Role of the locus coeruleus noradrenergic system in susceptibility and resilience following early life stress in male and female mice
Bibliographic record
Abstract
Abstract Child adversity (CA), encompassing emotional, physical, and sexual maltreatment or abuse, affects a substantial number of children worldwide. Moreover, it is the leading predictor of psychiatric disorders such as major depressive disorder (MDD), anxiety, and suicidal behavior. Despite the robust link between CA and psychopathology, individual outcomes vary significantly, with some children demonstrating resilience. Resilience is an adaptive and dynamic process, which mitigates the long-term effects of CA, suggesting potential protective mechanisms that remain underexplored. This study investigates behavioural susceptibility and resilience following early life stress (ELS) and examined whether these outcomes are associated with sex-dependent alteration of the locus coeruleus-norepinephrine (LC-NE) system, a critical modulator of stress, cognition, and emotion. Using a maternal deprivation model combined with limited nesting and bedding, we examined sex-dependent behavioral, physiological, and neurobiological markers associated with ELS outcomes in mice. Behavioral clustering revealed distinct phenotypes: resilient, anxious, and anhedonic-like with sex-specific differences in distribution. Early markers, including body weight and ultrasonic vocalization (USV) patterns, were linked to long-term susceptibility. Neuroanatomical analyses identified sex-specific LC-NE activation patterns associated with resilient and susceptible phenotype, particularly within the caudal-dorsal LC. These findings highlight sex-dependent behavioural trajectories of ELS that are associated with distinct LC-NE activation patterns, offering insights into potential interventions targeting resilience mechanisms in children exposed to CA.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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 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".