Exercise, cognition, and affective disorders

Anxiety and depressive disorders are major contributors to global disability and are frequently accompanied by cognitive impairment, stress-system dysregulation, and cardiometabolic comorbidity. Although pharmacological and psychotherapeutic treatments remain central, limited access, partial response, and persistent residual symptoms highlight the need for integrative and scalable interventions. This narrative review synthesizes evidence on physical activity and structured exercise as systemic biological interventions for depression and anxiety, integrating clinical findings with mechanistic pathways linking peripheral physiological adaptations to brain, cognitive, and emotional outcomes. We reviewed meta-analyses, randomized controlled trials, and mechanistic studies examining how exercise-induced mechanical, metabolic, endocrine, immune, and neurochemical signals converge on neural plasticity, stress regulation, and executive functioning. Across populations, habitual physical activity is consistently associated with lower depression risk, following nonlinear dose-response patterns, while exercise interventions show robust effects for depressive symptoms and smaller but consistent benefits for anxiety. Mechanistically, exercise acts as a predictable and dosable physiological stressor that improves stress-axis regulation, reduces low-grade systemic inflammation, modulates neurochemical systems, and promotes neuroplasticity in frontolimbic circuits. These adaptations are proposed to support improvements in executive functions and affective cognition, reducing rumination and strengthening neurobiological resilience. We propose cognition as a functional node linking systemic exercise-induced adaptations to clinical outcomes, positioning exercise not only as a symptom-reduction strategy but as a transdiagnostic intervention targeting core pathophysiological processes in depression and anxiety. This integrative framework supports the incorporation of exercise into multimodal mental health care and highlights priorities for individualized prescription and future mechanism-informed research.