Chronic constipation and diarrhea are associated with depression in the elderly: Insights from a large cross-sectional study

doi:10.21203/rs.3.rs-3966484/v1

Background: This study was to investigate the relationship between chronic constipation, diarrhea, and depression among the elderly, as the extent of their association remains elusive despite the well-established impact of gastrointestinal symptoms on depression.

Methods: Cross-sectional analyses were conducted using data from the 2005-2010 U.S. National Health and Nutrition Examination Surveys (NHANES), focusing on adults aged 60 and above with a sample size of 4878. Depressive symptoms were measured using Patient Health Questionnaire 9 (PHQ-9) scale. Information about chronic diarrhea or constipation was retrieved from the bowel health questionnaire. Multivariable weighted logistic regression analysis models were employed to estimate the relationship between gut health and depression status, adjusting for potential confounders (e.g., age, gender, race, education, marital status, education level, smoking status, drinking habits, and medical history).

Results: Probable depression (PHQ-9≥10) and depressive symptoms (PHQ-9≥5) were more prevalent among elderly individuals with diarrhea or constipation than among those without them (P <0.05). After adjusting for all-cause, the elderly with chronic diarrhea were more likely to have significant increases in their scores for several subtypes of depressive symptoms (P <0.05, six out of nine depressive symptoms). We observed a significantly positive correlation between patients with chronic constipation and the depressive symptoms for low mood/despair, appetite, and lack of concentration (P <0.05).

Conclusion: The elderly with depressive symptoms (PHQ-9 ≥5) may be associated with chronic constipation and diarrhea based on a nationally representative sample of the elderly in the U.S. from 2005 to 2010. These findings suggest that elderly individuals experiencing chronic diarrhea and constipation may have a higher prevalence of psychological depression symptoms.

Depression

Depressive symptoms

Chronic constipation

Chronic diarrhea

NHANES

Aging impacts the digestive systems of the elderly, and concerns about digestive diseases have been identified as psychological stressors. These stressors, combined with depressive symptoms, can affect intestinal transport function. This study discovered an association between depressive symptoms (PHQ-9 ≥5) in the elderly and chronic constipation and diarrhea, using a nationally representative sample from 2005 to 2010 in the U.S. Furthermore, we explored the exacerbating effects of diarrhea and constipation on depressive symptoms, highlighting the importance of developing effective strategies for managing chronic bowel symptoms in elderly patients.

Aging represents an inevitable trend in contemporary socioeconomic development, which brings forth numerous challenges to nations due to the escalating number of elderly individuals[1–3]. Healthy aging encompasses not only the physical well-being and material wealth of the elderly but also their psychological well-being and the fulfillment of their mental needs[4, 5]. Depression, as a crucial indicator of mental health, manifests as feelings of sadness and social impairment, severely limiting the psychosocial functioning of the elderly and reducing their life quality[6, 7]. Data from the World Health Organization revealed that more than 350 million of the global population are depressed. Over the past 30 years, the incidence of depression has increased by 0.6 times, and it is projected to become the largest global burden of disease by 2030, posing a critical threat to human health[8–10].

Psychological health issues, such as depression, exacerbate physical illnesses and increase suicidal tendencies among the elderly[3]. They also increase the risk of cognitive impairments. Notably, impairments in everyday activities are significantly associated with symptoms of late-life depression, and the incidence of depression is significantly higher among the elderly with severe physical impairments compared with those with moderate or mild impairments[10, 11]. Aging-related changes in the digestive system, including reduced gastrointestinal motility and decreased secretions of digestive enzymes (e.g., amylase, gastric protease, and pancreatic enzymes) and digestive fluids (e.g., saliva, bile, pancreatic juice, and intestinal secretions), contribute to common gastrointestinal symptoms, such as constipation and diarrhea, among the elderly[12]. Thus, elderly frailty is closely associated with diarrhea and constipation, with the prevalence of constipation ranging from 24–50% of the elderly population [13, 14]. In the United States (U.S.), the prevalence rates of diarrhea are 9.7% and 9.6% among elderly respondents aged 60–69 and ≥ 70 years, respectively [15, 16]. Among patients aged below 60 years, chronic diarrhea or constipation was positively associated with breast and colon cancers, cardiovascular diseases, and increased overall mortality risks, as well as cardiovascular disease–related mortalities[15, 17, 18]. However, thus far, no mechanism has been proposed to explain the relationship between gastrointestinal and depression symptoms among the elderly.

