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http://hdl.handle.net/11375/27527
Title: | Structural neuroimaging biomarkers of major depressive disorder and antidepressant response |
Authors: | Suh, Jee Su |
Advisor: | Frey, Benicio N. |
Department: | Neuroscience |
Publication Date: | 2022 |
Abstract: | Introduction: There is an ongoing interdisciplinary effort to identify objective biomarkers that could improve clinical treatment outcomes in major depressive disorder (MDD). MDD encompasses symptoms ranging from the affective and vegetative to the cognitive and executive domains, mainly marked by depressed mood and loss of interest/pleasure. With MDD prevalence rates on the rise, there is an increasing need to investigate the biological correlates of symptoms and response to antidepressants, which can vary widely between patients. In this thesis, we investigated the structural neuroimaging correlates of MDD and antidepressant response in living human participants using non-invasive magnetic resonance imaging (MRI). We endeavoured to describe structural brain features related to depressive symptoms and treatment response using both cross-sectional and longitudinal designs. We additionally investigated neuroimaging findings within the greater biological context of MDD by incorporating stress variables and molecular data pertaining to gene expression and epigenetics. Results: Analyses of baseline differences in brain structure between MDD and healthy control (HC) participants revealed that the cerebral cortex tends to be thinner in frontal and temporoparietal regions in MDD, including the middle rostral frontal cortex, orbitofrontal cortex, pars opercularis and lingual gyrus with a general emphasis on the left hemisphere. Although hypothalamus volume was not shown to be significantly different between MDD and HC groups, we observed a greater extent of epigenetic functional relevance and a stronger relationship between hypothalamus volume and DNA methylation of key genes controlling the physiological stress response (CRHBP, FKBP5 and NR3C1). Generally, with the exception of a weak correlation between left hypothalamus volume and current episode duration, we did not observe any reliable associations between structural neuroimaging features and symptom severity, antidepressant response or childhood maltreatment. Short courses of antidepressant treatment ranging from weeks to a few months did not seem to affect brain structure to an extent detectable with 3T MRI. Conclusion: The results suggest that there are certain structural features associated with major depressive disorder in the unmedicated state, most reliably thinner cerebral cortex in anterior frontal regions. Hypothalamus volume may additionally be linked to epigenetic characteristics to a greater extent in the disease state. We did not observe any structural features at 3T at baseline related to short-term antidepressant response. |
URI: | http://hdl.handle.net/11375/27527 |
Appears in Collections: | Open Access Dissertations and Theses |
Files in This Item:
File | Description | Size | Format | |
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Suh_Jee_Su_2022April_PhD.pdf | 2.58 MB | Adobe PDF | View/Open |
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