Document Type



Doctor of Philosophy



Date of Defense


Graduate Advisor

Carissa Philippi


Sandra Langeslag

Bettina Casad

Katie Jacobs


Previous resting-state functional connectivity (rsFC) research has identified aberrant connectivity in several large brain networks in depression, including the default mode (DMN), frontoparietal (FPN), and salience networks (SN). Connectivity of these networks is also related to depressive symptom severity and is affected by cortisol levels. To our knowledge, this is the first study to investigate the effects of acute cortisol administration on rsFC of DMN, FPN, and SN in individuals varying in depression history and severity. We collected resting-state fMRI scans for 74 women with and without a history of depressive disorder after administration of cortisol and placebo using a double-blind, crossover design. We conducted seed-based rsFC with seed regions from the DMN, FPN, and SN to examine the relationship between rsFC changes in these networks after cortisol, with depression history group predicting changes in rsFC after cortisol vs. placebo. To investigate rsFC changes in DMN, FPN, and SN due to the administration of cortisol as a function of depression severity we assessed the relationship between Beck Depression Inventory-II scores and rsFC changes in the networks of interest after cortisol vs. placebo administration for the entire sample. Results revealed that those with a history of depression exhibited increased connectivity between the left amygdala of the SN and left medial temporal gyrus of the DMN regardless of treatment. Further, we found that those who received cortisol had increased connectivity between the anterior insula of the SN and regions within the SN and DMN. Lastly, we found an interaction between depression symptom severity and rsFC between the PCC of the DMN and the right cerebellum of the SN, with greater depression symptoms associated with increased rsFC of the PCC and cerebellum. These findings are the first to show that women with greater depression severity may be more likely to normalize aberrant connectivity of DMN and SN regions after acute cortisol administration. Our results could help inform clinical treatments for depression that naturally increase endogenous cortisol levels and efficiency of glucocorticoid receptors, such as long-term daily exercise. Overall, these findings contribute to the literature on the neurobiological effects of exogenous cortisol in depression.