Study could lead to diagnostic blood test for schizophrenia

Scientists at Sanford Burnham Prebys have discovered how the levels of a protein could be used in the future as a blood diagnostic aid for schizophrenia. The activity of the protein, which is found in both the brain and the blood, affects neural connections in the human brain and is particularly imbalanced in people diagnosed with the disease. The research also provides directions for future analyzes of the molecular basis of this severe and disabling mental disorder.

The study, an international collaboration between groups from the Yokohama City University School of Medicine in Japan and the Department of Psychiatry at Harvard Medical School in Belmont, Massachusetts, was recently published in PNAS.

This study looked at the activity of CRMP2, a protein found in the brain (called a “cytoskeletal protein”) that regulates how neurons make connections with each other. CRMP2 is also found to be expressed in lymphocytes in the blood and can therefore be easily collected from humans by doing nothing more than a simple venipuncture.

Evan Y. Snyder, MD, Ph.D., director of the Center for Stem Cells and Regenerative Medicine at Sanford Burnham Prebys and co-lead author of the study

“There was an abundance of CRMP2 levels in samples from people with schizophrenia compared to people without the disorder. We also found structural abnormalities in the dendrites of neurons that could potentially be disabling because dendrites play an important role in receiving impulses from other nerve cells in the brain. “

Previous research has shown that most people maintain a balance between the two forms of CRMP2: its active non-phosphorylated form and its inactive phosphorylated form. The new research first looked at postmortem brain tissue and then blood samples from people with schizophrenia. The research team compared these levels to those of people without the disorder.

The results indicated that the amount of active CRMP2 was too high in people with schizophrenia and, at least in young people with schizophrenia, was not counterbalanced by an appropriate amount of increased inactive CRMP2. This imbalance between active and inactive CRMP2 could explain certain dysfunctions of neuronal connections.

Measuring an abundance of active CRMP2, particularly if its ratio to inactive CRMP2 is too low, could become a format for a rapid and minimally invasive blood test to support the diagnosis of schizophrenia.

“Schizophrenia can be difficult to diagnose early or in young patients for a number of reasons,” says Snyder. “Combining a blood test with psychiatric and neurobehavioural tests could help doctors distinguish schizophrenia from other conditions with somewhat similar symptoms, such as the manic phase of bipolar disorder or other behavioral disorders,” personality or thought.

“Our results were most striking in people under 40, and even more so in people under 30. Early diagnosis could improve clinical management for those affected and accelerate the development of new treatment options. “Snyder said. adds.

Researchers now want to dig deeper into the molecular biology of the disease to uncover the “regulator” that keeps most people’s CRMP2 levels on a level playing field. They also want to conduct a larger multicenter clinical study that compares schizophrenia with other psychiatric disorders. Future research will aim to include a wider range of ethnicities and age groups.