Metabolic changes in schizophrenia and human brain evolution.
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.


CONCLUSIONS
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.
Khaitovich
Philipp
P
Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Yue Yang Road, Shanghai, 200031, PR China. khaitovich@eva.mpg.de
Lockstone
Helen E
HE
Wayland
Matthew T
MT
Tsang
Tsz M
TM
Jayatilaka
Samantha D
SD
Guo
Arfu J
AJ
Zhou
Jie
J
Somel
Mehmet
M
Harris
Laura W
LW
Holmes
Elaine
E
Pääbo
Svante
S
Bahn
Sabine
S
D000328:Adult; D000368:Aged; D000818:Animals; D005075:Biological Evolution; D001921:Brain / Q000378:metabolism*; D003071:Cognition / Q000502:physiology; D004734:Energy Metabolism / Q000235:genetics; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D008253:Macaca mulatta / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019906:Nuclear Magnetic Resonance, Biomolecular; D020411:Oligonucleotide Array Sequence Analysis; D002679:Pan troglodytes / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger