence or absence of depression, greater numbers of baseline nSLEs were significantly associated with greater baseline hippocampal volumes bilaterally. Greater numbers of baseline nSLEs were also associated with reduction in hippocampal volume over two years in the right but not the left hemisphere. Neither perceived stress levels nor changes in stress measures were significantly associated with hippocampal volume measures. However, in secondary analyses, we found that increases in perceived stress over time was associated with volume reduction of the left hippocampus, but only in 5-HTTLPR L/L homozygotes. Our findings suggest different short- and long-term effects of negative life stressors on hippocampal volumes in older adults. These effects appear independent on the presence or absence of depression. Fu…
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Some studies have observed an association between the number of stressful life events and increased hippocampal volume in elderly, nondepressed subjects.
“Some studies have observed an association between the number of stressful life events and increased hippocampal volume in elderly, nondepressed subjects (53).”
From Neuroanatomic differences associated with stress susceptibility and resilience (2016) · cites this paper as [53]
Cites
Folstein, M. F., Folstein, S. E., & McHugh, P. R. (1975) · Journal of Psychiatric Research · doi:10.1016/0022-3956(75)90026-6 · Cited by 88,282 · see citing works
A new depression scale designed to be sensitive to change
Montgomery, S. A., & Åsberg, M. (1979) · British Journal of Psychiatry · doi:10.1192/bjp.134.4.382 · Cited by 13,962 · see citing works
Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene
Caspi, A., Sugden, K., Moffitt, T. E., Taylor, A., Craig, I. W., Harrington, H., McClay, J., Mill, J., Martin, J., Braithwaite, A., et al. (2003) · Science · doi:10.1126/science.1083968 · Cited by 8,120 · see citing works
Robins, L. N. (1981) · Archives of General Psychiatry · doi:10.1001/archpsyc.1981.01780290015001 · Cited by 5,219 · see citing works
Causal Relationship Between Stressful Life Events and the Onset of Major Depression
Kendler, K. S., Karkowski, L. M., & Prescott, C. A. (1999) · American Journal of Psychiatry · doi:10.1176/ajp.156.6.837 · Cited by 2,486 · cited 8× · see citing works
“The neurotoxicity hypothesis posits that chronic hyperactivity of the stress system in MDD leads to decreased neurogenesis, augmented neuroinflammation, dendritic retraction, and accelerated apoptosis (Lucassen et al., 2006; Sorrells et al., 2009).”
BackgroundInfluentialHippocampal 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 · see citing works
JACOBSON, L., & SAPOLSKY, R. (1991) · Endocrine Reviews · doi:10.1210/edrv-12-2-118 · Cited by 1,739 · see citing works
Hippocampal volume and depression: a meta-analysis of MRI studies
Videbech, P., & Ravnkilde, B. (2004) · American Journal of Psychiatry · doi:10.1176/appi.ajp.161.11.1957 · Cited by 1,590 · see citing works
Smith, M., Makino, S., Květňanský, R., & Post, R. M. (1995) · Journal of Neuroscience · doi:10.1523/jneurosci.15-03-01768.1995 · Cited by 1,429 · see citing works
Untreated Depression and Hippocampal Volume Loss
Sheline, Y. I., Gado, M. H., & Kraemer, H. C. (2003) · American Journal of Psychiatry · doi:10.1176/appi.ajp.160.8.1516 · Cited by 1,180 · see citing works
Early Life Stress and Morphometry of the Adult Anterior Cingulate Cortex and Caudate Nuclei
Cohen, R. A., Grieve, S., Hoth, K. F., Paul, R. H., Sweet, L., Tate, D., Gunstad, J., Stroud, L., McCaffery, J., Hitsman, B., et al. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.12.016 · Cited by 439 · see citing works
The Stressed CNS: When Glucocorticoids Aggravate Inflammation
Sorrells, S. F., Caso, J. R., Munhoz, C. D., & Sapolsky, R. M. (2009) · Neuron · doi:10.1016/j.neuron.2009.09.032 · Cited by 425 · cited 2× · see citing works
“The neurotoxicity hypothesis posits that chronic hyperactivity of the stress system in MDD leads to decreased neurogenesis, augmented neuroinflammation, dendritic retraction, and accelerated apoptosis (Lucassen et al., 2006; Sorrells et al., 2009).”
