New pathway that plays a role in schizophrenia identified

Scientists have found that inhibition of a basic cellular process may contribute to the development of schizophrenia.
Researchers found that an important cell-maintenance process called autophagy is reduced in the brains of schizophrenic patients.
The findings advance the understanding of schizophrenia and could enable the development of new diagnostic tests and drug treatments for the disease.
"We discovered a new pathway that plays a part in schizophrenia," said Professor Illana Gozes - the Lily and Avraham Gildor Chair for the Investigation of Growth Factors, the director of the Adams Super Center for Brain Studies at the Sackler Faculty of Medicine, and a member of the Sagol School of Neuroscience at Tel Aviv University.

"By identifying and targeting the proteins known to be involved in the pathway, we may be able to diagnose and treat the disease in new and more effective ways," Gozes said.
Autophagy is like the cell's housekeeping service, cleaning up unnecessary and dysfunctional cellular components. The process - in which a membrane engulfs and consumes the clutter - is essential to maintaining cellular health. But when autophagy is blocked, it can lead to cell death.

Brain-cell death also occurs in schizophrenics, so Gozes and her colleagues set out to see if blocked autophagy could be involved in the progression of that condition as well.

They found RNA evidence of decreased levels of the protein beclin 1 in the hippocampus of schizophrenia patients, a brain region central to learning and memory.
Beclin 1 is central to initiating autophagy - its deficit suggests that the process is indeed blocked in schizophrenia patients.
Developing drugs to boost beclin 1 levels and restart autophagy could offer a new way to treat schizophrenia, the researchers said.
"Paucity in beclin 1 may lead to decreased autophagy and enhanced cell death. Our research suggests that normalising beclin 1 levels in schizophrenia patients could restore balance and prevent harmful brain-cell death," Gozes said.

Researchers also looked at protein levels in the blood of schizophrenia patients. They found no difference in beclin 1 levels, suggesting that the deficit is limited to the hippocampus.
But they found increased levels of another protein, activity-dependent neuroprotective protein (ADNP), discovered by Gozes and shown to be essential for brain formation and function, in the patients' white blood cells.
The researchers think the body may boost ADNP levels to protect the brain when beclin 1 levels fall and autophagy is derailed. ADNP, then, could potentially serve as a biomarker, allowing schizophrenia to be diagnosed with a simple blood test.

The study was published in Nature's Molecular Psychiatry.