Abstract

Rodent models, especially chronic stress paradigms, are essential in depression research, yet existing behavioral assessments often struggle to capture pathophysiological heterogeneity. We developed the Multimodal Behavior Scoring (MBS) algorithm, which integrates results from standard behavioral tests (sucrose preference, open field, and forced swim tests) into a single severity metric. Validated in two distinct chronic stress models (CUMS and CSDS), MBS reliably distinguished stressed from control mice and demonstrated high cross-cohort reproducibility. Furthermore, MBS successfully stratified stress-resilient subpopulations and revealed model-specific phenotypic patterns. By providing an integrative, biologically grounded framework, MBS enhances the resolution of chronic stress-induced behavioral phenotyping and may support future biomarker discovery and pharmacological validation studies.

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