The digestive system is highly susceptible to external stimuli and is particularly sensitive to the mind-body connection in relation to disease[19, 20]. As aging affects the digestive systems of the elderly, concerns and fears about digestive diseases have emerged as psychological stressors that can combine with depressive symptoms to affect intestinal transport function[21, 22]. Studies have identified a significant relationship between depression and the severity of fecal incontinence has been confirmed to significantly correlate with any degree of depression[23, 24]. However, there are few studies investigating the specific impact of delayed gut transit and dissatisfaction with bowel movements in inducing depression symptoms. Although the extant studies demonstrated an association between gastrointestinal symptoms and depression, the extent to which colonic motility, including diarrhea and constipation, is associated with different levels of depression among the elderly remains uncertain[25]. In this study, we employed data from the National Health and Nutrition Examination Survey (NHANES) to investigate the association of depression with chronic constipation and diarrhea among the elderly.

2.1. Study population

NHANES is a nationally representative large-scale, multistage, continuous study that is conducted by the U.S. National Center for Health Statistics and Centers for Disease Control and Prevention (CDC). NHANES is a nationally representative cross-sectional survey that is aimed at comprehensively assessing the nutritional and health statuses of adults and children in the U.S. (more information on NHANES is available on the official website via https://www.cdc.gov/nchs/nhanes/index.htm). The sampling methods and data-collection details have been published elsewhere, and the research protocol was approved by the Institutional Review Board of the National Center for Health Statistics. All participants provided signed informed consent forms during the survey. The NHANES database is a public clinical database, and we employed data from three cycles spanning from 2005 to 2010 for this study.

2.2. Depression assessment

NHANES employs the PHQ-9 scale to assess participants’ depressive symptoms over the previous two weeks. This scale has been well-validated in multiracial/multiethnic populations. The questionnaire comprises nine items, with each item scored from 0 (not at all) to 3 (almost every day)[26]. The total score ranged from 0 to 27, with higher scores indicating higher degrees of depression. The PHQ-9 scale demonstrated high internal consistency, as well as good sensitivity (81.3%) and specificity (85.3%) in identifying depression risks[27]. To improve the quality of the PHQ-9 questionnaire, this study only included participants who answered a minimum of eight questions. PHQ-9 quantifies the prevalence of these symptoms over the previous two weeks. Throughout this study, we refer to the presence of clinical depressive symptoms rather than a clinical diagnosis. The PHQ-9 score is a composite of the answers to all nine questions, ranging from 0 to 27, and is categorized into three groups: scores of < 5 indicate the absence of depressive symptoms, scores of ≥ 5 indicate the presence of depressive symptoms, and scores of ≥ 10 indicate the probable presence of depression[28].

2.3. Assessments of chronic constipation and diarrhea

Based on the participants’ responses to the bowel health questionnaire, they were categorized as either having chronic diarrhea or constipation[29]. This questionnaire was completed using a computer-assisted face-to-face interview system at the mobile examination center. The researchers presented the participants with a card containing colored pictures and descriptions of the seven types (Types 1–7) of the Bristol Stool Form Scale (BSFS) and required them to, “Please look at this card and tell me the number that corresponds to your usual or most common stool type.”. Consistent with previous studies, chronic constipation was defined as corresponding the most to BSFS Type 1 (separate hard lumps, like nuts) or Type 2 (sausage-shaped, but lumpy) stool type, whereas chronic diarrhea was defined as corresponding mostly to BSFS Type 6 (fluffy pieces with ragged edges, mushy stool) or Type 7 (watery, no solid pieces) stool type[16]. The remaining participants were classified as having normal bowel characteristics. Stool frequency was assessed by asking participants, "How many bowel movements do you typically have per week?"[30]

