Blood test may predict psychosis risks

Schizophrenia is a serious brain disorder that affects millions of Americans. It is often diagnosed after an episode of psychosis during late adolescence or early adulthood. Common symptoms include hallucinations and delusions. Starting treatment soon after symptoms appear can aid recovery. But as with many mental health disorders, diagnosis depends on patient and family reports and assessment by a health professional. Medications are often settled on via trial and error.

Researchers have long sought more objective ways to inform diagnosis and treatment decisions. Toward this end, a research team led by Dr. Alexander B. Niculescu of Indiana University has been working to develop blood tests to improve the diagnosis of mental health conditions. Their earlier NIH-supported research identified biomarkers that might be used to detect risks for suicide, anxiety, post-traumatic stress disorder, mood disorders, and more.

In their latest study, the team searched for biomarkers relevant to psychosis. They drew on data collected over more a decade from people receiving treatment at the VA Medical Center in Indianapolis. All participants had been diagnosed with a major psychiatric disorder. These included schizophrenia, schizoaffective disorder, bipolar disorder, and major depressive disorder. Blood samples were collected every three to six months or during each hospitalization. Changes in the severity of hallucinations and delusions were also tracked. The findings were reported on February 8, 2024, in Molecular Psychiatry.

The team analyzed RNA in the blood to look for changes in gene expression—the levels at which genes are turned on or off—linked to the severity of hallucinations or delusions. They identified potential biomarkers by comparing gene expression in each participant during and outside of psychosis states. Using data from previous studies of psychotic disorders, they homed in on 98 biomarkers for hallucinations and 70 for delusions.

The researchers next identified biological pathways related to the biomarkers. Many biomarkers for hallucinations were linked to the glutamatergic signaling pathway. This pathway might trigger the brain to over-respond to sensory information. For delusions, the Rap1 signaling pathway was implicated. This pathway helps to form brain connections called synapses. Problems in this process might contribute to delusions.

The team was able to use the biomarkers to identify people in a different group of participants who were experiencing hallucinations or delusions. They also showed that biomarkers could be used to identify participants at increased risk of hospitalization for psychosis. Notably, the team found that some of the biomarkers are targeted by existing psychiatric drugs. These include clozapine, risperidone, and lithium.

The study findings will need to be confirmed in larger, more diverse groups of people. Other researchers are using different approaches to identify biomarkers for mental health conditions. Such biomarkers could one day be used to develop tests to help to guide treatment decisions and monitor patients’ responses.

“Schizophrenia is hard to diagnose, especially early on, and matching people to the right treatment from the beginning is very important,” Niculescu says. “Fortunately, some of the existing medications work quite well if initiated early in the right patients. There is reason for optimism in this era of emerging precision psychiatry.”

—by Vicki Contie