The hippocampus, amygdala and their principal output tracts in major depressive disorder
Citation:RODDY, DARREN WILLIAM, The hippocampus, amygdala and their principal output tracts in major depressive disorder, Trinity College Dublin.School of Medicine, 2019
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Major depressive disorder is a common, debilitating illness. Despite its high prevalence rate and global disease burden, the biological mechanisms underlying this disorder remain largely unknown. Evidence points towards the involvement of the limbic system deep within the brain. This system processes memory, emotion and arousal, all of which are affected by depression symptoms. Two key regions in the limbic system are the hippocampus and the amygdala. The hippocampus is important for memory formation, with the left hippocampus particularly important for episodic memory. The previously well-documented changes in this structure in depression may account for the common global memory and cognition impairments found in this condition. The amygdala has been shown to be fundamental to the generation and recognition of emotional responses, with the right side demonstrating more involvement in negative emotional responses compared to the left side, which processes more positive emotions. Although evidence exists for a role of this structure in depression, this evidence is less extensive than that of the hippocampus. Both of these structures have widespread connections across the entire brain and each has a clearly defined major white matter bundle, or output tract, that connects each structure to its principal downstream effectors. These tracts are the fornix, which conveys processed memory information from the hippocampus, and the stria terminalis, which conducts emotionally-laden output from the amygdala. Both these tracts terminate in the basal forebrain and hypothalamus, regions important for pleasure and stress responses, respectively. There is limited evidence for the involvement of both of these tracts in depression. Using advanced volumetric and diffusion neuroimaging methods, combined with novel bespoke analyses of these images, this study has found noteworthy differences in all four structures in a well-characterised group of eighty-three patients with depression compared to eighty controls. Hippocampal differences were found to be confined to the core processing areas, more so on the left. There was evidence of an extension of pathology in patients with recurrent depression when compared to first presentation patients who exhibited more restrictive structural changes. The amygdala showed an exaggeration in the normal right-left volume imbalance, driven by enlargement of right stress-associated centromedial output areas. Through measurement of the cortisol awakening response in a subset of participants, the right amygdala revealed an association with abnormal stress responses in depression. Both the fornix and the stria terminalis showed localised differences along distinct sections of their tracts suggestive of abnormal axonal connectivity in depression. The aforementioned centromedial areas of the amygdala were found to be predictors of a depression diagnosis. These amygdala areas and a specific substructure within the hippocampus, the CA1 region, were also found to be predictors of disease duration in depression. These findings reinforce a role for these four limbic regions in depression. The lateralised volume differences in each of these structures could account for many of the symptoms of depression, including low mood, anhedonia and cognitive disturbance found in the disorder. While these results are preliminary, they demonstrate the utility of my novel analyses by revealing deeper and more site-specific differences in depression. These findings place altered hippocampal and amygdala volumes at the centre of a limbic network influencing memory, emotion and arousal in depression. Further studies, refining these techniques and exploring the upstream and downstream components of these structures are already underway.
Author: RODDY, DARREN WILLIAM
Publisher:Trinity College Dublin. School of Medicine. Discipline of Psychiatry
Type of material:Thesis
Availability:Full text available