Blood Test May Predict Patients Likely to Develop Schizophrenia
Abstract
When combined with the scores from a clinical assessment, the test was able to predict individuals with prodromal symptoms of schizophrenia who later developed the disorder with 90 percent accuracy.
The earlier that a person is diagnosed with schizophrenia and begins treatment, the better his or her outcomes will likely be. However, predicting which of the patients who show early disturbances in perception, thought processing, language, and attention will develop schizophrenia presents a significant challenge, as studies show that the majority of patients will not.
Diana Perkins, M.D., M.P.H., a professor of psychiatry at the University of North Carolina School of Medicine, says a blood-based bioassay is not ready for bedside yet, but it’s on its way.
“There are limitations to using only the high-risk symptoms identified by clinical criteria to determine whether a person will go on to develop psychosis or not,” Diana Perkins, M.D., M.P.H., a professor of psychiatry at the University of North Carolina School of Medicine, told Psychiatric News. “In the end, clinical criteria are not going to be good enough to diagnose someone at highest risk. We will need a biomarker assay.”
In a paper published in July in Translational Psychiatry, Sabine Bahn, M.D., Ph.D., a professor of molecular psychiatry at the University of Cambridge, and her colleagues described a blood-based molecular biomarker test that when combined with the scores from a clinical assessment, predicted individuals with prodromal symptoms of schizophrenia who later developed the disorder with 90 percent accuracy.
To create the test, Bahn’s team first looked for differences in the serum proteins of 127 first-onset drug-naive schizophrenia patients and 204 controls. Ultimately, they decided to screen for 26 biomarkers—the majority of which were involved in immune system, inflammation, hormonal signaling, and lipid transport function—that were altered significantly in patients with schizophrenia compared with controls.
Sabine Bahn, M.D., Ph.D., says the goal of a biomarker test for schizophrenia is not to replace clinical assessments of the disorder, but to enhance questionnaires.
After determining the test’s ability to distinguish patients who went on to develop schizophrenia from healthy controls in two independent cohorts with 97 percent accuracy, the researchers analyzed blood samples collected from 76 people who met prodromal criteria (18 later developed schizophrenia and 58 did not).
The test was able to predict future episodes of psychosis with 82 percent accuracy in the at-risk group. However, when the positive subscale symptom scores from the Comprehensive Assessment of At-Risk Mental State—a questionnaire used to identify people at risk for developing a psychotic disorder—were incorporated into the model, the test predicted future episodes of psychosis with 90 percent accuracy.
“Our findings support previous work that suggests immune-related and metabolic changes in blood are associated with schizophrenia,” Bahn said. “The fact that such changes can be observed in individuals who as of yet have not developed schizophrenia supports the notion that these changes are linked to pathology.”
The test was also 90 percent accurate in predicting future schizophrenia in samples obtained from a group of U.S. military members who at the time of blood collection showed no psychiatric symptoms but later developed schizophrenia or bipolar disorder. However, the screen was able to predict bipolar disorder with only 53 percent accuracy—suggesting that the test was able to discriminate schizophrenia patients from bipolar disorder patients before symptoms emerged.
“Finding that kind of specificity for the prediction of schizophrenia is powerful,” Cheryl Corcoran, M.D., an assistant professor of clinical psychiatry at Columbia University, who was not involved with the study, told Psychiatric News. “It speaks to the analytes not simply reflecting general psychopathy but indicating potential mechanisms in the development of schizophrenia.”
Cheryl Corcoran, M.D., an assistant professor of clinical psychiatry at Columbia University, says that blood tests, such as the one developed by Bahn’s group, may offer clues about novel targets for the prevention and treatment of schizophrenia.
Corcoran noted that while more work is needed before the test can be used in general practice, “this panel offers clues about what we could possibly use for targets for prevention and treatment.”
Perkins, who was also not involved with the study, agreed. In a paper in Schizophrenia Bulletin in 2014, Perkins and her colleagues described a blood test that identified several differences in plasma analytes involved in immune status and oxidative stress in people with prodromal schizophrenia symptoms who developed psychosis from those who did not.
“We are seeing a consistent pattern of disruption that has to do with the immune system and hormonal dysregulation,” Perkins said. “The findings suggest to me that we are well on the way to developing a blood-based bioassay.”
The goal of developing a blood-based bioassay is not to take the place of descriptive analysis of the behavior of patients but to enhance these assessments, Bahn noted. “Schizophrenia is a disease that affects not only the brain but the rest of the body. We must not only look to diagnose earlier, but also think about new treatments.”
Bahn is the director of Psynova Neurotech, a company focused on the development and use of biomarkers for psychiatric disorders. The study was supported by grants from the Stanley Medical Research Institute and the European Commission. ■
