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Uric Acid a Potential Predictor of Bipolar Disorder

Serum uric acid (UA) levels may help predict conversion to bipolar disorder (BD) in patients with major depressive disorder (MDD).

In a study of inpatients with MDD, it was found that in those patients who converted to BD, UA blood levels were higher than in patients who did not convert. UA levels had “very good to excellent prognostic accuracy as a biomarker of conversion,” senior author Nuno Madiera, MD, from the Department of Psychiatry, Coimbra Hospital and University Center, Portugal, told Medscape Medical News.

This suggests that in the management of a depressive episode in the inpatient setting, routine evaluation of serum UA levels might be useful in distinguishing depressive episodes associated with MDD from those associated with BD, the study team says.

The study was published online October 30 in Bipolar Disorders.

Difficult Diagnosis

Early diagnosis of BD is difficult because onset is often characterized by a depressive episode that can be similar in presentation to unipolar depression. Although several clinical and demographic risk factors have been associated with conversion to BD, no laboratory or imaging marker that predicts conversion from unipolar depression has yet to be identified.

“We know that increased levels of UA are associated with accelerated purinergic transformation, and there is now accumulating evidence that impairment in the purinergic system may play a role in the pathophysiology of mood disorders like BD and MDD. So we set out to test this hypothesis,” Madeira explained.

The researchers took a look back at the records of 250 patients admitted to a psychiatry unit after having had an episode of MDD and whose serum UA levels had been measured during the inpatient stay. The patients were followed for about 10 years. During this time, 55 patients (22%) converted to BD, and 195 (78%) did not. None of the patients either had disorders or were taking drugs that were known to affect UA levels.

The patients who converted to BD (“BD-converters”) had significantly higher levels of plasma UA than the patients who did not convert (“nonconverters”) during their index hospitalization, irrespective of the sex of the patients.

Table. UA levels (μmol/L) in BD Converters vs Nonconverters*

  BD Converters Nonconverters
Overall 337.31 220.50
Male 403.84 270.81
Female 302.19 202.69
*For all, P < .001

 

For depressed inpatients, the optimal cutoff level for predicting bipolarity in was 318 μmol/L for men and 241 μmol/L for women.

Serum UA levels were highly accurate in predicting conversion to BD in inpatients with MDD (area under the curve [AUC], 0.90; 95% confidence interval [CI], 0.86 – 0.94).

The researchers also calculated the clinical utility index (CUI) as a risk biomarker for conversion to BD. The CUI combines discriminatory ability (negative predictive value and positive predictive value) and occurrence (sensitivity and specificity); it allows investigators to rule in the case patients and to rule out the non–case patients. This biomarker also demonstrated good to excellent clinical utility for ruling out non–case patients and moderate to good clinical utility for case finding.

“Remarkable” Finding

The researchers note that their study had several limitations. Although they controlled for some metabolic variables, they could not assess dietary patterns, caffeine intake, and body mass index, all of which are known to have an effect on UA levels.

In addition, because information on the patients’ preadmission use of psychiatric medications was “unreliable and fragmented,” the investigators could not assess whether variations in UA level might at least in part be explained by specific psychopharmacologic treatments.

“This is the first study of its kind, and the results suggest that a simple, inexpensive, and easy-to-use blood-based biomarker can provide valuable information for the differential diagnosis in early phases of BD and improve clinical decision making and therapeutic choices,” Madeira told Medscape Medical News.

“The results need to be replicated in a larger sample, and the use of this simple laboratory biomarker, in combination with bipolar at-risk clinical features, should be explored in future studies. Our group is set to replicate these findings in other clinical settings, namely, in a multicenter study,” added first author Pedro Oliveira, MD, also from Coimbra Hospital and University Center.

Reached for comment, Igor Galynker, MD, PhD, professor of psychiatry at the Icahn School of Medicine at Mount Sinai and director of the Zirinsky Center for Bipolar Disorder in New York City, said, “The findings seem to be very strong. What’s remarkable is that you see near complete separation of the two groups with regards to uric acid.

“Telling unipolar from bipolar depression during the first episode is one of the most important problems in psychiatry,” said Galynker. “If you had a biomarker that would allow you to tell bipolar from unipolar depression, that would be a remarkable achievement and incredibly important in the clinic. So this research is welcome.”

However, he cautioned, this is a “first preliminary study, and we know that the way things work in psychiatry, the more studies that are repeated, the weaker the effects are. The main flaw of the study is that the medication is not taken into account.”

The study had no specific funding. The authors and Dr Galynker have disclosed no relevant financial relationships.

Bipolar Disord. Published online October 30, 2018. Abstract

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