Nocturia and depression

Authors


Dr R. Asplund, Tallvägen 3, S-833 34 Strömsund, Sweden.
e-mail: r.asplund@telia.com or ragnar.asplund@jll.se

Abstract

OBJECTIVE

To assess the possible relationship between major depression (MD) and nocturia.

SUBJECTS AND METHODS

An unselected group of adult men and women, living in the city of Östersund, Sweden, were sent a postal questionnaire containing questions on somatic and mental health, sleep, sleepiness and nocturia. For depression diagnostics the Major Depression Inventory (MDI) was used.

RESULTS

The mean (sd) ages of the men and women were 48.0 (18.2) and 50.1 (19.1) years, respectively. Two or more nocturnal micturition episodes occurred in 15.6% of the men and 16.5% of the women. In a multiple logistic regression analysis independent correlates (with 95% confidence intervals) for ≥ 2 nocturnal voids in men were: MD 6.5 (2.6–15.6); health, fair vs good, 1.8 (1.0–3.9); health, poor vs good, 2.7 (1.1–4.8); age, 60–74 vs 18–29, 3.6 (1.5–8.4) and age ≥ 75 vs 18–29 6.7 (2.6–17.4); and in women: MD 2.8 (1.3–6.3); health, fair vs good, 1.9 (1.1–3.2); health, poor vs good, 4.3 (2.6–8.2); age, 60–74 vs 18–29, 3.8 (1.8–7.8), and age ≥ 75 vs 18–29, 8.6 (4.0–18.6). Age < 60 years was deleted by the logistic model in both sexes.

CONCLUSION

MD is associated with a six-fold increase in nocturia in men and a three-fold increase in women, after accounting for age and health. Possible pathogenetic mechanisms of this relationship 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.

Abbreviations
ADH

anti-diuretic hormone

MDI

Major Depression Inventory

MD

major depression.

INTRODUCTION

Nocturia, the need of nocturnal micturition, is a common complaint in adult and elderly people, and has a profound influence on their death rate, health and quality of life [1–3]. Sleep complaints, e.g. poor sleep, increased nocturnal awakening and difficulty in falling asleep after waking in the night, resulting in increased morning tiredness, sleepiness in the daytime and increased napping, are all increased in association with nocturia [1].

Increased prevalence rates of depressive symptoms have been reported in association with LUTS and incontinence [4–6] but we found no reports dealing with the possible connection between nocturia and depression. The finding of a close relation both between nocturia and sleep disorders [1], and between sleep disorders and depression [7], makes it reasonable to consider a link between nocturia and depression. Thus the aim of the present study was to investigate the possible relationship between nocturia and depression in a group of adult men and women.

SUBJECTS AND METHODS

All men and women aged ≥ 18 years and born on one of two defined days each month of the year and resident in any of three defined parishes in the city of Östersund, Sweden, were sent a postal questionnaire with an explanatory letter. Those who had not replied within 2 weeks were sent a reminder by postcard, and those who had not replied after two further weeks received a second reminder with a new copy of the questionnaire.

The questionnaire consisted of questions on depression, sleep and nocturia. To obtain data on nocturnal micturition, the question ‘I usually get up . . . (times) for micturition at night’ was included [1]. For depression diagnostics, the Major Depression Inventory (MDI) was used (Appendix) [8]. The MDI contains all nine symptoms of a DSM IV major depression episode [9]. Each of the questions 1–10 of the MDI could be answered by the alternative replies: (1) ‘All the time’; (2) ‘Most of the time’; (3) ‘Slightly more than half the time’; (4) ‘Slightly less than half the time’; (5) ‘Some of the time’; or (6) ‘At no time’. Questions 11–15 had the response alternatives ‘Yes’ or ‘No’. Answers were considered affirmative: (i) if the reply to questions 1–3 of the MDI was: ‘All the time’ or ‘Most of the time’; (ii) if the reply to questions 4–10 was ‘All the time’, ‘Most of the time’ or ‘Slightly more than half the time’; and (iii) if questions 11–15 were answered ‘Yes’.

Major depression (MD) was considered to be present: (i) if one of questions 1 and 2 was answered affirmatively; (ii) if four of the replies to questions 1–3; 4 or 5; 6 and 7; 8 or 9 and 10 were affirmative (if the strongest reply alternatives to questions 4 and 5 and to 8 and 9 were chosen); (iii) if any of the answers to questions 11–14 was ‘Yes’; and (iv) if question 15 was answered ‘Yes’.