2.4. Assessment of the covariates

The following covariates were included in this study: age; gender (male, female); race; education level; family income-to-poverty ratio (Family PIR) [< 1, ≥ 1]; marital status; smoking habit; alcohol consumption; body mass index (BMI); weight-adjusted-waist index (WWI); bowel frequency (assessed by the bowel health questionnaire with the question “How many times do you typically have a bowel movement per week?”); medical history: diabetes (yes/no), hypertension (yes/no), hyperlipidemias (yes/no), renal failure (yes/no), heart failure (yes/no), stroke (yes/no), liver diseases (yes/no), cancer (yes/no), constipation (yes/no), and diarrhea (yes/no). These issues were defined as self-reported, physician-diagnosed conditions. Alcohol status was obtained from an alcohol use questionnaire. The participants who reported that they consumed a minimum of 12 drinks of any type of alcoholic beverage in the previous year were considered alcohol users. A drink was defined as 12 ounces of beer, 5 ounces of wine, or 1.5 ounces of distilled spirits. Smoking status was assessed as current smokers (≥ 100 cigarettes and currently smoking every day or on some days). WWI was calculated by dividing the waist circumference (cm) by the square root of the participant’s weight (kg). Missing data were estimated using the missForest R package, which is a computationally efficient technique based on random forests for imputing data into high-dimensional datasets comprising categorical and continuous predictors.

2.5. Statistical analysis

Based on the complex multistage sampling design of NHANES, we adopted appropriate sample weights and other information for our primary analyses. As the data for this study spanned three survey cycles totaling six years, we followed the official NHANES guidelines to calculate the weights for the subsequent data analysis using the two-year mobile examination sampling weights for each of the relevant survey cycles (every two years). The continuous variables were presented as weighted means ± standard error (SE), whereas the categorical variables were presented as weighted percentages (%). Model 1 was adjusted for age, gender, race, education, marital status, education level, and Family PIR. Model 2 included the variables from Model 1 and was further adjusted for smoking status and drinking habits. Model 3 included the variables from Model 2 and was further adjusted for diabetes, hypertension, hyperlipidemia, renal failure, heart failure, stroke, liver diseases, and cancer. Model 4 included the variables from Model 3 and was further adjusted for BMI and WWI. The baseline characteristics were assessed using weighted chi-square and t-tests. The Pearson correlation coefficient was calculated to evaluate the correlations.

3.1. Baseline characteristics

Our analysis included 4878 participants (Fig. 1, average age = 70.41 ± 7.21 years). Table 1 presents the weighted baseline characteristics of the participants. Among the participants, 45% were male, and 55% were female. Additionally, 82% were non-Hispanic white, 8.5% were non-Hispanic black, 4% were Mexican American, 2.4% were other Hispanics, and 3% were from other racial backgrounds. After weighting, 5% of the participants were classified as having probable depression, whereas 14% were classified as exhibiting depressive symptoms. Probable depression and depressive symptoms were more prevalent among elderly individuals with diarrhea (7.2% vs. 11% vs. 19%, p < 0.001). Furthermore, the elderly with constipation were more likely to have depression than those without constipation (6.3% vs. 9.6% vs. 9.9%, p = 0.014). We also observed significant differences based on the genders, races, household incomes, education levels, marital statuses, and alcohol and smoking exposures, as well as comorbidities, such as diabetes, dyslipidemia, renal failure, heart failure, stroke, and liver diseases (p < 0.05).

