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Metabolic changes in schizophrenia and human brain evolution

Philipp Khaitovich12*, Helen E Lockstone3, Matthew T Wayland3, Tsz M Tsang4, Samantha D Jayatilaka4, Arfu J Guo15, Jie Zhou16, Mehmet Somel12, Laura W Harris3, Elaine Holmes4, Svante Pääbo2 and Sabine Bahn3*

Author Affiliations

1 Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Yue Yang Road, Shanghai, 200031, PR China

2 Max-Planck-Institute for Evolutionary Anthropology, Deutscher Platz, D-04103 Leipzig, Germany

3 Institute of Biotechnology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QT, UK

4 Department of Biomolecular Medicine, Division of SORA, Imperial College London, SW7 2AZ, UK

5 University of Science and Technology of China, Jinzhai Road, Hefei, 230026, PR China

6 Shanghai Jiao Tong University, Dongchuan Road, Shanghai, 200240, PR China

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Genome Biology 2008, 9:R124  doi:10.1186/gb-2008-9-8-r124

Published: 5 August 2008



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.


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.


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.