Standard methods were used for calculating the mean (sd); groups were compared for non-numerical data using the chi-square test, for numerical variables using Student's t-test and in a multivariate analysis by logistic regression analysis.

RESULTS

The questionnaire was initially sent to 2048 individuals; for 23 people the mailing address was out of date, eight were not in Sweden, 24 declined to participate, 12 were unable to answer for medical reasons (including dementia and stroke), four questionnaires were returned with no identification numbers, and six people had died between the time when the address list was obtained and the mailing of the questionnaire. The questionnaire was initially completed by 860 people; after reminders, a further 515 answers were received. Thus there were 1375 evaluable questionnaires, of which 609 (44.3%) were from men. Of the recipients who could be expected to answer (1971) the response rate was 69.8%.

The mean (sd) ages of the men and women participants are shown in Table 1; a somewhat larger proportion of elderly participants (≥ 75 years) were women (P < 0.05). Among the men, 15.6% reported having two or more nocturnal voids/night, and among the women 16.5%. The prevalence of nocturia (≥ two voids/night) increased with age (P < 0.001) in both sexes (Table 1).

Table 1.  The distribution of age , nocturnal voids and MD in men and the women of the study group
VariableAge, yearsTotal
20–2930–4445–5960–74 ≥  75
Distribution, %
Men21.122.828.18.71  9.1 
Women20.818.028.019.813.4 
Total20.920.128.219.311.5 
Nocturnal voids
Men
None78.870.547.330.218.453.4
One14.423.337.943.440.831.0
Two  6.8  6.214.826.440.815.6
Women
None58.665.146.029.118.845.9
One32.931.039.646.337.537.6
Two  8.6  3.914.424.643.816.5
MD
Men  0.0  7.4  5.6  6.1  3.8  4.8
Women  8.8  9.9  4.1  3.3  6.6  6.3

MD was recorded in 4.8% of the men and in 6.3% of the women (no significant difference), and nor was there a significant difference in the occurrence of MD in relation to age in either gender (Table 1). There was an increase in MD in association with an increased prevalence of nocturia in both men and women (Fig. 1). The multiple logistic regression analysis with age, somatic health and MD as independent variables, and nocturia as the dependent variable, showed that nocturia was increased in men and women in parallel with increasing age (after 60 years), impaired health and MD (Table 2).

Figure 1.

The percentage of men and women with MD in relation to the number of nocturnal voids (open, none; green, one; and red, two or more; both P < 0.001).

Table 2.  The final model of the stepwise multiple logistic regression, giving the probability of having two or more episodes of nocturnal voiding in relation to age, somatic health and MD
VariableOdds ratio (95% CI)
MenWomen
Age group, years
20–291.01.0
30–44 0.6 (0.2–1.8)0.4 (0.1–1.3)
45–591.7 (0.7–4.1)1.8 (0.9–3.7)
60–743.6 (1.5–8.4)3.8 (1.8–7.8)
≥  756.7 (2.6–17.4)8.6 (4.0–18.6)
Health (Good = 1.0)  
Fair1.8 (1.0–3.9)1.9 (1.1–3.2)
Poor2.7 (1.1–4.8)4.3 (2.6–8.2)
MD (‘No’ = 1.0)
Yes6.5 (2.6–15.6)2.8 (1.3–6.3)

DISCUSSION

The main finding in the present study was that MD was associated with increased nocturia in both men and women. We found no previous reports on such a relationship between these phenomena, although other connections between urinary symptoms and depressive symptoms have been described. In a study among the home-bound elderly with urinary incontinence, half had significant depressive symptoms, with 35.7% having scores indicating mild and 14.5% severe depression. Only 21.7% and 34.0% of these groups, respectively, had been prescribed an antidepressant [10].

Nocturia increased in parallel with increasing age and with deteriorating somatic health in both sexes, which is in accordance with previous reports (Table 1) [1,11,12]. Nocturia was increased six-fold in men and three-fold in women in association with MD, after accounting for age and somatic health. The mechanism that might explain a relationship between MD and nocturia is of interest. Nocturia can occur as a consequence of either increased nocturnal urine output or a decreased bladder capacity, or of a combination of these two [3]. A disturbance in the 24-h rhythm of antidiuretic hormone (ADH) with no nocturnal rise in the plasma ADH level is a common mechanism of nocturia caused by nocturnal polyuria in adult and elderly people [13–15]. In depressed patients, both the synthesis and release of ADH in the suprachiasmatic nucleus in the hypothalamus are reduced [16]. This nucleus is responsible for initiating and maintaining the circadian rhythm [17].

