Sex hormone influences on the transcriptome during adolescent development of the limbic system
Bibliographic record
Abstract
Background:Major depressive disorder (MDD) is a significant global burden, with females of reproductive age affected twice as often as males of reproductive age.This prevalence difference persists across cultures and after adjusting for help-seeking biases, suggesting a biological basis related to sex differences in the limbic system.Perinatal sex hormone actions establish sex-typical brain circuitry, which is further differentiated during puberty, coinciding with the emergence of MDD gender disparities in incidence. Methods:We examined gene expression changes in the prelimbic cortex (PL), the nucleus accumbens (NAc), and the ventral hippocampus (vHIPP), across 21 time points in male and female mice, spanning peri-puberty, puberty, and adulthood.Using iDREM (Interactive Dynamic Regulatory Events Miner), we reconstructed developmental dynamic gene regulatory networks per each region and sex. Results:We observed overlaps between paths of co-expressed genes following the same direction (increase or decrease from baseline) in both males and females in the three regions, as well as overlaps between paths following opposite directions in both sexes, signaling shared adolescent developmental processes and sex-specific developmental processes.For the PL and the VH, we found that the genes from the overlap of paths with increased expression in females and decreased expression in males were enriched for immune-related processes, including pro-inflammatory cytokines, and genes involved in their synthesis, furthermore, we observed genes related to monoaminergic signaling.The NAC demonstrated sex-differences in the trajectories of paths including genes involved with vitamin D synthesis and signaling.These region-specific variations suggest that each area of the brain contributes differently to the observed sex differences in vulnerability to depression. Conclusion:Overall, our results provide insights into the role of adolescent development across brain regions in the molecular mechanisms underpinning the sex-biased MDD susceptibility.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".