Cognitive performance and brain structural connectome alterations in major depressive disorder

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

doi:10.1017/S0033291722004007

Cognitive performance and brain structural connectome alterations in major depressive disorder

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

^*Corresponding author for this work

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

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.

Original language	English
Pages (from-to)	6611-6622
Number of pages	12
Journal	Psychological Medicine
Volume	53
Issue number	14
Early online date	8 Feb 2023
DOIs	https://doi.org/10.1017/S0033291722004007
Publication status	Published - Oct 2023

Bibliographical note

Funding Information:
This work was funded by the German Research Foundation (DFG, grant FOR2107 DA1151/5-1 and DA1151/5-2 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). TH was supported by the German Research Foundation (DFG grants HA7070/2-2, HA7070/3, HA7070/4). MP was supported by an ERC Consolidator grant (ERC-COG 101001062) and a NWO VIDI grant of the Dutch Research Council (Netherlands Organisation for Scientific Research Grant VIDI-452-16-015).

Funding Information:
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 brainimaging: 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. This work was funded by the German Research Foundation (DFG, grant FOR2107 DA1151/5-1 and DA1151/5-2 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). TH was supported by the German Research Foundation (DFG grants HA7070/ 2-2, HA7070/3, HA7070/4). MP was supported by an ERC Consolidator grant (ERC-COG 101001062) and a NWO VIDI grant of the Dutch Research Council (Netherlands Organisation for Scientific Research Grant VIDI-452-16-015).

Funding Information:
Tilo Kircher received unrestricted educational grants from Servier, Janssen, Recordati, Aristo, Otsuka, neuraxpharm. Markus Wöhr is a scientific advisor of Avisoft Bioacoustics. This cooperation has no relevance to the work that is covered in the manuscript. The other authors declare no financial interests or competing interests.

Funding Information:
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 brainimaging: 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.

Publisher Copyright:
© The Author(s), 2023.

Funding

This work was funded by the German Research Foundation (DFG, grant FOR2107 DA1151/5-1 and DA1151/5-2 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). TH was supported by the German Research Foundation (DFG grants HA7070/2-2, HA7070/3, HA7070/4). MP was supported by an ERC Consolidator grant (ERC-COG 101001062) and a NWO VIDI grant of the Dutch Research Council (Netherlands Organisation for Scientific Research Grant VIDI-452-16-015). 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 brainimaging: 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. This work was funded by the German Research Foundation (DFG, grant FOR2107 DA1151/5-1 and DA1151/5-2 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). TH was supported by the German Research Foundation (DFG grants HA7070/ 2-2, HA7070/3, HA7070/4). MP was supported by an ERC Consolidator grant (ERC-COG 101001062) and a NWO VIDI grant of the Dutch Research Council (Netherlands Organisation for Scientific Research Grant VIDI-452-16-015). Tilo Kircher received unrestricted educational grants from Servier, Janssen, Recordati, Aristo, Otsuka, neuraxpharm. Markus Wöhr is a scientific advisor of Avisoft Bioacoustics. This cooperation has no relevance to the work that is covered in the manuscript. The other authors declare no financial interests or competing interests. 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 brainimaging: 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.

Funders	Funder number
Carsten Konrad	KO 4291/4-1
Harald Renz	737/20-2, KI 588/17-1, RE 737/20-1, KI 588/15-1, DA 1151/6-1
International Myeloma Foundation	RE111604, RE 22 17 07, RE111722
International Myeloma Foundation
Janssen Pharmaceutica
Philipps-Universität Marburg	07/14
Philipps-Universität Marburg
Deutsche Forschungsgemeinschaft	FOR2107, 452-16-015
Deutsche Forschungsgemeinschaft
Nederlandse Organisatie voor Wetenschappelijk Onderzoek	DA1151/5-2, SFB-TRR58, FOR2107 DA1151/5-1, VIDI-452-16-015
Nederlandse Organisatie voor Wetenschappelijk Onderzoek
Westfälische Wilhelms-Universität Münster	HA7070/4, ERC-COG 101001062, HA7070/2-2, HA7070/3
Westfälische Wilhelms-Universität Münster
Medizinische Fakultät, Westfälische Wilhelms-Universität Münster	Dan3/012/17
Medizinische Fakultät, Westfälische Wilhelms-Universität Münster
Interdisziplinäres Zentrum für Klinische Forschung, Universitätsklinikum Würzburg
Servier

