Sex-specific impact of prenatal androgens on social brain default mode subsystems
Bibliographic record
Abstract
Early-onset neurodevelopmental conditions (e.g., autism) affect males more frequently than females. Androgens may play a role in this male-bias by sex-differentially impacting early prenatal brain development, particularly neural circuits that later develop specialized roles in social cognition. Here, we find that increasing prenatal testosterone in humans is associated with later reduction of functional connectivity between social brain default mode (DMN) subsystems in adolescent males, but has no effect in females. Since testosterone can work directly via the androgen receptor (AR) or indirectly via the estrogen receptor through aromatase conversion to estradiol, we further examined how a potent non-aromatizable androgen, dihydrotestosterone (DHT), acts via the AR to influence gene expression in human neural stem cells (hNSC)-particularly for genes of high-relevance for DMN circuitry. DHT dysregulates a number of genes enriched for syndromic causes of autism and intellectual disability and for genes that in later development are expressed in anatomical patterns that highly correspond to the cortical midline DMN subsystem. DMN-related and DHT-affected genes (e.g., MEF2C) are involved in a number of synaptic processes, many of which impact excitation-inhibition balance. Androgens have male-specific prenatal influence over social brain circuitry in humans and may be relevant towards explaining some component of male-bias in early-onset neurodevelopmental conditions.
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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) | 0.000 | 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".