Assessment of a multi-assay, serum-based biological diagnostic test for major depressive disorder: a Pilot and Replication Study

Abstract

Despite decades of intensive research, the development of a diagnostic test for major depressive disorder (MDD) had proven to be a formidable and elusive task, with all individual marker-based approaches yielding insufficient sensitivity and specificity for clinical use. In the present work, we examined the diagnostic performance of a multi-assay, serum-based test in two independent samples of patients with MDD. Serum levels of nine biomarkers (alpha1 antitrypsin, apolipoprotein CIII, brain-derived neurotrophic factor, cortisol, epidermal growth factor, myeloperoxidase, prolactin, resistin and soluble tumor necrosis factor alpha receptor type II) in peripheral blood were measured in two samples of MDD patients, and one of the non-depressed control subjects. Biomarkers measured were agreed upon a priori, and were selected on the basis of previous exploratory analyses in separate patient/control samples. Individual assay values were combined mathematically to yield an MDDScore. A 'positive' test, (consistent with the presence of MDD) was defined as an MDDScore of 50 or greater. For the Pilot Study, 36 MDD patients were recruited along with 43 non-depressed subjects. In this sample, the test demonstrated a sensitivity and specificity of 91.7% and 81.3%, respectively, in differentiating between the two groups. The Replication Study involved 34 MDD subjects, and yielded nearly identical sensitivity and specificity (91.1% and 81%, respectively). The results of the present study suggest that this test can differentiate MDD subjects from non-depressed controls with adequate sensitivity and specificity. Further research is needed to confirm the performance of the test across various age and ethnic groups, and in different clinical settings.

A Blood Test for Depression?

“…Bilello and colleagues 3 report excellent sensitivity and specificity of their test for MDD and have replicated a previous study 4 that used the same panel without including gender and BMI as variables. In the earlier study, the panel and associated algorithm produced good clinical sensitivity and specificity (92% and 81%, respectively) in differentiating MDD patients from normal healthy individuals.…”

“…The theoretical basis for this commercial test is that the 9 biomarkers in the panel are associated with alterations in key pathways associated with unipolar depression. [4][5][6][7][8][9][10] Having been down this path before, as a clinician and researcher, I would urge caution about embracing the utility of a blood test for depression for several reasons.…”

Consensus paper of the WFSBP Task Force on Genetics: Genetics, epigenetics and gene expression markers of major depressive disorder and antidepressant response

“…Therefore, replication of the results by independent investigators has not been possible. The multi-assay, serum-based test that included nine bio-markers for MDD diagnosis (Papakostas et al 2013) was performed on patients who already met the clinical DSM criteria for MDD, thus the cost/benefit balance of this test is not clear. Furthermore, the predictive properties of the serum-based test have not been replicated by an independent group of investigators.…”

“…Results are interesting, but replication by independent groups is also lacking. The test includes nine bio-markers (alpha1 antitrypsin, apolipoprotein CIII, BDNF, cortisol, epidermal growth factor, myeloperoxidase, prolactin, resistin and soluble TNF-a receptor type II) and it demonstrated a sensitivity and specificity of 91.7 and 81% in differentiating between MDD and healthy controls, respectively (Papakostas et al 2013). Similar findings were obtained in a further study by the same authors, with an overall test accuracy of 91-94%depending on the sample (Bilello et al 2015).…”

Personalized medicine in major depressive disorder — Opportunities and pitfalls

“…The association between these various biochemical domains and MDD has sparked interest in the development of a serum-based, multi-analyte biomarker panel utilizing a composite score rather than the traditional single analyte approach. Such panels remain under development [11,24].…”