Shared vulnerability for connectome alterations across psychiatric and neurological brain disorders

Siemon C de Lange, Lianne H Scholtens, Leonard H van den Berg, Marco P Boks, Marco Bozzali, Wiepke Cahn, Udo Dannlowski, Sarah Durston, Neeltje E M van Haren, Manon H J Hillegers, Kathrin Koch, Susanne Meinert, Roel A Ophoff, Jonathan Repple, René S Kahn, Martijn P van den Heuvel

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Abstract

Macroscale white matter pathways are the infrastructure for large-scale communication in the human brain and a prerequisite for healthy brain function. Disruptions in the brain's connectivity architecture play an important role in many psychiatric and neurological brain disorders. Here we show that connections important for global communication and network integration are particularly vulnerable to brain alterations across multiple brain disorders. We report on a cross-disorder connectome study comprising in total 1,033 patients and 1,154 matched controls across 8 psychiatric and 4 neurological disorders. We extracted disorder connectome fingerprints for each of these 12 disorders and combined them into a 'cross-disorder disconnectivity involvement map' describing the level of cross-disorder involvement of each white matter pathway of the human brain network. Network analysis revealed connections central to global network communication and integration to display high disturbance across disorders, suggesting a general cross-disorder involvement and the importance of these pathways in normal function.

Original languageEnglish
Pages (from-to)988-998
Number of pages11
JournalNature Human Behaviour
Volume3
Issue number9
Early online date5 Aug 2019
DOIs
Publication statusPublished - Sept 2019

Funding

L.H.v.d.B. serves on scientific advisory boards for Orion, Biogen and Cytokinetics; received an educational grant from Baxalta; serves on the editorial boards of Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration and the Journal of Neurology, Neurosurgery, and Psychiatry; and receives research support from the Prinses Beatrix Spierfonds, the Netherlands ALS Foundation, The European Community’s Health Seventh Framework Programme (grant agreement no. 259867) and The Netherlands Organization for Health Research and Development (Vici Scheme, JPND (SOPHIA, STRENGTH, ALSCare)). All other authors declare no competing interests.

FundersFunder number
European Community’s Health Seventh Framework Programme259867
National Institute on AgingU01AG024904
EU Joint Programme – Neurodegenerative Disease Research
ZonMw
Prinses Beatrix Spierfonds
Stichting ALS Nederland

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