Association between gastrointestinal diseases and depression severity among middle-aged and older Chinese women: the mediating effect of sleep duration

Abstract

Introduction

Gastrointestinal diseases and depression represent significant public health burdens among middle-aged and older women. This study investigated the association between gastrointestinal diseases and depression severity in Chinese women aged ≥ 45 years, and examined sleep duration as a potential mediator.

Methods

We performed a cross-sectional analysis of 6,433 women (aged ≥ 45) from the CHARLS database. Multivariable logistic regression evaluated the association between depression severity and gastrointestinal diseases, adjusting for confounders. Restricted cubic spline (RCS) models assessed nonlinear trends. Additionally, correlation and subgroup analyses were conducted to evaluate the consistency of this relationship across different population strata. Mediation analysis with nonparametric bootstrapping quantified sleep duration’s indirect effect.

Results

Among these women, the prevalence of gastrointestinal diseases was 24.8%, and that of depression was 43.7%. Both depression severity and reduced sleep duration showed significant associations with gastrointestinal diseases (p < 0.001). Each interquartile-range increase in depression score linked to an 11% higher risk of gastrointestinal diseases (OR: 1.11, 95% CI: 1.09–1.13). RCS analysis demonstrated a nonlinear relationship (p for non-linearity = 0.02), with risk accelerating when depression scores exceeded 8. Participants with scores of 20 had a 2.76-fold higher risk compared to those with scores of 9 (95% CI: 2.16–3.64). Sleep duration mediated 9.81% of the total association (p < 0.001).

Conclusion

Our findings indicate a positive association between depression severity and gastrointestinal diseases, while sleep duration exhibited a negative association in this population. Moreover, sleep duration played a mediating role in the relationship between depression and gastrointestinal diseases.

Clinical trial number

Not applicable.

Introduction

The digestive system is a crucial organ system in the human body, primarily responsible for digestion and nutrient absorption [1]. Gastrointestinal diseases include a variety of disorders affecting the digestive tract, such as gastroesophageal reflux disease (GERD), chronic gastritis, peptic ulcer, inflammatory bowel disease (IBD), and functional gastrointestinal disorders (FGIDs). Globally, gastrointestinal diseases impose a substantial morbidity burden, accounting for 18.2% of all disease incidence [2]. In China, the burden is similarly high and increasing, with approximately one-third of the population affected by common chronic gastrointestinal diseases, leading to recurrent symptoms, reduced quality of life, and increased health-care utilization [3, 4]. The etiology of gastrointestinal diseases involves a broad spectrum of factors, including genetics, environment, diet, pharmaceuticals, infections, obesity, gut microbiota, and psychological elements [5–7]. Previous studies have extensively characterized genetic contributions, especially in GERD and IBD [8, 9], and gut microbiota has more recently become a central research focus [10]. Accumulating evidence demonstrates that enhancing psychological well-being is crucial for the effective management and recovery of these conditions [11, 12]. The influence of psychosocial factors, particularly depression with its increasing prevalence, on gastrointestinal diseases merits further investigation.

Depression has been receiving increasing attention, with a global prevalence of around 30%. The first peak of onset occurs at the age of 20, and the second peak occurs at the age of 50. More than 50% of suicides are associated with depression [13, 14]. Numerous studies indicate that women have about double the risk of depression compared to men. Current research suggests that estrogen and progesterone may play important roles in this phenomenon [15]. The link between gastrointestinal diseases and depression has attracted growing attention from scholars. The overall depression rate among patients with gastrointestinal diseases is about 30%, and the depression rate significantly increases in individuals over the age of 70 [16]. Two Mendelian randomisation studies indicate that depression increases the risk of developing gastrointestinal diseases [17, 18]. Another meta-analysis demonstrated that patients with irritable bowel syndrome (IBS) had a threefold increase in the probability of depression compared to healthy subjects [19]. According to a systematic review, certain pro-inflammatory gut bacteria are implicated in the pathogenesis of anxiety and depression [20]. Multiple genetic studies have demonstrated a shared genetic architecture between depression and gastrointestinal diseases [21, 22].