Keywords

cognitive performance
connectomics
depressive symptoms
graph theory
processing speed
tractography

Access to Document

10.1017/S0033291722004007Licence: CC BY-NC-ND

Persistent URL (handle)

Persistent link

Cite this

Gruber, M., Mauritz, M., Meinert, S., Grotegerd, D., De Lange, S. C., Grumbach, P., Goltermann, J., Winter, N. R., Waltemate, L., Lemke, H., Thiel, K., Winter, A., Breuer, F., Borgers, T., Enneking, V., Klug, M., Brosch, K., Meller, T., Pfarr, J. K., ... Repple, J. (2023). Cognitive performance and brain structural connectome alterations in major depressive disorder. Psychological Medicine, 53(14), 6611-6622. https://doi.org/10.1017/S0033291722004007

@article{f0789523554f4a6eb1d6e4c6ca36b33c,

title = "Cognitive performance and brain structural connectome alterations in major depressive disorder",

abstract = "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.",

keywords = "cognitive performance, connectomics, depressive symptoms, graph theory, processing speed, tractography",

author = "Marius Gruber and Marco Mauritz and Susanne Meinert and Dominik Grotegerd and {De Lange}, {Siemon C.} and Pascal Grumbach and Janik Goltermann and Winter, {Nils Ralf} 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 Pfarr, {Julia Katharina} and Ringwald, {Kai Gustav} and Frederike Stein and Nils Opel and Ronny Redlich and Tim Hahn and Leehr, {Elisabeth J.} and Jochen Bauer and Igor Nenadi{\'c} and Tilo Kircher and {Van Den Heuvel}, {Martijn P.} and Udo Dannlowski and Jonathan Repple",

note = "Funding Information: This work was funded by the German Research Foundation (DFG, grant FOR2107 DA1151/5-1 and DA1151/5-2 to UD; SFB-TRR58, Projects C09 and Z02 to UD), the Interdisciplinary Center for Clinical Research (IZKF) of the medical faculty of M{\"u}nster (grant Dan3/012/17 to UD), IMF M{\"u}nster RE111604 to RR und RE111722 to RR, IMF M{\"u}nster RE 22 17 07 to Jonathan Repple and the Deanery of the Medical Faculty of the University of M{\"u}nster. The FOR2107 cohort project (WP1) was approved by the Ethics Committees of the Medical Faculties, University of Marburg (AZ: 07/14) and University of M{\"u}nster (AZ: 2014-422-b-S). TH was supported by the German Research Foundation (DFG grants HA7070/2-2, HA7070/3, HA7070/4). MP was supported by an ERC Consolidator grant (ERC-COG 101001062) and a NWO VIDI grant of the Dutch Research Council (Netherlands Organisation for Scientific Research Grant VIDI-452-16-015). Funding Information: 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 brainimaging: 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. This work was funded by the German Research Foundation (DFG, grant FOR2107 DA1151/5-1 and DA1151/5-2 to UD; SFB-TRR58, Projects C09 and Z02 to UD), the Interdisciplinary Center for Clinical Research (IZKF) of the medical faculty of M{\"u}nster (grant Dan3/ 012/17 to UD), IMF M{\"u}nster RE111604 to RR und RE111722 to RR, IMF M{\"u}nster RE 22 17 07 to Jonathan Repple and the Deanery of the Medical Faculty of the University of M{\"u}nster. The FOR2107 cohort project (WP1) was approved by the Ethics Committees of the Medical Faculties, University of Marburg (AZ: 07/14) and University of M{\"u}nster (AZ: 2014-422-b-S). TH was supported by the German Research Foundation (DFG grants HA7070/ 2-2, HA7070/3, HA7070/4). MP was supported by an ERC Consolidator grant (ERC-COG 101001062) and a NWO VIDI grant of the Dutch Research Council (Netherlands Organisation for Scientific Research Grant VIDI-452-16-015). Funding Information: Tilo Kircher received unrestricted educational grants from Servier, Janssen, Recordati, Aristo, Otsuka, neuraxpharm. Markus W{\"o}hr is a scientific advisor of Avisoft Bioacoustics. This cooperation has no relevance to the work that is covered in the manuscript. The other authors declare no financial interests or competing interests. Funding Information: This work is part of the German multicenter consortium {\textquoteleft}Neurobiology of Affective Disorders. A translational perspective on brain structure and function{\textquoteright}, 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 brainimaging: 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. Publisher Copyright: {\textcopyright} The Author(s), 2023.",