Table 1

Demographic, socioeconomic, and bowel health characteristics of study participants stratified by PHQ-9 scores
Characteristic	Overall	Patient Health Questionnaire-9 scores, No. (%) of participants
Characteristic	Overall	0–4	5–9	10–27	P Value³
No. of participants	4878 (100%)	3895 (81%)	679 (14%)	304 (5.0%)
Age					0.2
60–69	2,359 (51%)	1,849 (51%)	332 (49%)	178 (58%)
70–79	1,615 (32%)	1,299 (32%)	223 (34%)	93 (30%)
≥ 80	904 (17%)	747 (17%)	124 (17%)	33 (12%)
Sex					< 0.001
Male	2,445 (45%)	2,063 (48%)	266 (33%)	116 (36%)
Female	2,433 (55%)	1,832 (52%)	413 (67%)	188 (64%)
Race and Ethnicity					0.005
Mexican American	672 (4.0%)	498 (3.7%)	107 (4.6%)	67 (8.3%)
Other Hispanic	352 (2.4%)	251 (2.2%)	65 (3.0%)	36 (4.1%)
Non-Hispanic White	2,810 (82%)	2,296 (83%)	376 (80%)	138 (73%)
Non-Hispanic Black	928 (8.5%)	759 (8.4%)	116 (8.5%)	53 (9.8%)
Other Race	116 (3.0%)	91 (2.7%)	15 (3.9%)	10 (4.8%)
Marital Status					< 0.001
Married or living with partner	2,897 (64%)	2,417 (66%)	347 (55%)	133 (51%)
Widowed/Divorced/Separated/Never married	1981 (36%)	1478 (34%)	332 (45%)	171 (49%)
Education Level					< 0.001
< High school	878 (10%)	638 (9.2%)	152 (12%)	88 (19%)
High School	786 (13%)	597 (12%)	127 (18%)	62 (20%)
> High school	3,214 (77%)	2,660 (79%)	400 (69%)	154 (61%)
Family PIR					< 0.001
Poor	677 (7.9%)	469 (6.7%)	126 (11%)	82 (19%)
Not poor	4,201 (92%)	3,426 (93%)	553 (89%)	222 (81%)
BMI					0.001
< 18.5	1,800 (37%)	1,366 (35%)	300 (43%)	134 (46%)
18.5–24.9	1,777 (37%)	1,468 (38%)	207 (33%)	102 (34%)
25.0–29.9	1,154 (25%)	958 (26%)	140 (22%)	56 (19%)
BMI ≥ 30	62 (1.2%)	46 (1.1%)	11 (1.6%)	5 (1.3%)
Smoke					< 0.001
Current Smoker	606 (11%)	433 (9.9%)	101 (16%)	72 (23%)
None Smoker	4272 (89%)	3462 (90.1%)	578 (84%)	232 (77%)
Drink					0.019
Drinking	3,140 (67%)	2,552 (68%)	401 (61%)	187 (64%)
No drinking	1738 (33%)	1343 (32%)	278 (39%)	117 (36%)
History
Diabetes	1,128 (19%)	806 (17%)	208 (25%)	114 (34%)	< 0.001
Hypertension	3,487 (70%)	2,755 (69%)	507 (72%)	225 (75%)	0.14
Hyperlipidemias	2,409 (55%)	1,919 (56%)	321 (51%)	169 (63%)	0.050
Renal failure	222 (3.9%)	145 (3.2%)	51 (6.8%)	26 (6.6%)	< 0.001
Heart failure	343 (6.6%)	233 (5.5%)	68 (9.7%)	42 (16%)	< 0.001
Stroke	401 (7.7%)	278 (6.6%)	83 (12%)	40 (15%)	< 0.001
Liver Diseases	179 (3.4%)	108 (2.9%)	42 (5.0%)	29 (7.9%)	0.002
Cancer	995 (23%)	794 (23%)	143 (24%)	58 (23%)	0.8
Constipation	339 (6.9%)	247 (6.3%)	59 (9.6%)	33 (9.9%)	0.014
Diarrhea	482 (8.3%)	335 (7.2%)	85 (11%)	62 (19%)	< 0.001
BMI, mean (SD)	28.9 (6.1)	28.7 (5.9)	29.7 (6.9)	30.6 (7.1)	< 0.001
WWI, mean (SD)	7.89 (1.11)	7.84 (1.08)	8.04 (1.19)	8.21 (1.20)	< 0.001
Stool Frequency, mean (SD)	9.1 (5.3)	9.1 (5.2)	9.2 (6.2)	9.3 (5.9)	0.7
Depress Score, mean (SD)	2.5 (3.4)	1.1 (1.3)	6.4 (1.4)	13.3 (3.5)	< 0.001
Continuous variables are presented as mean ± standard error (SE); Categorical variables are presented as counts (weighted percentage).
Abbreviation: PIR, poverty income ratio; BMI, body mass index; WWI, weight-adjusted-waist index.

3.2. Association of depression with constipation and diarrhea

Table 2 presents the results of the multivariate logistic regression analysis. A positive correlation was observed between PHQ-9 ≥ 5 and diarrhea (OR = 1.08; 95%CI = 1.02–1.14) in the unadjusted model. After adjusting for age, gender, race, education level, marital status, and household income, the results were still similar (OR = 1.07; 95%CI = 1.00–1.13). Even after a further adjustment for other potential confounding factors, including smoking status, alcohol consumption, and BMI, the positive correlation remained significant (all p = 0.035). Furthermore, PHQ-9 ≥ 5 exhibited a positive correlation with constipation (OR = 1.02; 95%CI = 0.96–1.07), although the result was not statistically significant.

