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“This paper provides strong experimental evidence that subtle changes early on in life can lead to much bigger effects in adulthood. This helps explain how early life events can increase the risk of adult mental health disorders like schizophrenia," says Jeremy Hall. (Credit: Peter Alfred Hess/Flickr)

brains

Gene mutation early in life tied to schizophrenia

Subtle changes one week after birth may set the stage for schizophrenia, according to a new study with mice that focused on the gene DISC-1.

The gene first needs to bind with two other molecules known as Lis and Nudel in order for the brain’s synapses to develop normally.

Experiments in mice show that when DISC-1 doesn’t bind early in life, the mice lacked plasticity as adults. This prevented cells (cortical neurons) in the brain’s largest region from forming synapses—which damaged the ability to form coherent thoughts and to properly perceive the world.

7-day window

Preventing DISC-1 from binding with the molecules, when the brain was fully formed, showed no effect on its plasticity.

However, the researchers were able to pinpoint a seven-day window early on in the brain’s development—one week after birth—where failure to bind had an irreversible effect on the brain’s plasticity later on in life.

“We believe that DISC-1 is schizophrenia’s Rosetta Stone gene and could hold the master key to help us unlock our understanding of the role played by all risk genes involved in the disease,” says Professor Kevin Fox from Cardiff University’s School of Biosciences.

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“The potential of what we now know about this gene is immense. We have identified a critical period during brain development that directs us to test whether other schizophrenia risk genes affecting different regions of the brain create their malfunction during their own critical period.

“The challenge ahead lies in finding a way of treating people during this critical period or in finding ways of reversing the problem during adulthood by returning plasticity to the brain. This, we hope, could one day help to prevent the manifestation or recurrence of schizophrenia symptoms altogether.”

Professor Jeremy Hall, director of the Cardiff’s Neuroscience and Mental Health Research Institute, says the findings could help explain how events early in life raise the risk for disorders like schizophrenia. “This paper provides strong experimental evidence that subtle changes early on in life can lead to much bigger effects in adulthood.”

The Medical Research Council and the National Institutes of Health funded the study, which appears in Science.

Source: Cardiff University

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