DOI: 10.1192/j.eurpsy.2026.11798 ISSN: 0924-9338

Low Serum Uric Acid Levels and Risk of Psychiatric Disorders: A Population-Based Cohort Study

R. Leiba, O. Lencovsky, A. Leiba, A. Israel

Introduction

Uric acid (UA) is the end product of purine metabolism and a major plasma antioxidant. While elevated UA is linked to metabolic and vascular risk, low UA may diminish neuroprotection and increase vulnerability to oxidative stress.

Objectives

To assess whether low serum UA levels are associated with a higher incidence of psychiatric and neurocognitive disorders in adults.

Methods

A retrospective cohort study was conducted using electronic health records from Leumit Health Services (HMO) (2002–2024). Adults with ≥1 UA measurement were included. Examinees with elevated uric acid ( >6mg/dl for women, >7mg/dL for men) were excluded. Low UA was defined as <3 mg/dL; others served as controls. Exclusion criteria: malignancy, pregnancy, and insulin use. Any low UA level (even on a single occasion) would commit the examinee to the “low urate” group. Only incident (“New”) diagnoses were analyzed to reflect new-onset psychiatric morbidity during follow-up. Analyses used multivariate logistic regression adjusted for age, sex, socioeconomic status, and comorbidities. Mean follow-up: 3367 ± 578 days (≈9.2 ± 1.6 years).

Results

Among 51,348 participants (25,672 low-UA; 25,676 controls; mean age ≈ 51 years), low UA was associated with significantly higher odds of several psychiatric outcomes (Table 1).

Table 1.

Incidence and adjusted odds ratios for new psychiatric diagnoses

Table 1. Long description.

DIAGNOSIS
LOW UA N (%)
NORMAL UA N (%) OR (95% CI) P
DEPRESSION
593 (2.31)
427 (1.66) 1.40 (1.23–1.59) <0.001
ANXIETY
3,845 (15.0) 3,384 (13.2) 1.16 (1.10–1.22) <0.001
PTSD
271 (1.06) 214 (0.83) 1.27 (1.06–1.53) 0.009
SCHIZOPHRENIA
175 (0.68) 93 (0.36) 1.89 (1.46–2.46) <0.001
PERSONALITY DISORDER
292 (1.14) 185 (0.72) 1.59 (1.31–1.92) <0.001
COGNITIVE DISORDER
170 (0.66) 120 (0.47) 1.42 (1.12–1.81) 0.003
DEMENTIA
234 (0.91) 149 (0.58) 1.58 (1.28–1.95) <0.001
EPILEPSY
120 (0.47) 60 (0.23) 2.00 (1.46–2.78) <0.001
HEADACHE
5,013 (19.5) 4,344 (16.9) 1.19 (1.14–1.25) <0.001

Conclusions

Low serum UA levels are independently associated with an increased risk of depression, anxiety, and other psychiatric and neurocognitive disorders. UA may serve as a biomarker of reduced antioxidant defense and heightened neuropsychiatric vulnerability. Prospective and interventional studies should evaluate whether UA-modulating strategies can aid in mental-health prevention or treatment.

Disclosure of Interest

None Declared

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