Study finds potential biomarkers for bipolar disorders

Distinguishing between major depressive disorder and bipolar disorders has important clinical and public health implications. Although antidepressants are the cornerstone of treatment for major depressive disorder, that is not the case for bipolar depression, with additional concern that antidepressant treatment may destabilize mood and increase depressive episodes for some patients. Yet without biological validation to confirm the clinical diagnosis, accurate identification and differentiation of mood disorders can be challenging.

Because preliminary research has highlighted the potential usefulness of multiplex biomarkers, Mayo Clinic researchers undertook a feasibility study to determine whether high-throughput multiplexed immunoassay technology could be used to differentiate unipolar from bipolar depression.

"Unlike the evidence base in other fields of medicine, psychiatry doesn't have a blood test or brain scan to confirm a clinical diagnosis of a mood disorder. However, we know that biochemical dysregulation occurs with depression, and we wanted to see if this technology could ascertain differences and nuances in different types of depression," explains Mark A. Frye, M.D., a psychiatrist at Mayo Clinic's campus in Rochester, Minnesota, and lead study author.

In all, 288 volunteers were enrolled in the study:

  • 46 with diagnosed bipolar I depression
  • 49 with bipolar II depression
  • 52 with unipolar depression
  • 141 controls

Serum samples were drawn from each participant and profiled for 320 proteins using Myriad RBM's Multi-Analyte Profile platform. The platform originally was developed for immune and cytokine quantification for drug development; these same inflammatory and immune-mediated biomarkers are increasingly recognized in the underlying neurobiology of mood disorders.

After correcting for multiple testing and adjusting for a number of clinical variables, six proteins showed statistically significant differences among the four groups. Those proteins included growth differentiation factor-15 (GDF-15), hemopexin (HPX), hepsin (HPN), matrix metalloproteinase-7 (MMP-7), retinol-binding protein 4 (RBP-4) and transthyretin (TTR).

In a planned secondary analysis, the most significant differences for proteins GDF-15, HPX, HPN, RBP-4 and TTR were seen in the bipolar I group. Several of these proteins, including MMP-7, HPX and TTR, have been implicated in the neurobiology of bipolar disorder; GDF-15 and RBP-4 are associated with cognitive function, but HPN has not been linked to bipolar disorder until now. Study findings were published in Translational Psychiatry in 2015.

"Looking at this early study, we indeed see differences in certain serum proteins in people with mood disorders, with the most robust findings in bipolar I disorder," Dr. Frye says. "Having biological markers for mood disorders would make a huge difference in medical practice — not only to help clarify diagnosis but also, potentially, to help find the best treatment for these patients.

"Replication studies for confirmation and utility studies to assess proteomic expression profiling as an advanced decision-making tool or companion diagnostic are encouraged. As interesting and positive as these findings are, however, the science needs to be replicated, and a replication study is currently underway."

For more information

Frye MA, et al. Feasibility of investigating differential proteomic expression in depression: Implications for biomarker development in mood disorders. Translational Psychiatry. 2015;5:e689.