Evolutionary modifications in human brain connectivity associated with schizophrenia

• Type of Material: Article
• Authors: Martin P. van den Heuvel, Vrije Universiteit Amsterdam; Lianne H. Scholtens, Vrije Universiteit Amsterdam; Siemon C. de Lange, Vrije Universiteit Amsterdam; Rory Pijnenburg, Vrije Universiteit Amsterdam; Wiepke Cahn, Utrecht University; Neeltje E. M. van haren, Utrecht University; Iris E. Sommer, Utrecht University; Marco Bozzali, University of Sussex; Kathrin Koch, Technische Universität München; Marco P. Boks, Utrecht University; Jonathan Repple, University of Muenster; Michela Pievani, IRCCS Instituto Centro San Giovanni di Dio Fatebenefratelli; Longchuan Li, Emory University; Todd M. Preuss, Emory University; James K. Rilling, Emory University
• Language: English
• Date: 2019-11-14
• Publisher: Oxford University Press
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) (2019).
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): https://doi.org/10.1093/brain/awz330
• Title of Journal or Parent Work: Brain
• Volume: 142
• Issue: 12
• Start Page: 2991
• End Page: 4002
• Grant/Funding Agency: Netherlands Organization for Scientific Research; Washington University; Italian Ministry of Health; Human Connectome Project; National Chimpanzee Brain Resource; National Institutes of Health; Yerkes National Primate Research Center; Dutch Organization for Scientific Research; Center of Biomedical Research Excellence
• Grant/Funding Information: Data collection was performed at the Mind Research Network, and funded by a Center of Biomedical Research Excellence (COBRE) grant 5P20RR021938/P20GM103472 from the NIH to V.C. M.v.d.H. was supported by VIDI Grant 452-16-015 and Aard- en levenswetenschappen (ALW) Grant ALWOP.179 from the Netherlands Organization for Scientific Research and by a Mental Health and Quality of Life fellowship. This work was supported by National Institutes of Health Grants P01AG026423 and National Center for Research Resources P51RR165 (superseded by the Office of Research Infrastructure Programs/OD P51OD11132) to the Yerkes National Primate Research Center, and by the National Chimpanzee Brain Resource, R24NS092988. L.L. was supported by National Institutes of Health Grants P50MH100029, R01MH118534, R01MH118285. The Bipolar disorder imaging dataset BP-1 was supported by the National Institute of Mental Health (Grant number: R01MH 090 553). Human MRI data were partly provided by the Human Connectome Project, WU-Minn Consortium (Principal Investigators: David Van Essen and Kamil Ugurbil; 1U54MH091657) funded by the 16 NIH Institutes and Centers that support the NIH Blueprint for Neuroscience Research; and by the McDonnell Center for Systems Neuroscience at Washington University. M.P. was supported by the Italian Ministry of Health (GR2011-02349787 and Ricerca Corrente). The schizophrenia replication dataset 2 was funded by VIDI-grant 452-11-014 from the Dutch Organization for Scientific Research to NEM van Haren.
• Keywords: neuropathology; neuroimaging; schizophrenia; connectome; brain evolution
• Subject - Topics: Psychiatry; Cognitive neuroscience; Evolutionary neuroscience

Abstract

The genetic basis and human-specific character of schizophrenia has led to the hypothesis that human brain evolution may have played a role in the development of the disorder. We examined schizophrenia-related changes in brain connectivity in the context of evolutionary changes in human brain wiring by comparing in vivo neuroimaging data from humans and chimpanzees, one of our closest living evolutionary relatives and a species with which we share a very recent common ancestor. We contrasted the connectome layout between the chimpanzee and human brain and compared differences with the pattern of schizophrenia-related changes in brain connectivity as observed in patients. We show evidence of evolutionary modifications of human brain connectivity to significantly overlap with the cortical pattern of schizophrenia-related dysconnectivity (P < 0.001, permutation testing). We validated these effects in three additional, independent schizophrenia datasets. We further assessed the specificity of effects by examining brain dysconnectivity patterns in seven other psychiatric and neurological brain disorders (including, among others, major depressive disorder and obsessive-compulsive disorder, arguably characterized by behavioural symptoms that are less specific to humans), which showed no such associations with modifications of human brain connectivity. Comparisons of brain connectivity across humans, chimpanzee and macaques further suggest that features of connectivity that evolved in the human lineage showed the strongest association to the disorder, that is, brain circuits potentially related to human evolutionary specializations. Taken together, our findings suggest that human-specific features of connectome organization may be enriched for changes in brain connectivity related to schizophrenia. Modifications in human brain connectivity in service of higher order brain functions may have potentially also rendered the brain vulnerable to brain dysfunction.