Table 2

Weighted logistic regression analysis models showing the associations between constipation, diarrhea and depression.
Group	Diarrhea			P value	Constipation			P value
Group	Characteristic	OR	95% CI	P value	Characteristic	OR	95% CI	P value
PHQ-9 ≥ 10	Unadjusted	1.08	0.96, 1.22	0.2	Unadjusted	1.00	0.89, 1.13	> 0.9
	Model1	1.07	0.95, 1.20	0.3	Model1	1.01	0.88, 1.16	0.9
	Model2	1.06	0.95, 1.19	0.3	Model2	1.02	0.89, 1.17	0.7
	Model3	1.07	0.93, 1.23	0.3	Model3	0.88	0.72, 1.09	0.2
	Model4	1.08	0.92, 1.28	0.3	Model4	0.92	0.74, 1.14	0.4
PHQ-9 ≥ 5	Unadjusted	1.08	1.02, 1.14	0.012	Unadjusted	1.02	0.96, 1.07	0.5
	Model1	1.07	1.00, 1.13	0.036	Model1	1.02	0.97, 1.08	0.4
	Model2	1.07	1.00, 1.13	0.035	Model2	1.03	0.97, 1.08	0.3
	Model3	1.06	1.00, 1.12	0.056	Model3	0.99	0.93, 1.05	0.6
	Model4	1.05	0.97, 1.12	0.2	Model4	0.98	0.93, 1.04	0.5
OR = Odds Ratio. CI = Confidence Interval. PHQ = Patient Health Questionnaide-9.
Model 1: Adjusted for age, gender, race, marital status, ratio of family income to poverty, and education level.
Model 2: Adjusted for age, gender, race, marital status, ratio of family income to poverty, education level, alcohol consumption and smoking status.
Model 3: Adjusted for age, gender, race, marital status, ratio of family income to poverty, education level, alcohol consumption, smoking status, diabetes, hypertension, hyperlipidemias, renal failure, heart failure, stroke, liver disease, and cancer.
Model 4: Adjusted for age, gender, race, marital status, ratio of family income to poverty, education level, alcohol consumption, smoking status, BMI, WWI, diabetes, hypertension, hyperlipidemias, renal failure, heart failure, stroke, liver disease, and cancer.

Further analysis of the specific symptoms of depression (Model 4) revealed that the elderly with diarrhea exhibited a positive correlation with the expression of reduced interest/pleasure, feeling of downness/hopelessness, trouble sleeping, fatigue, appetite, and self-blame scores (all p < 0.05) compared with the elderly without diarrhea. Similarly, compared with the non-constipation elderly, the constipated ones exhibited a positive correlation with feelings of downness/hopelessness and appetite scores, indicating a positive correlation with the scores of trouble concentrating (p = 0.05, Fig. 2).

3.3. Association between depression and the study variables

Employing subgroup analysis, we assessed the associations of depression with diarrhea and constipation among the elderly. Figures 3 and 4 and Supplementary Tables 1 and 2 reveal that the stratifying factors included age, gender, race, marital status, Family PIR, education level, alcohol consumption, smoking status, BMI, WWI, diabetes, hypertension, hyperlipidemia, renal failure, heart failure, stroke, liver disease, and cancer. The results revealed a significantly positive correlation between diarrhea and the following factors: gender (male, female), age (60–69), nonsmoker status, drinking habit, BMI < 18.5, presence/absence of diabetes, absence of renal failure, absence of a heart failure, and absence of liver disease. Similarly, constipation exhibited a significantly positive correlation with gender (male), age (60–69), nonsmoking status, drinking habit, absence of diabetes but the presence of hypertension and hyperlipidemia, and absence of a renal failure, absence of a heart failure, and absence of a liver disease (all p < 0.05). These findings indicate that the association of diarrhea/constipation with depression among the elderly did not depend on their current smoking and drinking statuses, BMI ≥ 18.5, and presence of a renal, heart, or liver issue (all p > 0.05).

This study was conducted to assess the association of depression with diarrhea and constipation among the elderly. After weighting, 5% of the participants were classified as having probable depression, whereas 14% were classified as exhibiting depressive symptoms. We observed that probable depression and depressive symptoms were more prevalent among elderly individuals with diarrhea or constipation than among those without them. Multiple specific depression symptoms correlated with diarrhea and constipation, and the elderly with diarrhea exhibited significantly positive correlations with reduced interest/pleasure, feeling down/hopeless, trouble sleeping, fatigue, appetite, and self-blame symptoms; those with constipation exhibited significantly positive correlations with feelings down/hopeless, loss of appetite, and trouble-concentrating symptoms. Importantly, our findings indicate that the association of depression with diarrhea and constipation among the elderly was independent of their current smoking status and drinking statuses, BMI, and the presence of renal, heart, or liver issues, as indicated by their p-values of > 0.05. These results provide valuable insights into the factors related to gastrointestinal symptoms and their relationship with depression among the elderly.

