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Unraveling the mystery of white matter in depression: A translational perspective on recent advances

Research output: Contribution to journalReview articlepeer-review

Mate Abraham, Annakarina Mundorf, Katja Brodmann, Nadja Freund

Original languageEnglish
Article numbere2629
JournalBrain and Behavior
Issue number7
Accepted/In press2022
PublishedJul 2022

Bibliographical note

Funding Information: Graphical abstract was created with Mate Abraham has received funding from the FoRUM‐Research Fund of the Medical Faculty of the Ruhr‐University Bochum. We acknowledge support by the Open Access Publication Funds of the Ruhr‐Universität Bochum. Publisher Copyright: © 2022 The Authors. Brain and Behavior published by Wiley Periodicals LLC.

King's Authors


Background: Numerous cortical and subcortical structures have been studied extensively concerning alterations of their integrity as well as their neurotransmitters in depression. However, connections between these structures have received considerably less attention. Objective: This systematic review presents results from recent neuroimaging as well as neuropathologic studies conducted on humans and other mammals. It aims to provide evidence for impaired white matter integrity in individuals expressing a depressive phenotype. Methods: A systematic database search in accordance with the PRISMA guidelines was conducted to identify imaging and postmortem studies conducted on humans with a diagnosis of major depressive disorder, as well as on rodents and primates subjected to an animal model of depression. Results: Alterations are especially apparent in frontal gyri, as well as in structures establishing interhemispheric connectivity between frontal regions. Translational neuropathological findings point to alterations in oligodendrocyte density and morphology, as well as to alterations in the expression of genes related to myelin synthesis. An important role of early life adversities in the development of depressive symptoms and white matter alterations across species is thereby revealed. Data indicating that stress can interfere with physiological myelination patterns is presented. Altered myelination is most notably present in regions that are subject to maturation during the developmental stage of exposure to adversities. Conclusion: Translational studies point to replicable alterations in white matter integrity in subjects suffering from depression across multiple species. Impaired white matter integrity is apparent in imaging as well as neuropathological studies. Future studies should focus on determining to what extent influencing white matter integrity is able to improve symptoms of depression in animals as well as humans.

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