BackgroundCzéh, B., & Lucassen, P. J. (2007) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-007-0728-0 · Cited by 419 · see citing works
Hippocampal volume in geriatric depression
Steffens, D. C., Byrum, C. E., McQuoid, D. R., Greenberg, D. L., Payne, M. E., Blitchington, T. F., MacFall, J. R., & Krishnan, K. R. R. (2000) · Biological Psychiatry · doi:10.1016/s0006-3223(00)00829-5 · Cited by 375 · see citing works
Self-citationIsgor, C., Kabbaj, M., Akil, H., & Watson, S. J. (2004) · Hippocampus · doi:10.1002/hipo.10207 · Cited by 341 · see citing works
Bell-McGinty, S., Butters, M. A., Meltzer, C. C., Greer, P. J., Reynolds, C. F., & Becker, J. T. (2002) · American Journal of Psychiatry · doi:10.1176/appi.ajp.159.8.1424 · Cited by 338 · see citing works
Serotonin and Hippocampal Neurogenesis
Gould, E. (1999) · Neuropsychopharmacology · doi:10.1016/s0893-133x(99)00045-7 · Cited by 328 · see citing works
Prospective reports of chronic life stress predict decreased grey matter volume in the hippocampus
Gianaros, P. J., Jennings, J. R., Sheu, L. K., Greer, P. J., Kuller, L. H., & Matthews, K. A. (2007) · NeuroImage · doi:10.1016/j.neuroimage.2006.10.045 · Cited by 324 · see citing works
Cole, J., Costafreda, S. G., McGuffin, P., & Fu, C. H. Y. (2011) · Journal of Affective Disorders · doi:10.1016/j.jad.2011.05.057 · Cited by 319 · see citing works
Serotonin activates the hypothalamic–Pituitary–Adrenal axis via serotonin 2C receptor stimulation
Heisler, L. K., Pronchuk, N., Nonogaki, K., Zhou, L., Raber, J., Tung, L., Yeo, G. S. H., O'Rahilly, S., Colmers, W. F., Elmquist, J. K., et al. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.2584-06.2007 · Cited by 292 · see citing works
Stress, Depression and Hippocampal Apoptosis
Lucassen, P. J., Heine, V. M., Müller, M. B., van der Beek, E. M., Wiegant, V. M., de Kloet, E. R., Joëls, M., Fuchs, E., Swaab, D. F., & Czéh, B. (2006) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/187152706778559273 · Cited by 253 · see citing works
Decreased hippocampal volume in healthy girls at risk of depression
Chen, M. C., Hamilton, J. P., & Gotlib, I. H. (2010) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2009.202 · Cited by 220 · see citing works
The effects of exercise and stress on the survival and maturation of adult‐generated granule cells
Snyder, J. S., Glover, L. R., Sanzone, K. M., Kamhi, J. F., & Cameron, H. A. (2009) · Hippocampus · doi:10.1002/hipo.20552 · Cited by 181 · see citing works
Taylor, W. D., Steffens, D. C., Payne, M. E., MacFall, J. R., Marchuk, D. A., Svenson, I. K., & Krishnan, K. (2005) · Archives of General Psychiatry · doi:10.1001/archpsyc.62.5.537 · Cited by 180 · see citing works
Self-citationO'Hara, R., Schröder, C. M., Mahadevan, R., Schatzberg, A. F., Lindley, S., Fox, S., Weiner, M., Kraemer, H. C., Noda, A., Lin, X., et al. (2007) · Molecular Psychiatry · doi:10.1038/sj.mp.4001978 · Cited by 171 · see citing works
Depression and the hippocampus: cause or effect?
