Scripps discovery could lead to way to reverse schizophrenia

Existing schizophrenia treatments combat hallucinations, delusional behavior and other symptoms of the debilitating condition, with a heady number of side effects. But what if a drug could be deployed to address the underlying genetic cause?

That may be possible, at least theoretically, according to new research led by Elizabeth Thomas at The Scripps Research Institute. Thomas' finding, published online in the new journal Translational Psychiatry, is very early-stage, based on post-mortem brain samples from healthy and schizophrenia patients. If it bears out in animal testing and in human patients, drugs already under development could help minimize and even reverse symptoms of the disorder, particularly in younger patients, Thomas and her crew say.

Here's what they found: A mechanism that promotes DNA expression in certain brain cells is out of whack in schizophrenia patients, or "too tightly wound," as Scripps notes in its promotional materials. Yes, the phrase conjures up an image of a really nervous, high-strung person, but there's a bit more to the distortion, which has been identified in previous research involving Huntington's and Parkinson's disease patients.

It's all about the histones and the process that takes place when they're acetylated. Scripps describes histones as structural proteins that DNA wraps around, which are modified chemically to either relax or repack DNA. The acetylation process exposes parts of DNA so genes can be used. By looking at post-mortem samples from schizophrenic and healthy brains, they found that the schizophrenic brain samples contained altered acetylation levels in select histone portions of the brain that would block gene expression. Brain samples from younger schizophrenia patients were even worse off, the researchers found.

Based on their findings, the researchers believe that histone deacetylase inhibitors could be used to prevent or at least reverse the progression of schizophrenia, with the best benefit in younger patients. Interestingly, some neurodegenerative conditions in older folks appear similar biologically to schizophrenia, so the drugs might work for them, too.

- here's the release
- read the study

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