In a new proof of principle study, European scientists say they have demonstrated that depression can be detected by a blood test. While blood tests for mental illnesses have until recently been regarded as impossible, researchers at the MedUni Vienna say the technique may be in place in the not too distant future.
Researchers used functional magnetic resonance imaging of the brain and pharmacological investigations to monitor and predict levels of serotonin. They have known that serotonin transporter (SERT) is a protein in the cell membrane that facilitates the transport of the neurotransmitter serotonin into the cell. In the brain, serotonin transporter regulates neural depression networks. Depressive conditions can frequently be caused by a lack of serotonin. As a result, the serotonin transporter is also the point of action for the major antidepressant drugs. The serotonin transporter, however, also occurs in large quantities in numerous other organs such as the intestines or blood.
Recent studies have shown that the serotonin transporter in the blood works in exactly the same way as in the brain. In the blood, it ensures that blood platelets maintain the appropriate concentration of serotonin in the blood plasma.
During the study, researchers used functional imaging of the brain and pharmacological analysis to demonstrate that there is a close relationship between the speed of the serotonin uptake in blood platelets and the function of a depression network in the brain.
This network is termed the “default mode network” because it is primarily active at rest and processes content with strong self-reference. Findings from recent years have also demonstrated that it is actively suppressed during complex thought processes, which is essential for adequate levels of concentration.
Interestingly, patients with depression find it difficult to suppress this network during thought processes, leading to negative thoughts and ruminations as well as poor concentration.
“This is the first study that has been able to predict the activity of a major depression network in the brain using a blood test. While blood tests for mental illnesses have until recently been regarded as impossible, this study clearly shows that a blood test is possible in principle for diagnosing depression and could become reality in the not too distant future,” explains study leader Lukas Pezawas.
The US Study
The first blood test to diagnose major depression in adults has been developed by Northwestern Medicine scientists, a breakthrough approach that provides the first objective, scientific diagnosis for depression. The test identifies depression 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."
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. However, 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."
One of the study’s interesting facets – which surprised Redei, a neuroscientist – was that cognitive behavioral therapy actually seemed to change the biomarkers in the blood. All the patients in the “depressed” group met and spoke with a therapist. After more than four months had passed, the blood test was repeated on 22 of them. The patients in this group reported in clinical follow-up interviews that they were no longer depressed; they also had changes in their RNA markers, indicating that they benefited from this type of treatment. However, three of their biomarker levels still were not the same as those of non-depressed patients, suggesting some individuals might be more genetically susceptible to depression than others might.
In addition, the researchers say, the blood test was able to predict who would get well from cognitive behavioral therapy after they observed a distinct pattern, or “fingerprint,” of the nine markers at baseline in patients who found relief.
These findings might allow scientists to identify who responds to various therapies or medications. “I think this opens the possibility to begin to look at whether there are biomarkers that may be able to predict response to a behavioral treatment like cognitive behavioral therapy vs. [medicines] – people who maybe do better on pharmacotherapy or other forms of treatment,” Mohr says.
"The mental health profession has, for decades, been seeking an objective measure for detecting major psychiatric disorders," said Dr. Glen Elliott, chief psychiatrist and medical director of the Children's Health Council in Palo Alto, Calif. "That the authors seem to have found a measure in such a small sample that appears to be sensitive to a specific treatment -- and a psychological intervention at that -- is striking if it holds up."
However, he noted that the small number of study participants means that it is too soon to know the significance of the findings or what the drawbacks of the test could be.
"It is too early to tell how a test of this nature -- even if proven reliable, sensitive and specific -- would be best used in a clinical setting," Elliott said. But he said the findings fit into the larger effort to personalize diagnoses and treatments based on biological data from patients.
"It is an exciting possibility that could, in theory, greatly enhance treatment efficacy and efficiency," Elliott said. "However, especially in psychiatry, we are still a long way from having a reliable product that will accomplish those goals."
The new blood test is not yet available because additional studies with large groups of people must first confirm its accuracy and effectiveness before it can be considered by the U.S. Food and Drug Administration for approval.
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