Sleep plays an essential role in maintaining both physical and mental health [23]. Sleep disorders have a multifactorial etiology involving genetic, environmental, behavioral, and physiological factors [24]. A report from a gastroenterology clinic indicates that nearly all gastrointestinal diseases elevate the prevalence of sleep disturbances, with 72% of IBS patients affected [25]. Separately, a study involving 3,228 respondents demonstrated that 874 individuals (27%) reported sleep difficulties, and a significant correlation was observed between sleep patterns and gastrointestinal symptoms [26]. In an animal study, sleep deprivation was shown to induce intestinal barrier dysfunction by inhibiting melatonin production and activating the NF-κB pathway via oxidative stress [27]. Therefore, to reduce the risk of gastrointestinal diseases, particularly among middle-aged and older female patients, it is essential to understand the relationship between gastrointestinal diseases and depression and to examine whether sleep acts as a mediating factor.

Currently, there is a scarcity of research utilizing national databases to investigate the relationships between depression and gastrointestinal diseases and between sleep duration and gastrointestinal diseases. Furthermore, previous studies have typically reported these associations separately, while neglecting the mediating role of sleep duration in the relationship between depression and gastrointestinal diseases. Most previous studies investigating the relationship between depressive symptoms and diseases have treated depressive symptoms as categorical variables—classifying them into mild, moderate, and severe—assuming that a certain range of depressive severity indicates the same level of severity [28]. However, our study does not rely on such categorical classifications; instead, it uses depressive scores as a continuous variable to emphasise the association between depression and diseases. Therefore, this study explores the association between gastrointestinal diseases and depression severity in middle-aged and older Chinese women using cross-sectional data, and examines whether sleep duration mediates this relationship. Specifically, we hypothesized that depression severity is associated with an increased prevalence of gastrointestinal diseases, and that sleep duration serves as a crucial mediator in this complex pathway.

Method

Study population

The China Health and Retirement Longitudinal Study (CHARLS) is a nationally representative survey comprising individuals aged 45 years and older from randomly selected households. It collects comprehensive data on social, economic, and health conditions from participating communities. After approval by the Peking University Institutional Review Board (IRB00001052-11015), all participants provided written informed consent and agreed to data sharing, having been fully informed of study-related risks and benefits. This study was conducted in accordance with the Declaration of Helsinki.

CHARLS initially recruited 17,705 participants in 2011. After systematic exclusions detailed in Fig. 1, male participants (n = 8,483) were excluded. Missing data were assessed prior to analysis, and a complete case analysis approach was adopted; participants with missing data on key variables were excluded, including age (n = 12), marital status (n = 7), smoking/alcohol status (n = 67), sleep duration (n = 629), depression (n = 514), and gastrointestinal disease data (n = 24). In addition, participants with BMI outliers (n = 1,301) and those aged under 45 years (n = 235) were excluded. The final analytical cohort comprised 6,433 middle-aged and older Chinese women.

Fig. 1.

Participant selection flowchart. Abbreviation: BMI, body mass index

Assessment of depressive symptoms

The CHARLS assesses depressive symptoms using the Center for Epidemiologic Studies Depression Scale (CES-D), a widely validated instrument for assessing depressive symptoms in Chinese populations [29]. For each of its 10 items, the CES-D scale assigns scores from 0 to 3 based on symptom frequency: 0 (rarely; < 1 day/week), 1 (sometimes; 1–2 days/week), 2 (occasionally; 3–4 days/week), and 3 (frequently; 5–7 days/week). After the scores of items 5 and 8 were reversed, total scores (range: 0–30) were calculated, with higher scores indicating more severe depression. In line with previous studies, this research used a cutoff score of 10 to define depression status, with scores ≥ 10 indicating clinically significant depression [30].

Previous studies typically categorized depression as binary (present/absent) or three-tiered classifications (mild/moderate/severe), implicitly assuming uniform severity within each category [31, 32]. However, the relationship between depressive severity and gastrointestinal diseases remains unclear. Our analysis uses CES-D scores as continuous variables to examine this association directly.

Assessment of gastrointestinal diseases

Gastrointestinal diseases status was determined from participants’ responses to the survey question: “Have you been diagnosed with stomach or other digestive diseases (excluding tumors or cancers) by a doctor?” Gastrointestinal diseases were defined to include disorders of the oesophagus, stomach, small intestine, and colon. Participants reporting “yes” were classified as having gastrointestinal diseases, whereas those responding “no” were considered free of these conditions.

