The predictive factors of nocturia in young Asian adult males: an online survey

The present study investigated the association between severity of depressive mood and nocturia in young Asian adult men. Participants were 3127 adult male Facebook users aged 20–40 years who could read and write traditional Chinese. Participants completed online questionnaires on demographic characteristics, frequency of waking to urinate during the night (International Prostate Symptoms Score [IPSS]), and frequency of depressive symptoms (Taiwanese Depression Questionnaire [TDQ]). Those who awoke to pass urine during the main sleep period were considered to have nocturia. Student’s t test and Pearson’s chi square test were used to compare participants with and without nocturia. Univariate and multivariate logistic regression were used to evaluate predictive factors for nocturia. One thousand four hundred thirty (45.7%) participants had nocturia, and 21.9% were suspected to have depression. Age over 30 years, body mass index over 25 kg/m2, and higher IPSS score (except times of nocturnal voiding) were factors predictive of nocturia. Higher TDQ somatic subscores, rather than affective/cognitive subscores, were also predictive of nocturia. Associations were found between normal-high TDQ scores and nocturia. Young men with nocturia at risk of developing depression should be identified with a culturally relevant questionnaire. Early referral for psychiatric assessment and intervention may be warranted.

www.nature.com/scientificreports/ month, how many times did you most typically get up to urinate from the time you went to bed at night until the time you got up in the morning?" Waking to pass urine during the main sleep period was considered an indication of nocturia, according to the International Continence Society (ICS) 2018 definition 6 . The third part was the Taiwanese Depression Questionnaire (TDQ), which was used to assess the level of depression. The TDQ is a culturally-relevant questionnaire composed of 18 questions regarding the frequency of somatic symptoms and emotional distress within the past week. The response scale is as follows: 0 = fewer than one day per week, 1 = 1-2 days per week, 2 = 3-4 days per week, and 3 = 5-7 days per week. The total score ranges from 0 to 54. The questionnaire has been validated with a sensitivity of 0.89 and specificity of 0.92, at a cutoff score of 19 7 . The scores on the TDQ can be used to classify individuals into four groups: normal (score 0-8), normal-low (score [9][10][11][12][13][14], normal-high (score [15][16][17][18], and depression (score ≥ 19) 8 . The 18 items are either affective/cognitive questions or somatic questions; therefore, an affective/cognitive symptoms subscore and a somatic symptoms subscore were calculated for further analysis 8  Ethics statement. All procedures were in accordance with the ethics committee and with the principles of the Declaration of Helsinki. The ethics committee confirmed that no written informed consent was warranted from participants included in this study.
In the univariate analysis, all the parameters were significantly associated with nocturia ( Table 2). Three multivariate analysis models with different parameters were used to evaluate the effect of depression on nocturia. Age over 30 years, BMI over 25 kg/m 2 , and IPSS score (except times of nocturnal voiding) were predictive factors for nocturia in all three models. With regard to depressive symptoms, in the first model, depression based on TDQ score (≥ 19) was not a significant predictor of nocturia (odds ratio 1.045, 95% confidence interval [0.869 1.257], p = 0.64) ( Table 2). In the second model, only TDQ somatic subscores (odds ratio 1.042, 95% confidence interval [1.008 1.078], p = 0.01) predicted nocturia. In the third model, normal-high depressive mood rather than depression was a significant predictor of nocturia, when compared to a normal mood. An analysis was also conducted to examine the depressive symptoms predictive of nocturia, based on the questions listed in the TDQ. Questions related to crying, irritability, poor sleep, chest tightness, tiredness, and body discomfort were associated with nocturia in young Asian males after adjustment with age, BMI, and IPSS (except times of nocturnal voiding) (Table S1). Among the somatic depressive symptoms, only the question with reference to poor sleep (odds ratio 1.103, 95% confidence interval [1.003 1.212], p = 0.042) was significantly predictive of nocturia.

