This cross-sectional study enrolled patients with recurrent cystitis who visited the Urology Department of Guro Hospital, Korea University, from April 2018 to June 2022. Female patients (aged ≥18 years) with recurrent UTIs (defined as 2 or more acute symptomatic infections in 6 months or 3 or more infections within 1 year) were included. Patients who had urological abnormalities, systemic sepsis, an immune-compromised state, conditions that could lead to UTI-like symptoms (e.g., yeast vaginitis and interstitial cystitis), or a history of psychological disease before the history of recurrent cystitis based on a selfreport or chart review were excluded. Patients who were pregnant were also excluded.

Data on clinical variables such as marital status, menopause, presence of comorbidities (hypertension [HTN], diabetes mellitus, history of immune-stimulating agent use, history of surgery [incontinence surgery and gynecologic surgery]), disease duration (defined as the time from the first onset of symptoms to the latest medical visit), and the number of recurrences was collected. Patients were divided into subgroups according to the number of recurrences and disease duration. Differences in the levels of anxiety and depression between these subgroups were analyzed. Among the clinical characteristics, factors that independently affected the levels of depression and anxiety were also analyzed. Also, the correlation between the number of recurrences of UTI and the level of anxiety and depression was assessed.

Continuous variables are presented as means for parametric data and medians for nonparametric data. Categorical variables are expressed as percentages or ratios. Correlation analysis was performed on the levels of depression and anxiety based on clinical characteristics, including the number of recurrences, disease duration, and age. A t-test or 1-way analysis of variance was applied to demonstrate statistical differences.

Independent factors that affected depression and anxiety scores were determined using linear regression models. Only factors that exhibited P-values below 0.05 in the univariate analysis were incorporated into the multivariate analysis. The regression coefficient was analyzed between depression or anxiety scores and the presence of other diseases (HTN, malignancy), disease duration, and the number of recurrences. All probabilities were 2-tailed, and the significance level was set at 0.05. Statistical analyses were performed using IBM SPSS Statistics ver. 25.0 (IBM Co., Armonk, NY, USA).

The State-Trait Anxiety Inventory (STAI-S) revealed that a significant number of participants experienced severe (68.8%) and moderate (22.3%) anxiety, averaging a score of 56.11±11.88. The average number of recurrences was 3.64±1.11, with 46.4% experiencing 4 or more (Table 1). Multivariate linear regression analysis indicated that higher recurrence significantly predicted increased anxiety levels (B=6.278, P<0.001) (Table 2). A positive correlation was observed between the number of recurrences and STAI-S scores (Pearson correlation coefficient 0.362, P<0.001) (Table 3).

The PHQ-9 scores showed mild (33.9%) and moderate (8.0%) depression, with an average score of 4.12±3.68 (Table 1). There were significant differences in PHQ-9 scores for 2, 3, and ≥4 recurrences (P =0.046), and a notable correlation was found with disease duration (P=0.027) (Table 2). Regression analysis revealed that higher recurrence was a predictor of increased depression (B=1.056, P=0.041), and disease duration significantly predicted the PHQ score (B=0.287, P=0.031) (Table 2). The PHQ-9 score was positively correlated with the number of recurrences (Pearson correlation coefficient 0.248, P=0.009) and disease duration (P=0.027) (Table 3).

This study demonstrated that patients with recurrent UTIs frequently experience high anxiety levels, with 68.8% reporting severe and 22.3% moderate anxiety complementarily, another study found that 30% of patients with recurrent UTI suffered from anxiety, 4% from depression, and 24% from both [10]. Notably, an improvement in anxiety related to clinic visit satisfaction was observed, with STAI-S scores indicating higher anxiety in 6 patients with recurrent UTIs compared to those without, prior to their visit. The limited sample size was acknowledged as a constraint [11]. Nevertheless, our study established a positive correlation between the number of recurrences and anxiety (coefficient=0.362, P<0.001), corroborating Renard et al. [5]’s findings using the Hospital Anxiety and Depression (HAD) score. Significant variations in STAI-S scores were identified across different recurrence counts (P<0.001), particularly between the third and fourth recurrences, though not between the second and third, possibly due to different reference periods (6 months and 12 months). Despite these discrepancies, it was consistently evident that anxiety levels escalated with an increase in UTI recurrences.

