Scientists have discovered a protein that could serve as the foundation for the development of a rapid, minimally invasive blood test for the early detection of schizophrenia. CRMP2 is a protein found in both the brain and the blood that influences neural connections in human brains. The study discovered that in human brain tissue and blood, the active, non-phosphorylated form of this protein is balanced by its inactive, phosphorylated form.
Sanford Burnham Prebys scientists have discovered how protein levels could be used as a blood-based diagnostic aid for schizophrenia in the future. The protein’s activity, which is found in both the brain and the blood, affects neural connections in human brains and is uniquely imbalanced in people with the condition. The findings also provide direction for future studies into the molecular basis of this serious and disabling mental disorder.
The study, which was conducted by researchers from Yokohama City University Graduate School of Medicine in Japan and the Department of Psychiatry at Harvard Medical School in Belmont, Massachusetts, was recently published in PNAS.
Study reveals an abundance of the CRMP2 protein in people with schizophrenia. The findings could lead to a blood-based biomarker test for the mental health disorder.
“This study looked at CRMP2, a protein found in the brain (called a ‘cytoskeletal protein’) that regulates how neurons connect with one another,” says 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. “CRMP2 is also found in lymphocytes in the blood and can thus be easily sampled in people using nothing more than a simple venipuncture.
“When samples from people with schizophrenia were compared to samples from people who did not have the disorder, there was an abundance of CRMP2 levels. We also discovered structural abnormalities in neurons’ dendrites, which could be disabling because dendrites play an important role in receiving impulses from other nerve cells in the brain.”
“CRMP2 is also expressed in lymphocytes in the blood and can thus be easily sampled in people by doing nothing more than a simple venipuncture [i.e., collecting blood from a vein],” said Dr. Evan Snyder, director of the Center for Stem Cells and Regenerative Medicine at Sanford Burnham Prebys in the United States and study co-author. “Our findings were most striking in people under 40, and even more so in people under 30,” he explained.
Previous research has shown that most people maintain an even balance of CRMP2’s two forms: active, non-phosphorylated CRMP2 and inactive, phosphorylated CRMP2. The new study looked at postmortem brain tissue and then blood samples from people who had schizophrenia. The researchers compared these levels to those of people who did not have the disorder.
The findings indicated that the amount of active CRMP2 in people with schizophrenia was excessive and, at least in young people with schizophrenia, was not balanced by an adequate amount of increased inactive CRMP2. The imbalance between active and inactive CRMP2 could explain some neural connection dysfunctions.
Measuring the abundance of active CRMP2, especially if the ratio with inactive CRMP2 is too low, could become a format for a quick, minimally invasive blood test to support the diagnosis of schizophrenia.
“Schizophrenia can be difficult to diagnose early on or in young patients for a variety of reasons,” Snyder says. “Pairing a blood test with psychiatric and neurobehavioral exams could help doctors differentiate schizophrenia from other conditions with similar symptomologies, such as the manic phase of bipolar disorder or other behavioral, personality, or thought disorders.”
This shows the outline of a woman and a brain
The imbalance between active and inactive CRMP2 could explain some neural connection dysfunctions. “Our findings were most striking among people under the age of 40, and even more so among those under the age of 30.” “An early diagnosis could improve clinical management of affected individuals while also hastening the development of new therapeutic options,” Snyder adds.
The researchers now want to delve deeper into the disease’s molecular biology to find the “regulator” that keeps most people’s CRMP2 levels in check. They also intend to conduct a larger, multi-center clinical trial comparing schizophrenia to other psychiatric disorders. Future studies will seek to include a broader range of ethnicities and age groups.
