Time heals all wounds? A 2-year longitudinal diffusion tensor imaging study in major depressive disorder

Time heals all wounds? A 2-year longitudinal diffusion tensor imaging study in major depressive disorder

J Psychiatry Neurosci 2019;44(6):407-413 | PDF | Appendix

Jonathan Repple, MD; Dario Zaremba, MSc; Susanne Meinert, MSc; Dominik Grotegerd, PhD; Ronny Redlich, PhD; Katharina Förster, MSc; Katharina Dohm, PhD; Nils Opel, MD; Tim Hahn, PhD; Verena Enneking, MSc; Elisabeth J. Leehr, PhD; Joscha Böhnlein, MSc; Fanni Dzvonyar, MSc; Lisa Sindermann, MSc; Nils Winter, MSc; Janik Goltermann, MSc; Harald Kugel, PhD; Jochen Bauer, PhD; Walter Heindel, MD; Volker Arolt, MD; Udo Dannlowski, MD, PhD

Background: Cross-sectional studies have repeatedly shown impaired white matter integrity in patients with major depressive disorder. Longitudinal analyses are missing from the current research and are crucial to elucidating the impact of disease trajectories on white matter impairment in major depressive disorder.

Methods: Fifty-nine patients with major depressive disorder receiving inpatient treatment, as well as 49 healthy controls, took part in a prospective study. Participants were scanned twice (baseline and follow-up), approximately 2.25 years apart, using diffusion tensor imaging. We analyzed diffusion metrics using tract-based spatial statistics.

Results: At baseline, patients had higher mean diffusivity in a large bilateral frontal cluster comprising the body and genu of the corpus callosum, the anterior and superior corona radiata, and the superior longitudinal fasciculus. A significant group × time interaction revealed a decrease of mean diffusivity in patients with major depressive disorder over time, abolishing group differences at follow-up. This effect was observed irrespective of disease course in the follow-up period.

Limitations: Analyzing the course of illness is challenging because of recollection biases in patients with major depressive disorder.

Conclusion: This study reports follow-up diffusion tensor imaging data in patients with major depressive disorder after an acute depressive episode. We demonstrated impaired prefrontal white matter microstructure (higher mean diffusivity) at baseline in patients with major depressive disorder, which normalized at follow-up after 2 years, irrespective of disease course. This might have been due to a general treatment effect and might have reflected recovery of white matter integrity.


Submitted Dec. 6, 2018; Revised Jan. 16, 2019; Accepted Jan. 29, 2019; Published online May 16, 2019

Acknowledgements: We acknowledge support from the Open Access Publication Fund of the University of Münster.

Affiliations: From the Department of Psychiatry, University of Münster, Germany (Repple, Zaremba, Meinert, Grotegerd, Redlich, Förster, Dohm, Opel, Hahn, Enneking, Leehr, Böhnlein, Dzvonyar, Sindermann, Winter, Goltermann, Arolt, Dannlowski); and the Institute of Clinical Radiology, Medical Faculty, University of Münster, and University Hospital Münster, Germany (Kugel, Bauer, Heindel).

Funding: This work was funded by the German Research Foundation (grants FOR2107 DA1151/5-1 and DA1151/5-2 to U. Dannlowski; SFB-TRR58, Projects C09 and Z02 to U. Dannlowski), the Interdisciplinary Centre for Clinical Research of the medical faculty of Münster (grant Dan3/012/17 to U. Dannlowski), IMF Münster RE111604 and RE111722 to R. Redlich, IMF Münster RE 221707 to J. Repple and the Deanery of the Medical Faculty of the University of Münster.

Competing interests: H. Kugel has received consultation fees from MR:comp GmbH, Testing Services for MR Safety, outside the submitted work. V. Arolt is a member of the advisory boards of Allergan, Janssen-Cilag, Lundbeck, Otsuka, Servier and Trommsdorff and has received speaker fees from Janssen-Cilag, Lundbeck, Otsuka, Servier, outside the submitted work. No other competing interests declared.

Contributors: J. Repple, R. Redlich, K. Dohm, H. Kugel and U. Dannlowski designed the study. J. Repple, S. Meinert, D. Grotegerd, R. Redlich, K. Förster, K. Dohm, N. Opel. T. Hahn, V. Enneking, E. Leehr, J. Böhnlein, F. Dzvonyar, L. Sindermann, N. Winter, J. Goltermann, H. Kugel, J. Bauer, W. Heindel and V. Arolt acquired the data, which J. Repple, D. Zaremba, S. Meinert, D. Grotegerd, R. Redlich, K. Förster, K. Dohm, V. Arolt and U. Dannlowski analyzed. J. Repple and U. Dannlowski wrote the article, which all authors reviewed. All authors approved the final version to be published and can certify that no other individuals not listed as authors have made substantial contributions to the paper.

DOI: 10.1503/cjs.180243

Correspondence to: U. Dannlowski, Department of Psychiatry, University of Münster, Albert-Schweitzer-Campus 1, A9, 48149 Münster, Germany; dannlow@uni-muenster.de