Breakthrough research links deformed proteins with schizophrenia.

New research from medical scientists at Johns Hopkins Univ. linked abnormally formed proteins in the human brain with the psychiatric illness called schizophrenia, in a significant number of patients. While they’re not yet sure what the connection is, the study reports that deformed proteins were found in the brains of many patients who were diagnosed with schizophrenia.

This leads researchers to guess that deformed proteins had a role in the disease, either as a cause or an effect. The team says this link is an important clue to gaining knowledge about schizophrenia. It’s a mysterious + incurable illness that’s not well understood.

The team analyzed post-mortem brain tissue from 42 schizophrenia patients, donated by brain banks across 3 different institutions. They compared these with post-mortem brain samples (from the same collections) of 41 people who had not been diagnosed with schizophrenia. Having samples from different collections enabled the team to test and re-test their results for consistency.

The researchers looked at 2 areas of the brain they believe are disrupted in patients with schizophrenia.

the pre-frontal cortex
the superior temporal gyrus

The team looked closely at proteins in those sections of the human brain, dividing them into 2 groups.

proteins that dissolve in water — called soluble
proteins that do not dissolve in water — called insoluble

After they’re assembled by the human body, proteins normally fold-up in a way that makes them soluble. Mis-folded proteins are often insoluble, don’t function properly, or at all — and are linked to many diseases.

The team — thinking about how clumps of insoluble, mis-folded proteins are seen in the brains of patients with Alzheimer disease and other illnesses — wanted to see if they could find evidence of similar pathology in schizophrenia. Unable to access these key brain areas in living patients, they could only look at post-mortem brains.

The results of this research were impressive: 20 of the 42 schizophrenia brains that were analyzed contained significantly more insoluble proteins — compared with the other 22 schizophrenia brains, and the 41 control brains. The researchers then used a physics technique called mass spectrometry to learn more about the proteins in the insoluble portion. They found unique and abnormal proteins in greater abundance.

In a nutshell, mass spectrometry uses high-tech devices to accurately measure the mass of different molecules in a sample. Even large bio-molecules like proteins are identifiable by mass, which means that biologists can perform interesting experiments using mass spectroscopy, adding a new dimension to their research.

The study’s discovery of deformed proteins is consistent with a theory of schizophrenia that says the illness is related to abnormal brain development.

Abnormal proteins were present in only half of the brain samples from schizophrenia patients. The team said this could be evidence of a sub-type of schizophrenia — which has implications for diagnosis and treatment development.

More research is under way to link insoluble proteins with the cause of schizophrenia, its specific clinical symptoms, and to explore if similar irregularities are present in other psychiatric illnesses.