Abstract
There is a need to develop imaging biomarkers of response to antidepressant medications in major depressive disorder (MDD). Currently, treatment of MDD is based on a trial-and-error approach, with more than half of patients not responding to their initial antidepressant treatment. If we were able to identify markers of poor prognosis in these patients, we could develop personalised treatment algorithms and pathways based on prognostic markers. Identifying such markers requires a deeper understanding of the pathophysiology and potential subtypes of MDD.This thesis aimed to investigate the neuroanatomical basis of three complementary neurocognitive aspects of MDD, namely self-blaming biases, emotional perception biases, and dysfunction of task-independent neural networks, and probe their prognostic potential in a primary care setting. The findings confirmed the pathophysiological relevance of emotional biases in current MDD and showed that self-blame-selective connectivity between the right superior anterior temporal lobe and posterior subgenual cortex (BA25), amygdala activation in response to subliminal sad vs happy faces, and subgenual frontal region resting-state functional connectivity have prognostic potential in treatment-resistant depression. Combining these complementary measures has the potential to capture a meaningful proportion of clinical variability, paving the way for personalised approaches to treatment. It will be key to determine whether these neural signatures in part represent trait-like features of a fully remitting subtype of MDD, or whether they are modulated by depressive state and can be normalised by treatments.
| Date of Award | 1 Dec 2022 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | Roland Zahn (Supervisor) & Gareth Barker (Supervisor) |