Underappreciated role of environmental enrichment in alleviating depression and anxiety: Quantitative evidence synthesis of rodent models

Abstract

Environmental enrichment has long been recognized as a non-pharmacological intervention to mitigate mental health issues, yet its efficacy, and heterogeneity of treatment effects across experimental contexts remain underexplored. Heterogeneity of treatment effects, which reflects variability in individual responses to interventions, is a critical factor in determining the generalizability and personalization needs of treatments. Here, we conducted a registered meta-analysis of 62 studies and 1,112 comparisons in rodent models to evaluate the impact of environmental enrichment on depressive and anxiety-like behaviours. We found that environmental enrichment reduced these behaviours of animal models by 16% on average and decreased inter-individual variability by 12%, indicating not only effectiveness but also low heterogeneity of treatment effects, which suggests consistent effects across individuals. Environmental enrichment further nullified the adverse effects of stressors, demonstrating a significant antagonistic interaction. These effects were robust across multiple sensitivity analyses, including model-based predictions, post-stratification, multi-model inference, publication bias correction, and critical appraisal of study quality. Moderator analyses highlighted the importance of exposure timing and the inclusion of social enrichment components. Taken together, our pre-clinical evidence on rodent models supports environmental enrichment as a low-cost, scalable, and biologically grounded intervention with translational relevance for developing equitable and accessible treatments for depression and anxiety. Given the importance of innovation and personalization in mental health care, the low heterogeneity of treatment effects of environmental enrichment positions it as a promising avenue for non-pharmacological therapeutic strategies that can be broadly applied without extensive tailoring.