White matter network alterations in patients with depersonalization/derealization disorder

White matter network alterations in patients with depersonalization/derealization disorder

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J Psychiatry Neurosci 2018;43(5):347-357

Anika Sierk, PhD (candidate)*; Judith K. Daniels, PhD*; Antje Manthey; Jelmer G. Kok, PhD; Alexander Leemans, PhD; Michael Gaebler, PhD; Jan-Peter Lamke, PhD; Johann Kruschwitz, PhD; Henrik Walter, PhD


Background: Depersonalization/derealization disorder (DPD) is a chronic and distressing condition characterized by detachment from oneself and/or the external world. Neuroimaging studies have associated DPD with structural and functional alterations in a variety of distinct brain regions. Such local neuronal changes might be mediated by altered interregional white matter connections. However, to our knowledge, no research on network characteristics in this patient population exists to date.

Methods: We explored the structural connectome in 23 individuals with DPD and 23 matched, healthy controls by applying graph theory to diffusion tensor imaging data. Mean interregional fractional anisotropy (FA) was used to define the network weights. Group differences were assessed using network-based statistics and a link-based controlling procedure.

Results: Our main finding refers to lower FA values within left temporal and right temporoparietal regions in individuals with DPD than in healthy controls when using a link-based controlling procedure. These links were also associated with dissociative symptom severity and could not be explained by anxiety or depression scores. Using network-based statistics, no significant results emerged. However, we found a trend for 1 subnetwork that may support the model of frontolimbic dysbalance suggested to underlie DPD symptomatology.

Limitations: To ensure ecological validity, patients with certain comorbidities or psychotropic medication were included in the study. Confirmatory replications are necessary to corroborate the results of this explorative investigation.

Conclusion: In patients with DPD, the structural connectivity between brain regions crucial for multimodal integration and emotion regulation may be altered. Aberrations in fibre tract communication seem to be not solely a secondary effect of local grey matter volume loss, but may present a primary pathophysiology in patients with DPD.

*These authors contributed equally to this work.

Submitted June 7, 2017; Revised Dec. 1, 2017; Accepted Jan. 21, 2018; Published online first June 6, 2018

Acknowledgments: This work was funded by the grant II/84051 from the Volkswagen Foundation to H. Walter, the German Research Foundation (DFG) grant DA 1222/4-1 to J.K. Daniels, the EU Rosalind-Franklin Fellowship Program to J.K. Daniels, and the German National Merit Foundation grant to A. Sierk. The research of A. Leemans is supported by VIDI Grant 639.072.411 from the Netherlands Organisation for Scientific Research (NWO). The authors thank Lea Waller for technical support regarding the usage of GraphVar.

Affiliations: From the Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany (Sierk, Manthey, Lamke, Kruschwitz, Walter); the Institute of Cognitive Neuroscience, University College London, London, UK (Sierk); the Department of Clinical Psychology, University of Groningen, Groningen, The Netherlands (Daniels); the Department of Neurology, University of Groningen, University Medical Center Groningen, The Netherlands (Kok); the PROVIDI Lab, University Medical Center Utrecht, Utrecht, the Netherlands (Leemans); and the Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany (Gaebler).

Competing interests: J.-P. Lamke declares personal fees from BIOTRONIK SE & Co. KG, outside the submitted work. No other competing interests declared.

Contributors: J. Daniels, M. Gaebler, J.-P. Lamke and H. Walter designed the study. J. Daniels, M. Gaebler and J.-P. Lamke acquired the data, which A. Sierk, J. Daniels, A. Manthey, J. Kok, A. Leemans and J. Kruschwitz analyzed. A. Sierk 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/jpn.170110

Correspondence to: J. Daniels, Department of Clinical Psychology Kruisstraat 2, 9712 TS Groningen, Netherlands; J.K.Daniels@rug.nl