Levels of a cytoskeletal protein found in the blood and the brain could form the basis of the first ever blood-based diagnostic test for schizophrenia.
Researchers at Sanford Burnham Prebys, in collaboration with research teams at the Department of Psychiatry at Harvard Medical School in Belmont, Massachusetts and Yokohama City University Graduate School of Medicine in Japan have been studying the activity of the CRMP2 protein, which is known to affect neural connections in the brain. The protein regulates how neurons make connections with each other, and the protein is also expressed in lymphocytes in the blood.
The researcher found there was an abundance of CRMP2 in blood samples taken from patients diagnosed with schizophrenia compared to the levels typically seen in patients without the disorder. The researchers also identified structural abnormalities in the dendrites of neurons in patients with schizophrenia, which they suggest could potentially be disabling due to the important role dendrites play in receiving impulses from other nerve cells in the brain.
There are two forms of the CRMP2 protein, one of which – the active form – is non-phosphorylated, while the inactive form is phosphorylated. Previous studies have shown that the balance between the two forms of the protein is well balanced in most people. The researchers compared postmortem brain tissue and blood samples from healthy patients and people with schizophrenia and found that patients with schizophrenia had significantly higher levels of the active form of the protein, and the inactive and active forms were notable out of balance, at least in younger patients.
Since lymphocytes can easily be sampled in a blood test, a diagnostic test could be devised that measures the abundance of the CRMP2 protein in the blood and also the ratio with the inactive form of the protein. If CRMP2 levels are high, or if the ratio with the inactive form is low, the blood test could help with the diagnosis of schizophrenia.
Currently, diagnosing schizophrenia can be a challenge, especially in younger patients. Diagnosis is currently based on psychiatric and neurobehavioral examinations, but it can be difficult to distinguish between schizophrenia and other conditions as the symptoms can be similar. For example, the symptoms experienced during a manic phase of bipolar disorder can easily be confused with schizophrenia.
Having a blood-based diagnostic test that can be used in conjunction with psychiatric and neurobehavioral exams could be an invaluable tool that could greatly improve the accuracy of diagnosis of schizophrenia in younger individuals
“Our results were most striking in people under the age of 40, and even more so in people under the age of 30. An early diagnosis could improve the clinical management of affected individuals as well as accelerate the development of new therapeutic options,” said Evan Y. Snyder, M.D., Ph.D., director of the Center for Stem Cells and Regenerative Medicine at Sanford Burnham Prebys and co-senior author of the study.
The researchers are now investigating the molecular biology of schizophrenia to try to identify the regulator that keeps the two forms of the CRMP2 balanced.
You can read more about the study in PNAS on this DOI: 10.1073/pnas.2100032118