By Martin S. Lipsky, MD
Adjunct Professor, Institute on Aging, School of Community Health, Portland State University;
Dean Emeritus, University of Illinois College of Medicine, Rockford
Dr. Lipsky is a retained consultant for Health Solutions & Strategies.
SYNOPSIS: An objective, laboratory-based diagnostic tool for depression would be extremely helpful to primary care physicians. This study using nine biomarkers holds promise that a blood test may be able to identify depressed patients among nondepressed primary care patients
SOURCE: Redei EE, et. al. Blood transcriptomic biomarkers in adult primary care patients with major depressive disorder undergoing cognitive behavioral therapy. Transl Psychiatry 2014;4,e442 published online September 2014.
Major depressive disorder (MDD) is a complex psychiatric disease affecting 6.7% of the U.S. population.1 Currently, the diagnosis of depression is based on self-reported symptoms and the evaluation of a provider such as a primary care physician, psychiatrist, or psychologist. Unfortunately depressed patients often underreport symptoms or inadequately characterize them. In addition, there is often discordance among the commonly used depression scales. It is not surprising then that only about half of MDD patients are recognized and treated by their primary care physician.2
An objective blood test that could accurately identify MDD would be an important and useful tool. This study used nine RNA transcript blood markers previously identified in animal models of depression and subsequently tested in a pilot study that distinguished subjects with early-onset MDD from matched controls.3 Redei and her research team explored whether these markers could distinguish patients with MDD from non-depressed patients and also used them to follow MDD patients treated with cognitive behavioral therapy (CBT).
The study included 32 patients ranging in age from 21 to 79 years, who were seen at a university primary care clinic and were diagnosed with MDD and undergoing CBT and compared them to 32 non-depressed (ND) patients in the same age range. The study excluded patients who had initiated antidepressant pharmacotherapy in the past 10 days and patients with other psychiatric illnesses, hearing or visual problems, substance or alcohol abuse, exhibited severe suicidality, or who were undergoing or planning to receive individual psychotherapy.
At baseline, the blood marker levels in the control group differed significantly from patients with MDD. After 18 weeks of CBT therapy (either face-to-face or by telephone) biomarkers were retested. Differences in the blood markers differentiated patients who responded to CBT and were no longer clinically depressed (based on clinical interview and self-report) from those patients who remained depressed.
Based on their findings, the authors conclude that the blood levels of different transcript panels may identify the depressed from the non-depressed among primary care patients and potentially predict response and/or permanent monitoring of response to CBT.
COMMENTARY
Depression is a serious disease that is frequently underdiagnosed in the primary care setting. Having the ability to augment the clinical diagnosis of depression with a blood test would clearly be of value to the primary care practitioner. In addition, having the ability to document changes in biomarkers associated with depression would convince patients of the biologic nature of the illness and that MDD is not just a weakness of spirit. This test also holds the promise of objectively tracking improvement and may be useful for individualizing therapy to the patient.
While the possibility of having such a diagnostic tool as part of the primary care provider’s tool box is enticing, this test is still a long way from being ready for prime time. As the authors note, the study has several limitations. First, the sample size was modest and there were only two samples for each MDD subject and only one ND sample. Second, it may be that the biomarkers would not have been stable over time in the ND sample. The results could also have been strengthened by measuring the markers at different time points to see if changes correlated with the improvement of mood. In addition to the small sample size, the study involved only one practice setting and it will be important to see if the results are similar in other non-university settings.
Despite significant limitations, these early findings seem promising. Clearly there will need to be future studies with larger populations and also with study groups that include other psychiatric illnesses. However, while normally I would not report a study like this, which is still quite a ways off from being widely useful, I felt this test has such potential usefulness that it should be on the "watch list" of primary care providers. I suspect that if these preliminary findings hold up biomarker testing for depression will be embraced by PCPs and enhance their ability to diagnose and target treatment for depression.
REFERENCES
- 1. Kessler RC, et al. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 2005;62:593-602.
- 2.Pence BW, et al. The depression treatment cascade in primary care: a public health perspective. Curr Psychiatry Rep 2012;14:328–335.
- 3.Pajer K, et al. Discovery of blood transcriptomic markers for depression in animal models and pilot validation in subjects with early-onset major depression. Transl Psychiatry 2012;2:e101.
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