Investigating Biomarkers for Antidepressant Efficacy via Cognitive Behavioral Assessment and fMRI

Abstract

Although many treatment options have been developed to treat Major Depressive Disorder, the efficacy of these treatment options remain limited. Past studies on antidepressant efficacy have identified a range of cognitive improvements associated with treatments, yet the complexity of these studies and the lack of inconsistency across paradigms in existing literature hinders the understanding of antidepressant efficacy and highlights the importance of further investigation (Atique-Ur-Rehman & Neill, 2019). Additionally, research has indicated significant trends in anatomical regions and brain networks, but no single biomarker may exist that can be translated across every antidepressant or patient sub-population (Dunlop et al., 2019). Despite the inconsistencies in past results, it is clear that abnormalities in cognition and functional connectivity are important components of the manifestation of depression and further research is necessary to fully understand the mechanisms behind how antidepressants ameliorate these symptoms. The overarching purpose of this research is to investigate a more specific niche of antidepressant research by analyzing cognitive outcomes, specific to working memory and attentional control, and the Citalopram-specific connectivity biomarkers associated with treatment in patients. However, this thesis represents the initial steps of this project by assessing the validity of specific cognitive tasks, known as Anti-saccade, Flanker DL, Operation Span, and Symmetry Span, that will be used as the primary behavioral measures of working memory and attention in the depressed subjects. Results demonstrate a consistent relationship across task performance in subjects and reveal multiple statistically significant correlations between average primary measures of the different tasks. This successful validation of these four tasks as appropriate measures of attentional control and working memory is crucial before these tasks can be applied in the future as primary measures of change in cognition in response to the administration of an anti-depressant.