Recent work done by a group of Hopkins researchers has shed new light on the factors contributing to the development of schizophrenia in individuals.
The findings, published in Cell, highlight the connections between schizophrenia and the combination of both genetic and environmental risk factors that can increase the chances of developing this disorder.
According to the study, a newborn can either carry defects in schizophrenia-risk genes or be subjected to environmental stress soon after birth, but still have the same chances to grow and develop normally as do a newborn without such difficulties. However, when defective genes and stress both occur together, the chances of schizophrenia development rise by nearly 140 percent.
In order to gain some real quantitative data, the Hopkins team examined Disrupted-in-Schizophrenia (DISC1), which is a protein necessary for brain development, and the brain chemical GABA, a key ingredient for normal brain function.
The scientists then genetically engineered mice to produce lower levels of DISC1 in the hippocampus of the brain.
The results showed that the neurons of the mutant mice actually are similar in size and morphology to neurons of normal, un-mutated mice. Next, the researchers increased levels of GABA in mice and found the neurons to be longer and contain more projections when compared with their normal counterparts.
Finally, when the two mutations were combined in the same cell, the neurons were found to be the longest and have the most projections.
The findings suggested that while a single defect could still lead to normal growth, the occurence of both defects together would more likely alter brain development, causing increase in susceptibility to disease.
While the team at Hopkins continued their research, another group at the University of Calgary had teamed with the National Institute of Physiological Sciences in Japan to perform their own experiments on environmental stress and its effects on newborn mice development.
The joint team also worked with the DISC1 protein, but in their study, they also incorporated stress factors in the mice, They did so by separating newborns from their mothers for three hours everyday in the first ten days of birth.
What they found seemed to agree with the data obtained by the Hopkins team: stress alone often led to normal growth, but a combination of stress and reduced levels of DISC1 expression yielded neurons sending projections into the wrong regions of the brain.
Furthermore, the researchers examined the genomes of 2,961 schizophrenia patients and healthy individuals, looking at the DNA sequences coding for DISC1 and a protein called NKCC1, which regulates GABA in the brain.
They found that people with a single base mutation in both genes resulted in 1.4 times higher chance of having schizophrenia. Meanwhile, having a mutation in only one of the genes yielded no change in the possibility of schizophrenia development.
The research offers a new and exciting method to attack the schizophrenia disease from a genetic standpoint. With greater insights on the genetic factors, researchers can determine novel and effective drug treatments to combat this psychiatric disorder.
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