Discussion
Most previous studies on nocturia have focused on men older than 50 years. For this purpose, the present study recruited younger men who have rarely been investigated in the literature. Moreover, this study excluded causes of nocturia from organic diseases of the lower urinary tract, such as benign prostate hyperplasia, which are infrequent among younger men. Results of the online questionnaire survey revealed that the prevalence of nocturia in Asian adult males younger than 40 years of age was 45.7%. This finding is consistent with other studies. The reported prevalence rate of nocturia in young males aged 20 to 40 ranged from 11 to 35.2% 9 . Another recent study showed the estimated prevalence of nocturia was 56.8% among young men in the U.S., 10 . Thus, the sample of the present study, recruited from Facebook, could be representative of younger men in the general population.
Other studies including younger and older adults have revealed that increased age and BMI were both risk factors for nocturia. Madhu et al. 11 conducted a secondary analysis of the EpiLUTS data using participants with nocturia. Age, BMI, anxiety, depression, and a history of bed-wetting were significantly associated with nocturia. Fitzgerald et al. 2 found that the odds ratio of nocturia increased with age and BMI in a multivariate model. Other www.nature.com/scientificreports/ studies also reported that nocturia was significantly associated with obesity 12,13 . Similarly, in the present study, age older than 30 years, BMI over 25 kg/m 2 , and higher IPSS score (except times of nocturnal voiding) were predictive factors for nocturia in the sample of young Asian men. Goessaert et al. 14 found that reduced functional bladder capacity was associated with nocturia in younger participants, which deteriorated with aging. Obesity increased intra-abdominal pressure and led to nocturia 15 . In addition, those with obesity had a higher chance of obstructive sleep apnea, which resulted in nocturnal polyuria and detrusor instability 16,17 . One supportive evidence in this study was that the participants with nocturia had a higher IPSS (except times of nocturnal voiding) score, especially with regards to the storage scores. This relationship has been found to be more profound in men 18 and younger patients 19,20 , similar to the present study's population.
One of the key findings of the present study was the association between nocturia and level of depression in young men, which differed from previous findings. Asplund et al. 21 found that major depression was associated with a six-fold increase in nocturia in men. A cohort study by Johnson et al. 22 showed that depressed and nondepressed patients reported a mean of 2.7 and 1.9 episodes of nocturia per night, respectively. Patients with five or more episodes of nocturia per night experienced a 6.5-fold increased risk of depression. Häkkinen et al. 3 noted a unidirectional effect of depressive symptoms on the incidence of moderate or severe nocturia. A systematic review concluded a bidirectional association between depression and nocturia: nocturia increased the odds ratio of depression (OR 1.2-20.24), while depression similarly increased the odds ratio of nocturia (OR 1.2-7.73) 4 . The findings of this study indicated that depression based on TQD criteria was not associated with nocturia in young Asian men. Instead, young men with normal-high depressive mood were at risk of having nocturia. One possible explanation is that this study only focused on young men aged between 20 and 40 years, which is different from other studies that included men of both young and old ages.
There are several potential mechanisms underlying the relationship between depression and nocturia. One possibility is through poor sleep quality. Nocturia has been shown to have close relationships with early waking and decreased total sleep time 23 . In a cohort of patients treated for depression, depression severity significantly correlated with sleep quality 24 . Przydacz et al. 25 even argued that it was not depression severity, but rather sleep quality that correlated with nocturia. The present study also found that poor sleep was the only somatic symptom in TDQ scores significantly predictive of nocturia. Second, depression has been shown to have a negative effect on perception, development, and prolongation of LUTS, including nocturia 26 . Third, depression may involve both increased nocturnal diuresis via a disturbed 24-h rhythm of antidiuretic hormone secretion, and a decrease in nocturnal bladder capacity through a central and/or peripheral serotonergic effect 21 . Fourth, in a previous study 27 , patients being treated with selective serotonin-reuptake inhibitors for depression had twice the incidence of nocturia. Another study 28 also showed that the incidence and severity of overactive bladder, whose symptoms include nocturia, increased in men using antidepressants.
The present study found that somatic rather than affective/cognitive symptoms were related to nocturia, especially poor sleep, chest tightness, tiredness, and body discomfort. One possible explanation is the different expression of depression in different cultures. For example, Vietnamese patients were prone to endorse higher levels of somatic symptoms than German patients despite similar levels of depression severity 29 . Similarly, somatic complaints predicted depression in Vietnamese and Vietnamese American adolescents, whereas no relationship was found in European American adolescents 30 . Furthermore, only normal-high depressive mood could predict the presence of nocturia among young Asian men. Thus, the complaints of nocturia in young Asian males could be a red flag signaling a depressive mood, which could progress to major depressive disorder without early intervention. Therefore, by utilizing a culturally-relevant depression screening instrument, such as the TDQ, with young male patients complaining of nocturia in urology clinics, early identification of those who are at risk of developing a depressive disorder would be possible.
There are several limitations to this study that should be mentioned. First, this study recruited participants from a social media site (i.e., Facebook) as opposed to a community-based population. As such, selection bias may exist. It is reported that social media use was significantly associated with, or even causal of depression among young adults, especially among problematic users [31][32][33] . Nighttime-specific social media users experienced lower self-esteem, higher levels of anxiety and depression, and poorer sleep quality 34 , which may also impact the occurrence of nocturia. However, 98-99% of Taiwanese aged between 20 and 40 are Internet users, and therefore participant recruitment from social media may be feasible for studies involving young adults. Second, this study did not investigate comorbidities, medical history, diet, physical activity, or psychiatric history of the participants, which may also have an influence on the occurrence of nocturia. Nevertheless, it focused on young men instead of older adult men; it was posited that they would have less comorbidities and medications related to nocturia, and therefore, less confounding factors. Third, the information from a 24-h voiding diary, which could help determine the etiology of nocturia, is nearly impossible to obtain from an online survey. Nevertheless, there are some advantages of the present study. Over 3,000 young men were recruited; a population that has been less investigated for LUTS including nocturia. This study also evaluated the associations between depression and nocturia with a culturally-relevant questionnaire. The findings of the present study have practical implications for urologists when treating young men with nocturia. Early assessment of depressive symptoms can be preventative by enabling referrals for psychological evaluation and treatment of psychological symptoms.

Conclusion
This study demonstrated that about 45.7% of men between the ages of 20 and 40 had nocturia. Age over 30 years, BMI over 25 kg/m 2 , and higher IPSS score (except times of nocturnal voiding) were independently predictive of nocturia. Especially, those with normal-high depressive mood (TDQ score [15][16][17][18] were also at risk of having nocturia. Because the expression of depression in people from Eastern cultures may be predominantly somatic in nature, it would be imperative to use a culturally-relevant questionnaire to uncover the potential psychosomatic