Sheline, Y. I. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.06.006 · Cited by 159 · see citing works
Pruessner, M., Pruessner, J. C., Hellhammer, D. H., Bruce Pike, G., & Lupien, S. J. (2007) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2006.12.007 · Cited by 150 · see citing works
Hippocampal volume and antidepressant response in geriatric depression
Hsieh, M., McQuoid, D. R., Levy, R. M., Payne, M. E., MacFall, J. R., & Steffens, D. C. (2002) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.611 · Cited by 136 · see citing works
Self-citationEarly Life Stress and Inherited Variation in Monkey Hippocampal Volumes
Lyons, D. M., Yang, C., Sawyer-Glover, A. M., Moseley, M. E., & Schatzberg, A. F. (2001) · Archives of General Psychiatry · doi:10.1001/archpsyc.58.12.1145 · Cited by 134 · see citing works
Ganzel, B. L., Kim, P., Glover, G. H., & Temple, E. (2008) · NeuroImage · doi:10.1016/j.neuroimage.2007.12.010 · Cited by 127 · see citing works
Papagni, S. A., Benetti, S., Arulanantham, S., McCrory, E., McGuire, P., & Mechelli, A. (2011) · Stress · doi:10.3109/10253890.2010.522279 · Cited by 126 · see citing works
Steffens, D. C., McQuoid, D. R., Payne, M. E., & Potter, G. G. (2010) · American Journal of Geriatric Psychiatry · doi:10.1097/jgp.0b013e3181d6c245 · Cited by 125 · see citing works
Self-citationPayne, M. E., Fetzer, D. L., MacFall, J. R., Provenzale, J. M., Byrum, C. E., & Krishnan, K. (2002) · Psychiatry Research Neuroimaging · doi:10.1016/s0925-4927(02)00009-4 · Cited by 96 · see citing works
Self-citationKarg, K., Burmeister, M., Shedden, K., & Sen, S. (2011) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2010.189 · Cited by 87 · see citing works
The Duke Somatic Treatment Algorithm for Geriatric Depression (STAGED) Approach
Steffens, D. C., McQuoid, D. R., MHS, McQuoid, D. R., Bartolomé Iglesias, S., Krishnan, A. K. R. R., & Rush, A. J. (2025) · Psychopharmacology Bulletin · doi:10.64719/pb.4224 · Cited by 84 · see citing works
Self-citationEker, M. C., Kitiş, Ö., Okur, H., Eker, Ö. D., Ozan, E., Işıklı, S., Akarsu, N. A., & Gönül, A. S. (2010) · Neuropsychobiology · doi:10.1159/000321834 · Cited by 69 · see citing works
Psychosocial and physical correlates of chronic depression
Hays, J. C., Krishnan, K. R., George, L. K., Pieper, C. F., Flint, E. P., & Blazer, D. G. (1997) · Psychiatry Research · doi:10.1016/s0165-1781(97)00105-4 · Cited by 67 · see citing works
Everaerd, D., Gerritsen, L., Rijpkema, M., Frodl, T., van Oostrom, I., Franke, B., Fernández, G., & Tendolkar, I. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2012.32 · Cited by 58 · see citing works
Zannas, A. S., McQuoid, D. R., Steffens, D. C., Chrousos, G. P., & Taylor, W. D. (2012) · Stress · doi:10.3109/10253890.2011.634263 · Cited by 40 · see citing works
Self-citationLongitudinal changes in hippocampal volumes and cognition in remitted geriatric depressive disorder
Hou, Z., Yuan, Y., Zhang, Z., Bai, F., Hou, G., & You, J. (2011) · Behavioural Brain Research · doi:10.1016/j.bbr.2011.10.025 · Cited by 39 · see citing works
Allelic Differences in the Serotonin Transporter-Linked Polymorphic Region in Geriatric Depression
Steffens, D. C., Svenson, I. K., Marchuk, D. A., Levy, R. M., Hays, J. C., Flint, E. P., Krishnan, K., & Siegler, I. C. (2002) · American Journal of Geriatric Psychiatry · doi:10.1097/00019442-200203000-00009 · Cited by 35 · see citing works
Self-citationAllelic Differences in the Serotonin Transporter-Linked Polymorphic Region in Geriatric Depression
Steffens, D. C. (2002) · American Journal of Geriatric Psychiatry · doi:10.1176/appi.ajgp.10.2.185 · Cited by 5 · see citing works
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- Authors
- Zannas, A. S., McQuoid, D. R., Payne, M. E., Steffens, D. C., MacFall, J. R., Ashley-Koch, A., & Taylor, W. D.
- Affiliations
- Duke Medical Center (US)
- UConn Health (US)
- Vanderbilt University (US)
- Corresponding author
- Taylor, Warren D.
- Venue
- Journal of Psychiatric Research
- Publisher
- Elsevier BV
- Published
- 2013-06
- Volume
- 47
- Issue
- 6
- Pages
- 829-834
- ISSN
- 0022-3956 (ISSN-L)
- PMC
- PMC3622849
- OpenAlex
- W2163181233
- Cited by
- 53
- References
- 42
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 3 · 2022: 5 · 2021: 1 · 2020: 4 · 2019: 4 · 2018: 5 · 2017: 2 · 2016: 8 · 2015: 7 · 2014: 7 · 2013: 2
- FWCI
- 3.64
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Journal of Psychiatric Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (K24MH070027, R01MH054846, R01MH077745)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Social Sciences › Psychology › Clinical Psychology › Health and Well-being Studies
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- hippocampal volume, major depressive disorder, older adults, perceived stress, 5-HTTLPR polymorphism, brain aging, genetic moderation
- MeSH terms
- Aged, Aging, Depressive Disorder, Female, Follow-Up Studies, Hippocampus, Homozygote, Humans, Functional Laterality, Male, Polymorphism, Genetic, Stress, Psychological, Time Factors, Serotonin Plasma Membrane Transport Proteins
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