REVIEW article

Front. Psychol.

Sec. Movement Science

Volume 16 - 2025 | doi: 10.3389/fpsyg.2025.1554062

This article is part of the Research TopicInsights and Reviews In Movement Science 2023View all 20 articles

Inflammation and Depression: An Evolutionary Framework for the Role of Physical Activity and Exercise

Provisionally accepted
Pedro BastosPedro Bastos1Breno BottinoBreno Bottino2Matthew A. Stults-KolehmainenMatthew A. Stults-Kolehmainen3*Felipe Barreto SchuchFelipe Barreto Schuch4Fernando Mata-OrdoñezFernando Mata-Ordoñez5PAULO DE TARSO MULLERPAULO DE TARSO MULLER2Jose-Ramon BlancoJose-Ramon Blanco6Daniel BoullosaDaniel Boullosa7
  • 1European University of Madrid, Villaviciosa de Odón, Madrid, Spain
  • 2Federal University of Mato Grosso do Sul, Campo Grande, Mato Grosso do Sul, Brazil
  • 3Yale-New Haven Hospital, New Haven, United States
  • 4Federal University of Santa Maria, Santa Maria, Rio Grande do Sul, Brazil
  • 5Universidad Europea de Madrid, Madrid, Spain
  • 6Hospital San Pedro, Logroño, La Rioja, Spain
  • 7University of León, León, Spain

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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.

Keywords: Major Depressive Disorder, systemic low-grade chronic inflammation, Neuroinflammation, mismatch, Exercise, lifestyle

Received: 31 Dec 2024; Accepted: 29 Apr 2025.

Copyright: © 2025 Bastos, Bottino, Stults-Kolehmainen, Schuch, Mata-Ordoñez, MULLER, 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) or licensor 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.

* Correspondence: Matthew A. Stults-Kolehmainen, Yale-New Haven Hospital, New Haven, United States

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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