Schizophrenia Research Project, Department of Psychiatry and Behavioral Sciences, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan Unit for Mental Health Promotion, Research Center for Social Science & Medicine, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan Department of Psychiatry, Tokyo Metropolitan Matsuzawa Hospital, Tokyo, Japan
Syudo Yamasaki
Unit for Mental Health Promotion, Research Center for Social Science & Medicine, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan
Schizophrenia Research Project, Department of Psychiatry and Behavioral Sciences, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan Department of Community Mental Health, School of Medicine, Shinshu University, Nagano, Japan
Koichi Tabata
Schizophrenia Research Project, Department of Psychiatry and Behavioral Sciences, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan Department of Psychiatry and Behavioral Sciences, Institution of Science Tokyo, Tokyo, Japan
Satoshi Yamaguchi
Unit for Mental Health Promotion, Research Center for Social Science & Medicine, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan
Satoshi Usami
Center for Research and Development on Transition from Secondary to Higher Education, The University of Tokyo, Tokyo, Japan
Masanari Itokawa
Schizophrenia Research Project, Department of Psychiatry and Behavioral Sciences, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan Department of Psychiatry, Tokyo Metropolitan Matsuzawa Hospital, Tokyo, Japan
Atsushi Nishida
Unit for Mental Health Promotion, Research Center for Social Science & Medicine, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan
Hidenori Kamiguchi
Neuroscience Drug Discovery Unit, Takeda Pharmaceutical Company Ltd, Tokyo, Japan
Background 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. Aims 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. Methods 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. Results 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]). Conclusions 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.