In the standard urological terminology, nocturia is defined as ‘. . . the complaint that the individual has to wake at night one or more times to void’[18]. Among the present subjects some could have been awake at night as a consequence of depression or for other reasons, and thus any specific number of nocturnal voids might not meet the criteria. However, in a questionnaire survey among 1115 men and women (39.5% men), in those who reported three or more nocturnal voids the reported numbers of nocturnal awakenings were 3.4 and 3.5 in men and women, respectively [15]. This supports the interpretation that most awakenings at night occur in association with micturition, i.e. that the definition of nocturia was met for most nocturnal voiding episodes.

Most of the ADH secretion takes place in neurones in the supraoptic and paraventricular nuclei in the hypothalamus, and the secretion is essentially unaffected by age [19]. ADH is thought to be important in the pathophysiology of affective disorders [20]. Patients with MD have more circulating ADH levels, both in the daytime and at night, than do healthy controls, but there is no nocturnal rise in the ADH level [21]. A circadian rhythm of circulating ADH is necessary for maintaining the circadian diuresis rhythm, with high urine output in the daytime and low diuresis at night [13,14]. We cannot therefore exclude that the disturbed diurnal ADH secretion pattern might contribute to the increased nocturia in MD. Treatment with an ADH analogue, desmopressin, has been shown to normalize the 24-h diuresis pattern both in enuretic children and in elderly subjects with a lack of circadian ADH rhythm and consequent nocturia [22,23].

The nocturnal urine output is also increased in association with sleep impairment [15,24]. The urine output is lower during superficial sleep than in the awake state and is even more decreased in deep sleep [15,24,25]. Sleep deterioration is a common finding in patients with MD, and nocturia may therefore be a consequence of the change in the diurnal diuresis pattern resulting from sleep impairment [26].

MD and nocturia might also have a pathogenetic mechanism in common. Reduction of the serotonin and noradrenaline levels in the CNS can lead to depression, increased urinary frequency and a hyperactive bladder in experimental animals [27]. Altered concentrations of monoamines in the CNS could result in both depression and an overactive bladder, leading to nocturia [27]. In rats and cats, activation of the central serotonergic system by serotonin reuptake inhibitors, as well as by 5-HT1A and 5-HT2 receptor agonists, depresses reflex bladder contractions and increases the bladder volume threshold for inducing micturition [28]. If these mechanisms are present in man they could explain the concomitant occurrence of MD and nocturia, and could also partly explain why antidepressant drugs have been proved to reduce urinary urge [5,28,29].

In a study of incontinent patients [5] twice as many with idiopathic urge incontinence had, or had a history of, depression, according to the Beck Depression Inventory, compared with continent controls (P < 0.001). Patients with incontinence of other origin (stress or urge caused by neuropathology or obstruction) had no greater odds of having depression than continent controls.

In conclusion, MD is associated with a six-fold increase in nocturnal voiding in men and a three-fold increase in women, after accounting for age and health. Possible pathogenetic mechanisms of this relationship may involve both an increase in nocturnal diuresis through a disturbed 24-h rhythm of ADH secretion, and a decrease in nocturnal bladder capacity occurring through a central and/or peripheral serotonergic mechanism.

CONFLICT OF INTEREST

None declared.

Appendix

The MDI [8]. The following questions concern how you have been feeling over the last 2 weeks. Please put a tick in the box which is closest to how you have been feeling.

(columns 1–6 with boxes aligned )

  • 1Have you felt low in spirits or sad?
  • 2Have you lost interest in your daily activities?
  • 3Have you felt lacking in energy and strength?
  • 4Have you felt less self-confident?
  • 5Have you had a bad conscience or feelings of guilt?
  • 6Have you felt that life wasn’t worth living?
  • 7Have you had difficulty in concentrating?
  • 8Have you felt very restless?
  • 9Have you felt subdued?
  • 10Have you had trouble sleeping at night?
  • 11Have you suffered from reduced appetite?
  • 12Have you suffered from increased appetite?
  • 13Have you suffered from an unintentional weight gain?
  • 14Have you suffered from an unintentional weight loss?
  • 15If you have or have had any of the above mentioned symptoms, has it/they implied significant suffering?

Each of the questions 1–10 could be answered by the alternative replies: (1) ‘All the time’, (2) ‘Most of the time’, (3) ‘Slightly more than half the time’, (4) ‘Slightly less than half the time’, (5) ‘Some of the time’ or (6) ‘At no time’. Questions 11–15 had the responses ‘Yes’ or ‘No’.

Ancillary