Assessment of sleep duration

Sleep duration was assessed based on participants’ responses to the survey question: “During the past month, how many hours of actual sleep did you get at night (average hours for one night)? (This may be shorter than the number of hours you spend in bed.)” Reported number of hours was recorded for each participant. In the primary analyses, sleep duration was treated as a continuous variable to preserve data variability and maximize statistical power. To rigorously evaluate potential threshold effects, it was dichotomized (< 7 and ≥ 7 h) in the stratified subgroup analyses.

Covariates

Additional covariates included in this study encompassed demographic characteristics, health behaviors, physiological parameters, and chronic conditions. Demographic variables included age, education level (junior high school and below, high school, or college and above), marital status (married or unmarried), and residence before age 16 (urban or rural). Health behaviors included smoking status (yes or no) and alcohol consumption frequency (> 1/month, < 1/month, or never). Physiological measures were obtained through standardized protocols: blood pressure (mean of three consecutive systolic/diastolic readings after 5-minute rest), waist circumference (measured horizontally at umbilical level during end-exhalation using a non-elastic tape), grip strength (average of four measurements from bilateral trials), and body mass index (BMI). BMI was calculated as weight (kg) divided by height squared (m²). Implausible values of height (< 80 or > 200 cm) and weight (< 25 or > 150 kg), identified based on data distribution and biologically plausible ranges, were excluded prior to BMI calculation. Self-reported physician-diagnosed chronic conditions included diabetes, hypertension, dyslipidemia, and cardiovascular disease.

Statistical analysis

The following statistical approaches were employed to examine the associations between depression, sleep duration, and gastrointestinal diseases. First, baseline characteristics were compared between participants with and without gastrointestinal diseases. Continuous variables were expressed as mean ± standard deviation or median (interquartile range), all rounded to one decimal place, while categorical variables were summarized as frequencies (percentages), with percentages also rounded to one decimal place. Group comparisons were performed using one-way ANOVA or Kruskal-Wallis tests for continuous variables and chi-square tests for categorical variables. Second, logistic regression models were utilized to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for gastrointestinal disease risk. Specifically, three models were constructed to evaluate the relationship between depression severity—analyzed both as a continuous variable (per Interquartile Range (IQR) increase) and in quartiles—and gastrointestinal diseases: Model 1 was unadjusted; Model 2 adjusted for age, education, residence, and marital status; and Model 3 further adjusted for smoking, alcohol use, hypertension, dyslipidemia, cardiovascular diseases, BMI, and grip strength. Additionally, RCS models were fitted to assess potential nonlinear relationships between depression and gastrointestinal diseases. Third, stratified analyses were conducted to evaluate the consistency of these associations across subgroups defined by age, marital status, education, residence, smoking/alcohol status, and sleep duration. Finally, mediation analysis was performed using Baron and Kenny’s causal steps approach, supplemented by nonparametric bootstrap sampling with 1000 iterations to test the mediating effect of sleep duration and estimate its magnitude with 95% CIs. All models were adjusted for age, residence, marital status, alcohol consumption, smoking, and education level to enhance the robustness of the findings. All analyses were conducted using R version 4.4.1, and p < 0.05 was considered statistically significant.

Results

Baseline characteristics

A total of 6,433 participants were included in the cross-sectional analysis. As summarized in Table 1, the median age was 58 years with IQR spanning 51 to 65 years, reflecting the target demographic of perimenopausal and postmenopausal women. Geographically, 91.3% (n = 5,872) resided in rural villages while only 8.7% (n = 559) lived in urban areas. Educational attainment was predominantly low, with 92.1% (n = 5,928) having junior high school education or below, and merely 1.1% (n = 69) holding college degrees.

Table 1.

