Schizophrenia becomes increasingly likely when you combine two things early in infancy: genetic risk factors and trauma. But each element on its own doesn't necessarily lead to the debilitating mental disorder that often results in a complete break with reality.
Scientists at the Johns Hopkins School of Medicine concluded this after a study involving the genetic sequences of 2,961 schizophrenic and healthy patients from Scotland, Germany and the U.S., and lots and lots of genetically engineered newborn mice. Details are published in the journal Cell.
Now that the genetic risks are known for the disease, researchers can be more precise in searching for drugs to correct the identified defects, study co-author Hongjun Song, professor of neurology and director of the stem cell program at Johns Hopkins's Institute for Cell Engineering, said in a statement. The research certainly allows for a more focused drug-discovery process, but it could be years before they determine how successful this new approach is. Still, the findings do suggest some common genetic and environmental traits for schizophrenia patients.
Step one: The scientists engineered in mice reduced levels of the DISC1 protein, which helps fuel brain development. They also engineered more robust production of GABA, a chemical that's crucial to helping brains function normally. Mice with reduced levels of DISC1 alone had similar neurons as their brethren with normal DISC1 levels. But the combined GABA/DISC1 changes as seen in the neurons of stressed infant mice suggested the combination could hurt neuron development longer term.
Why does this matter? Previous research at the University of Calgary and in Japan showed that newborn mice that faced routine stress and other environmental developed an impaired GABA process. Subsequently, they saw that mice with lower DISC1 levels that faced similar stress levels (and resulting GABA production not working properly) ended up with disorganized neurons and more projections, among other issues, suggesting stress and genetics combined were more lethal.
Next, after looking at genetic sequences of 2,961 schizophrenia and healthy patients, the scientists figured out that specific variations of DNA letters found in the DISC1 and NKCC1 gene--which controls how GABA works--more often were in schizophrenia patients than healthy ones, according to Johns Hopkins. But, they also found that a certain genetic defect combo with those two genes made a patient 1.4 times more likely to develop schizophrenia than patients without the defects, but those factors alone didn't lead to developing the condition.
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