Kevin Kunzmann

Serum uric acid levels, a key marker for metabolic disease and chronic conditions including 

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.

 “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.

 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:

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 (

 <.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.

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. 

 Published online August 13, 2024. DOI: 10.7759/cureus.66784

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

Articles

Uric acid levels, commonly used to indicate gout, are closely associated with bipolar-affected mania.

Serum Uric Acid May Be Biomarker for Bipolar Affective Disorder

An analysis of blood samples identified 31 differently expressed proteins (DEPs) that were either significantly up-regulated or down-regulated in participants with 

 versus healthy controls. The collection of observed inflammatory proteins impacted by the presence of atopic dermatitis may provide clinicians a better understanding of the common skin disease’s complex mechanisms—as well as clearer targets for direct pharmacological intervention.

A team of investigators from Korea conducted a 1:1 analysis of blood samples from a cohort of atopic dermatitis patients, versus healthy controls, in order to observe the spectrum of proteins associated with dermatitis inflammation, as well as the link between systemic biomarkers and disease severity.

“Atopic dermatitis is a chronic inflammatory cutaneous disorder, that emerges from intricate interplays among genetic predisposition, immune dysregulation, environmental factors, and compromised skin barrier,” the team wrote. “Understanding the inflammatory pathway in AD is important due to its fundamental role in the pathogenesis of AD.”

Led by Yu Ri Woo, of the department of dermatology at Incheon St. Mary’s Hospital at The Catholic University of Korea College of Medicine, investigators enrolled 48-adult cohorts of those living with atopic dermatitis and health controls for their assessment. Patients were aged 18 – 90 years old, and were excluded if they were pregnant or breastfeeding, or had been currently or previously diagnosed with other inflammatory skin diseases, autoimmune disorders, malignancy or acquired immunodeficiency syndrome. The team assessed atopic dermatitis disease severity via Eczema Area Severity Index (EASI) to establish mild (<16), moderate (16 – 23), and severe (≥23) diseases.

Investigators generated blood proteomics data via the Olink platform, using an inflammation panel to assess factors of atopic dermatitis.

Participant demographics across the 2 cohorts were fairly similar; mean age was approximately 32 years old, and two-thirds of participants were male. Among the atopic dermatitis cohort, a majority (n = 26 [57.8%]) of patients had severe EASI scores and eosinophil percent was 11.43%. A combined 10 patients were on either cyclosporine or methotrexate for their condition.

The Olink proteomics platform assessed 92 inflammatory proteins. Of them, 31 DEPs were identified as significantly affected in patients with atopic dermatitis versus the healthy control cohort. A majority were up-regulated (n = 29); only the IL-20RA and FGF5 proteins were significantly down-regulated versus the healthy control results.

The 5 most significantly impacted that which showed a positive correlation with atopic dermatitis severity were:

Investigators additionally observed positive correlations between atopic dermatitis patient age and 3 DEPs:

Woo and colleagues additionally observed positive correlation between serum eosinophil counts, total immunoglobulin E (IgE) levels and a handful of other proteins among patients with atopic dermatitis.

“Eosinophils, essential in atopic dermatitis-associated allergic inflammation, show increased production, recruitment, and delayed apoptosis,” investigators noted. “The correlation between CD5, IL-18, IL-13, TNFRSF9, and total IgE levels in AD suggests a complex interplay of immune responses.”

Thought the trial emphasized blood proteomics, the team believes that skin proteomic analysis as a follow-up may provided them a “more localized view” of inflammation and its interaction in the skin. Though this analysis was limited by a small sample size of a homogenous population, Woo and colleagues concluded their research may help provide a progression into clinically-applicable intervention strategies for atopic dermatitis.

“These DEPs correlate with clinical severity, suggesting their potential as biomarkers for disease progression,” they wrote. “This paves the way for targeted therapies and personalized medicine in atopic dermatitis, improving diagnostic and therapeutic strategies.”

Woo YR, Moon JH, Shin HY, Bang YJ, et al. Systemic Inflammatory Proteomic Biomarkers in Atopic Dermatitis: Exploring Potential Indicators for Disease Severity. J Korean Med Sci. 2024 Aug 12;39(31):e223. English. Published online Jul 11, 2024.
https://doi.org/10.3346/jkms.2024.39.e223

Simon D, Braathen LR, Simon HU. Eosinophils and atopic dermatitis. Allergy 2004;59(6):561–570.

Identified proteins impacted by the presence of atopic dermatitis may provide clinicians a better understanding of how to treat it.

Analysis: 31 Inflammatory Proteins Impacted by Atopic Dermatitis

Glucose control measures via glycated hemoglobin (HbA1c) may be a significant, singular predictor of 

non-alcoholic fatty liver disease (NAFLD)

 severity in patients, according to new data.

A recent regression analysis of patients with NAFLD uncovered data showing that HbA1c is a major contributor to the severity of the liver disease. In fact, investigators observed that in patients who received treatment that resulted in reduced HbA1c, measures of steatosis similarly improved. The findings emphasize the importance to incorporate glucose control monitoring into the comprehensive management strategy of patients with NAFLD.