Characteristics of the participants at baseline (n = 6,433)

Variable	Overall	Without gastrointestinal diseases	With gastrointestinal diseases	p
	n = 6,433	n = 4,836	n = 1,597
Age	58.0 [51.0, 65.0]	58.0 [51.0, 65.0]	58.0 [51.0, 64.0]	0.339
Education				0.018
College or above	69 (1.1)	60 (1.2)	94 (5.9)
High shcool	436 (6.8)	342 (7.1)	94 (5.9)
Junior high school and below	5,928 (92.1)	4,434 (91.7)	1,494 (93.6)
Marital				0.552
Married	5,084 (79.0)	3,813 (78.8)	1,271 (79.6)
Unmarried	1,349 (21.0)	1,023 (21.2)	326 (20.4)
Location				0.142
City	559 (8.7)	435 (9.0)	124 (7.8)
Village	5,872 (91.3)	4,399 (91.0)	1,473 (92.2)
Smoking				0.780
No	5,878 (91.4)	4,422 (91.4)	1,456 (91.2)
Yes	555 (8.6)	414 (8.6)	141 (8.8)
Drinking				0.763
Drink but less than once a month	336 (5.2)	247 (5.1)	89 (5.6)
Drink more than once a month	441 (6.9)	333 (6.9)	108 (6.8)
None of these	5,656 (87.9)	4,256 (88.0)	1,400 (87.7)
Sleep duration	6.0 [5.0, 8.0]	7.0 [5.0, 8.0]	6.0 [4.0, 7.0]	< 0.001
SBP	127.0 [114.3, 143.3]	127.7 [115.0, 144.0]	124.7 [111.7, 140.7]	< 0.001
DBP	74.3 [67.3, 83.0]	74.7 [67.7, 83.7]	73.3 [66.3, 81.7]	< 0.001
Grip	24.3 [19.6, 28.8]	24.5 [19.6, 29.0]	24.0 [19.5, 28.3]	0.025
BMI	23.7 [21.3, 26.4]	23.8 [21.4, 26.5]	23.4 [20.7, 25.9]	< 0.001
WC	85.2 [78.0, 92.3]	86.0 [78.4, 93.0]	84.1 [76.6, 91.1]	< 0.001
Diabetes				0.937
No	5,958 (93.4)	4,486 (93.4)	1,472 (93.5)
Yes	422 (6.6)	319 (6.6)	103 (6.5)
Hypertension				0.344
No	4,737 (74.0)	3,552 (73.7)	1,185 (75.0)
Yes	1,663 (26.0)	1,267 (26.3)	396 (25.0)
Dyslipidemia				0.002
No	5,691 (90.2)	4,321 (90.9)	1,370 (88.2)
Yes	619 (9.8)	435 (9.1)	184 (11.8)
Heart diseases				< 0.001
No	5,430 (84.8)	4,182 (86.7)	1,248 (78.7)
Yes	976 (15.2)	639 (13.3)	337 (21.3)
Depression	8.0 [4.0, 14.0]	7.0 [4.0, 12.0]	11.0 [6.0, 16.0]	< 0.001
Quartiles of depression				< 0.001
Q1	1,776 (27.6)	1,510 (31.2)	266 (16.7)
Q2	1,481 (23.0)	1,174 (24.3)	307 (19.2)
Q3	1,763 (27.4)	1,280 (26.5)	483 (30.2)
Q4	1,413 (22.0)	872 (18.0)	541 (33.9)

Data are shown as median (interquartile range), or numbers (percentages)

Abbreviation: SBP, systolic blood pressure; DBP, diastolic blood pressure; BMI, body mass index; WC, waist circumference

Gastrointestinal diseases were confirmed in 1,597/6,433 participants (24.8%). Using the CES-D with a cutoff score of ≥ 10, 2,810/6,433 (43.7%) middle-aged and older female participants were identified with significant depression. Of those with gastrointestinal diseases, 931/1,597 (58.3%) individuals had depression. Compared to individuals without gastrointestinal diseases, gastrointestinal diseases group showed statistically significant differences across multiple domains. Most notably, the gastrointestinal diseases group showed substantially higher depression scores (median 11.0, IQR 6.0–16.0 vs. 7.0, IQR 4.0–12.0; p < 0.001) and shorter median sleep duration (median 6.0 h, IQR 4.0–7.0 vs. 7.0 h, IQR 5.0–8.0; p < 0.001). In the gastrointestinal disease group, the values of these covariates all showed a certain degree of reduction: systolic blood pressure (median 124.7 mmHg, IQR 111.7-140.7 vs. 127.7 mmHg, IQR 115.0-144.0), diastolic blood pressure (median 73.3 mmHg, IQR 66.3–81.7 vs. 74.7 mmHg, IQR 67.7–83.7), grip strength (median 24.0 kg, IQR 19.5–28.3 vs. 24.5 kg, IQR 19.6–29.0), body mass index (median 23.4, IQR 20.7–25.9 vs. 23.8 kg/m², IQR 21.4–26.5), and waist circumference (median 84.1 cm, IQR 76.6–91.1 vs. 86.0 cm, IQR 78.4–93.0) (all p < 0.05). Regarding comorbidities, both dyslipidemia and cardiovascular diseases showed significantly higher prevalence rates (dyslipidemia: 11.8% [184/1,597] vs. 9.1% [435/4,836], p = 0.002; cardiovascular diseases: 21.3% [337/1,597] vs. 13.3% [639/4,836], p < 0.001).

