Researchers Find Major Clues on How Schizophrenia Develops

Scientists have found some major clues in learning more about why schizophrenia develops. The new research may lead to better medications to correct gene-related problems that can lead to schizophrenia.

The researchers found that a gene called GAD1, which makes an enzyme essential for production of the chemical messenger called GABA, is turned on at increasingly high rates during normal development of the prefrontal cortex, but that this normal increase may not occur in people with schizophrenia. The prefrontal cortex is involved in higher functions like thinking and decision-making.

While scientists have known that abnormalities in brain development and in GABA synthesis play a role in schizophrenia, this study shows that defects in specific biochemical reactions that regulate gene activity—such as turning genes on and off so that they can make substances like the GAD1 enzyme—are also involved.

"This discovery opens a new area for exploration of schizophrenia," said NIMH Director Thomas R. Insel, MD. "Studies have yielded very strong evidence that schizophrenia involves a decrease in the enzymes, like GAD1, that help make the neurotransmitter GABA. Now we’re starting to identify the mechanisms involved, and our discoveries are pointing to potential new targets for medications."

The researchers also found that people with three different variations of the GAD1 gene that have been associated with schizophrenia also were more likely to have indicators of a malfunction in brain development. Among them were indicators of altered epigenetic actions related to GABA synthesis.

Clozapine and other antipsychotic medications are effective for many patients, but some patients choose to discontinue treatment because of the side effects they experience on these drugs. For this reason, scientists are working to find more precise molecular targets for the development of new medications that can correct the epigenetic flaws.

"We’ve known that schizophrenia is a developmental disease, and that something happens in the maturation of the prefrontal cortex during this vulnerable period of life. Now we’re beginning to find out what it is, and that sets the stage for better ways of preventing and treating it," says the study’s lead author, Schahram Akbarian, MD, PhD.

Results of the research were published in the October 17 issue of the Journal of Neuroscience, by Schahram Akbarian, MD, PhD, Hsien-Sung Huang, PhD student, and colleagues at the University of Massachusetts Medical School and Baylor College of Medicine. The study was funded by the National Institutes of Health’s National Institute of Mental Health (NIMH) and National Institute of Child Health and Human Development.


  • National Institutes of Health
  • Journal of Neuroscience, October 17, 2007

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