Possible Biomarkers for identifying BiPolar 1 diagnosis

Mental Health Studies | Psychiatric diagnoses are still based on criteria that focus on behavioral observation and symptom endorsement without corresponding biological validation.

This contrasts with other fields of medicine, where diagnosis and treatment are often based not only on a sound clinical examination, but also biological tests based on validated biomarkers.

A group of researchers has identified a series of protein biomarkers that, if validated through replication, may be useful in diagnosing bipolar I disorder. Here are some of the key findings, with full disclosure published in Translational Psychiatry.

• “Although these discovery results need to be replicated in independent samples, this study demonstrates feasibility of a multiplex blood-based testing for bipolar disorder,” wrote researchers from the Mayo Clinic, Rochester, MN. “This investigation has both identified new proteins possibly implicated in mood disorder and further refines our previous understanding of specific proteins in mood disorder.”

For the study, researchers examined 272 different proteins in blood samples from a total 288 volunteers: 46 with bipolar I depression, 49 with bipolar II depression, 52 with unipolar depression, and 141 without mood disorders. After adjusting for variables, researchers found 73 proteins differed among the four groups studied. However, six proteins differed significantly between people with bipolar I depression and participants without mood disorders.

The next step, they emphasized, is to replicate the research with a larger sample and follow-up to determine how representative and unique the six proteins are for bipolar I disorder.

“The potential of having a biological test to help accurately diagnose bipolar disorder would make a huge difference to medical practice,” said the study’s first author Mark Frye, MD, head of psychiatry and psychology at the Mayo Clinic. “It would then help clinicians to choose the most appropriate treatment for hard-to-diagnose individuals.”

• The strengths of this study include a single recruitment site for depression treatment-seeking patients and rigorous exclusion criteria to eliminate non-specific inflammatory contributions from systemic illness and anti-inflammatory/biotic drug therapy.

While there was no evidence of different level of symptom severity of anxiety, depression, alcohol use, between case groups, we did not conduct a protein level analysis with index episode duration, previous treatment trials nor SCID lifetime assessment of psychiatric diagnoses.

For the six proteins significantly associated with mood disorders, values of proteins by diagnosis and medication groups (antipsychotics, lithium, antiepileptic mood stabilizers, antidepressants, sedatives/hypnotics). These comparisons suggest that the effect may be driven by the diagnostic group, rather than medication. Although some differences appear to be further augmented by certain medications, differences between BP-I cases and controls (not on medication) appear to still be present for patients that are currently not taking these medications.

The lifetime assessment of manic illness burden (that is, episodes), history of psychosis or age of illness onset may have provided greater understanding of the striking BP-I proteomic expression. The multiple correction testing was conservative.

Furthermore, the more conservative adjustment for multiple covariates not commonly done in cross-sectional biomarker mood studies (fasting status, years education, lifetime drug abuse history and lifetime alcohol use) may have reduced power. Nonetheless, even after adjustment for these variables, this discovery has identified a number of proteins that differ significantly in patients with mood disorders, in particular bipolar I disorder.

• In conclusion, 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.

Further functional studies of the identified proteins will increase our understanding of the pathophysiology of mood disorders, which may lead to the discovery of novel pharmacological targets.  

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