The extant studies consistently revealed the significant correlation between late-life depression and a myriad of chronic conditions such as diabetes, hypertension, hyperlipidemia, renal failure, heart failure, stroke, liver diseases, and cancer [31, 32]. Further, the stress associated with physical discomfort increases depression risks, resulting in a significantly higher prevalence of depression among individuals with chronic diseases compared with the general population[33, 34]. Tel et al. demonstrated that the longer the duration of hypertension among the elderly, the more severe their depressive symptoms[35]. Huang et al. identified stroke, heart disease, and chronic lung diseases as risk factors that exacerbate depression among the elderly[36]. Sociodemographic characteristics, including gender, age, household registration type, living arrangement, education level, and marital status were found to be significantly associated with depressive symptoms among the elderly[37, 38]. Studies have also demonstrated that elderly women experience a greater burden of depression than elderly men and older men without spouses are more susceptible to depressive symptoms than their married counterparts[39]. Moreover, Freeman et al. demonstrated that an increase in the socioeconomic status index was associated with a significantly lower probability of depression among the elderly[40]. Depression exacerbates the existing physical conditions and is associated with higher-than-expected mortality and incidence rates[41]. Thus, the effective management of depression among the elderly with chronic diseases is crucial.

Chronic diarrhea, defined as unformed stools lasting over four weeks, is a common symptom among all age groups [16]. A survey of the residents of an elderly community aged 65–93 years in the U.S. revealed an adjusted prevalence rate of chronic diarrhea at 14.2% (95%CI = 10.1–18.2%)[17, 42]. Recent nationwide surveys have reported a prevalence rate of 6.7% (95%CI = 5.8–7.4%) for chronic diarrhea. Additionally, the significantly higher prevalence of chronic diarrhea among individuals aged 70 years or older compared to those in the 20–29 year age group (P = 0.005) suggests that it may be more common among the elderly than in the general population[16]. The prevalence of constipation is 16% among the general adult population[43]. The economic impact of constipation on healthcare costs results in frequent medical visits; its risk factors include medication use (anticholinergic drugs, antidepressants, and opioids), lack of physical activities, low income, depression, and living in nursing homes[13, 29, 44]. Chronic diarrhea and constipation can cause physical discomfort, social difficulties, and reduced life quality, all of which can trigger or worsen depressive symptoms[18, 45, 46].

The extant studies revealed that factors, such as genetics, environment, psychosocial factors, diet, and gastrointestinal inflammation, contribute to the development of gastrointestinal symptoms through mechanisms, such as disrupted gastrointestinal motility, dysbiosis of the gut microbiota, visceral hypersensitivity, and brain–gut axis dysfunction[18, 45, 47, 48]. Numerous clinical studies have demonstrated the association between gastrointestinal symptoms and psychological factors that can affect patients’ digestive systems by influencing visceral sensory and gastric motor functions[49, 50]. The limbic system of the central nervous system participates in bidirectional communication for visceral pain and perception, where external emotional stimuli can influence gastric sensory processing, gastric motility, and secretion functions, and vice versa[51–53]. Furthermore, visceral responses can also affect central sensory emotions and behaviors[54, 55].

Chronic constipation is a prevalent global health challenge, and the process of stool elimination is controlled by complex interactions between the brain–gut axis, intestinal motility, and the function of the pelvic floor muscles and anal sphincters[56]. The multifaceted pathogenesis of chronic constipation involves dynamic interactions between biological and psychosocial factors[29, 57, 58]. Meanwhile, mental disorders might influence constipation. In our study, we observed a significantly positive correlation between patients with chronic constipation and the scores for low mood/despair, appetite, and lack of concentration, indicating that the exacerbation of constipation may reduce productivity and life quality, possibly resulting in depressive symptoms among the elderly. The relationship between depression and chronic diarrhea can be partially explained by the correlation between depression and immune disorders[31]. Studies have revealed a close association between immune system dysregulation and mild depression[59, 60]. Studies have also demonstrated that the excessive production of proinflammatory cytokines can affect brain function and cause mental disorders[61, 62]. Regarding intestinal immune system dysregulation, the stimulation of peripheral antigen-presenting cells can induce the production of various cytokines, such as TNF-α, IL-1β, and IL-6, some of which can cross the blood–brain barrier and activate microglial cells that are involved in the development of depression[63–65]. In this study, we observed a positive correlation between PHQ-9 scores of ≥ 5 and diarrhea. Additionally, patients with chronic diarrhea were more likely to have significant increases in their scores for several subtypes of depressive symptoms (six out of nine). Compared to chronic constipation, diarrhea shows a stronger positive correlation with the “Little interest/pleasure”, “Fatigue”, and “Self-blame” subscales of the PHQ-9. This indicates that the exacerbation of chronic diarrhea is more likely to trigger a diverse range of depressive symptoms. Finally, the high healthcare costs associated with managing chronic diarrhea and constipation among the elderly, along with their comorbidities, also contribute to psychological symptoms[66, 67].

