Biomaterial Database

Cognitive performance and brain structural connectome alterations in major depressive disorder. 2023

Marius Gruber, and Marco Mauritz, and Susanne Meinert, and Dominik Grotegerd, and Siemon C de Lange, and Pascal Grumbach, and Janik Goltermann, and Nils Ralf Winter, and Lena Waltemate, and Hannah Lemke, and Katharina Thiel, and Alexandra Winter, and Fabian Breuer, and Tiana Borgers, and Verena Enneking, and Melissa Klug, and Katharina Brosch, and Tina Meller, and Julia-Katharina Pfarr, and Kai Gustav Ringwald, and Frederike Stein, and Nils Opel, and Ronny Redlich, and Tim Hahn, and Elisabeth J Leehr, and Jochen Bauer, and Igor Nenadić, and Tilo Kircher, and Martijn P van den Heuvel, and Udo Dannlowski, and Jonathan Repple

Institute for Translational Psychiatry, University of Münster, 48149 Münster, Germany.

BACKGROUND Cognitive dysfunction and brain structural connectivity alterations have been observed in major depressive disorder (MDD). However, little is known about their interrelation. The present study follows a network approach to evaluate alterations in cognition-related brain structural networks. METHODS Cognitive performance of n = 805 healthy and n = 679 acutely depressed or remitted individuals was assessed using 14 cognitive tests aggregated into cognitive factors. The structural connectome was reconstructed from structural and diffusion-weighted magnetic resonance imaging. Associations between global connectivity strength and cognitive factors were established using linear regressions. Network-based statistics were applied to identify subnetworks of connections underlying these global-level associations. In exploratory analyses, effects of depression were assessed by evaluating remission status-related group differences in subnetwork-specific connectivity. Partial correlations were employed to directly test the complete triad of cognitive factors, depressive symptom severity, and subnetwork-specific connectivity strength. RESULTS All cognitive factors were associated with global connectivity strength. For each cognitive factor, network-based statistics identified a subnetwork of connections, revealing, for example, a subnetwork positively associated with processing speed. Within that subnetwork, acutely depressed patients showed significantly reduced connectivity strength compared to healthy controls. Moreover, connectivity strength in that subnetwork was associated to current depressive symptom severity independent of the previous disease course. CONCLUSIONS Our study is the first to identify cognition-related structural brain networks in MDD patients, thereby revealing associations between cognitive deficits, depressive symptoms, and reduced structural connectivity. This supports the hypothesis that structural connectome alterations may mediate the association of cognitive deficits and depression severity.