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January 10, 2018.

In the 30 years since Prozac first hit the U.S. market, antidepressants have revolutionized modern treatments for major depressive disorder, while screening for depression has remained largely unchanged. To diagnose depression, healthcare providers still rely primarily on patient responses to questions based on criteria from the Diagnostic and Statistical Manual of Mental Disorders.

Even after a recent update, these criteria have lower reliability for establishing a diagnosis than those for almost any other psychiatric disorder. This is a serious shortcoming given that, according to the World Health Organization, depression is the number one cause of disability worldwide, and the U.S. Preventive Services Task Force has issued a recommendation that primary care providers should screen all adults for this condition.

Could a test for biomarkers improve diagnosis and help lighten the global burden of depression? Biomarkers are substances produced by the body, such as proteins, that indicate a specific process or disease. Some experts believe that a recent shift toward studying multi-biomarker panels that reflect depression's true complexity could become an unexpected breakthrough for certain patient populations.

Researchers have found numerous biomarkers associated with depression, but the statistical significance of each of these alone has not been strong enough to make a diagnosis, according to Richard Shelton, MD, vice chair of research in the department of psychiatry at the University of Alabama at Birmingham School of Medicine. By combining the results from measuring many of these biomarkers, however, scientists are beginning to create tests that could potentially wield real predictive power.

Dr. Shelton collaborated with a research team to develop a test known as MDDScore that measures nine biomarkers in the blood associated with changes observed during major depression. Using the pattern of these biomarkers' concentrations as well as body-mass index, an algorithm then calculates a score on a scale of 1 to 9 that is adjusted for sex, indicating the probability that a patient has depression.

A pair of studies led by John Bilello, PhD, chief scientific officer of Ridge Diagnostics, and George Papakostas, MD, associate professor of psychiatry at Harvard Medical School, showed that MDDScore could differentiate between depressed and non-depressed individuals. The test demonstrated good sensitivity and specificity (both >90%), which have been validated in a replication study.

Currently, MDDScore is not widely available. So far, one laboratory offers MDDScore and it has not yet been approved by the Food and Drug Administration (FDA).

As researchers who study depression embrace multianalyte panels, they still face hurdles on the road to developing an FDA-approved test that clinical labs across the country could use. The most significant of these, according to Shelton, is creating a test that performs well, not just in research samples, but in depressed patients seen in clinical settings. Most biomarker investigations study patients who are depressed but otherwise healthy. In reality, however, patients with major depressive disorder often have other conditions that could interfere with test results, such as heart disease, diabetes, and lupus. While both published studies on MDDScore were conducted in somewhat restricted patient populations, researchers have gone on to evaluate the test in patients with conditions such as chronic pain and intend to further validate it in populations with other conditions such as HIV infection.

If and when FDA approves a test for depression, the ultimate question is, will it be useful? Interestingly, healthcare providers report that MDDScore has helped with an issue that is not unusual in primary care. When patients are clearly depressed but in denial about it, clinicians have discovered that an MDDScore result indicative of depression can help convince patients to accept treatment.

In psychiatric practices where patients have already committed to treatment, the test might be useful when patients want to stop their medication prematurely and a high MDDScore result might dissuade them. Dr. Bilello also envisions that MDDScore will help identify depression in adolescents and the elderly, two populations that might not communicate their internal states as accurately as adults in their prime.


This article was adapted from AACC's Clinical Laboratory News. For the full article see:
(March 1, 2016) DeLong, Christine. The Elusive Blood Test for Depression, Novel Study Designs Breathe New Life Into Decades-Long Search. Available online at