Lower urinary tract symptoms are elevated with depression in Japanese women

Depression might worsen lower urinary tract symptoms (LUTS), but the correlation is still disputed. This study examined the influence of depression on LUTS in Japanese women.

with storage symptoms, namely 23.4% with nocturia, 23.3% with urgency, and 18.9% with SUI. 3 In Japanese cohorts, our previous study revealed that 21.4% of women had urgency symptoms, and 16.7% had SUI. 4 While LUTS are not life-threatening, they reduce quality of life.
In contrast, suicide is strongly correlated with depression, making depression a life-threatening disease. 5,6 A total of 264 million people are estimated to have depression globally, accounting for approximately 4.4% of the entire global population. 7,8 A recent study suggested that the prevalence of depression is double the actual reported values, and the prevalence of depression in women is twice that in men. 8 Requel et al. revealed that elderly women with depression had a particularly high risk of developing LUTS. 8 However, Melville et al. noted no correlation between LUTS and depression. 9 The correlation between depression and LUTS therefore remains controversial. No large study has yet reported on the relationship between depression and LUTS in Japanese women.
The present study therefore investigated the relationship between depression symptoms and LUTS in Japanese women using a web-based questionnaire.

| MATERIALS AND METHODS
We conducted a web-based questionnaire analysis using 4.5 million Asian Japanese panels with an internet research company (Freeasy; iBRIDGE, Tokyo, Japan). We asked a total of 5400 women to respond concerning LUTS (Overactive Bladder Symptom Score, OABSS; International Consultation on Incontinence Questionnaire-Short Form, ICIQ-SF) and their feelings of depression (Quick Inventory of Depressive Symptomatology-Japanese version, QIDS-J). Of these individuals, 4151 (76.9%) answered the questionnaire completely. We also collected data on respondents' age, household income, type of residency, occupation, marital status, and number of children.
The OABSS, originally developed in Japan, is a 4-item questionnaire that expresses OAB symptoms on a single scale. 12 The OABSS question items address the following individual symptoms: daytime frequency, nocturia, urgency, and urgency incontinence. Gotoh et al.
reported that the OABSS was useful for assessing the effects of treatment on OAB symptoms and was responsive to treatmentrelated changes. 13 The OABSS consists of the following four questions (Q) regarding specific symptoms: daytime frequency (Q1), night-time frequency (Q2), urgency (Q3), and urgency incontinence (Q4). The OABSS was defined as the sum of the total OABSS, with OAB defined as the presence of both a total score of ≥3 and an OABSS Q3 score of ≥2. The OABSS defined urgency urinary incontinence (UUI) as an OABSS Q4 score of ≥1. Daytime frequency was defined as an OABSS Q1 score of ≥1. Nocturia was defined as an OABSS Q2 score of ≥2. The ICIQ-SF was developed to screen for incontinence; obtain a brief yet comprehensive summary of the level, impact, and perceived causes of symptoms of incontinence; and facilitate patient-clinician discussions. 14 The ICIQ-SF score was calculated as the sum of the Q1, Q2, and Q3 scores. UUI (ICIQ-SF definition) was defined by a positive response to "leaks occur before you can get to the toilet." SUI was defined by a positive response to at least one of the following questions: "leaks occur when you cough or sneeze" and "leaks occur when you are physically active/ exercising." Mixed urinary incontinence was defined as both UUI (ICIQ-SF definition) and SUI. Post-micturition dribble was defined as a positive response to "leaks occur when you have finished urinating and are dressed." The QIDS-J was translated and validated from the QIDS-Self Report (QIDS-SR), which consists of 16 questions and plays a role in T A B L E 1 Patients' background characteristics.
In all age groups, the prevalence of OAB and UUI was positively correlated with the depression status (Table 2). In the young subjects

| DISCUSSION
This study is the first to examine the correlation between depression status and LUTS in women using a large cohort of approximately 4100 Japanese women. Some studies have suggested that depression worsens urinary symptoms, particularly nocturia. 10 The QIDS-J score was relatively high in young subjects and gradually decreased with age ( Figure 1) with MDD are three times more likely to have depression than those without MDD. 13,14 More than 40% experience their initial depressive episode before the age of 20 and progress to depression around the age of 25. 15 Depression is twice as prevalent in women as in men.
The detailed mechanism underlying the higher prevalence of depression in women than in men is unknown, but the involvement of hormones or neurogenesis has been suspected. 16 The mean OABSS increased as the QIDS-J score increased. Our results suggest that depression caused endothelial sclerosis and a worsened bladder function, especially in the young group.
Recent studies have shown that depression worsens endothelial sclerosis. 22 Phosphodiesterase type 5 (PDE-5) inhibitors inhibit PDE-5, which is distributed in the vascular endothelium and smooth muscles of the bladder, and also increase the concentration of cyclic guanosine monophosphate produced in response to the level of nitric oxide in tissue. 23 Based on these mechanisms, the blood flow and oxygen supply increase in tissue, resulting in an improvement in the blood flow of the lower urinary tract. 23 The present and previous findings suggest that endothelial sclerosis has a greater impact on LUTS in young LUTS patients than in elderly patients. In conclusion, this study revealed that worsening LUTS was correlated with depression. The RR of OAB and UUI influenced by depression was higher in younger groups than in older groups.

ACKNOWLEDGMENT
There are no applicable grant numbers associated with this study.

CONFLICT OF INTEREST
We declare no conflicts of interests.

DATA AVAILABILITY STATEMENT
Research data are not shared.

ETHICS STATEMENT
This study has been approved by the institutional review board of Yokohama City University Medical Center (approval no. B201000052).

INFORMED CONSENT
Following an institutional review board-approved protocol, informed consent was obtained from the participants before answering the questionnaires.