Source: The New Scientist
Date: 20 October 2003

Gene linked to poorer memory

Polly Curtis

One form of a common brain protein makes us rather worse at remembering things, researchers have discovered. It is a first step towards finding the genes for intelligence.

Human intelligence is partly inherited - studies of parents and children show that about half our cleverness, or lack of it, is down to genes rather than environment. Now Dominique de Quervain and colleagues at the University of Zurich in Switzerland have found one of those genes.

People who inherit the less common form of a serotonin receptor have worse short-term memory than people with the more common form. It is not - by itself - a gene for intelligence.

But scientists suspect that eventually, a set of such genes will be identified that together make the difference between a smart brain and a dull one. Intelligence is made up of many things including concentration and reasoning, but memory is certainly important.

Amino acid swap

The neurotransmitter serotonin is better known for its involvement in depression, but drugs that block a particular serotonin receptor in the brain, 5HT2a, are known to also block short-term memory.

About nine per cent of people have at least one copy of a gene for 5HT2a that call for the amino acid tyrosine at one point in the receptor protein. The rest call for histamine. People with the tyrosine variant make receptors that are less readily stimulated by serotonin.

De Quervain's team compared 70 people with the tyrosine form to 279 with the histamine form. The tyrosine group was 21 per cent worse at remembering a list of five words or simple shapes five minutes after seeing them.

Their immediate recall was just as good, showing their attention and motivation were the same, while the difference between the groups was no worse a day later, showing the genetic difference had no separate effect on long-term memory.

Neuronal activity

"This is the first time this has been seen with the serotonin system," says de Quervain. But Daniel Weinberger and colleagues at the US National Institute of Mental Health reported a similar effect in January 2003.

They found that people with a particular genetic variant of a neural growth factor performed worse on certain memory tasks. During the tests, they also observed less neuronal activity in the hippocampus, a brain region associated with memory.

Such studies linking genetic variation in brain chemicals to real cognitive differences, and differences in brain activity, are only just beginning, says Joseph Callicott, a colleague of Weinberger.

De Quervain suspects the serotonin effect might also occur in the hippocampus. One way to track it down might be to look for different levels of activation in various brain regions with magnetic resonance imaging while subjects are performing memory tasks.

Callicott says his group has collected genetic data on a large group of people, alongside data on cognitive function, including similar memory tests to those used by de Quervain, and imaging of brain activity. "We can look for that serotonin receptor in the genetic database and see if it correlates with any differences in cognitive capabilities or imaging," he told New Scientist.

Journal reference: Nature Neuroscience (DOI: 10.1038/nn1146)

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