Ancestral Stress Alters Lifetime Mental Health Trajectories and Cortical Neuromorphology via Epigenetic Regulation
Bibliographic record
Abstract
Experiences during early development are powerful determinants of lifetime mental health. Here we investigated if ancestral stress regulates the brain's epigenetic memory to alter neuromorphology and emotionality in the remote F4 progeny. Pregnant female rat dams of the parental F0 generation were exposed to stress on gestational days 12-18. To generate a transgenerational stress lineage, their pregnant daughters (F1), grand-daughters (F2) and great-grand-daughters (F3) remained undisturbed. To generate a multigenerational stress lineage, pregnant dams of each generation (F1-F3) were stressed. A lineage of non-stress controls (F0-F3) was also produced. Multigenerational stress exceeded the impact of transgenerational stress by increasing anxiety-like behaviours and stress response in young and middle-aged F4 males but not females. Functional changes were accompanied by reduced spine density in the male medial prefrontal cortex with opposite effects in the orbital frontal cortex. Ancestral stress regulated cortical miR-221 and miR-26 expression and their target genes, thus downregulating ntrk2 and map1a genes in males while downregulating crh and upregulating map1a genes in females. These miRNA-dependent pathways are candidates for developmental programming of lifetime mental health. Thus, multigenerational stress in particular determines sexually dimorphic predisposition to stress vulnerability and generates a phenotype resembling symptoms of post-traumatic stress disorder.
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How this classification was reachedexpand
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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".