Protein Levels May Help Diagnose Bipolar Disorder

A series of proteins have been discovered that could be diagnostic markers to identify bipolar I disorder and if this discovery sample can be validated through replication, these markers may help as a diagnostic tool for psychiatrists treating mood disorders.

It is critical to differentiate bipolar disorder from other mood disorders as the treatments differ and a medication suited to one condition may be dangerous to patients with another. Up to now psychiatrists have relied on observed symptoms and patient assessments based on interviews, and that information is then compared to established diagnostic criteria.


Psychiatrists at the Mayo Clinic, Rochester, MN, USA) recruited study volunteers, 46 had been diagnosed with bipolar I (history of mania) depression, 49 with bipolar II (history of hypomania) depression, and 52 with unipolar depression. They were compared with 141 individuals without mood disorders, known as controls. A urine drug screen was performed by study personnel using a One Step Multi-Drug Urine Test Panel kit (W.H.P.M.; Irwindale, CA, USA) to screen for any current illicit substances after participants signed the study consent form.

About 288 serum samples (141 controls, 52 unipolar, 49 bipolar II, 46 bipolar I) were randomized to four plates (72 wells × 4). There was no difference in plate by group allocation and age of sample from collection to analysis. The 320 proteins (were measured in 250 μL serum samples using the DiscoveryMAP multiplexed immunoassays (Myriad RBM Inc.; Austin, TX, USA).

In total, after adjusting for variables, 73 proteins were found to differ among the four groups studied. The results however showed a significant difference for six proteins in individuals with bipolar I depression (BP-1) versus controls. These were growth differentiation factor 15 (GDF-15), hemopexin (HPX), hepsin (HPN), matrix metalloproteinase-7 (MMP-7), retinol-binding protein 4 (RBP-4) and transthyretin (TTR). GDF-15, RBP-4 and TTR were good predictors of BP-I with ROC-AUC of 0.81, while HPX and HPN were fair predictors of BP-I with ROC-AUC of 0.74 and 0.78, respectively.

Mark A. Frye, MD, head of psychiatry and lead author of the study said, “The potential of having a biological test to help accurately diagnose bipolar disorder would make a huge difference to medical practice. It would then help clinicians to choose the most appropriate treatment for hard-to-diagnose individuals.” The study was published on December 8, 2015, in the journal Translational Psychiatry.

Related Links:
Mayo Clinic 
W.H.P.M.
Myriad RBM Inc.