An Integrated Exercise–Neurobiology Model linking exercise prescription with coordinated physiological and neurobiological adaptations that may guide future mechanistic research and precision exercise interventions is proposed.
Abstract
Major Depressive Disorder (MDD) is frequently associated with persistent cognitive deficits that often remain despite remission of depressive symptoms. Executive dysfunction, including impairments in working memory, inhibitory control, cognitive flexibility, planning, and decision-making, contributes to poorer psychosocial functioning and increased relapse risk. Although exercise is an established treatment for depression, its role in restoring executive functioning remains less well understood.This narrative review evaluated current evidence on the effects of exercise on executive function recovery in individuals with MDD, identified exercise characteristics associated with the greatest cognitive benefits, and summarized the underlying neurobiological mechanisms.A structured narrative review was conducted using PubMed, Scopus, and Web of Science. Priority was given to systematic reviews, meta-analyses, randomized controlled trials, and mechanistic studies investigating exercise, executive functioning, and neurobiological adaptations relevant to MDD.Structured exercise consistently improved executive functioning in individuals recovering from MDD. The greatest benefits were observed following moderate-to-vigorous aerobic exercise performed approximately three times per week, with sessions lasting 45–60 minutes for at least 13 weeks. Improvements were associated with enhanced neuroplasticity, reduced neuroinflammation, improved cerebral perfusion, neurotransmitter modulation, mitochondrial adaptations, and functional brain network reorganization.Structured exercise should be regarded as a mechanism-based intervention that extends beyond symptom reduction by promoting executive function recovery and long-term functional rehabilitation. We propose an Integrated Exercise–Neurobiology Model linking exercise prescription with coordinated physiological and neurobiological adaptations that may guide future mechanistic research and precision exercise interventions.
This narrative review evaluated current evidence on the effects of exercise on executive function recovery in individuals with MDD, identified exercise characteristics associated with the greatest cognitive benefits, and summarized the underlying neurobiological mechanisms.
The neurobiological basis of cognitive impairment in MDD is explored, key biomarkers associated with these deficits are identified, and their implications for diagnosis, prognosis, and therapeutic intervention are discussed.
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INTRODUCTION
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