Glucuronic acid (GlcA) is crucial in the glucuronidation pathway, facilitating the metabolism and elimination of various substances and drugs. Recent studies have noted elevated GlcA levels in patients with schizophrenia (SCZ) compared with healthy individuals. However, it remains unclear whether this elevation contributes to SCZ pathophysiology or results from medication effects.

This study investigated the relationship between peripheral GlcA levels and clinical characteristics in patients with SCZ and assess whether these associations persist independently of psychotropic medication effects to provide insight into the potential role of GlcA in the pathophysiology of SCZ.

Plasma GlcA levels were analysed in 218 patients with SCZ, examining their association with clinical features. The correlation between GlcA levels and symptom severity, assessed using the Positive and Negative Syndrome Scale (PANSS), was analysed in 35 patients. In addition, multiple regression analysis was conducted to adjust for age and psychotropic medication effects.

Significant correlations were observed between GlcA levels and PANSS scores for negative symptoms, general psychopathology and total scores. After adjustment for age and psychotropic medications, significant correlations between GlcA levels and PANSS scores persisted for negative symptoms (adjusted β [95% CI], 13.926 [2.369, 25.483]) and general psychopathology (adjusted β [95% CI], 19.437 [3.884, 34.990]), while the total score was no longer significant (adjusted β [95% CI], 34.054 [–0.517, 68.626]).

Elevated GlcA levels in patients with SCZ are associated with specific symptom severity irrespective of the medication dose, suggesting a potential role of GlcA in SCZ pathophysiology.