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Precision Psychiatry

Is a Blood Test for Schizophrenia on the Horizon?

... and will future diagnostic assessment include it?

Key points

  • There is no blood test to definitively diagnose schizophrenia.
  • A number of blood gene expression biomarkers have been found to correlate with schizophrenia.
  • Many of these gene expressions are believed to be related to glutamate.
  • Most medications for schizophrenia don't affect glutamate; however, new treatments often utilize this pathway.

I remember sitting in the adolescent psychiatric unit flipping through a pamphlet I had been given to read on schizophrenia. To my knowledge, I had not been diagnosed with schizophrenia, but I had received a barrage of other changing diagnoses in a short period, including a few involving psychosis, an experience common in schizophrenia. I wasn't sure those treating me knew what was going on with me any more than I did.

The staff thought this would be helpful for me to read. But the brochure and the idea of the illness scared me. I didn't fully understand.

I flipped to a page on diagnosing schizophrenia and read that there was no blood test for it. Of course not. How would they measure a mental health condition in someone's blood? My own experiences at that point had shown that EEGs, an MRI, psychological assessment, and multiple psychiatric examinations have led to a string of changing and conflicting diagnostic impressions. An objective test at that time would have been so appreciated.

Biomarkers in a Blood Test

Twenty years later, last week, I spotted an article in U.S. News and World Report titled "Blood Test to Predict Schizophrenia Shows Promise." I thought to myself, this has to be a mistake.

Schizophrenia is such a variable condition. Up until the most recent publication of the Diagnostic and Statistical Manual came out in 2013, schizophrenia had been split into at least six categories. Even today, many believe that the phenomenon represents a collection of illnesses. It's been mysterious.

Yet the source publication—a 2024 study (Hill et al., 2024) seeking to identify blood gene expression biomarkers—had drawn some ground on the topic. While no "schizophrenia gene" has been identified, it appears certain gene expression markers have been found to correlate with psychotic symptoms. Specific genetic biomarkers listed included expression of PPP3CB, DLG1, ENPP2, ZEB2, RTN4, AUTS2, MACROD2, NR4A2, PDE4D, PDP1, and RORA.

Many of these genetic biomarkers are believed to affect dynamics involving a specific neurotransmitter, glutamate. Except for its role in one antipsychotic medication, Clozapine, glutamate has only recently become a target of psychiatric intervention with most anti-psychotic medications involving antagonism of another neurotransmitter, dopamine, instead.

Glutamate is believed to be one of the most common excitatory neurotransmitters in the brain with linkage to learning, memory, and general brain function. It is also thought to play a role in neuroplasticity, or the forming of new connections within the brain. While the research has risen to a level of use in diagnosis, several differences have been noted in functional connectivity in the brains of those with schizophrenia (Ramirez-Mahaluf et al., 2023).

A New Test in the Future

While there is still no definitive blood test for schizophrenia, testing for genetic biomarkers related to schizophrenia is likely to be of use in the future as part of the diagnostic and assessment process. A test is in development, and according to the U.S. News article (Miller, 2024) is expected to be released later this year. This is groundbreaking.

Such a test may also have implications for customizing medical treatment. This could make a meaningful difference with diagnostic clarification, which still contains quite a level of guesswork in the world of psychosis thereby meaning a lot to the individuals and families walking through this diagnostic process and working toward mental health recovery.

References

Hill, M. D., Gill, S. S., Le-Niculescu, H., MacKie, O., Bhagar, R., Roseberry, K., & Niculescu, A. B. (2024). Precision medicine for psychotic disorders: objective assessment, risk prediction, and pharmacogenomics. Molecular Psychiatry, 1-22.

Miller, C. (2024, February 13). Blood Test to Predict Schizophrenia Shows Promise. US News and World Report. Blood Test to Predict Schizophrenia Shows Promise (usnews.com)

Ramirez-Mahaluf, J. P., Tepper, Á., Alliende, L. M., Mena, C., Castañeda, C. P., Iruretagoyena, B., ... & Crossley, N. A. (2023). Dysconnectivity in schizophrenia revisited: abnormal temporal organization of dynamic functional connectivity in patients with a first episode of psychosis. Schizophrenia Bulletin, 49(3), 706-716.

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