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New research from medical scientists at Johns Hopkins University linked abnormally formed proteins in the human brain with the disease called schizophrenia, in a significant number of patients. While they’re not yet sure what the connection is, the study said that deformed proteins were found in the brains of many patients who were diagnosed with schizophrenia.
This leads researchers to guess that those proteins had a role in the disease: either as a cause or an effect. The research team explained that this link is an important clue to gaining knowledge about schizophrenia, which is highly mysterious and not well understood.
auditory processing and language comprehension
— the research —
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 prefrontal cortex
— the superior temporal gyrus
Within those sections of the brain, the team looked closely at proteins, 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.
— report —
organization: Johns Hopkins Univ.
publication: American Journal of Psychiatry
The results of this research were striking. Twenty 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 method called mass spectrometry to learn more about the proteins in the insoluble portion. In the brains with more insoluble proteins, they found unique and, also, abnormal proteins in greater abundance.
Further analysis indicated that many of these abnormal proteins were components in pathways involved in the development of the nervous system. Specifically, they were involved in generating the connections neurons use to communicate with one another; the process by which new neurons are generated (neurogenesis); and the process by which neurons recognize the axons of other neurons.
The main finding of abnormal proteins and the processes they affect are consistent with theories of schizophrenia that trace its origins to the brain’s development, and to problems that emerge in neural communication.
The fact that the abnormal proteins were present in only half of the brain samples from schizophrenia patients suggests that the observed protein abnormalities are likely to be found only in a subset of schizophrenia patients, the team said. This work thus provides evidence that subtypes of the illness exist, which has implications for diagnosis and treatment development.
More research is under way to link insoluble proteins with disease causation, specific clinical symptoms of schizophrenia, and to discover if similar irregularities are present in other psychiatric illnesses.
The team also included: first author Leslie Nucifora, Ph.D., a 2017 BBRF Young Investigator; Akira Sawa, M.D., Ph.D., a BBRF Scientific Council member and 2011 Distinguished Investigator and 2004 and 2002 Young Investigator; Carol Tamminga, M.D., also a Scientific Council member, a 2011 Lieber Prizewinner and 2010 and 1988 Distinguished Investigator; Christopher Ross, M.D., Ph.D., a 2004 and 1995 BBRF Distinguished Investigator and 1990 Young Investigator; Robert Sweet, M.D., a 2017 BBRF Distinguished Investigator; Russell Margolis, M.D., 2007 BBRF Distinguished Investigator, 2003 and 1999 Independent Investigator, and 1994 Young Investigator; and Matthew MacDonald, Ph.D., a 2014 BBRF Young Investigator.
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deck: On the trail of a mysterious illness.
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