year = "2023",

month = oct,

doi = "10.1017/S0033291722004007",

language = "English",

volume = "53",

pages = "6611--6622",

journal = "Psychological Medicine",

issn = "0033-2917",

publisher = "Cambridge University Press",

number = "14",

}

Gruber, M, Mauritz, M, Meinert, S, Grotegerd, D, De Lange, SC, Grumbach, P, Goltermann, J, Winter, NR, Waltemate, L, Lemke, H, Thiel, K, Winter, A, Breuer, F, Borgers, T, Enneking, V, Klug, M, Brosch, K, Meller, T, Pfarr, JK, Ringwald, KG, Stein, F, Opel, N, Redlich, R, Hahn, T, Leehr, EJ, Bauer, J, Nenadić, I, Kircher, T, Van Den Heuvel, MP, Dannlowski, U & Repple, J 2023, 'Cognitive performance and brain structural connectome alterations in major depressive disorder', Psychological Medicine, vol. 53, no. 14, pp. 6611-6622. https://doi.org/10.1017/S0033291722004007

TY - JOUR

T1 - Cognitive performance and brain structural connectome alterations in major depressive disorder

AU - Gruber, Marius

AU - Mauritz, Marco

AU - Meinert, Susanne

AU - Grotegerd, Dominik

AU - De Lange, Siemon C.

AU - Grumbach, Pascal

AU - Goltermann, Janik

AU - Winter, Nils Ralf

AU - Waltemate, Lena

AU - Lemke, Hannah

AU - Thiel, Katharina

AU - Winter, Alexandra

AU - Breuer, Fabian

AU - Borgers, Tiana

AU - Enneking, Verena

AU - Klug, Melissa

AU - Brosch, Katharina

AU - Meller, Tina

AU - Pfarr, Julia Katharina

AU - Ringwald, Kai Gustav

AU - Stein, Frederike

AU - Opel, Nils

AU - Redlich, Ronny

AU - Hahn, Tim

AU - Leehr, Elisabeth J.

AU - Bauer, Jochen

AU - Nenadić, Igor

AU - Kircher, Tilo

AU - Van Den Heuvel, Martijn P.

AU - Dannlowski, Udo

AU - Repple, Jonathan

N1 - Funding Information: This work was funded by the German Research Foundation (DFG, grant FOR2107 DA1151/5-1 and DA1151/5-2 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). TH was supported by the German Research Foundation (DFG grants HA7070/2-2, HA7070/3, HA7070/4). MP was supported by an ERC Consolidator grant (ERC-COG 101001062) and a NWO VIDI grant of the Dutch Research Council (Netherlands Organisation for Scientific Research Grant VIDI-452-16-015). Funding Information: 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 brainimaging: 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. This work was funded by the German Research Foundation (DFG, grant FOR2107 DA1151/5-1 and DA1151/5-2 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). TH was supported by the German Research Foundation (DFG grants HA7070/ 2-2, HA7070/3, HA7070/4). MP was supported by an ERC Consolidator grant (ERC-COG 101001062) and a NWO VIDI grant of the Dutch Research Council (Netherlands Organisation for Scientific Research Grant VIDI-452-16-015). Funding Information: Tilo Kircher received unrestricted educational grants from Servier, Janssen, Recordati, Aristo, Otsuka, neuraxpharm. Markus Wöhr is a scientific advisor of Avisoft Bioacoustics. This cooperation has no relevance to the work that is covered in the manuscript. The other authors declare no financial interests or competing interests. Funding Information: 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 brainimaging: 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. Publisher Copyright: © The Author(s), 2023.

PY - 2023/10

Y1 - 2023/10

N2 - 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.

AB - 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.

KW - cognitive performance

KW - connectomics

KW - depressive symptoms

KW - graph theory

KW - processing speed

KW - tractography

UR - http://www.scopus.com/inward/record.url?scp=85178030732&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85178030732&partnerID=8YFLogxK

U2 - 10.1017/S0033291722004007

DO - 10.1017/S0033291722004007

M3 - Article

C2 - 36752136

SN - 0033-2917

VL - 53

SP - 6611

EP - 6622

JO - Psychological Medicine

JF - Psychological Medicine

IS - 14

ER -

Cognitive performance and brain structural connectome alterations in major depressive disorder

Abstract

Bibliographical note

Funding

Keywords

Access to Document

Persistent URL (handle)

Other files and links

Fingerprint

Cite this