Structural alterations in a rumination-related network in patients with major depressive disorder

Rumination is a common symptom in major depressive disorder (MDD) and has been linked to risk for that disorder, its prognosis, and relapse likelihood. Previous work has linked individual differences in rumination to structural properties in a variety of brain regions. Some of these regions, such as the dorsolateral prefrontal cortex (dlPFC), have also been highlighted as being altered in MDD, suggesting a connection between structural changes and ruminative symptoms. Although informative, such localised relations have some limitations in the context of a network view of the brain. To further investigate rumination-related structural changes in depression and to situate these within potential functional networks, we acquired structural data from patients with MDD (n = 32) and controls (n = 69). Analysis of cortical grey-matter identified group differences in the dlPFC that were, however, not related to rumination. Instead, rumination was correlated with grey-matter properties in the right precuneus. Using normative functional connectivity analysis on a large independent sample, we show that these two regions are interconnected. It was further shown that the rumination-related precuneus region is highly connected with networks associated with processes such as executive function, autobiographical memory, and visual perception. Notably, each of these processes has been connected to rumination. These results suggest that rumination in depression may be linked to focal structural changes that disrupt a distributed functional network. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by funding from the Taiwan National Science and Technology Council to TJL (105-2632-H038-001-MY3), TYH (111-2410-H-038-009-MY2) and NWD (110-2628-H-038-001-MY4). This work was also supported by the Taiwan Ministry of Education Higher Education Sprout Project. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the Taipei Medical University Joint Institutional Review Board (N201603080). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.