Dose–response relationship between depression and gastrointestinal diseases

Multivariable logistic regression analyses, employing three sequential adjustment models, consistently showed a graded exposure-response relationship between depression severity and gastrointestinal disease risk. As presented in Table 2, after comprehensive adjustment for age, education, residence, marital status, smoking, alcohol consumption, hypertension, dyslipidemia, cardiovascular diseases, BMI, and grip strength (Model 3), each IQR increase in CES-D score significantly increased gastrointestinal disease risk by 11% (OR: 1.11, 95% CI: 1.09–1.13; p < 0.001). When examining depression severity categorically by quartiles, participants in the highest quartile (Q4) showed 21% greater odds of gastrointestinal diseases compared to the reference quartile (Q1) (OR: 1.21, 95% CI: 1.17–1.25; p < 0.001), with statistically significant trend across increasing quartiles (p for trend < 0.001). Gastrointestinal diseases showed a negative correlation with sleep duration (OR: 0.98, 95% CI: 0.98–0.99; p < 0.001).

Table 2.

Association of depression with the risk of gastrointestinal diseases

	Model1	p	Model2	p	Model3	p
Depression per IQR	1.14 [1.12, 1.16]	< 0.001	1.14 [1.12,1.16]	< 0.001	1.11 [1.09,1.13]	< 0.001
Quartiles of depression
Q1	Ref		Ref		Ref
Q2	1.06 [1.03,1.09]	< 0.001	1.06 [1.03,1.09]	< 0.001	1.05 [1.02, 1.08]	< 0.001
Q3	1.13 [1.10, 1.16]	< 0.001	1.14 [1.10, 1.17]	< 0.001	1.11 [1.08, 1.14]	< 0.001
Q4	1.26 [1.22, 1.30]	< 0.001	1.27 [1.23, 1.31]	< 0.001	1.21 [1.17, 1.25]	< 0.001
p for trend	< 0.001		< 0.001		< 0.001
Sleeping duration	0.97 [0.97, 0.98]	< 0.001	0.98 [0.98, 0.99]	< 0.001	0.98 [0.98, 0.99]	< 0.001

a Model 1 was unadjusted

b Model 2 was adjusted for age, education, residence, and marital status

c Model 3 was adjusted for smoking, alcohol use, hypertension, dyslipidemia, cardiovascular diseases, BMI, and grip strength

Figure 2 shows the dose-response relationship between depression severity and gastrointestinal disease risk. RCS analysis revealed a nonlinear association (p_nonlinear = 0.02), with the risk of gastrointestinal diseases increasing progressively and accelerating at higher depression scores. The odds ratio exceeded 1 when depression scores surpassed 8. Notably, participants with a score of 20 exhibited 2.76-fold higher odds of gastrointestinal diseases compared to those with a score of 9 (OR: 2.76, 95% CI: 2.16–3.64). This represents a 176% excess risk for severely depressed individuals relative to the near-threshold reference group.”

Fig. 2.

