Madness, a Price for Maths

An intact human brain.Image via Wikipedia

Scientists suggest that schizophrenia may be a result of the evolutionary demand for bigger brain size in humans.

Some people might be paying a price for humanity’s capacity to engage in mathematics, philosophy, science and the arts. A new study of brains and genes suggests that schizophrenia, the chronic debilitating brain disorder that sometimes defies treatment and remains a medical mystery, might be an undesirable by-product of evolution that has given humans unique, highly-evolved brains.

Researchers in China, Germany and the UK have discovered a large overlap across key genetic and molecular processes in the brain that have changed during human evolution and the biological processes observed in schizophrenia.

Philipp Khaitovich at the Max Planck Institute of Evolutionary Anthropology, Leipzig (Germany), and his colleagues have found that the activity levels of several genes that are altered in schizophrenia changed rapidly during evolution. Most of these changes involve genes that play a key role in energy consumption by the brain which happens to be the most energy-demanding organ in the body.

The new findings suggest that schizophrenia is a by-product of the increased energy demand brought about during human brain evolution, says Khaitovich, currently at the Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Shanghai. The researchers presented their findings last week in the journal Genome Biology.

The study is part of an effort to search for the molecular changes that can account for the evolution of human cognitive abilities — intellect, higher thinking and reasoning. Scientists believe the human brain has dramatically evolved over the past five to seven million years since the split from the common ancestor of humans and chimpanzees, humans’ closest living relatives.

But efforts to compare gene activity in brains and pinpoint these molecular mechanisms that might account for the differences between the capabilities of human and chimpanzees haven’t thrown up any dramatic insights into what makes humans, well, humans. Such studies have revealed differences in gene activities, but the ones specifically related to higher thought processes remain unknown.

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Khaitovich and his colleagues reasoned that an alternative approach would be to study how genes change in disorders of the brain that affect thought processes. They picked schizophrenia, an illness marked by delusions, hallucinations and disordered thinking which, psychiatrists say, affects about one in 100 people.

The researchers studied post-mortem brains of healthy people and of schizophrenia patients and compared them with chimpanzee and rhesus monkey brains. They also looked for differences in gene activity and levels of brain chemicals.

The analysis revealed that selected genes and chemicals relating to the energy needs of the brain are altered in schizophrenia and, simultaneously, appear to have changed during human evolution.

These results suggest that the brain’s energy use could be a key factor underlying its capacity for higher thought processes, not observed in other species. This is not surprising at all. The human brain is an energy guzzler. Humans spend about 20 per cent of their total energy on the brain, compared to only about 12 per cent by non-human primates and about 2 per cent to 8 per cent by other vertebrates.

And several studies have shown that brain energy use is altered in brain disorders such as schizophrenia. They have revealed deficiencies in blood flow — the source of energy to brain cells — in the region called the prefrontal cortex in patients with schizophrenia, who were asked to perform complex tasks. Post-mortem studies of schizophrenia brains also show depressed activity of energy-related genes.

The findings may lead to new ways of investigating the brain mechanisms that make humans humans, and those that account for schizophrenia, a condition recognised as a distinct disorder by German psychiatrist Emil Kraepilin nearly 120 years ago.

“Our brains are unique among all species in their enormous metabolic (energy) demand,” says Khaitovich. “If we can better explain how our brains sustain such a tremendous metabolic flow, we will have a much better chance to understand how the brain works and why it sometimes breaks.”

But some neuroscientists believe the new findings should be viewed as preliminary, requiring further authentication because disruptions in energy use by brain cells isn’t a problem exclusively associated with schizophrenia. “Problems with energy metabolism also show up in a number of other brain disorders,” says Vijayalakshmi Ravindranath, director of the National Brain Research Institute, Gurgaon.

Khaitovich and his colleagues concede that more research involving a wider range of neuropsychiatric disorders would be necessary. Who knows, there might also be other potential penalties the human brain is forfeiting for all its superior capabilities!

Sources: The Telegraph (Kolkata, India)

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