Overactive bladder (OAB) is a common and bothering lower urinary tract disorder marked by a sudden urge to urinate and frequent voiding which exert negative impact on quality of life. As the symptoms endure, it is anticipated to develop psychological and psychosocial abnormalities in this group of patients. Although literatures have suggested a strong association between OAB and depression/anxiety, few mechanistic studies has been presented. The aim of this study is to explore the impact of anxiety/depression on symptoms of female OAB patients. We also attempted to discover potential metabolic mechanisms between psychological disorders in relation to OAB in mice model. 
To explore the mechanisms between mood psychological disorders and in relation to OAB, we collected urine from developed restraint-stressed mice model (a classic common model for depression model) and collected urine sample for performed targeted neurotransmitter-metabolomics analysis.

Clinical patients and settings：103 female adults  with OAB symptoms who seek medical consultant in our hospital from June 2024 to December 2024 were included as the study subjects. Another 47 OAB symptom-free female were participated voluntarily as control. The severity of OAB was assessed using the Overactive Bladder Syndrome Score (OABSS). The Hamilton Anxiety and Depression Scale (HAMA and HAMD) were used to assess anxiety and depression emotions. The features of depression/anxiety in the female OAB patients were investigated, followed by a correlation analysis between these two identities.
Animal model development and Targeted metabolomics：Restrained stress (RS) mice model was developed by enclosing the female mice in an open-ended 50ml centrifuge tubes for 2 h from ZT4 to ZT6. RS was applied for 21 days (from RS1 to RS21) to reach a stable psychological state. Urine samples were collected and subjected to metabolomics analysis of changes in the levels of 33 neurotransmitters and their derivatives using a targeted metabolomics approach based on multiple reaction monitoring (MRM) technology.

(1)	The severity of depression and anxiety showed a positive correlation with OABSS (HAMD: R2=0.3039, p-value<0.0001; HAMA: R2=0.3448,p-value<0.0001). Unlike the phenomenon observed in OAB patients, there was no significant correlation between the HAMD/HAMA score and OABSS in the age-matched controls (HAMD: R2= 9.236e-006, p-value=0.9838; HAMA: R2=0.0656, p-value=0.0858). OAB patients were divided into mild (3-5), moderate (6-11) and severe (12-15) groups based on OABSS, the anxiety and depression levels increased accordingly as the severity grows which showed significant differences.
(2)	Targeted-metabolomics analysis identified 8 significantly changed neurotransmitters (fold change>1.5,p-value<0.05) including serotonin and its derivatives. KEGG enrichment analysis indicated RS group significantly downregulated tryptophan metabolism. These results suggest that RS may affect overactive bladder in mice via the tryptophan-serotonin pathway.

This preliminary study found that female patients with OAB are prone to develop anxiety and depression, and the severity of OAB is positively correlated with anxiety and depression degree. Laboratory study using restrained stress mice and metabolomic analysis showed that depression may affect the bladder activity of mice by disrupting the tryptophan-serotonin pathway.

The presence of psychological disorders is high correlated with OAB symptom severity. The two identities shared interrelated metabolic pathways, which could be a potential therapeutic target not just for the regulation of bladder function, but also for the affective disturbance. Future studies are needed to explore the precise mechanisms between depression and OAB, with a focus on the tryptophan-serotonin pathway.