Brains today are expensive—metabolically speaking, that is. Pound for pound, the human brain demands a huge amount of energy to support its recently evolved language and social skills. Now a study offers some of the first strong evidence that the rapid development of our metabolically costly brain may have led to an unfortunate by-product: when energy problems arise, the result may be schizophrenia.

No one knows exactly what causes schizophrenia, a debilitating disorder characterized by psychosis and severe cognitive impairments. One theory, which suggests it is a consequence of our brain’s high metabolism, has been around for years—but until now scientists had not developed a way to test it.

In the new study—a rare combination of evolutionary genetics and medicine—researchers in China, Germany and the U.K. compared gene expression (when and where in the body certain genes are active) and concentrations of metabolites (small molecules crucial for metabolic processes) in the postmortem brains of people without schizophrenia with those in the brains of chimpanzees, rhesus macaques and human schizophrenics. They determined that the genes and metabolites that are altered in schizophrenia appear to have changed rapidly in recent human evolution. More important, they are related to energy metabolism.

Because these changes may have happened recently (on an evolutionary scale), we may not yet have developed ways to cope with energy problems that arise, according to study co-author Philipp Khaitovich, an evolutionary biologist at the joint Max Planck/Chinese Academy of Sciences Institute for Computational Biology in Shanghai. Khaitovich suggests that the brain could be operating at the limit of its energy-regulating abilities, so it might be easy for something to go wrong, as in the case of schizophrenia.

This study may begin to explain why schizophrenia exists but not necessarily why some people are more predisposed to it than others, says Matthew Keller, an evolutionary behavioral geneticist at the University of Colorado at Boulder, who was not involved with the study.

Khaitovich agrees that the work is just a glimpse into the mechanisms responsible for our uniquely human abilities, but the findings do put metabolism in the spotlight for future research. Once we understand what makes our brains special, we can begin to understand what goes wrong in schizophrenia, he says.

Note: This article was originally published with the title, "Schizophrenia's Roots".