A Review of Translational Behavioral Assays in Depression Research

Major depressive disorder is a highly prevalent psychiatric disease, and many patients remain symptomatic despite treatment. Rodent models are central to preclinical depression research, but their translational impact is often constrained by the lack of direct human analogs. We conducted a review to identify behavioral tasks with direct cross-species analogs between rodents and humans. We focused on tests with comparable assay structures that measure depressive symptoms and related constructs. We followed PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and included all relevant studies. After screening 9680 studies and applying inclusion and exclusion criteria, 62 studies were included. We identified 10 behavioral tests with comparable human and rodent versions. These tests include assays of positive and negative valence systems, affective bias, and cognitive systems. These cross-species behavioral tests help close the gap between animal and human paradigms and advance the understanding of the neurobiology underlying depression. Each test has distinct strengths and limitations in its implementation across species. These assays offer a promising bridge between human and rodent research, and continued efforts to standardize and develop these tests will help maximize their utility in enhancing the understanding of depression and developing more effective treatments for mood disorders.