Aberrant Grey Matter Structures And Cortical Network Topology In Depression

Major depressive disorder(MDD) is the second highest health burden among the global. Previous studies indicated that there are focal grey matter deficits in the brain of depression patient. However, the human brain is a complex system formed by tens of billions neurons, the neuro-psychopathology in MDD should not simply reduce to focal grey matter loss. The non-trivial properties emerged from the brain should take into account. Secondly, human cerebral cortices are highly folded in the cranial cavity, the basic components of cortical structures(i.e. thickness,area, folding pattern) are found to be influenced by distinctive factors(either from nature or nurture), and these basic components are independent to each other. It would be more biological interpretable to separate these cortical measurements.In chapter 1-3, the primary study design is cross-sectional. Depression outpatients were recruited from local hospital(n =76), and healthy controls(n =116) were recruited by advertisements posted in nearby community.We collected clinical profiles and high-resolution MRI anatomical images.Free Surfer software suite was used for cortical surface reconstruction, as well as sub-cortical segment, then calculated cortical thickness, area,gyrification and volume.We discovered multi-loci changes and group-sex interaction in cortical measurement, but not in subcortical and hippocampal subfields. By using acquired group and sex-specific cortical differences as features, we’ve trained a highly accurate diagnoistic classifier. Then we used grey matter measurements to construct covariance networks. We found that small-world property was disrupted in thickness network, driven by lowered clustering. Disrupted nodal topology anchored in the default mode, salience network and central executive networks. We also discovered reconfiguration of community structure in cortical thickness network. Hierarchical modular organization which support normal brain function loss its integraty in depression. Less intra-modular connectivity was detected in the community of which combine cognitive control, social cognition and self-referential process; higher inter-modular connectivity was detected between temporal-insula community of which support semantic, emotional and saliency process. Hubs in modules were degenerated and rearranged into a new module, the merged pathological modular might resulted in generation of neuropsychopathy in depression.This abnormal compensatory mechanism is associated with decreased local efficiency in depression, and may also be related to disrupted regional cerebral metabolite. In summary, using this large sample we discovered a systematic topological and functional disturbance in depressed brain network. These abnormalities may reflect disrupted cerebral developmental process related to early-life stress.In chapter 4 we analysed longitudinal resting-state functional connectivity changes in 19 depressioni patient with 4 weeks psychotherapy. We discovered mood-congruent changes in functional connectivity between amygdala/ subgenual cingulate and anterior/ posterior cingulate. These connectivities were modulated by higher insular activity in depression state;psychotherapy induced dorsal prefrontal and parietal activity to modulate the abnormal connectivity. The findings suggest disrupted modulatory activity in insular play a role in depression pathogenesis. Treatment response was associated with altered dorsal prefrontal-parietal network modulatory effects on the disrupted connectivity.