Restricted cubic spline of the association between depression with the risk of gastrointestinal diseases. The p-value for the nonlinear relationship is 0.02. The curve illustrates the nonlinear relationship between gastrointestinal diseases and depression

Subgroup analysis

To determine whether the association between depression severity and gastrointestinal disease risk varied across subgroups stratified by age, marital status, education level, residence, smoking/alcohol use, and sleep duration, subgroup analyses were conducted as illustrated in Fig. 3. The analysis showed consistent effects of depression severity on gastrointestinal disease risk across all subgroups (all p > 0.05). A significant association between gastrointestinal diseases and depression was observed in all subgroups except among university-educated individuals. In this subgroup, an exception was found, with a non-significant association (OR: 0.94, 95% CI: 0.78–1.13), indicating a weak relationship between depression and gastrointestinal disease in this population. Given the small sample size (n = 69), larger-scale studies are warranted to verify this association.

Fig. 3.

Forest plot of stratified analysis of the association of depression with the risk of gastrointestinal diseases. The forest plot shows the OR values and 95% CI for the correlations between gastrointestinal diseases and depression, based on stratified subgroup analyses of age, residence, marital status, educational level, smoking status, drinking status, and sleep duration

The mediating effect of sleep duration on the relationship between gastrointestinal diseases and depression degree

A correlation analysis was performed (Table 3). Sleep duration showed a negative correlation with gastrointestinal diseases (r = -0.12, p < 0.001) and with depression (r = -0.31, p < 0.001), whereas a positive correlation was observed between depression and gastrointestinal diseases (r = 0.20, p < 0.001). We conducted additional mediation analysis. Mediation analysis (Fig. 4) showed that sleep duration played a significant mediating role in the association between depression severity and gastrointestinal diseases. After adjusting for covariates (age, education level, marital status, and residence), the direct effect of depression on gastrointestinal diseases was 0.0121 (95% CI: 0.0104, 0.0138; p < 0.001), and the indirect effect through sleep duration was 0.0013 (95% CI: 0.0008, 0.0019; p < 0.001). The proportion of the effect mediated by sleep duration was 9.81%. These results indicate that nearly one-tenth of the association between depression and gastrointestinal pathology is mediated through the mechanism of sleep deficiency.

Table 3.

Associations between depression and gastrointestinal diseases and between sleep duration and gastrointestinal diseases

Variables	gastrointestinal disease	Depression	Sleep duration
gastrointestinal disease	1
Depression	0.198***	1
Sleep duration	-0.117***	-0.307***	1

*** p < 0.001

Fig. 4.

Model of the mediating role of sleep duration between depression and gastrointestinal diseases. Model control for age, residence, marital status, educational level, smoking status, drinking status. ***p < 0.001

Discussion

This cross-sectional analysis, utilizing data from the CHARLS database, investigated the association between depression and the prevalence of gastrointestinal diseases among middle-aged and older women, along with the mediating role of sleep. Our results demonstrated that depression levels were positively associated with gastrointestinal disease prevalence, and this relationship was partially mediated by sleep duration, which is consistent with our initial hypothesis. To our knowledge, this represents the first large-scale database study examining the mediating effect of sleep in the depression-gastrointestinal disease relationship in middle-aged and older women. We also identified a nonlinear relationship between depression severity and gastrointestinal diseases, with an accelerated increase in disease risk at higher depression scores. By focusing on middle-aged and older Chinese women in a nationally representative cohort, this study extends prior work by identifying sleep duration as a modifiable pathway linking depression with gastrointestinal diseases.

Numerous studies have consistently demonstrated a significant association between depression and an elevated risk of gastrointestinal diseases. In a U.S. primary care cohort, the prevalence of major depression was five times higher in individuals with gastrointestinal symptoms than in asymptomatic controls [33]. Approximately one-third of patients with GERD experience comorbid anxiety and depression, suggesting potential bidirectional causality between these conditions. Older patients with peptic ulcers exhibit a 4.35-fold increased risk of depression compared to those without ulcers [34]. Multiple studies indicate a bidirectional causal relationship between IBD and depression: IBD progression exacerbates depressive symptoms, while depression increases susceptibility to IBD onset [35–37]. Notably, some evidence suggests that depressive manifestations may represent phenotypic expressions of early clinical symptoms of IBD. Our findings corroborate this significant association. In terms of mechanisms, these two-way connections are mainly driven by the microbiota-gut-brain axis. First, depression disrupts this axis from the top down, causing the sympathoadrenal system to become overactive. This causes abnormal increases in gastrointestinal inflammatory cells, mucosal barrier damage, heightened susceptibility to Helicobacter pylori, and neuroendocrine dysfunction. These changes impair digestive and gastric-emptying functions, contributing to various gastrointestinal diseases [38–43]. Second, the relationship between depression and the gut microbiota has received growing attention. Depression can induce gut microbiota dysbiosis, which in turn promotes various gastrointestinal diseases. Additionally, H. pylori infection impairs the absorption of iron and folic acid; these deficiencies may be linked to altered brain function and the development of depression [40, 44]. Third, individuals with depression are more prone to health-risk behaviors such as smoking and excessive alcohol consumption, both of which are established risk factors for peptic ulcers and other gastrointestinal diseases [42]. In a study of shared genetic risk factors for depression and gastrointestinal diseases, potential risk genes common to both conditions were also identified [22].

