Neurobiological, molecular, and systemic mechanisms of exercise in the treatment of mental health disorders

Jan 31, 2026Journal of psychiatric research

How Exercise Affects Brain, Body, and Molecular Systems to Help Treat Mental Health Disorders

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Abstract

Exercise is associated with structural and functional changes in the brain that may improve mental health outcomes.

Exercise stimulates brain-derived neurotrophic factor (BDNF), which is important for brain health.
It regulates neurotransmitters such as serotonin, dopamine, and norepinephrine, which are linked to mood and anxiety.
Exercise may modulate pathways related to inflammation and oxidative stress.
It promotes neurogenesis, the creation of new neurons, and synaptic plasticity, which are vital for learning and memory.
Systemic mechanisms, including the gut-brain axis and myokine signaling, could play a role in how exercise impacts mental health.
Exercise may influence psychological factors like emotion regulation and cognitive reappraisal, connecting physical activity to mental health treatment.

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Exercise is a potent modulator of mental health, with accumulating evidence highlighting its ability to produce structural and functional changes in the brain. This review synthesizes findings across neurobiological, molecular, and systemic domains to explain how exercise improves outcomes in mood, anxiety, and stress-related disorders. We examine how exercise stimulates brain-derived neurotrophic factor (BDNF), regulates monoaminergic systems (serotonin, dopamine, norepinephrine), modulates inflammatory and oxidative stress pathways, and promotes neurogenesis and synaptic plasticity. The review also explores systemic mechanisms including the gut-brain axis, myokine signaling (e.g., irisin, cathepsin B), and the regulation of the hypothalamic-pituitary-adrenal (HPA) axis. Furthermore, we discuss how exercise influences key psychological mechanisms, including emotion regulation, self-efficacy, and cognitive reappraisal, offering a translational bridge between physiology and psychotherapy. Understanding these overlapping mechanisms can guide clinicians in prescribing exercise as an evidence-based adjunct or standalone therapy for mental health disorders. This model of exercise as medicine has the potential to enhance both accessibility and efficacy of mental health care. Implications for clinical integration, mechanistic research, and policy development are discussed.

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Neurobiological, molecular, and systemic mechanisms of exercise in the treatment of mental health disorders

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