Mechanistic advances in exercise intervention for anxiety and depression via regulation of mitochondrial function

Anxiety and depressive disorders are the most prevalent psychiatric conditions worldwide, characterized by complex pathophysiological mechanisms involving neuroplasticity, inflammatory responses, and disturbances in energy metabolism. Mitochondrial dysfunction has been proposed as one contributor, but causal evidence in patients remains limited. Exercise is an evidence-based adjunctive option for reducing depressive and anxiety symptoms, although effect estimates vary. In this narrative review, we comprehensively summarize the current understanding of how exercise may modulate mitochondrial function, including biogenesis, dynamics and energy metabolism, and how these changes could regulate neurotransmitter systems, reduce neuroinflammation, and promote neurogenesis. By integrating findings from both preclinical and clinical studies, we assess the strength of the proposed relationship, outline requirements for causal testing, and discuss the limits of clinical translation. Furthermore, we discuss existing challenges and propose future research directions to optimize exercise-based therapeutic strategies targeting mitochondrial pathways for the prevention and treatment of anxiety and depressive disorders.