Evolutionary modifications in human brain connectivity associated with schizophrenia

van den Heuvel, Martijn P, Scholtens, Lianne H, de Lange, Siemon C, Pijnenburg, Rory, Cahn, Wiepke, van Haren, Neeltje E M, Sommer, Iris E, Bozzali, Marco, Koch, Kathrin, Boks, Marco P, Repple, Jonathan, Pievani, Michela, Li, Longchuan, Preuss, Todd M and Rilling, James K (2019) Evolutionary modifications in human brain connectivity associated with schizophrenia. Brain, 142 (12). pp. 3991-4002. ISSN 1460-2156

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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.

Item Type: Article
Keywords: brain evolution, schizophrenia, neuroimaging, neuropathology, connectome
Schools and Departments: Brighton and Sussex Medical School > Neuroscience
Subjects: R Medicine > RC Internal medicine > RC0321 Neurosciences. Biological psychiatry. Neuropsychiatry > RC0346 Neurology. Diseases of the nervous system Including speech disorders
Depositing User: Patricia Butler
Date Deposited: 04 Dec 2019 09:09
Last Modified: 11 Dec 2019 12:00
URI: http://sro.sussex.ac.uk/id/eprint/88382

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