Dose-dependent changes in cognitive function with exercise augmentation for major depression: results from the TREAD study.

Cognitive dysfunction has been repeatedly observed in major depressive disorder (MDD), particularly in areas of attention, verbal and nonverbal learning and memory, and executive functioning. Exercise has been shown to improve cognitive outcomes in other populations, including age-associated cognitive decline, but has not to our knowledge been investigated as an augmentation strategy in depression. This study evaluated the effectiveness of exercise augmentation on cognitive performance in persons with MDD and residual symptoms that included cognitive complaints following initial treatment with a selective serotonin reuptake inhibitor (SSRI). Participants enrolled in the Treatment with Exercise Augmentation for Depression (TREAD) study were randomized to receive either a low or high dose exercise regimen. TREAD participants who provided informed consent for the current study completed Cambridge Neuropsychological Test Automated Battery measures assessing Attention, Visual Memory, Executive Function/Set-shifting and Working Memory, and Executive Function/Spatial Planning domains. Data were analyzed for 39 participants completing both baseline and Week 12 cognitive testing. Overall tests indicated a significant task × group × time interaction for the Executive Function/Set-shifting and Working Memory domain. Post-hoc tests indicated improvements in high dose exercisers' spatial working memory, but decreases in spatial working memory and set-shifting outcomes in low dose exercisers. Both groups improved on measures of psychomotor speed, attention, visual memory and spatial planning. This study suggests a dose-response effect of exercise in specific executive function and working memory tasks among depressed persons with a partial response to SSRI and cognitive complaints, with some cognitive functions improving regardless of exercise dose.