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Severity of current depression and remission status are associated with structural connectome alterations in major depressive disorder

Molecular Psychiatry volume 25, pages 1550–1558 (2020)Cite this article

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Abstract

Major depressive disorder (MDD) is associated to affected brain wiring. Little is known whether these changes are stable over time and hence might represent a biological predisposition, or whether these are state markers of current disease severity and recovery after a depressive episode. Human white matter network (“connectome”) analysis via network science is a suitable tool to investigate the association between affected brain connectivity and MDD. This study examines structural connectome topology in 464 MDD patients (mean age: 36.6 years) and 432 healthy controls (35.6 years). MDD patients were stratified categorially by current disease status (acute vs. partial remission vs. full remission) based on DSM-IV criteria. Current symptom severity was assessed continuously via the Hamilton Depression Rating Scale (HAMD). Connectome matrices were created via a combination of T1-weighted magnetic resonance imaging (MRI) and tractography methods based on diffusion-weighted imaging. Global tract-based metrics were not found to show significant differences between disease status groups, suggesting conserved global brain connectivity in MDD. In contrast, reduced global fractional anisotropy (FA) was observed specifically in acute depressed patients compared to fully remitted patients and healthy controls. Within the MDD patients, FA in a subnetwork including frontal, temporal, insular, and parietal nodes was negatively associated with HAMD, an effect remaining when correcting for lifetime disease severity. Therefore, our findings provide new evidence of MDD to be associated with structural, yet dynamic, state-dependent connectome alterations, which covary with current disease severity and remission status after a depressive episode.

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Acknowledgements

This work is part of the German multicenter consortium “Neurobiology of Affective Disorders. A translational perspective on brain structure and function“, funded by the German Research Foundation (Deutsche Forschungsgemeinschaft DFG; Forschungsgruppe/Research Unit FOR2107). Principal investigators (PIs) with respective areas of responsibility in the FOR2107 consortium are: Work Package WP1, FOR2107/MACS cohort and brain imaging: Tilo Kircher (speaker FOR2107; DFG grant numbers KI 588/14-1, KI 588/14-2), Udo Dannlowski (co-speaker FOR2107; DA 1151/5-1, DA 1151/5-2), Axel Krug (KR 3822/5-1, KR 3822/7-2), Igor Nenadic (NE 2254/1-2), Carsten Konrad (KO 4291/3-1). CP1, biobank: Petra Pfefferle (PF 784/1-1, PF 784/1-2), Harald Renz (RE 737/20-1, 737/20-2). CP2, administration. Tilo Kircher (KI 588/15-1, KI 588/17-1), Udo Dannlowski (DA 1151/6-1), Carsten Konrad (KO 4291/4-1). Martijn van den Heuvel was supported by an ALW open (ALWOP.179), and VIDI (452-16-015) grant from the Netherlands Organization for Scientific Research (NWO) and a Fellowship of MQ. Data access and responsibility: All take responsibility for the integrity of the respective study data and their components. All authors and coauthors had full access to all study data. Acknowledgements and members by Work Package (WP): WP1: Henrike Bröhl, Katharina Brosch, Bruno Dietsche, Rozbeh Elahi, Jennifer Engelen, Sabine Fischer, Jessica Heinen, Svenja Klingel, Felicitas Meier, Tina Meller, Torsten Sauder, Simon Schmitt, Frederike Stein, Annette Tittmar, Dilara Yüksel (Dept. of Psychiatry, Marburg University). Mechthild Wallnig, Rita Werner (Core-Facility Brainimaging, Marburg University). Carmen Schade-Brittinger, Maik Hahmann (Coordinating Center for Clinical Trials, Marburg). Michael Putzke (Psychiatric Hospital, Friedberg). Rolf Speier, Lutz Lenhard (Psychiatric Hospital, Haina). Birgit Köhnlein (Psychiatric Practice, Marburg). Peter Wulf, Jürgen Kleebach, Achim Becker (Psychiatric Hospital Hephata, Schwalmstadt-Treysa). Ruth Bär (Care facility Bischoff, Neunkirchen). Matthias Müller, Michael Franz, Siegfried Scharmann, Anja Haag, Kristina Spenner, Ulrich Ohlenschläger (Psychiatric Hospital Vitos, Marburg). Matthias Müller, Michael Franz, Bernd Kundermann (Psychiatric Hospital Vitos, Gießen). Christian Bürger, Katharina Dohm, Fanni Dzvonyar, Verena Enneking, Stella Fingas, Katharina Förster, Janik Goltermann, Dominik Grotegerd, Hannah Lemke, Susanne Meinert, Nils Opel, Ronny Redlich, Jonathan Repple, Kordula Vorspohl, Bettina Walden, Dario Zaremba (Dept. of Psychiatry, University of Münster). Harald Kugel, Jochen Bauer, Walter Heindel, Birgit Vahrenkamp (Dept. of Clinical Radiology, University of Münster). Gereon Heuft, Gudrun Schneider (Dept. of Psychosomatics and Psychotherapy, University of Münster). Thomas Reker (LWL-Hospital Münster). Gisela Bartling (IPP Münster). Ulrike Buhlmann (Dept. of Clinical Psychology, University of Münster). CP1: Julian Glandorf, Fabian Kormann, Arif Alkan, Fatana Wedi, Lea Henning, Alena Renker, Karina Schneider, Elisabeth Folwarczny, Dana Stenzel, Kai Wenk, Felix Picard, Alexandra Fischer, Sandra Blumenau, Beate Kleb, Doris Finholdt, Elisabeth Kinder, Tamara Wüst, Elvira Przypadlo, Corinna Brehm (Comprehensive Biomaterial Bank Marburg, Marburg University). All authors have approved the final article.

