Structural Brain Network Alteration and its Correlation With Structural Impairments in Patients With Depression in de novo and Drug-Naïve Parkinson's Disease

Abstract

Purpose: Depression is common in Parkinson's disease (PD) and is correlated with the severity of motor deficits and quality of life. The present study aimed to investigate alterations in the structural brain network related to depression in Parkinson's disease (d-PD) and their correlations with structural impairments of white matter (WM).Materials and Methods: Data were acquired from the Parkinson Progression Markers Initiative (PPMI) database. A total of 84 de novo and drug-naïve PD patients were screened and classified into two groups according to the 15-item Geriatric Depression Scale (GDS-15): d-PD (n = 28) and nondepression in PD (nd-PD, n = 56). Additionally, 37 healthy controls (HC) were screened. All subjects underwent DTI and 3D-T1WI on a 3.0 T MR scanner. Individual structural brain networks were constructed and analyses were performed using graph theory and network-based statistics (NBS) at both global and local levels. Differences in global topological properties were explored among the three groups. The association models between node and edge changes and the GDS-15 were constructed to detect regions that were specifically correlated with d-PD. Tract-based spatial statistics (TBSS) was used to detect structural impairments of WM between the d-PD and nd-PD groups. The correlations between altered global topological properties and structural impairments were analyzed in the d-PD group.Results: The global efficiency and characteristic path length of the structural brain network were impaired in the d-PD group compared with those in the nd-PD and HC groups. Thirteen nodes and 1 subnetwork with 10 nodes and 12 edges specifically correlated with d-PD were detected. The left hippocampus, left parahippocampal, left lingual, left middle occipital, left inferior occipital, left fusiform, left middle temporal, and left inferior temporal regions were all involved in the results of node and edge analysis. No WM microstructural impairments were identified in the d-PD group.Conclusion: Our study suggests that the integration of the structural brain network is impaired with disrupted connectivity of limbic system and visual system in the de novo and drug-naïve d-PD patients.The topological properties assessing integration of the structural brain network can serve as a potential objective neuroimaging marker for early diagnosis of d-PD.

Microstructural White Matter Characteristics in Parkinson's Disease With Depression: A Diffusion Tensor Imaging Replication Study

“…Foremost, these findings do not support the replication of a recent investigation by Huang et al (7) that compared DTI metrics of white matter integrity between PD groups with high and low symptoms of depression. However, the results of the current study did replicate the results of a more recent investigation of depression in PD, who likewise used PPMI data and comparable analysis techniques, and found no significant FA or MD white matter differences between a dPD and ndPD group (10). Overall, several studies using comparable methods to both the current study and Huang et al (7) have found mixed results (6, 9, 10).…”

“…Even with these more sensitive approaches, there were no significant differences found between the extreme dPD and ndPD groups. Previous studies that had not found differences between these groups interpreted it as a result of using mild depression scores to distinguish the depressed group (10). However, the extreme group analysis in the current study suggests that there are not significant differences even when individuals with clinically significant levels of depression are compared to individuals with no depression.…”

“…Furthermore, correcting for multiple comparisons in voxel-wise statistical comparisons is especially important in analyses requiring a high number of voxel-based comparisons, like in TBSS, in order to reduce the risk of false discovery rates, or Type 1 error (20). Only two studies cited herein have reported whether or not their results were corrected for multiple comparisons (7, 10). Notably, although TBSS has gained popularity, perhaps as a result of its user-friendly framework, there have also been challenges the reliability of the technique, which has yet to be thoroughly established (18).…”

“…Findings from Huang et al (7) revealed reduced integrity in the frontal regions and connections to the subcortical-limbic regions, similar to other neuroimaging studies (8, 9). However, the most recent investigation found no statistically significant white matter integrity differences between PD individuals with and without depression, nor did FA and MD values correlate with symptoms of depression, contributing to mixed findings (10). Altogether, results across studies are conflicting and investigations of depression in PD need to be expanded upon and replicated.…”

Assessing White Matter Pathology in Early-Stage Parkinson Disease Using Diffusion MRI: A Systematic Review

“…Gou et al found no significant WM microstructural differences between depressed and non-depressed PD groups using TBSS (59), a finding that was replicated by Lacey et al using data from PPMI (53). However, connectivity analysis revealed significant network changes associated with PD patients with depression (59). Parkinson disease with apathy has also been associated with bilateral microstructural alterations in the medial corticostriatal limbic system; more specifically, decreased FA and increased MD were observed in the anterior striatum and pregenual anterior cingulate cortex, along with concomitant serotonergic dysfunction (62).…”