TY - JOUR
T1 - Evolutionary modifications in human brain connectivity associated with schizophrenia
AU - van den Heuvel, Martijn P.
AU - Scholtens, Lianne H.
AU - de Lange, Siemon C.
AU - Pijnenburg, Rory
AU - Cahn, Wiepke
AU - van Haren, Neeltje E.M.
AU - Sommer, Iris E.
AU - Bozzali, Marco
AU - Koch, Kathrin
AU - Boks, Marco P.
AU - Repple, Jonathan
AU - Pievani, Michela
AU - Li, Longchuan
AU - Preuss, Todd M.
AU - Rilling, James K.
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
KW - brain evolution
KW - connectome
KW - neuroimaging
KW - neuropathology
KW - schizophrenia
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U2 - 10.1093/brain/awz330
DO - 10.1093/brain/awz330
M3 - Article
C2 - 31724729
AN - SCOPUS:85074154616
SN - 1460-2156
VL - 142
SP - 3991
EP - 4002
JO - Brain : a journal of neurology
JF - Brain : a journal of neurology
IS - 12
ER -