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New Blood Test Developed for Anxiety

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Scientists from Indiana University School of Medicine report a new a blood test that can predict a patient’s state of anxiety and their future risk. The test, published in the journal Molecular Psychiatry, is now being developed by an Indiana-based start-up company.

Diagnosing anxiety disorders

The Institute for Health Metrics and Evaluation’s Global Burden of Disease study reported that an estimated 792 million people are living with a mental health disorder globally. Approximately 284 million are experiencing an anxiety disorder, an umbrella term that comprises conditions such as phobic, social, obsessive compulsive (OCD), post-traumatic disorder or generalized anxiety disorders. “Many people are suffering from anxiety, which can be very disabling and interfere with daily life,” says Alexander Niculescu, professor of psychiatry at Indiana University School of Medicine and senior author of the new study.

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Niculescu’s team previously developed tests for the diagnosis of pain, depression, bipolar and post-traumatic stress disorder using blood-based biomarkers. The tests were developed using a four-step approach: 1) explore blood RNA changes in patient cohorts vs healthy individuals, 2) prioritize candidate biomarkers for further exploration, 3) validate the biomarkers and 4) test the biomarkers for clinical utility.

Now, Niculescu has applied a similar methodology to create a blood test for anxiety, which can be used to evaluate a persons’ current level of anxiety, predict future risk and explore which pharmacological treatment options could be most suitable for them. “The current approach [for diagnosing anxiety] is to talk to people about how they feel to see if they could be on medications, but some medications can be addictive and create more problems,” Niculescu explains. “We wanted to see if our approach to identify blood biomarkers could help us match people to existing medications that will work better and could be a non-addictive choice.”

A systematic and comprehensive approach for precision medicine

The research team recruited three independent cohorts from the Indianapolis VA Medical Center who were required to undergo a blood test every three–six months, or in the instance that a psychiatric hospitalization occurred. All participants included in the study had been diagnosed with a psychiatric disorder among other co-morbidities, and medication data was collected at each study visit. “Our goal is to find biomarkers that track anxiety, regardless if the reason for it is internal biology or it is driven by external medications or drugs,” the researchers write in the paper.

The study was organized in a stepwise fashion, which the authors describe as a “systematic” and “comprehensive” approach to move the field towards precision medicine.

“First, we endeavored to discover blood gene expression biomarkers for anxiety using a longitudinal design, looking at differential transcription of genes in the blood of male and female subjects with major psychiatric disorders […] and high-risk populations prone to anxiety, which constitute an enriched pool in which to look for biomarkers,” the authors say. They then compared low anxiety states to high anxiety states to create a list of differentially transcribed genes.

Breakdown of the study cohort

  • Biomarker discovery participants –experienced at least one change in their anxiety state from one visit to another (58 subjects, 41 males and 17 females).
  • Biomarker validation participants – in which the top candidate biomarker findings from the discovery cohort were validated (40 subjects, 32 male and 8 female).
  • Biomarker testing participants – used to predict high anxiety state (161 male and 36 female subjects) and clinically severe anxiety (159 male and 36 female subjects) using the validated biomarkers.

Niculescu and team next used a convergent functional genomics (CFG) approach – which gathers data from the wider field – to prioritize biomarkers for further study. “CFG integrates multiple independent lines of evidence: genetic, gene expression and protein data, from brain and periphery, from human and animal model studies, as a Bayesian strategy for identifying and prioritizing findings, reducing the false-positives and false-negatives inherent in each individual approach,” the researchers explain.

To validate the biomarkers, Niculescu and colleagues explored whether the transcription levels of the prioritized biomarkers changed dramatically in an independent cohort of participants that had been diagnosed with clinically severe anxiety. Their fourth and final step involved testing the biomarkers in a final cohort of psychiatric patients, and identifying which of the biomarkers could be targeted by existing drugs. “The biomarkers with the best overall evidence were GAD1, NTRK3, ADRA2A, FZD10, GRK4 and SLC6A4,” the researchers note. “We also used our biomarker gene transcription signature to identify drugs that could be repurposed for treating anxiety, such as estradiol, pirenperone, loperamide and disopyramide.”

“Prevention is better”

Based on the data presented in Molecular Psychiatry, the blood tests are now being developed by an Indianapolis-based startup company for use by physicians, according to the Indiana University School of Medicine’s press release.

Niculescu believes that, with further development, the new test for anxiety could be used alongside other blood tests his team has developed, offering a personalized medicine approach for diagnosing various health concerns: “This is something that could be a panel test as part of a patient’s regular wellness visits to evaluate their mental health over time and prevent any future distress,” he says. “Prevention is better in the long run, so our goal is to be able to provide a comprehensive report for patients and their physicians using simply one tube of blood.”

Reference: Roseberry K, Le-Niculescu H, Levey D, et al. Towards precision medicine for anxiety disorders: objective assessment, risk prediction, pharmacogenomics and repurposed drugs. Mol Psych. 2023:1-19. doi:10.1038/s41380-023-01998-0.

This article is a rework of a press release issued by the Indiana University School of Medicine. Material has been edited for length and content.