Serum Uric Acid May Be Biomarker for Bipolar Affective Disorder

Serum uric acid levels, a key marker for metabolic disease and chronic conditions including gout, could serve as a biomarker for bipolar affective disorder (BPAD) severity, according to data from India.¹

A new analysis of the relationship between blood uric acid levels and psychiatric conditions shows a potentially significant link between dysfunction in the purine system and progression of BPAD. While the findings contribute to the understood biological development of bipolar disorders in patients, it even more particularly provides a new target for much-needed therapy development.

Led by Sylviah Immanuel, MD, MBBS, of the SRM Medical College Hospital and Research Center in Kanchipuram, the team of investigators sought to establish link between serum uric acid and BPAD subtypes as well as major depressive disorder (MDD). They additionally wanted to interpret whether changes in blood uric acid levels following treatment resulted in changes to psychiatric conditions, as well as the effectiveness of various therapies in reducing uric acid levels.

Immanuel and colleagues noted recent research has shown patients with BPAD generally report elevated uric acid levels versus patients without mental health disorders, or even different mental health disorders.

“Other studies suggest that uric acid levels may be a useful biomarker for distinguishing BPAD from MDD, particularly during manic episodes,” they wrote.² “However, another study failed to find significant differences in uric acid levels between BPAD and MDD. Serum uric acid levels can be influenced by various factors, including metabolic syndrome, substance abuse, kidney disorders, gout, and medication use.”

The team prioritized clinical variables including patients with diagnosed BPAD-mania, BPAD-depression, as well as MDD, in their assessment.¹ They recruited patients from a tertiary care psychiatry hospital in Visakhapatnam, conducting their prospective analysis from September 2019 – August 2020.

The analysis included 223 adult patients aged 18 – 55 years old. Among them, 93 were diagnosed with MDD, 78 were diagnosed with BPAD-mania, and 53 were diagnosed with BPAD-depression. Immanuel and colleagues collected baseline measures with 5 mL fasting blood for the following factors:

• Serum uric acid
• Creatinine
• Blood sugar
• Triglycerides
• High-density lipoprotein (HDL)
• Blood pressure
• Waist circumference
• Young Mania Rating Scale (YMRS), for symptom severity
• Hamilton Depression Rating Scale (HAM-D), for BPAD-depression or MDD

The latter 2 psychiatric analyses were monitored weekly until a treatment response was evident—defined as 50% reduction in baseline YMRS and HAM-D scores. The team additionally assessed serum uric acid levels on the same day that psychiatric treatment response was achieved.

Mean patient age was approximately 38 years old; a majority of patients in all 3 cohorts were male, married, and unemployed. Patients with BPAD-mania had a mean duration of 9.7 years with their condition; mean duration was 3.6 years for those with BPAD-depression, and 3.5 for those with MDD.

The investigators observed a significant and positive association between the length of psychiatric illness and serum acid levels across all 3 cohorts—indicating that as illness duration increases, serum uric acid levels increase as well. They additionally noted a link between increasing age and blood uric acid levels. Patients with BPAD-depression showed a significantly greater elevation in serum uric acid levels versus patients with MDD, however.

“Given these findings and those from the literature, it appears reasonable to hypothesize that uric acid levels may serve as a biomarker for distinguishing between BPAD and unipolar depression,” investigators wrote.

Mean serum uric acid levels decreased from 5.2 ± 0.9 mg/dL in the BPAD-mania group at baseline, to 3.1 ± 0.8 mg/dL after achieving psychiatric treatment response (P <.01). Investigators observed a similar change in serum uric acid levels among patients with BPAD-depression cohort, and a slightly lesser change in the MDD cohort.

“The study showed that the reduction in serum uric acid levels was significantly correlated with the severity of illness in patients with BPAD-mania, but not in those with BPAD-depression or MDD,” investigators wrote. “Furthermore, the study found that treatment with lithium carbonate, sodium valproate, or carbamazepine was equally effective in reducing serum uric acid levels, regardless of the mood stabilizer used.”

The team concluded that their findings provide “strong evidence” that purine system dysfunction is a pivotal factor in the development of BPAD—regardless of patient chronicity or medication.

“These results suggest a previously unknown mechanism underlying the pathophysiology of BPAD, offering new insights into the disease's complex nature,” they wrote.

References

1. ^{Immanuel S, Kaki A, Jetty RR, Vupputuri SM, et al. Uric Acid as a Biomarker for Mood Disorders: A Comparative Study of Blood Uric Acid Levels Correlating With the Symptom Severity and Treatment Response. Cureus. Published online August 13, 2024. DOI: 10.7759/cureus.66784}
2. ^{Machado-Vieira R: Purinergic system in the treatment of bipolar disorder: uric acid levels as a screening test in mania. J Clin Psychopharmacol. 2012, 32:735-6. 10.1097/JCP.0b013e318268391d}