Funding

This work was funded by the German Research Foundation (DFG, grant FOR2107 DA 1151/5-1 and DA 1151/5-2 to UD; SFB-TRR58, Projects C09 and Z02 to UD), the Interdisciplinary Center for Clinical Research (IZKF) of the medical faculty of Münster (grant Dan3/012/17 to UD), IMF Münster RE111604 to RR und RE111722 to RR, IMF Münster RE 22 17 07 to Jonathan Repple and the Deanery of the Medical Faculty of the University of Münster. The FOR2107 cohort project (WP1) was approved by the Ethics Committees of the Medical Faculties, University of Marburg (AZ: 07/14), and University of Münster (AZ: 2014-422-b-S).

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  1. These authors contributed equally: Udo Dannlowski, Martijn P. van den Heuvel

Authors and Affiliations

  1. Department of Psychiatry, University of Muenster, Muenster, Germany

    Jonathan Repple, Marco Mauritz, Susanne Meinert, Dominik Grotegerd, Nils Opel, Ronny Redlich, Tim Hahn, Katharina Förster, Elisabeth J. Leehr, Nils Winter, Janik Goltermann, Verena Enneking, Stella M. Fingas, Hannah Lemke, Lena Waltemate & Udo Dannlowski

  2. Connectome Lab, Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam, The Netherlands

    Siemon C. de Lange & Martijn P. van den Heuvel

  3. Department of Clinical Genetics, Amsterdam University Medical Center, Amsterdam Neuroscience, Amsterdam, The Netherlands

    Siemon C. de Lange & Martijn P. van den Heuvel

  4. Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany

    Igor Nenadic, Axel Krug, Katharina Brosch, Simon Schmitt, Frederike Stein, Tina Meller, Andreas Jansen, Olaf Steinsträter & Tilo Kircher

  5. Department of Psychiatry, Melbourne Medical School, The University of Melbourne, Melbourne, VIC, Australia

    Bernhard T. Baune

  6. The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, VIC, Australia

    Bernhard T. Baune

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Correspondence to Jonathan Repple.

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TK received unrestricted educational grants from Servier, Janssen, Recordati, Aristo, Otsuka, neuraxpharm. MW is scientific advisor of Avisoft Bioacoustics. This cooperation has no relevance to the work that is covered in the manuscript. The other authors declare no conflict of interest.

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Repple, J., Mauritz, M., Meinert, S. et al. Severity of current depression and remission status are associated with structural connectome alterations in major depressive disorder. Mol Psychiatry 25, 1550–1558 (2020). https://doi.org/10.1038/s41380-019-0603-1

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