Mechanisms by which exercise promotes cognitive function in both depressed and non-depressed individuals

Abstract

Major depressive disorder (MDD) is a debilitating disease characterized by low mood, memory deficits, poor sleep quality and alterations in biochemical markers associated with neuroplasticity. Less than half of MDD patients receive an efficacious treatment, warranting the need for novel treatment strategies. Exercise as an add-on therapy is a promising approach shown to improve mood, however, its mechanism of action remains unknown. To advance our understanding of the mechanisms by which exercise affects brain function this thesis studied both healthy and MDD individuals. Study One used a functional magnetic resonance imaging (fMRI) subsequent memory paradigm to investigate the effects of an eight-week exercise intervention on neural function in healthy and MDD groups. FMRI results showed significant deactivation in the hippocampus and across several memory-associated regions in both groups suggesting a potential increase in neural efficiency. Study Two evaluated exercise as an add-on to antidepressant medication (ADM) and cognitive behavioural group therapy (CBGT) for MDD. Exercise led to a robust decrease in depression scores (p=0.007, d=2.06), with 75% of the patients achieving either response or remission compared to 25% of those who received ADM and CBGT only. Exercise also led to greater improvements in sleep quality (p=0.046, d=1.28), cognitive function (p=0.046, d=1.08) and plasma brain-derived neurotrophic factor (BDNF), p=0.003, d=6.46. Furthermore, BDNF was positively correlated with improvements in depression (p=0.002, R2 = 0.50) and sleep quality (p=0.011, R2 = 0.38). Study Three found that exercise for healthy, young adults did not improve cognitive performance or biomarkers, despite the neural changes seen in the fMRI study. Overall, this thesis demonstrates that exercise promotes neuroplasticity in both healthy and MDD patients, substantially improving mood and cognitive performance in MDD. Plasma BDNF levels and sleep quality appear to be good indicators of treatment response and potential biomarkers associated with the clinical recovery of MDD.