Sex-dependent gene expression during puberty has potential mechanistic implications for the development of major depressive disorder
Bibliographic record
Abstract
Major Depressive Disorder (MDD) is a complex illness with heterogeneous symptom profiles, affecting 5% of the global population. Recent molecular studies across biological systems suggest that the manifestations of MDD are significantly shaped by sex. In response, this narrative review organizes up-to-date findings on sex-specific, MDD-related gene expression into multiple biological systems-primarily available from adult human and rodent studies. This adult-centric focus highlights a critical gap: when and how sex-dependent, MDD-associated gene expression patterns emerge, and contribute to adult manifestations. We identify puberty as a sensitive developmental window during which sex-dependent gene expression and regulatory patterns may emerge and carry their impacts into adulthood. We define this as a sex-specific framework established during puberty. To address the "how," we synthesize empirical evidence on the molecular mechanisms associated with the emergence and long-term influence of this framework. Finally, we explore how perturbations acting on this framework may further bifurcate expression patterns and ultimately give rise to the sex-divergent manifestations of MDD observed in adulthood. Overall, this review positions puberty as a key developmental window and calls for future sex-stratified functional genomic studies that span the pubertal timeline.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 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".