Decreased hippocampal volume in healthy girls at risk of depression
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CONTEXT: Researchers have documented that the hippocampus is smaller in individuals with depression than in those without. The temporal or causal association of this reduction in hippocampal volume in depression, however, is not known. OBJECTIVE: To test the hypothesis that reduced hippocampal volume precedes and therefore may be implicated in the onset of depression. DESIGN: We used magnetic resonance imaging to examine brain structure volume in individuals at high and low familial risk of depression. Anatomic images from magnetic resonance imaging were analyzed using both whole-brain voxel-based morphometry and manual tracing of the bilateral hippocampus. SETTING: A research university. PARTICIPANTS: Fifty-five girls aged between 9 and 15 years: 23 daughters of mothers with recurrent episodes of depression in the daughter's lifetime (high risk) and 32 age-matched daughters of mothers with no history of psychopathology (low risk). None of the girls had any past or current Axis I psychopathology. MAIN OUTCOME MEASURES: Group differences in voxel-based morphometry brain matter density estimates and traced hippocampal volume. RESULTS: Voxel-based morphometry analyses indicated that individuals at high risk of depression had significantly less gray matter density in clusters in the bilateral hippocampus (P < .001) than low-risk participants. Tracing yielded a volumetric reduction in the left hippocampus in the high-risk participants (P < .05). CONCLUSIONS: Compared with individuals at low familial risk of the development of depression, high-risk individuals have reduced hippocampal volume, indicating that neuroanatomic anomalies associated with depression may precede the onset of a depressive episode and influence the development and course of this disorder.
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Some studies indicate that these structural changes may represent a pre-existing vulnerability to a major depressive episode, especially in people with particular genetic profiles or early life stress histories.
“several other studies have found that these structural changes may reflect a pre-existing vulnerability to a MDE, particularly for individuals with certain genetic profiles and/or early life stress (ELS) histories (39–45).”
From The Impact of Stress and Major Depressive Disorder on Hippocampal and Medial Prefrontal Cortex Morphology (2019) · cites this paper as [39]
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Groenewold, N. A., Wedderburn, C. J., Pellowski, J. A., Fouché, J.-P., Michalak, L., Roos, A., Woods, R. P., Narr, K. L., Zar, H. J., Donald, K. A., et al. (2022) · NeuroImage: Clinical · doi:10.1016/j.nicl.2022.103206 · Cited by 22 · see citing works
Hippocampal volume and the course of depressive symptoms over eight years of follow‐up
Buddeke, J., Kooistra, M., Zuithoff, N. P. A., Gerritsen, L., Biessels, G. J., van der Graaf, Y., Geerlings, M. I., & the SMART Study Group (2017) · Acta Psychiatrica Scandinavica · doi:10.1111/acps.12662 · Cited by 14 · see citing works
- Authors
- Chen, M. C., Hamilton, J. P., & Gotlib, I. H.
- Affiliations
- Stanford University (US)
- Venue
- Archives of General Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2010-03-01
- Volume
- 67
- Issue
- 3
- Pages
- 270
- ISSN
- 0003-990X (ISSN-L)
- PMC
- PMC2845291
- OpenAlex
- W2155962001
- Cited by
- 220
- References
- 62
- Citations by year
- 2026: 8 · 2025: 6 · 2024: 5 · 2023: 12 · 2022: 13 · 2021: 10 · 2020: 14 · 2019: 7 · 2018: 12 · 2017: 12 · 2016: 11 · 2015: 14 · 2014: 25 · 2013: 16 · 2012: 19
- FWCI
- 9.41
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Archives of General Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (R01MH074849, MH074849)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- hippocampal volume, depression, adolescent girls, gray matter density, hippocampal atrophy, maternal depression, brain structure
- MeSH terms
- Adolescent, Adult, Atrophy, Brain, Child, Depressive Disorder, Major, Major Depressive Disorder, Female, Health Status, Hippocampus, Humans, Image Interpretation, Computer-Assisted, Functional Laterality, Magnetic Resonance Imaging, Middle Aged, Mothers, Surveys and Questionnaires, Recurrence, Risk Factors, Child of Impaired Parents
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.
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