Will Doctors Soon Be Able to Diagnosis Bipolar Disorder with a Simple Blood Test?

Many people believe that diagnoses of psychiatric disorders are entirely subjective, and that there are no true “biomarkers” — biological processes found in a blood test or with medical imaging that prove the indisputable existence of disease.

While that isn’t entirely true for all psychiatric conditions, there has been no biomarker identified for bipolar disorder — until now. In research published in the December edition of Lancet Psychiatry, researchers have shown that a protein called CRP is elevated in people who are bipolar, particularly during periods of mania.1 CRP suggests a heightened state of inflammation.

This discovery could lead to better treatments. Because bipolar can be and often is misdiagnosed, not to mention highly stigmatized, discovery of a true biomarker may help resolve questions or issues of skepticism about treatment for some patients.

“In my opinion, CRP shows great promise as a biomarker, helping to define who would benefit most from treatments that target inflammation, which is one of the major goals of precision medicine – defining who will, and will not, benefit from each treatment,” senior author Brisa S. Fernandes of Deakin University School of Medicine in Australia told Medscape Medical News. “As a psychiatrist myself, I would assess CRP levels in all my patients.”

She added, “Since bipolar disorder is also associated with increased cardiovascular risk, that would be another reason for the routine evaluation of CRP in the disorder.”

CRP levels can be measured via a simple blood test.

The groundbreaking research, led by Fernandes, arrived at its conclusion after a systematic review and meta-analysis of 27 previous studies. Those studies included a combined 2,161 people with bipolar disorder and 81,932 healthy controls.

“CRP concentrations are increased in bipolar disorder regardless of mood state, but are higher during mania than in depression and euthymia (normal, stable mood), suggesting an increased inflammatory burden in mania,” the authors interpreted from their findings. They noted that CRP levels dipped “moderately” after resolution of manic episodes and “slightly” after depressive episodes.

Landmark 2009 Paper Predicted a Future that Has Arrived

Finding biomarkers for psychiatric illness has been a goal for the National institute of Mental Health since at least 2009. Dr. Thomas Insel published a highly-cited opinion piece that year in the former Archives of General Psychiatry, now known as JAMA Psychiatry.

In the piece, he laid out a roadmap for using advances in medicine to find biomarkers for psychiatric conditions. He noted that general medicine was making progress in this regard much faster than psychiatric medicine.

“While we have seen profound progress in research (with molecular, cellular and systems neuroscience revealing new, unexpected insights about the brain), the gap between the surge in basic biological knowledge and the state of mental health care in this country has not narrowed and may be getting wider.”

Pertinent to the findings reported in Lancet, he noted the power of research focusing on proteins. “It will be important to remember that genes do not code for disorders, they code for proteins, and there will be many genes involved in the categories we now define as singular disorders. The task will be to define the combinatorial code of genomic variations that alter protein expression which, in turn, affects brain development, biasing brain circuits toward disease or resilience. Just as understanding the key tyrosine kinase (an enzyme attached to a protein) involved in chronic myeloid leukemia led to a cure for this once fatal disorder, understanding the pathophysiology of mental disorders is our best strategy for finding targets for new generations of far more effective treatments.”

Medical Companies Fear Low Bang for Buck in Mental Illness Diagnostics

In a recently published Scientific American piece, Dr. Nathaniel P. Morris of Stanford writes about how there have been biomarkers for some psychiatric conditions, although not many. He acknowledges that scientific advancements are changing that and ponders what it means for the future of psychiatry.4

“Our specialty has been relegated to the medicine of the unknown,” he writes. “We can’t test your blood for schizophrenia. We’re unable to diagnose bipolar disorder on imaging. We’re left with the Diagnostic and Statistical Manual of Mental Disorders and its inherently subjective criteria for defining illness.”

He notes yet another breakthrough in bipolar disorder biomarkers. “Recent studies have found associations between mania and elevated uric acid levels in the blood,” he writes. “Giving medications (e.g., allopurinol) that lower serum uric acid for bipolar patients with mania has been found to improve treatment responses in randomized placebo-controlled trials. If this relationship were to be true, could bipolar disorder become another everyday medical condition, just like gout?”

But the piece asks an interesting question. As biomarkers are found for more mental illnesses, what will happen to the profession of psychiatry? As it stands, in instances where such discoveries already have occurred, general medicine tends to step in with a “We’ll take it from here” approach, he wrote.

In a piece published in December in Newsweek, Dr. Sabine Bahn, a neurotechnology professor at Cambridge, said the biggest challenge to developing biomarker tests for mental illness is the lack of willingness on the part of medical companies to develop them. “As the development costs of a test are very high, there is a risk that the test will not be commercially viable,” she said.5

The same can be said for developing medicines that target certain pathologies, especially for rare conditions such as schizophrenia or conditions like bipolar where medications work for some but not others who have the illness.

In his landmark 2009 piece, Insel showed that this is backward thinking. The cost of disability payments (SSI) in 2008 for people with mental illness totaled $25 billion.

“For bipolar disorder, the long-term picture is equally concerning (as that of the little progress made toward schizophrenia treatment),” he said. “Sixty percent of affected individuals currently exhibit comorbid substance abuse dependency, and 20 percent experience ideas of suicide. Major depressive disorder, which one might consider more responsive to treatment, remains too often a chronic, disabling illness.”