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Title: Neural correlates of treatment in depression and potential predictors of diagnosis and clinical response
Author: Sankar, Anjali
ISNI:       0000 0004 5372 0351
Awarding Body: King's College London
Current Institution: King's College London (University of London)
Date of Award: 2015
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The works presented in this thesis examine the neural effects of treatment on different features of depression, such as affective biases, working memory impairments and dysfunctional thinking. The thesis opens with a review of longitudinal studies that examined the effects of antidepressants and psychological therapies on the neural correlates of affective and cognitive processing. Motivated by the paucity in the number of fMRI studies that examined psychotherapy in depression, Chapter 2 examines the effects of Cognitive Behavioural Therapy (CBT) on dysfunctional thinking in depression. In Chapter 3, the effects of a dual acting serotonin norepinephrine reuptake inhibitor, duloxetine, on affective biases are examined using implicit affective paradigms comprising happy and sad facial expressions. Chapter 4 investigates the neural effects of duloxetine on working memory in depression utilizing a modified version of the Sternberg Working Memory Task. Another key focus in the thesis is to examine the potential of structural neuroimaging data to identify depression and predict clinical remission using machine learning algorithms in a sample of wide ethnic diversity from the community. Findings from this study are presented in Chapter 5. Overall, the results showed antidepressant treatment related increases in posterior cingulate during sad facial effect processing, consistent with preliminary findings that show increases in this region with antidepressants that potentiate the noradrenergic systems. The neural correlates of working memory, on the other hand, showed a significant group by time interaction during the rehearsal phase, such that there was a tendency for reductions in brain activations at the follow up scan compared to baseline in healthy controls in a network of brain areas extending from the prefrontal, to the cingulate, temporal and cerebellar regions, while no change was observed in patients. The tendency for decreased activations in controls in the follow up scan is perhaps indicative of less recruitment of these regions with increased familiarity with the task, while no change in activation in patients may reflect persistent recruitment of regions associated with working memory to maintain task performance. In the CBT study, an interaction effect was found in the left parahippocampal gyrus, which showed less attenuation in patients relative to controls at the follow up scan, perhaps reflecting an improvement in dysfunctional thinking with CBT with some persistent vulnerability. Investigation of neuroimagingbased biomarkers in depression indicated that structural neuroanatomy combining white and grey matter distinguished patients from controls at the highest accuracy of 81% with the most stable pattern being at around 70%. In contrast, the whole brain structural correlates of depression showed limited potential as a prognostic marker. These findings suggest some distinct neural effects of treatment on cognitive and affective processing and provide preliminary evidence to indicate that identification of depression is possible within a multi-ethnic group from the general community.
Supervisor: Fu, Cynthia ; Costafreda, Sergi Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available