One of the most devastating types of mental illness could be a by-product of the evolution of human beings’ uniquely sophisticated intelligence, a new genetic study has suggested.

Scientists have discovered that a common version of a particular gene appears both to enhance a key thinking circuit in the brain, and to be linked to a raised risk of schizophrenia.

The findings, from a study by the US National Institute of Mental Health (NIMH), provide fresh evidence for the theory that schizophrenia is the price that some people pay for our species’s peculiarly advanced intellectual abilities.

The research hints that some of the genetic factors that underpin the human brain’s cognitive capacities can also go wrong to leave a sizeable minority prone to mental illness.

In the study, the NIMH team examined a common variant of a gene called DARPP-32. Three quarters of the subjects studied had inherited at least one copy of the variant.

This common version of the gene appears to make the brain’s most sophisticated thinking region more efficient, the researchers found. It improves the way that information is exchanged between the striatum, a brain region that processes reward, and the prefrontal cortex, the brain’s executive hub that manages thoughts and actions.

When this circuit works efficiently, the normal outcome is more flexible thinking and improved working memory. As a result, genes such as DARPP-32 that enhance it have probably been favoured by evolution.

The same circuit, however, has also been linked to brain functions that go wrong in patients with schizophrenia. An investigation of 257 families with a history of the condition showed that the improving version of DARPP-32 was more common among people who had developed the mental illness.

Daniel Weinberger, of NIMH, said it was possible that while a more efficient link between the prefrontal cortex and striatum normally im- proves cognitive ability, it may have a negative effect when other genetic and environ- mental factors interfere. The result could be a predisposition to schizophrenia, which is known to be caused by a combination of genes and a person’s environment.

“Our results raise the question of whether a gene variant favoured by evolution, that would normally confer advantage, may translate into a disadvantage if the prefrontal cortex is impaired, as in schizophrenia,” Dr Weinberger said.

“Normally, enhanced cortex connectivity with the striatum would provide increased flexibility, working memory capacity and executive control. But if other genes and environmental events conspire to render the cortex incapable of handling such information, it could backfire — resulting in the neural equivalent of a superhighway to a dead end.”

Andreas Meyer-Lindenberg, another member of the team, said: “We have found that DARPP-32 shapes and controls a circuit coursing between the human striatum and prefrontal cortex that affects key brain functions implicated in schizophrenia, such as motivation, working memory and reward related learning.”

Details of the study are published in the Journal of Clinical Investigation.

Previous research, notably by Paul Greengard, of Rockefeller University, a Nobel laureate, has established that DARPP-32 acts in the striatum to route information to the brain’s cortex for processing. It operates through the neurotrans- mitter dopamine, which is thought to be overactive in people with schizophrenia.

The new work, to which Dr Greengard contributed, is the first study to show a direct link between the gene and more efficient brain circuity, and possibly to schizophrenia as well.

“Although groups have looked for possible clinical relevance of DARPP-32, they have not met with great success. This study shows a strong connection between this molecule and human cognition — and perhaps with schizophrenia.”

Troubled minds

John Nash Mathematical genius whose 30-year battle against mental illness ended in triumph when he was awarded the 1994 Nobel Prize in economics. His life was recreated in the 2001 film A Beautiful Mind

Syd Barrett Enigmatic founder of Pink Floyd developed schizophrenia as the psychedelic band’s popularity took off

Jack Kerouac The Beat Generation’s most famous member was given a diagnosis of “dementia praecox”, an archaic term for schizophrenia, after enlisting in the Navy

Vaslav Nijinsky The Russian ballet dancer moved in and out of mental sanitoriums from 1919 until his death in 1950

Source www.schizophrenia.com

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