Extensive evidence links sleep disturbances to various gastrointestinal diseases, including Crohn’s disease, IBS, GERD, and peptic ulcers, often exacerbating both somatic pain and psychological distress [45–48]. Our findings demonstrate an inverse relationship between sleep duration and gastrointestinal diseases, which aligns with previous studies. Furthermore, our research establishes sleep duration as a mediating factor between gastrointestinal diseases and depressive symptoms, providing novel insights into this field of research. To explain this mediation at the neuropsychiatric and biological levels, circadian rhythm disruption is pivotal. First, sleep deprivation suppresses melatonin, a neurohormone that protects the intestinal mucosa and exerts potent anti-inflammatory effects; its depletion directly exacerbates both depressive mood and gastrointestinal vulnerability [49]. For example, an in vivo murine model demonstrated that sleep deprivation severely degrades colonic tight junctions and triggers depression-like phenotypes, both of which are completely rescued by targeted exogenous melatonin administration [27]. Secondly, sleep disruption can trigger systemic inflammatory responses and intestinal dysbiosis. Studies using sleep-fragmented animal models have demonstrated alterations in the intestinal microbiota, including increased abundance of enterotoxic Clostridium, accompanied by elevated levels of pro-inflammatory cytokines IL-1α and IL-6 [50, 51]. These changes compromise the mucosal barrier, promoting the translocation of microbial enterotoxins into the systemic circulation. Crucially, this circulating inflammation can cross the blood-brain barrier, driving neuropsychiatric depressive symptoms while simultaneously sustaining localized intestinal pathology [52].

This study focuses on the relationship between gastrointestinal diseases and depression in older female patients, a demographic with twice the depression risk of men [53], peaking during perimenopause [54], and higher rates of sleep disturbances and gastrointestinal diseases [55]. To explain this pronounced comorbidity, emerging evidence highlights the unique mechanisms of the gut-brain axis in this population. From a geriatric perspective, gut–brain axis dysregulation may result from the combined effects of age-related chronic inflammation and depression-associated neuroinflammation [56]. In middle-aged and older women, the postmenopausal decline of protective sex hormones may further exacerbate this inflammatory imbalance. Several studies report that inflammatory markers such as IL-6 and CRP are significantly elevated in women with depression compared with healthy controls, whereas similar associations are not consistently observed in men [57]. IL-6 has been linked to somatic symptoms such as fatigue [58], while CRP correlates with anhedonia and suicidal ideation [59]. Conversely, IL-8 levels have been reported to be reduced in depressed women, possibly reflecting the loss of its neuroprotective and neurotrophic effects [60, 61]. Hormonal regulation may partially underlie these sex-specific inflammatory differences. Estradiol exerts protective effects against depression and modulates immune responses, whereas its sharp decline after menopause may exacerbate inflammatory dysregulation [62]. In contrast, testosterone levels in men remain relatively stable across aging, potentially maintaining a degree of neuroprotective and immunomodulatory regulation [63]. Together, these inflammatory and hormone-related mechanisms may contribute to gut–brain axis dysregulation and help explain why depression-related gastrointestinal symptoms are more prevalent in middle-aged and older women. This contributes to increased disease burden associated with depression and adversely affects the lives of middle-aged and older women [64].

