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Metabolic changes in schizophrenia and human brain evolution.


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Authors

Khaitovich, Philipp 
Lockstone, Helen E 
Wayland, Matthew T 
Tsang, Tsz M 
Jayatilaka, Samantha D 

Abstract

BACKGROUND: Despite decades of research, the molecular changes responsible for the evolution of human cognitive abilities remain unknown. Comparative evolutionary studies provide detailed information about DNA sequence and mRNA expression differences between humans and other primates but, in the absence of other information, it has proved very difficult to identify molecular pathways relevant to human cognition. RESULTS: Here, we compare changes in gene expression and metabolite concentrations in the human brain and compare them to the changes seen in a disorder known to affect human cognitive abilities, schizophrenia. We find that both genes and metabolites relating to energy metabolism and energy-expensive brain functions are altered in schizophrenia and, at the same time, appear to have changed rapidly during recent human evolution, probably as a result of positive selection. CONCLUSION: Our findings, along with several previous studies, suggest that the evolution of human cognitive abilities was accompanied by adaptive changes in brain metabolism, potentially pushing the human brain to the limit of its metabolic capabilities.

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Keywords

Adult, Aged, Animals, Biological Evolution, Brain, Cognition, Energy Metabolism, Female, Gene Expression, Gene Expression Profiling, Humans, Macaca mulatta, Male, Middle Aged, Nuclear Magnetic Resonance, Biomolecular, Oligonucleotide Array Sequence Analysis, Pan troglodytes, RNA, Messenger, Schizophrenia

Journal Title

Genome Biol

Conference Name

Journal ISSN

1474-760X
1474-760X

Volume Title

Publisher

Springer Science and Business Media LLC