Inflammation and depression: an evolutionary framework for the role of physical activity and exercise
Carrera-Bastos, Pedro, Bottino, Breno, Stults-Kolehmainen, Matthew, Schuch, Felipe Barreto, Mata-Ordoñez, Fernando, Müller, Paulo T., Blanco, José Ramón, and Boullosa, Daniel (2025) Inflammation and depression: an evolutionary framework for the role of physical activity and exercise. Frontiers in Psychology, 16. 1554062.
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Abstract
Major Depressive Disorder (MDD) is a leading global health challenge, affecting nearly 5% of the population. Mounting evidence suggests that systemic low-grade chronic inflammation (SLGCI) plays a central role in the development and progression of MDD. This persistent inflammatory state results from unresolved immune activation and sustained exposure to modern lifestyle factors, such as sedentary behavior, poor diet, inadequate sleep, and psychological stress. Regular physical activity (PA), particularly exercise, has been shown to modulate inflammatory processes and improve depressive symptoms. This narrative review examines the complex interactions between inflammation and MDD, focusing on the role of PA and exercise in mitigating SLGCI and neuroinflammation. This is approached through an evolutionary lens, exploring how the mismatch between ancestral and modern activity levels may contribute to the rise of MDD. In addition, it highlights the potential risks of excessive exercise, including overtraining and its association with depressive symptoms. Finally, this work proposes a practical framework for optimizing PA and exercise as preventive and therapeutic tools for MDD by aligning modern PA patterns with ancestral behavioral norms.
| Item ID: | 88730 |
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| Item Type: | Article (Research - C1) |
| ISSN: | 1664-1078 |
| Keywords: | exercise, lifestyle, Major Depressive Disorder, mismatch, neuroinflammation, systemic low-grade chronic inflammation |
| Copyright Information: | © 2025 Carrera-Bastos, Bottino, Stults-Kolehmainen, Schuch, Mata-Ordoñez, Müller, Blanco and Boullosa. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
| Date Deposited: | 24 Jun 2026 03:47 |
| FoR Codes: | 32 BIOMEDICAL AND CLINICAL SCIENCES > 3204 Immunology > 320403 Autoimmunity @ 50% 52 PSYCHOLOGY > 5203 Clinical and health psychology > 520304 Health psychology @ 50% |
| SEO Codes: | 20 HEALTH > 2001 Clinical health > 200105 Treatment of human diseases and conditions @ 100% |
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