Translational Psychiatry· 2026Q1
Sex specific metabolic predictors of stress responses in adult C57Bl/6 mice
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- 2026year
Short summary
Baseline whole-blood metabolomics identified sex-specific metabolic profiles predicting vulnerability to chronic stress in mice: elevated 3-methyl-2-oxovaleric acid, valeric acid, valine, serine, and erythrose in males, and succinic acid, serine, thymidine, and erythrose in females.
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Key points
- Male and female mice exhibit distinct behavioral responses to chronic stress.
- Specific baseline metabolites predict stress vulnerability in a sex-dependent manner.
- In males, elevated 3-methyl-2-oxovaleric acid, valeric acid, valine, serine, and erythrose correlated with vulnerability.
- In females, succinic acid, serine, thymidine, and erythrose discriminated resilient from vulnerable subjects.
- Integrating multiple metabolic variables enhanced the correlation with behavioral classification.
AI-generated from the title and abstract; the full text is not read.
Abstract
Major depressive disorder results from complex genetic and environmental interactions, with chronic stress as a key precipitating factor. Yet, individual variability in stress resilience remains poorly understood. We combined longitudinal behavioral profiling with pre-stress whole-blood metabolomics in male and female C57BL/6 mice exposed to unpredictable chronic mild stress. Behavioral trajectories revealed sex-dependent dynamics: males displayed coherent, temporally stable stress responses, whereas females exhibited modular and variable behavioral patterns. Baseline metabolomic profiles may be associated to vulnerability in a sex-specific manner. In males, our data suggest that elevated 3-methyl-2-oxovaleric acid, valeric acid, valine, serine, and erythrose correlated with vulnerability; in females, succinic acid, serine, thymidine, and erythrose discriminated resilient from vulnerable subjects. Integrating multiple metabolic variables improved correlation with behavioural classification. These findings suggest pre-existing, sex-specific metabolic states which are associated with stress susceptibility, highlighting peripheral metabolism as a potential biomarker of either resilience or vulnerability to depression.
The authors' abstract, as published at the source. Translational Psychiatry, 2026 · DOI ↗
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Field: Behavioral Neuroscience
Behavioral NeuroscienceNeuroscience