Abstract
Reduced fractional anisotropy (FA) associated with Major Depressive Disorder (MDD) overlaps anatomically with effects of childhood maltreatment experiences. The aim of this study was, therefore, to replicate the negative effect of childhood maltreatment on white matter fiber structure and to demonstrate, that alterations in MDD might be partially attributed to the higher occurrence of childhood maltreatment in MDD. Two independent cohorts (total N = 1 256) were investigated in a diffusion tensor imaging study: The Münster Neuroimaging Cohort (MNC, N = 186 MDD, N = 210 healthy controls, HC) as discovery sample and the Marburg-Münster Affective Disorders Cohort Study (MACS, N = 397 MDD, N = 462 HC) as replication sample. The effects of diagnosis (HC vs. MDD) and Childhood Trauma Questionnaire (CTQ) scores on FA were analyzed. A main effect of diagnosis with higher FA in MDD patients compared with HC was found in the MNC (pFWE = 0.021), but not in the MACS (pFWE = 0.52) before correcting for CTQ. A significant negative correlation of FA with CTQ emerged in both cohorts (MNC: pFWE = 0.006, MACS: pFWE = 0.012) in several tracts previously described in the literature. No CTQ × diagnosis interaction could be detected. Any main effect of diagnosis was abolished after correcting for CTQ (MNC: pFWE = 0.562, MACS: pFWE = 0.115). No differences in FA between MDD and HC could be found after correcting for childhood maltreatment, suggesting that previously reported group differences might be attributed partially to higher levels of maltreatment experiences in MDD rather than diagnosis itself. Furthermore, a well-established finding of reduced FA following childhood maltreatment experiences was replicated.
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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 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). WP2, animal phenotyping: Markus Wöhr (WO 1732/4-1, WO 1732/4-2), Rainer Schwarting (SCHW 559/14-1, SCHW 559/14-2). WP3, miRNA: Gerhard Schratt (SCHR 1136/3-1, SCHR 1136/3-2). WP4, immunology, mitochondriae: Judith Alferink (AL 1145/5-2), Carsten Culmsee (CU 43/9-1, CU 43/9-2), Holger Garn (GA 545/5-1, GA 545/7-2). WP5, genetics: Marcella Rietschel (RI 908/11-1, RI 908/11-2), Markus Nöthen (NO 246/10-1, NO 246/10-2), Stephanie Witt (WI 3439/3-1, WI 3439/3-2). WP6, multi-method data analytics: Andreas Jansen (JA 1890/7-1, JA 1890/7-2), Tim Hahn (HA 7070/2-2), Bertram Müller-Myhsok (MU1315/8-2), Astrid Dempfle (DE 1614/3-1, DE 1614/3-2). CP1, biobank: Petra Pfefferle (PF 784/1-1, PF 784/1-2), Harald Renz (RE 737/20-1, RE 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). Data access and responsibility: All PIs 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 1: Henrike Bröhl, Bruno Dietsche, Rozbeh Elahi, Jennifer Engelen, Sabine Fischer, Jessica Heinen, Svenja Klingel, Felicitas Meier, Torsten Sauder, Annette Tittmar, Dilara Yüksel (Dept. of Psychiatry, Marburg University). Mechthild Wallnig, Rita Werner (Core-Facility Brainimaging, Marburg University). Carmen Schade-Brittinger, Maik Hahmann (Coordinating Centre 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, Fanni Dzvonyar, Stella Fingas, Hannah Lemke, 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). This work was funded by the German Research Foundation Deutsche Forschungsgemeinschaft DFG (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; SEED 11/18 to NO), IMF Münster (grant RE111604 and RE111722 to RR, RE221707 to JR, LE121703 to EJL), and the Deanery of the Medical Faculty of the University of Münster.
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Meinert, S., Repple, J., Nenadic, I. et al. Reduced fractional anisotropy in depressed patients due to childhood maltreatment rather than diagnosis. Neuropsychopharmacol. 44, 2065–2072 (2019). https://doi.org/10.1038/s41386-019-0472-y
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