The role of physical exercise on hippocampal volume in depressive symptoms: a systematic review and multi-level...

Hippocampal atrophy is a commonly observed structural impairment in depressive disorders. Conversely, physical exercise has demonstrated potential benefits for increasing hippocampal volume. Consequently, both animal and human studies have explored the effect of exercise on hippocampal volume in the context of depressive symptoms, although their findings have been inconsistent.

This systematic review and meta-analysis aims to evaluate whether exercise reduces hippocampal decline in animal and human depression models and identify optimal exercise parameters for this potential effect. We searched Web of Science, SportDiscus, PubMed (MEDLINE), PsycINFO, Google Scholar, and Cochrane up to April 8th, 2025. Separate multi-level meta-analyses for animal and human studies were performed.

Fourteen studies were included. In the animal model meta-analysis (k = 5, 6 effects, 99 animals), a large significant average effect was observed (g = 0.90, 95 % CI 0.23 to 1.58, p=.013), with very large heterogeneity (PI=-0.78 to 2.59, I²_(2)+(3)=81 %). Hippocampal subregions was a significant moderator (p = .048), with the CA4 / dentate gyrus and whole hippocampus showing the largest effect sizes. Changes in depressive symptoms (p = .316), exercise duration (p = .354), and training volume (p = .134) were also tested but did not reach statistical significance. The human model meta-analysis (k = 9, 11 effects, 423 subjects) showed a very small and non-significant average effect (g = 0.05, 95 % CI -0.05 to 0.16, p=.312) with small heterogeneity (PI=-0.05 to 0.15, I²_(2)+(3)=0 %). Because of heterogeneity limitations, no moderator analyses were conducted. GRADE quality of evidence was moderate in both meta-analyses.

Our systematic review and multi-level meta-analysis partially confirmed the positive effects of physical exercise on hippocampal volume in animal models with depressive symptoms, but not in humans. Further research is needed, including longer intervention durations, varied intensity settings, and strategies to maximise attendance rates.