Common gene version optimizes thinking -- but with a possible downside

February 8, 2007

Most people inherit a version of a gene that optimizes their brain's thinking circuitry, yet also appears to increase risk for schizophrenia, a severe mental illness marked by impaired thinking, scientists at the National Institutes of Health's (NIH) National Institute of Mental Health (NIMH) have discovered. The seeming paradox emerged from the first study to explore the effects of variation in the human gene for a brain master switch, DARPP-32.

The researchers identified a common version of the gene and showed how it impacts the way two key brain regions exchange information, affecting a range of functions from general intelligence to attention.

Three fourths of subjects studied had at least one copy of the version that results in more efficient filtering of information processed by the brain's executive hub, the prefrontal cortex. However, the same version was also more prevalent among people who developed schizophrenia, a severe mental illness marked by delusions, hallucinations and impaired emotion that affects one percent of the population.

"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," explained Andreas Meyer-Lindenberg, M.D.

"Our results raise the question of whether a gene variant favored by evolution, that would normally confer advantage, may translate into a disadvantage if the prefrontal cortex is impaired, as in schizophrenia," added Daniel Weinberger, M.D. "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."

Meyer-Lindenberg, Weinberger and colleagues in the NIMH Genes, Cognition and Psychosis program report their results in the February 9, 2007 issue of the Journal of Clinical Investigation.

Previous studies in animals over two decades, most notably by Nobel Laureate and NIMH grantee Paul Greengard, M.D., Rockefeller University, had established that DARPP-32 in the striatum switches streams of information from multiple brain chemical systems for processing by the cortex. Both the neurotransmitter that it works through, dopamine, and the chromosomal site of its gene have been implicated in schizophrenia.

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

"These first glimpses of DARPP-32 at work in the living human brain build on a quarter century of investigations by Greengard's team that ultimately linked this pivotal protein to depression and substance abuse as well as to schizophrenia," added NIMH Director Thomas Insel, M.D.

To understand DARPP-32's role in the human brain, the NIMH researchers used genetic, structural and functional magnetic resonance imaging, and post-mortem techniques to identify the human gene's variants and their functional consequences. Seventy five percent of subjects had the most common version of the gene, which boosted circuit activation, structural and functional connectivity and performance on thinking tasks, likely by increasing gene expression. In 257 affected families, people with schizophrenia were more likely to have this common version of the DARPP-32 gene.

Source: NIH/National Institute of Mental Health

Explore further: Altering RNA helicases in roundworms doubles their lifespan

Related Stories

Altering RNA helicases in roundworms doubles their lifespan

July 21, 2015

The things we do to extend our lives—quitting smoking, cutting back on carbs, taking up jogging —all have some impact on our longevity, if only just a little. But no matter how hard we work towards chasing the dream ...

Making sense of our evolution

July 13, 2015

The science about our our special senses - vision, smell, hearing and taste - offers fascinating and unique perspectives on our evolution.

Can gene editing provide a solution to global hunger?

July 6, 2015

According to the World Food Program, some 795 million people – one in nine people on earth – don't have enough food to lead a healthy active life. That will only get worse with the next global food crisis, predicted to ...

Recommended for you

Machine Translates Thoughts into Speech in Real Time

December 21, 2009

(PhysOrg.com) -- By implanting an electrode into the brain of a person with locked-in syndrome, scientists have demonstrated how to wirelessly transmit neural signals to a speech synthesizer. The "thought-to-speech" process ...

Quantum Theory May Explain Wishful Thinking

April 14, 2009

(PhysOrg.com) -- Humans don’t always make the most rational decisions. As studies have shown, even when logic and reasoning point in one direction, sometimes we chose the opposite route, motivated by personal bias or simply ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.