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theses

Major depressive disorder (MDD) is a common and economically burdensome neuropsychiatric disorder characterized by the two cardinal features of low mood and anhedonia. These symptoms coincide with a wide range of secondary symptoms, including significant weight loss or weight gain, fatigue, feelings of worthlessness, and diminished ability to concentrate. While MDD is often diagnosed as a single disorder, it is a highly heterogeneous disease with poor treatment outcomes. Due to high symptom variability, matching an individual to optimal treatments is difficult and is a barrier to precision medicine approaches for clinical practice. Thus, identifying clinical and neurophysiological markers associated with treatment response or that can be altered as depressive symptoms change with treatment is critical. Aerobic exercise has garnered considerable support as a robust behavioral treatment intervention for MDD; however, the underlying neurophysiological mechanisms of action are not well understood. In study 1, we examined whether the reward positivity (RewP) event-related brain potential (ERP) component could be used to index abnormal reward processing in MDD, and whether this neurophysiological measure was correlated with depressive symptom severity. RewP amplitudes were significantly reduced among individuals with MDD relative to healthy, non-depressed controls, and this effect was moderated by depressive symptom severity, such that a smaller RewP was observed in individuals with greater depressive symptom severity. These findings demonstrate that individuals with MDD show impaired reward processing during the initial evaluation of a rewarding stimulus. In study 2, we examined two separate candidate neural markers of emotion, the RewP and late positive potential (LPP), following a single bout of moderate-intensity aerobic exercise in young adults with variable symptoms of depression. Acute exercise was shown to modify the LPP component, such that increased LPP amplitude to pleasantly valenced content was found following exercise relative to seated rest. Regardless of symptom severity, acute exercise did not modify RewP amplitude. Findings from this study suggest that these emotional processes are modifiable through exercise, suggesting potential targets for future exercise interventions. Lastly, in study 3 we examined the effects of an 8-week moderate-intensity aerobic exercise intervention performed three days per week on reward processing and cognitive control, two candidate transdiagnostic mechanisms that are disrupted in MDD. Significant reductions in depressive symptoms were found following both treatment arms, but were larger following moderate-intensity aerobic exercise relative to a light-intensity stretching condition. Pre-to-post changes in cognitive control (i.e., smaller error-related negativity [ERN]) were correlated with pre-to-post changes in depressive symptoms. ERN was also a significant predictor of treatment response; larger pre-treatment ERN amplitude was associated with a greater antidepressant treatment response. Although exercise did not impact RewP, larger pretreatment RewP amplitude was also associated with treatment response (≥ 50% pre-to-post treatment reduction in depressive symptoms). These findings highlight the use of exercise as an antidepressant treatment option for MDD, and suggest that differential patterns of reward processing and cognitive control may have utility for selecting appropriate treatments for individuals with MDD.

ETD_9665

Ph.D.

Includes bibliographical references

doi:10.7282/t3-xhbk-ag63

ETD doctoral

The author owns the copyright to this work.