In this study, a mere 8% of patients exhibited signs of depression (moderate, 8%; severe, 0%), indicating that the incidence of depression in those with recurrent UTI is significantly lower than that of anxiety disorders (severe, 68.8%; moderate, 22.3%). A multicenter trial assessing QoL in patients with recurrent UTI using the HAD and Leicester scales found that approximately 12.9% exhibited depression initially [5]. Medina et al. [12] suggested that feelings of guilt due to restrictions in social activity or daily life among patients with recurrent UTIs might contribute to clinical symptoms of depression. Despite the low incidence, our study revealed a significant difference in PHQ-9 scores with an increase in the number of recurrences (P=0.046), supporting another study which reported decreased depression following UTI treatment and reduced incidence of UTIs, which documented significantly less depression after patients were treated for UTIs and the incidence of UTIs decreased [5]. Reflecting on the chronicity of the disease, we explored the relationship between UTI chronicity, STAI-S, and PHQ-9 scores using disease duration as a measure. Here, disease duration correlated only with PHQ-9 (correlation coefficient 0.234, P = 0.013), while no significant correlation was found with STAI-S. Moreover, no substantial difference was noted between PHQ-9 and STAI-S scores in relation to disease duration. Ellis and Verma [1] using the 36-item Short Form health survey (SF-36) indicated that disease duration did not markedly affect overall QoL, yet a negative correlation was observed within the SF-36 subsections (mental health section and disease duration). Given the SF-36 evaluates mental health on both depression and anxiety scales, it’s challenging to isolate the correlation specifically to depression, confirming our findings [13]. Consequently, further research is essential to elucidate the relationship between disease duration, depression, and anxiety comprehensively.

The present study is subject to several limitations. Firstly, the absence of a matched healthy control group is a notable drawback. Despite this, discerning which patients with recurrent UTIs experienced more severe psychological issues was feasible. Secondly, the potential impact of inherent personality traits on anxiety levels was not examined. For individuals predisposed to anxiety, differentiating between anxiety stemming from the disease and their baseline state is complex. This is underscored by research indicating a strong association between neurotic personality traits and symptoms of depression and anxiety, with such traits potentially leading to behaviors that increase UTI risk [14, 15]. Acknowledging depression and anxiety as secondary symptoms of recurrent cystitis is vital, along with a comprehensive understanding of the patients’ psychological profiles. Measuring STAI-T scores could have mitigated this limitation by providing a more nuanced view of the anxiety’s origin. Thirdly, the non-randomized design of the study may introduce self-selection bias, a common issue in stress-related research. This is reflected in the disproportionately high percentage of patients with severe anxiety (severe, 68.8%; moderate, 22.3%) in this study, possibly indicative of higher participation rates among those experiencing greater anxiety. Moving forward, reevaluating the sampling method when adequate data are available will be considered to address these issues. As the fourth limitation, it should be noted that our study did not capture comprehensive treatment histories or any data on the severity or presence of UTI symptoms. The retrospective design inherently limited the scope of information we could collect. Given the critical importance of these variables, it is crucial for future prospective studies to include such detailed data. This would allow for a more nuanced analysis of the relationships between treatment approaches, symptom details, and psychological health outcomes in patients with recurrent UTIs.

In conclusion, our study reveals that recurrent cystitis notably increases patients’ anxiety, correlating with the frequency of recurrences. Disease duration is also linked to depression. These findings emphasize the importance of preventing UTI recurrences to reduce psychological complications. To reinforce these results, larger cohort studies are necessary.