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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.

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Acknowledgements

These studies were funded by Ridge Diagnostics.

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Correspondence to G I Papakostas.

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Competing interests

George Papakostas: Dr Papakostas has served as a consultant for Abbott Laboratories, AstraZeneca PLC, Brainsway, Bristol-Myers Squibb Company, Cephalon, Eli Lilly, GlaxoSmithKline, Evotec AG, Inflabloc Pharmaceuticals, Jazz Pharmaceuticals, Otsuka Pharmaceuticals, PAMLAB LLC, Pfizer, Pierre Fabre Laboratories, Ridge Diagnostics (formerly known as Precision Human Biolaboratories), Shire Pharmaceuticals and Wyeth. He has received honoraria from Abbott Laboratories, Astra Zeneca PLC, Bristol-Myers Squibb Company, Brainsway, Cephalon, Eli Lilly, Evotec AG, GlaxoSmithKline, Inflabloc Pharmaceuticals, Jazz Pharmaceuticals, Lundbeck, Otsuka Pharmaceuticals, PAMLAB LLC, Pfizer, Pierre Fabre Laboratories, Ridge Diagnostics, Shire Pharmaceuticals, Titan Pharmaceuticals and Wyeth. He has received research support from Bristol-Myers Squibb Company, Forest Pharmaceuticals, the National Institute of Mental Health, PAMLAB LLC, Pfizer and Ridge Diagnostics (formerly known as Precision Human Biolaboratories). Finally, Dr Papakostas has served (in the past, but not currently) on the speaker's bureaus for Bristol-MyersSquibb Co and Pfizer.

Richard Shelton: Dr Shelton has received Grant/research support from Eli Lilly and Company; GlaxoSmithKline Pharmaceuticals; Janssen Pharmaceutica; Pfizer; Sanofi Pharmaceutica; Wyeth-Ayerst Laboratories; AstraZeneca Pharmaceutica; Ridge Diagnostics; and Abbott Laboratories. He has been a paid consultant to Pfizer; Ridge Diagnostics and Janssen Pharmaceutica. He has served on speaker's bureaus for Bristol-Myers Squibb Company; Eli Lilly and Company; Janssen Pharmaceutica; Pfizer; GlaxoSmithKline Pharmaceuticals; Solvay Pharmaceuticals; Wyeth-Ayerst Laboratories and Abbott Laboratories.

Gustavo Kinrys: Dr Kinrys has served as an Advisor and/or consultant to AstraZeneca, Cephalon, Forest Laboratories, Glaxo SmithKline, Pfizer, Sepracor, UCB Pharma and Wyeth-Ayerst. Dr Kinrys has received research support from AstraZeneca, Bristol Myers Squibb, Cephalon, Elan Pharmaceuticals, Eli Lilly, Forest Laboratories, Glaxo SmithKline, Janssen, Pfizer, Ridge Diagnostics, Sanofi-Aventis, Sepracor, UCB Pharma and Wyeth-Ayerst. Dr Kinrys has served on the speaker's bureaus of Glaxo SmithKline, Janssen, and Wyeth-Ayerst.

Michael Henry: Dr Henry has received consulting fees from Ridge Diagnostics and research support from Shire, Forest, Sunovion, Eli Lilly, Bracco Diagnostics, Pfizer, GlaxoSmithKline, NARSAD and Ridge Diagnostics.

Bo Pi: Dr Pi is an employee of and holds stock in Ridge Diagnostics. Dr Pi has received research funding from the National Science Foundation as well as the National Institute of Mental Health. Dr Pi holds several patents and has several patents pending involving the use of biomarkers in major depressive disorder.

Linda Thurmond: Dr Thurmond is an employee of and holds stock in Ridge Diagnostics. Dr Thurmond has received research funding from the National Science Foundation as well as the National Institute of Mental Health.

John Bilello: Dr Bilello is an employee of and holds stock in Ridge Diagnostics Inc. Dr Bilello also holds stock in GlaxoSmithKline. Dr Bilello has received research funding from the National Science Foundation as well as the National Institute of Mental Health. Dr Bilello holds several patents and has several patents pending involving the use of biomarkers in major depressive disorder.

The remaining authors do not declare any conflict of interest.

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Papakostas, G., Shelton, R., Kinrys, G. et al. Assessment of a multi-assay, serum-based biological diagnostic test for major depressive disorder: a Pilot and Replication Study. Mol Psychiatry 18, 332–339 (2013). https://doi.org/10.1038/mp.2011.166

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Keywords

  • major depressive disorder
  • biomarkers
  • diagnosis
  • test

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