Brain study reveals type of schizophrenia similar to neurodegenerative disease
Research from Johns Hopkins Medicine has revealed some cases of schizophrenia can be associated with abnormal protein buildup in the brain similar to that seen in cases of Alzheimer's and other neurodegenerative disorders. It's hoped the discovery will lead to better diagnostic strategies identifying specific types of schizophrenia.
A compelling wave of research over the last few years has consistently expanded our understanding of schizophrenia. From uncovering intriguing links to gut bacteria and the immune system, to homing in on the disease's developmental foundations in the womb, scientists are increasingly discovering schizophrenia is a more physiologically complex condition that previously thought.
One of the more interesting implications of this growing body of study is the suggestion schizophrenia may consist of a variety of different subtypes. However, the big research challenge ahead is to develop ways to classify those different subtypes by identifying pathological biomarkers instead of simply observing clinical symptoms.
This new study set out to examine whether schizophrenic brains accumulate volumes of abnormal proteins in a way similar to that which presents in cases of neurodegenerative disease. To do this, researchers examined post-mortem samples of brains from 42 subjects with schizophrenia. More specifically, samples of the prefrontal cortex and superior temporal gyrus were studied for traces of abnormal levels of misfolded proteins.
The results revealed half of the brain samples contained significantly higher levels of abnormal proteins, compared to a number of healthy control samples. These particular brain samples also showed elevated levels of a protein called ubiquitin, known to be a marker for protein aggregates in neurodegenerative disorders. These abnormal proteins were only identified in about half of the schizophrenic brain samples, suggesting this biomarker is a characteristic of a certain subtype of schizophrenia. It is unclear at this stage exactly what physical or behavioral symptoms can be associated with the potential schizophrenia subtype identified.
"The brain only has so many ways to handle abnormal proteins," says lead on the study, Frederick Nucifora Jr. "With schizophrenia, the end process is mental and behavioral, and doesn't cause the pronounced physical neural cell death we see with neurodegenerative diseases, but there are clearly some overall biological similarities."
To clarify that these abnormal proteins were related to the disease, and not a result of the anti-psychotic medications often administered to patients, a subsequent rat study was conducted. A number of animals were treated with common anti-psychotic drugs for nearly five months. Brain samples were then examined revealing no abnormal protein accumulations or ubiquitin increases, suggesting the disease itself as the primary source of the build-up identified in the human subjects.
"Researchers have been so focused on the genetics of schizophrenia that they've not paid as much attention to what is going on at the protein level and especially the possibility of protein aggregation," says Nucifora. "This may be a whole new way to look at the disorder and develop more effective therapies."
Homing in on these abnormal proteins the researchers discovered those identified play a role in nervous system development and function. This affirms the hypothesis that schizophrenia can be traced back to disruptions in brain development. Unlike in neurodegenerative disorders, where these kinds of abnormal brain proteins can directly result in neuronal death, it is hypothesized in schizophrenia these similar protein aggregations are potentially genetically or environmentally triggered at earlier points in a person's life, resulting in dysfunctional neurodevelopment.
The next stage in the research is to examine levels of these abnormal proteins at different stages in the development of living subjects with schizophrenia. To achieve this the Johns Hopkins scientists have developed an extraordinary new method that can take samples of neurons from a living patient's nose, and use those samples to effectively track levels of these abnormal proteins.
The new study was published in The American Journal of Psychiatry.
Source: Johns Hopkins Medicine