Piecing Together The Cause of Schizophrenia: Unifying Research

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Some pieces of the puzzle that we call schizophrenia came together for researchers at Duke University.

It is hoped that the new insights will lead to more effective schizophrenia treatments, some that might alleviate symptoms before they become debilitating.

Three Interlocking Pieces

Although Arp2/3 sounds like the name of a sci-fi robot, it is actually the name of a gene that the Duke researchers studied. They chose to research Arp2/3 since it plays a significant role in forming connections between neurons, and they analyzed its function by removing this gene from mice.

When mice had Arp2/3 removed they displayed schizophrenia-like behaviors that became severer over time, and the behaviors were relieved with antipsychotic medication. Researchers looked at the physical and chemical brain change in these mice and found three linked abnormalities.

The three linked abnormalities - earlier thought to be unrelated - are also found in people diagnosed with schizophrenia:

  1. Cells in the frontal area of the brain, those responsible for planning and making decisions, had fewer “dendritic spines” than normal. The spines are branches that facilitate connections between neurons. As the mice aged, more of these spines were lost, or “pruned.”
  2. Mice without Arp2/3 had overactive neurons in the brain’s frontal region. These neurons could bypass the diminished dendritic spines that are supposed to keep overactive neurons in check. Consequently, the cells revved into overdrive.
  3. The hyperactive neurons in the frontal region of the mice brains caused an overproduction of the neurotransmitter dopamine. (The antipsychotic drug haloperidol works by blocking dopamine transmission).

The Most Exciting Part

This research suggests that too much dopamine, too few frontal dendrites, and hyperactive frontal neurons - instead of being separate causes of schizophrenia as earlier suggested - are all brain misfires related to the missing Arp2/3 gene.

“The most exciting part was when all the pieces of the puzzle fell together,” said researcher Scott Soderling, Ph.D. “When Dr. Kim and I finally realized that these three outwardly unrelated phenotypes—spine pruning, hyperactive neurons, and excessive dopamine—were actually functionally interrelated with each other, that was really surprising and also very exciting for us.”

Sources: IFL Science; Nature Neuroscience; Science Daily
Photo credit: Hartwig HKD

 
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