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. 2008;9(8):R124.
doi: 10.1186/gb-2008-9-8-r124. Epub 2008 Aug 5.

Metabolic changes in schizophrenia and human brain evolution

Philipp Khaitovich  1 , Helen E Lockstone, Matthew T Wayland, Tsz M Tsang, Samantha D Jayatilaka, Arfu J Guo, Jie Zhou, Mehmet Somel, Laura W Harris, Elaine Holmes, Svante Pääbo, Sabine Bahn
Affiliations

Metabolic changes in schizophrenia and human brain evolution

Philipp Khaitovich et al. Genome Biol. 2008.

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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Figures

Figure 1
Figure 1
The proportion of biological processes showing evidence of recent positive selection on the human lineage that is differentially expressed in schizophrenia. The height of the bar represents the number of GO groups showing evidence of recent positive selection on the human lineage; (a) all 22 and (b) the 7 relating to energy metabolism. The darker shade of color represents the number of GO groups differentially expressed in schizophrenia among the 22 or the 7 GO groups (Wilcoxon rank sum test, p < 0.03, FDR = 11%). Left bar, expected by chance; right bar, observed.
Figure 2
Figure 2
Principal component analysis of the metabolite abundance profiles in 33 individuals. The analysis is based on 21 detected metabolites. Each point represents an individual. The colors indicate: blue, human controls; black, human schizophrenia patients; purple, chimpanzees; red, rhesus macaques.
Figure 3
Figure 3
Divergence in metabolite abundance on the human and chimpanzee lineages. The trees are based on the abundance measurements of (a) 9 metabolites with significant concentration difference between human controls and schizophrenia patients and (b) 12 metabolites with no difference between these two groups. The trees were built using a neighbor-joining algorithm.
See this image and copyright information in PMC

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