The Connectome Study Of Cerebral Small Vessel Disease Related Depressive Disorders

Objective The vascular pathological lesions of cerebral small vessel disease(SVD)can lead to dysfunction of the mood regulation pathway and lead to the occurrence of depressive disorders.Depressive disorders will appear in about 10%of SVD patients at different stages of the disease course.Many studies using structural and functional magnetic resonance imaging(MRI)have shown that depression is a network"disconnected" syndrome,and not merely diseases caused by the impairment of certain brain structures.To get a better understanding of this systemic "disconnected"syndrome,we applied brain connectome methods to study the mechanisms of the SVD related depressive disorders.Method This study included 20 SVD subjects with depressive disorders(SVD+D),20 SVD subjects without depressive disorders(SVD-D),and 16 healthy control subjects(HC).Using diffusion tensor imaging(DTI)and blood oxygen level dependent(BOLD)fMRI techniques along with graph-theory based connectome methods,we constructed structural and functional network of all the subjects,and then analyzed the differences of network topological properties between groups.In addition,through the methods of multiple linear regression analysis and mediating effect models,we tested whether changes in global topological network parameters have a possible mediating effect between SVD-related vascular lesions and depressive disorders.Results The structural and functional networks of all subjects showed typical "small-world" network characteristics.The topological properties of both SVD groups in the global and regional levels were changed in varying degrees,while structural network topological changes were more pronounced than functional networks.Comparing with global network properties of the structural network,these of the functional network in SVD+D were not significantly reduced,only two "small-world" network parameters were damaged and the network tended to be randomized.The regional network analysis found that the SVD+D group suffered from impairment of the node properties and edge strength in nodes of the fronto-limbic system pathways including the hippocampus,amygdala and regions of frontal and temporal lobe,and the functional connective strength and node degree of caudate nucleus and regions of default mode network were found enhanced.We also found that the SVD related lesions were associated with depressive disorders.Meanwhile,the global topological properties of structural networks are related to lesions of SVD and depressive disorders,which was not significant in the functional network,only the cluster coefficient was found related to the depressive disorders.There is no significant mediating effect of global topological properties between pathological changes in SVD and depressive disorders.Conclusion The depressive disorders in SVD patients is related to the topological impairment of the structural and functional networks.The change of structural networks is more obvious than that of functional networks.The impaired network topology in the fronto-limbic system pathway and the enhanced functional connection of the caudate nucleus are closely related to the onset of depression in SVD.This study provides a new basis for us to understand the pathogenesis of SVD-related depressive disorders from the systemic perspective of "disconnection" of the brain network.Changes of topological properties of the brain connectome network may become important imaging biomarkers for diagnosis of SVD-related depressive disorders.