Our analysis was based on a large-scale, nationally representative sample drawn from surveys conducted between 2005 and 2010, and this ensured the reliability of the experimental data. Furthermore, we controlled for several potential confounding factors, including sociodemographic characteristics, medical history, smoking and drinking statuses. However, our study has some limitations. First, owing to the cross-sectional design of the study, we could not establish a causal relationship between depression and chronic constipation or diarrhea. The bowel conditions examined in our study are closely linked to appetite and may overlap with certain components of the "Appetite" subscale of the PHQ-9. This ultimately provides an incomplete reflection of the relationship between patients' bowel movements and depression. Additionally, although we adjusted for potential confounding factors that may influence the results, studies have revealed significant variations in depression scores based on various factors, such as the presence of multiple chronic diseases, different age groups, marital status, educational level, and per capita monthly household income. As older individuals are more likely to suffer from chronic diseases, including multiple comorbidities, there might be other confounding factors that might influence the results of our multiple regression analysis. Despite these limitations, this study is to the best of our knowledge the first to assess the relationship between the PHQ-9 scores and chronic constipation and diarrhea among the elderly, providing valuable insights into the potential associations between these conditions and depression.

In conclusion, this is the first study to assess the relationship between depression and gastrointestinal symptoms (particularly chronic constipation and diarrhea) based on a nationally representative sample of the elderly in the U.S. from 2005 to 2010. We confirmed that the elderly with depressive symptoms (PHQ-9 ≥ 5) were more likely to experience chronic constipation and diarrhea. Moreover, maintaining good gut health is crucial for the elderly, and it is necessary to evaluate the psychological well-being of elderly patients with chronic diarrhea and constipation. However, further studies are required to establish the relationship between gastrointestinal symptoms and depression.

Acknowledgements

This study was supported by the Capital Health Development Scientific Research Special Project (2022-4-5032). The funding agency was not involved in any aspect of the study design, data collection, data analysis, or manuscript writing.

Consent for publication

All authors have agreed on the publication of this manuscript. The authors thank the NCHS for their efforts in creating the data for the NHANES.

Competing interests

The authors declared no conflicts of interest.

Authors' contributions

The study was conceptualized by Zhanqi Tong. Data analysis was conducted by Mingjun Chen. Mingjun Chen wrote the original draft of the manuscript. The manuscript was reviewed and edited by Hengheng Dai and Mingjun Chen.

Availability of data and materials

The publicly available and de-identified data used in this analysis can be accessed from the National Center for Health Statistics (NCHS) at https://wwwn.cdc.gov/nchs/nhanes/Default.aspx.

Ethics statement

The protocol for the NHANES survey was approved by the NCHS Institutional Research Ethics Review Board. Informed consent was obtained from all participants in accordance with the approved protocol.

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No competing interests reported.

SupplementaryTable1andSupplementaryTable2.docx

Chronic constipation and diarrhea are associated with depression in the elderly: Insights from a large cross-sectional study

Status:

Version 1

Abstract

Figures

Translational Significance

1. Introduction

2. Materials and methods

2.1. Study population

2.2. Depression assessment

2.3. Assessments of chronic constipation and diarrhea

2.4. Assessment of the covariates

2.5. Statistical analysis

3. Results

3.1. Baseline characteristics

3.2. Association of depression with constipation and diarrhea

3.3. Association between depression and the study variables

4. Discussion

5. Conclusion

Declarations

References

Additional Declarations

Supplementary Files

Status:

Version 1