Effects of Variations in Daily Cortisol Pattern and Long-Term Cortisol Output on Hippocampal Subfield Volumes in the Adult Human Brain
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Bibliographic record
Abstract
Animal models of adult chronic stress indicate that the cornu ammonis 1–3 (CA1–3) and dentate gyrus (DG) hippocampal subfields are most susceptible to cellular changes associated with prolonged psychogenic stressors and glucocorticoid overexposure. However, no study reported to date has examined associations between long-term cortisol output, chronic stress, and hippocampal subfield volumes in healthy adults experiencing different levels of chronic stress. The main goal of the current study was to test whether higher long-term cortisol output measured by hair cortisol concentration would be associated with atrophy of CA1–3 and DG hippocampal subfields. We examined associations between short- and long-term cortisol output and hippocampal subfield volumes in healthy adults ( N = 40). High-resolution structural magnetic resonance imaging datasets were acquired together with diurnal salivary cortisol and hair cortisol measures. Hair cortisol concentration was analyzed using the high-resolution liquid chromatography–mass spectrometry method. Higher hair cortisol concentration was associated with smaller volumes of all hippocampal subfields in the anterior hippocampus and smaller DG volumes in both the anterior and posterior hippocampus. We found that a larger increase in morning cortisol level after awakening was associated with smaller DG and CA1–3 volumes, while a smaller decrease in cortisol level in the afternoon from awakening was associated with smaller CA1–3 volume in the anterior hippocampus. The observed associations between cortisol and hippocampal subfield volumes were not predicted by individual chronic stress levels or history of childhood trauma. Our results suggest that both increased hair cortisol concentration and daily cortisol fluctuations can have a negative impact on the CA1–3 and DG subfields. Stress activates the hypothalamic-pituitary-adrenal (HPA) axis, resulting in the release of corticosteroid hormones. While brief HPA axis activation maximizes survival potential in the face of acute or daily stressors, continuous or excessive HPA axis activation can be maladaptive and eventually lead to mental and physical health conditions. In the current study, we found that long-term cortisol output measured by hair cortisol concentration was associated with atrophy of specific hippocampal subfields. The observed associations between cortisol and hippocampal subfield volumes were not predicted by individual chronic stress levels or history of childhood trauma.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it