A team of UK-based investigators, led by Jeremy W. Tomlinson, MB BCh, PhD, FRCP, professor of metabolic endocrinology at Oxford Centre for Diabetes, Endocrinology and Metabolism at the University of Oxford, sought to better establish the relationship between HbA1c and NAFLD severity in patients either with or without type 2 diabetes. They noted that current non-invasive NAFLD stage scoring systems do not prioritize patients’ glucose control, despite evidence suggesting it may play a role.

Indeed, prior research presented as recently as at last year’s American College of Gastroenterology (ACG) Annual Scientific Meeting suggested that elevated HbA1c may be an independent risk factor. While the exact cause of fatty liver diseases including NAFLD is unknown, it is very often associated with overweight status, high LDL-C and triglyceride levels, and diabetes.

Tomlinson and colleagues used data from 857 patients with liver biopsy staged NAFLD. The relationship between histological NAFLD severity and factors including patient age, HbA1c and body mass index (BMI) were defined via generalized-linear models and binomial regression analysis.

The team further paired biopsies from 421 patients who participated in interventional trials to observe how changed BMI and HbA1c levels, as well as active versus placebo treatment, improved patients’ steatosis, nonalcoholic steatohepatitis (NASH), and fibrosis levels.

Among the 687 patients included in the discovery cohort, investigators observed a positive correlation between HbA1c and patients’ risk of severe steatosis, NASH and advanced fibrosis when adjusting for obesity status and age. The findings were further validated in an analysis of the second cohort of 170 patients.

A predictive model suggested that HbA1c and patient age were non-inferior to fibrosis-4 index (FIB-4) scores, a principal noninvasive biomarker for NAFLD, for predicting disease severity. Interestingly, another trial this month suggested FIB-4 may be a poorly interpreted biomarker to interpret fatty liver disease-related fibrosis.

“Previous studies have shown FIB-4 to have low accuracy for screening liver fibrosis, especially among obese and diabetic patients,” Mazen Noureddin, MD, MHSc, medical director of the Houston Research Institute and professor of medicine at Houston Methodist Academic Institute, and colleagues wrote on those findings. “Thus, there is a concern that classifying patients with FIB-4 can lead to misclassification and missed diagnosis.”

When assessing the interventional trial cohort biopsies, Tomlinson and colleagues noted that reduced HbA1c was linked to improved patient steatosis and NASH after adjusting for patient weight change and treatment status. However, fibrosis change was only associated with patient weight change and treatment status, not reduced HbA1c.

The team concluded that HbA1c is “highly informative” in predicting NAFLD severity, and in fact contributes more to interpreting disease status than BMI does. A single percent-point difference in HbA1c was associated with the same risk to patients’ liver as 8 kg in weight.

“Assessments of HbA1c must be a fundamental part of the holistic assessment of patients with NAFLD and, alongside age, can be used to identify patients with highest risk of advanced disease,” they wrote.

Colosimo S, Miller H, Koutoukidis DA, et al. Glycated haemoglobin is a major predictor of disease severity in patients with NAFLD. Diabetes Res Clin Pract. Published online August 13, 2024. doi:10.1016/j.diabres.2024.111820

Brooks A. Insulin Resistance Aids Detection of NAFLD in Lean Patients. 

. Published October 25, 2023. https://www.hcplive.com/view/insulin-resistance-aids-detection-of-nafld-in-lean-patients

Brooks A. Study Describes Fibrosis Risk Misclassification with FIB-4 Compared to Transient Elastography. 

. Published August 9, 2024. https://www.hcplive.com/view/study-describes-fibrosis-risk-misclassification-fib-4-transient-elastography

A new analysis suggests HbA1c may be more informative to fatty liver disease severity than BMI, and should be included in screenings.

HbA1c Highly Predicts NAFLD Disease Severity

Mora and Sadreameli join Lungcast to provide a back-to-school health blueprint, including topics like rescue inhalers, vaccination, vaping and air quality.

Prepare Your Lungs for Back-to-School with Juanita Mora, MD & S. Christy Sadreameli, MD

 Discussing vaccines with children and parents


Back-to-school season is officially upon the US, as 

 are gradually subsiding and giving way to the mid-August tradition of fall clothes shopping, classroom orientations and the return of routine for students.

Perhaps understated in the annual preparation stage for the first September school bell is the tradition of health planning for many at-risk children. At a time when pediatric allergy and asthma rates are continually rising, there’s plenty of conference between caregivers, pediatricians and school nurses regarding rescue medication, as well as how to avoid seasonal and environmental risks for children this school year.

Asthma and allergic triggers are only scratching the surface of what should be discussed with caregivers leading into the school year, though.

For the August 2024 episode of Lungcast, a pair of allergic and pulmonary disease experts join to provide a blueprint of back-to-school health strategies for children and their parents. Juanita Mora, MD, physician and chief executive officer of the Chicago Allergy Center, and S. Christy Sadreameli, assistant professor of pediatrics at Johns Hopkins University School of Medicine, review asthma, vaping, vaccines and more.

Throughout their half-hour conversation, Mora and Sadreameli touch on strategic conversations surrounding pediatric asthma control, immunization updates and collaborative care with school nurses. The duo also delve into trends in pediatric health that may affect classrooms, including Asthma Peak Week, poor indoor air quality, and the e-cigarette epidemic among young Americans.

Lungcast is a monthly respiratory news podcast series hosted by Albert Rizzo, MD, chief medical officer of the ALA, and produced by HCPLive.