Distinguishing major depressive disorder and bipolar disorder might be about to get far easier. Koya979/Shutterstock

An easy and reliable method of distinguishing bipolar disorder from major depressive disorder could save tens of thousands of lives, and transform millions more. Now researchers at Chongqing Medical University, China, claim to have found just that in a study based on biomarkers in urine.

The popular image of someone with bipolar disorder is epitomized by prominent figures such as Robin Williams – bouts of severe depression punctuated by off-the-wall mania. In reality, it is often not so easy to recognize; even Williams said he was never officially diagnosed. Moreover, as a new paper in The Journal Proteome research notes, “Multiple depressive episodes usually occur prior to the first manic episode in many bipolar patients.”

In these cases, the symptoms of bipolar can be very difficult to distinguish from those of major depressive disorder (MDD). Since MDD is the more common condition, clinicians often jump to an MDD diagnosis; indeed, many don’t even think to investigate the possibility of bipolar. Studies have found that as many as 39% of patients diagnosed with MDD have unrecognized bipolar.

The paper adds: “A large percentage of BD subjects are incorrectly treated with antidepressants in clinical practice.” The consequences can be lethal. Selective seratonin reuptake inhibitors (SSRIs) such as Prozac and Celexa probably don’t help people with bipolar. SSRIs are alleged to increase suicide risk among bipolar patients, a major concern since bipolar sufferers have suicide rates around 20 times the population as a whole.

While efforts have been made to alert doctors to the dangers of this sort of misdiagnosis, as long as we continue to rely only on multiple subtle signs, the problem will remain.

The Chongquing team think they have found a way out of this problem, having identified biomarkers whose concentrations are different for people with bipolar or MDD.

The authors note that some of these biomarkers have been investigated before, but individually did not provide a sufficiently reliable method for diagnosis. However, senior author Dr. Peng Xie proposed that multiple markers in combination might succeed where each had failed.

For the study, experienced psychiatrists recruited 71 people with bipolar disorder, 126 whose diagnosis of MDD was considered reliable, and 126 "healthy controls." Each group was divided into a training set and a test set. For the training set, the researchers knew the subject’s condition ahead of time and used this to identify relevant markers, while in the other set it was a blinded test to confirm the predictive capacity of these markers. The researchers examined the urine of those in the training set to identify 20 metabolites associated with either MDD or bipolar.

An initial trial on the test set identified 76% of those with MDD and 79% of those with bipolar, falling short of what would be required clinically. However, when the results were reanalyzed, six metabolites stood out.

After normalizing these six metabolites to creatinine concentration in urine, the authors found they could achieve 90% reliability in distinguishing between the two conditions.

The authors note that the study’s subjects had a common ethnicity and had been treated at the same hospital, necessitating further research to see whether the results can be generalized. However, the research adds to work published last year suggesting biomarkers could play a major role in depression diagnosis.