Studies Examine Gene Impact in Schizophrenia

Schizophrenia continues to be a puzzling disease and one that doctors cannot always effectively treat and scientists still don’t fully understand. A recent Science Daily release examined a report of two new studies in which researchers led by Johns Hopkins say they have identified the mechanisms rooted in anatomical brain abnormalities that could explain the onset of schizophrenia.

Symptoms of this disease do not appear until young adulthood and researchers believe this is partly driven by the types of anatomical glitches that are influenced by a gene known as DISC1. This gene’s mutant form was first identified in a Scottish family with a strong history of schizophrenia and other related mental disorders.

Rat nerve cells were examined to determine where DISC1 was most active. The highest activity was found in connections between nerve cells. Through continued study and analysis, scientists determined that a defective DISC1 gene could lead nerve cells to maintain weaker connections with unusually low numbers of neighboring neurons.

“Connections between neurons are constantly being made and broken throughout life, with a massive amount of broken connections, or ‘pruning,’ happening in adolescence,” said Akira Sawa, M.D., Ph.D., professor of psychiatry and director of the program in molecular psychiatry at the Johns Hopkins University School of Medicine. “If this pruning doesn’t happen correctly, it may be one reason for the pathogenesis of schizophrenia.”

The second study created a new model of schizophrenia by temporarily shutting off the DISC1 gene in mice in the prefrontal cortex. This allowed for the study of other roles for DISC1 in the brain. The shut-off was temporary and when it was reactivated, scientists could study that part of the brain over time.

Sawa said that taken together, the results of both studies suggest these anatomical differences, which seem to be influenced by the DISC1 gene, cause problems before birth that do not surface until young adulthood.

“If we can learn more about the cascade of events that lead to these anatomical differences, we may eventually be able to alter the course of schizophrenia. During adolescence, we may be able to intervene to prevent or lessen symptoms,” Sawa added.

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