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Title: Neuroimaging studies of affective disorders and antidepressant drug effects
Author: Chen, C. H.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2007
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This thesis investigated abnormalities in the brain circuitry for affect processing in patients with affective disorders, and effects of antidepressant drugs on this circuitry. The first experimental study examined brain activation in response to an implicit and explicit facial recognition task by employing functional magnetic resonance imaging (fMRI) in a group of 8 manic and 8 depressed patients with bipolar disorder and 8 healthy comparison controls. This comparison showed that depressed and manic patients exhibited over activated responses to fearful faces, as well as to mood-incongruent facial expressions, with the depressed group exhibiting over-activity in fronto-striato-thalamic systems in response to happy faces, and the manic group over-activity in the fusiform gyrus in response to sad faces. For manic patients, task type also affected the neural response to sad faces, with the cortico-limbic regions showing over-activation for implicit processing and under-activation for explicit processing. In the following part of the thesis, the neurophysiology underlying major depression and neural correlates of antidepressant drug effects were studied. Brain activation in response to the implicit sad facial recognition task, and brain structure, were examined in a group of 17 patients with major depression using functional and structural MRI before and after a course of 8 weeks antidepressant treatment. Faster rates of symptom improvement were strongly associated with greater grey matter volume in the anterior cingulated cortex, insula and right temporo-parietal cortex. Patients with greater than median grey matter volume in this system had faster rates of improvement and significantly lower residual symptoms scores after treatment. Faster improvement was also predicted by greater functional activation of the anterior cingulated cortex. Depressive symptom severity was negatively correlated with greater grey matter volume in the dorsal prefrontal and anterior midcingulate regions anatomically distinct from the pregenual and subgenual cingulate regions predicting treatment response. Furthermore, patients with major depression were compared with 19 matched healthy controls to investigate changes in the effective connectivity between the amygdala and all other brain areas in response to facial emotions at baseline and after antidepressant treatment. The results indicate that antidepressant drug effects can be measured in terms of altered connectivity between components of cortico-limbic systems.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available