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Why symptoms of schizophrenia emerge in young adulthood
Date:2/25/2010

In reports of two new studies, researchers led by Johns Hopkins say they have identified the mechanisms rooted in two anatomical brain abnormalities that may explain the onset of schizophrenia and the reason symptoms don't develop until young adulthood. Both types of anatomical glitches are influenced by a gene known as DISC1, whose mutant form was first identified in a Scottish family with a strong history of schizophrenia and related mental disorders. The findings could lead to new ways to treat, prevent or modify the disorder or its symptoms.

In one of the studies, published in the March issue of Nature Neuroscience, researchers examined DISC1's role in forming connections between nerve cells. Numerous studies have suggested that schizophrenia results from abnormal connectivity. The fact that symptoms typically arise soon after adolescence, a time of massive reorganization of connections between nerve cells, supports this idea.

The scientists began their study by surveying rat nerve cells to see where DISC1 was most active. Unsurprisingly, they found the highest DISC1 activity in connections between nerve cells. To determine what DISC1 was doing in this location, the researchers used a technique called RNA interference to partially shut off DISC1 activity. Consequently, they saw a transient increase and eventual reduction in size and number of dendritic spines, spikes on nerve cells' branch-like extensions that receive input from other nerve cells.

To determine how DISC1 regulates dendritic spine formation, the researchers studied which brain proteins interact with the protein expressed by the DISC1 gene. They identified one, called Kal-7, which earlier studies suggested is critical for proper dendritic spine formation. Further experiments suggested that the DISC1 protein acts as temporary holding place for Kal-7, binding it until it can be released to trigger a molecular cascade that results in dendritic spine formation.
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Contact: Christen Brownlee
cbrownlee@jhmi.edu
410-955-7832
Johns Hopkins Medical Institutions
Source:Eurekalert

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