Northwestern Medicine researchers say they have developed the first blood test to diagnose major depression in adults, by measuring the levels of nine RNA blood markers.

RNA molecules are the messengers that interpret the DNA genetic code and carry out its instructions. 

The blood test also predicts who will benefit from cognitive behavioral therapy based on the behavior of some of the markers. This will provide the opportunity for more effective, individualized therapy for people with depression. In addition, the test showed the biological effects of cognitive behavioral therapy, the first measurable, blood-based evidence of the therapy's success. The levels of markers changed in patients who had the therapy for 18 weeks and were no longer depressed.  

"This clearly indicates that you can have a blood-based laboratory test for depression, providing a scientific diagnosis in the same way someone is diagnosed with high blood pressure or high cholesterol," said Eva Redei, who developed the test and is a professor of psychiatry and behavioral sciences at Northwestern University Feinberg School of Medicine. "This test brings mental health diagnosis into the 21st century and offers the first personalized medicine approach to people suffering from depression."

Redei is co-lead author of the study, which will be published Sept. 16 in Translational Psychiatry.

Redei previously developed a blood test that diagnosed depression in adolescents. Most of the markers she identified in the adult depression panel are different from those in depressed adolescents.

Decades-Long Search for Biological Depression Test

The search for a biological diagnostic test for major depression has been ongoing for decades.

The current method of diagnosing depression is subjective and based on non-specific symptoms such as poor mood, fatigue and change in appetite, all of which can apply to a large number of mental or physical problems. A diagnosis also relies on the patient's ability to report his symptoms and the physician's ability to interpret them. But depressed patients frequently underreport or inadequately describe their symptoms.

"Mental health has been where medicine was 100 years ago when physicians diagnosed illnesses or disorders based on symptoms," said co-lead author David Mohr, a professor of preventive medicine and director of the Center for Behavioral Intervention Technologies at Feinberg. "This study brings us much closer to having laboratory tests that can be used in diagnosis and treatment selection."

The new blood test will allow physicians for the first time to use lab tests to determine what treatments will be most useful for individual patients.

"Currently we know drug therapy is effective but not for everybody and psychotherapy is effective but not for everybody, " Mohr said. "We know combined therapies are more effective than either alone but maybe by combining therapies we are using a scattershot approach. Having a blood test would allow us to better target treatment to individuals."

Major depressive disorder affects 6.7 percent of the U.S. adult population in a year, a number that is rising. There is a two-to 40- month delay in diagnosis, and the longer the delay, the more difficult it is to treat depression. An estimated 12.5 percent of patients in primary care have major depression but only about half of those cases are diagnosed. A biologically based test has the potential to provide a more timely and accurate diagnosis.

How the Study Worked

The study included 32 patients, ages 21 to 79, who had been independently diagnosed as depressed in a clinical interview, and 32 non-depressed controls in the same age range. Some of the patients had been on long-term antidepressants but were still depressed. The patients, from Northwestern general internal medicine clinics, also were participating in a previously reported study comparing the effectiveness of face-to-face and telephone-administered cognitive behavioral therapy.

At baseline before the therapy, Northwestern scientists found nine RNA blood markers with levels significantly different in the depressed patients from those of controls. These markers were able to diagnose depression.

After 18 weeks of therapy (face-to-face and telephone), the changed levels of certain markers could differentiate patients who had responded positively and were no longer depressed (based on a clinical interview and patients' self-reported symptoms) from patients who remained depressed. This is the first biological indicator of the success of cognitive behavioral therapy, the study authors said.

"Fingerprint" Predicts Who Will Benefit from Therapy

In addition, the blood test predicts who will benefit from the cognitive behavioral therapy based on a distinct pattern or fingerprint of the levels of the nine marker levels at baseline in patients who recover from depression as a result of the therapy. The blood levels of these markers did not show this pattern in the patients who did not improve with the therapy

"This distinction could be used in the future to predict who would respond to the therapy," Redei said.

Test Indicates Vulnerability to Depression

The blood concentration of three of the nine RNA markers remained different in depressed patients and non-depressed controls, even if the depressed patients achieved remission from depression after the therapy. This appears to indicate a vulnerability to depression.

"These three markers move us towards the ultimate goal of identifying predisposition to depression, even in the absence of a current depressive episode," said Redei, also the David Lawrence Stein Research Professor of Psychiatric Diseases Affecting Children and Adolescents.

"Being aware of people who are more susceptible to recurring depression allows us to monitor them more closely," Mohr noted. "They can consider a maintenance dose of antidepressants or continued psychotherapy to diminish the severity of a future episode or prolong the intervals between episodes."

Next Redei plans to test the results in a larger population. She also wants to see if the test can differentiate between major depression and bipolar depression.

Redei's and Mohr's research represents a pillar of Northwestern's Strategic Plan by discovering new ways to treat disease in the biomedical sciences.

The paper is titled "Blood transcriptomic biomarkers in adult primary care patients with major depressive disorder undergoing cognitive behavioral therapy."