Six Protein Markers May ID Mood Disorders

Serum-based proteomic profiles may be useful in identifying and differentiating mood disorders, according to a study published online Dec. 8, 2015 in Translational Psychiatry. While these findings need further validation, psychiatrists are hopeful that such research will help move psychiatric diagnoses away from exclusive reliance on clinical observation of behavioral symptoms and towards empirical use of biologically based test results.

A consecutive sample of patients with a confirmed diagnosis of major (unipolar) depression (UP; n=52) or bipolar depression (BP-I, n=46; BP-II, n=49) and controls (n=141) were tested using a blood sample. Initial analysis was based upon a proteomic multiplex profile of 320 proteins utilizing Myriad RBM's Discovery Multi-Analyte Profiling (MAP) platform. DiscoveryMAP is a quantitative multiplexed immunoassay service product, based on Luminex xMAP technology platform that was initially based upon immune mediator and cytokine quantification, increasingly recognized in the underlying neurobiology of mood disorders. Rigorous exclusion criteria were used to eliminate participants with non-specific inflammatory contributions from systemic illness and anti-inflammatory/biotic drug therapy.

The researchers found that six of the 320 proteins analyzed—growth differentiation factor 15 (GDF-15), hemopexin (HPX), hepsin (HPN), matrix metalloproteinase-7 (MMP-7), retinol-binding protein 4 (RBP-4) and transthyretin (TTR)—showed statistically significant differences between the patients and the healthy controls. The protein levels were higher in BP-I compared to all other patient groups and controls. MMP-7 was significantly different in mood disorder patients (BP-I, BP-II, and UP) versus controls; MMP-7, GDF- 15, and HPN were significantly different in bipolar cases (BP-I and BP-II) versus controls; and GDF-15, HPX, HPN, RBP-4 and TTR proteins were all significantly different in BP-I versus controls.

"The results of this feasibility study support the possibility of developing a diagnostic test using the discovered biomarkers, which need to be validated, to help facilitate accurate diagnosis and rapid treatment initiation with improved clinical outcomes," write the authors led by Mark Frye, M.D., from the Mayo Clinic (Rochester, Minn.). "A proteomic-based differential diagnosis as an advanced decision making tool or companion diagnostic to guide evidence-based algorithms for mood stabilizer versus unimodal antidepressant therapy would have great clinical impact."

Takeaway: The discovery of six protein markers capable of distinguishing mood disorder patients, particularly BP-I, from healthy controls is a promising development in moving psychiatric diagnoses towards one driven by biomarker-based testing.