These findings suggest that middle-aged and older women represent a priority population for early screening and targeted intervention. We therefore recommend incorporating the CES-D short form and routine sleep assessment into primary care physical examinations for middle-aged and older women, particularly those presenting with gastrointestinal symptoms. Early identification of depressive symptoms and sleep disturbances may facilitate timely intervention and reduce the risk of gastrointestinal morbidity. More broadly, these results support the development of comorbidity management and integrated care models that address psychological, sleep, and gastrointestinal health in a coordinated manner, thereby improving overall quality of life in this population.

This study has several strengths. First, we used data from the CHARLS database, a large and nationally representative cohort in China. This improves the generalizability of our findings to middle-aged and older Chinese women. Second, this study examines the relationship between depression and gastrointestinal diseases within the framework of the gut–brain axis. Mediation analysis further explored the role of sleep duration as a potential link between psychological symptoms and gastrointestinal conditions. This finding provides additional evidence for the gut–brain axis pathway. Third, RCS models were used to assess the nonlinear association between depression severity and gastrointestinal diseases. This approach allowed a clearer characterization of the dose–response relationship and potential risk thresholds. Finally, all analyses were adjusted for multiple confounders and stratified by key covariates, which improves the robustness and reliability of the results.

However, several limitations should be considered. First, gastrointestinal diseases were assessed using a single self-reported question. This approach may introduce recall bias and does not capture the heterogeneity of specific conditions (e.g., GERD or IBD). Future studies should incorporate objective clinical diagnoses or electronic medical records for validation. Second, the sample mainly consisted of individuals with relatively low educational attainment and rural residence in early life. While this reflects the historical demographic characteristics of this generation in China, it may limit generalizability to more urban or highly educated populations. Therefore, the findings for the small college-educated subgroup (n = 69) should be interpreted as exploratory. Future studies should validate these findings in more diverse populations, particularly in urban settings and among individuals with higher educational attainment. Third, the mediated proportion of sleep duration was modest (9.81%), suggesting that the relationship between depression and gastrointestinal diseases is multifactorial. Furthermore, the information regarding the use of antidepressant drugs in the CHARLS database is not detailed enough, and therefore could not be accounted for. This might imply the presence of potential confounding factors related to drug use. Future studies should apply multi-mediator models that include other potential factors, such as systemic inflammation, health behaviors, and medication use. Finally, the cross-sectional design does not allow clear conclusions about temporal relationships. The identified mediating pathway should therefore be interpreted as a statistical association rather than a causal mechanism. Future longitudinal studies and mechanistic investigations involving inflammatory biomarkers and gut microbiota are needed to clarify causality and further elucidate the biological mechanisms of the gut–brain axis.

Conclusions

This cross-sectional study utilizing the CHARLS database demonstrated that depression constitutes a significant risk factor for gastrointestinal diseases among middle-aged and older Chinese women, with sleep duration exhibiting a partial mediating effect. These findings suggest that maintaining psychological and sleep health may represent a viable approach to preventing gastrointestinal diseases in this population. Thus, healthcare institutions—particularly community-based primary care centers—should implement systematic mental health and sleep screening for middle-aged and older women, coupled with early intervention strategies for detected issues, as this may serve as an important measure for reducing the burden of gastrointestinal diseases.

Author contributions

Z. Liu. and X. Sun. incubate and design experiments. Z. Liu. and J. Su. collect data. Z. Liu., Y. Zhang., J. Su., contributed to analysis and interpretation of data. Z. Liu. and Y. Zhang. grafted the manuscript. X. Sun., Q. Han., and X. Pan. revised the manuscript. X. Sun. accesses to research funding. All authors agree to be fully accountable for ensuring the integrity and accuracy of the work, and read and approved the final manuscript. The corresponding author had full access to all data in the study and assumed final responsibility for the decision to submit the manuscript for publication.

Funding

This work was supported by the National Natural Science Foundation of China (No. 82374251); 2023 Shanghai Health Leading Talent Plan (No. 2022LJ013); Discipline construction project of Pudong New Area Health Commission (No. PWZxq2022–04); The Leading Project of Shanghai’s Oriental Talent Program in 2023; 2022 High-level key discipline Construction Project of Traditional Chinese Medicine of the National Administration of Traditional Chinese Medicine (No. zyyzdxk-2023060).

Data availability

The data used in this study was obtained from the CHARLS database. More data can be obtained from the official website of the CHARLS database. (https://charls.pku.edu.cn/).

Declarations

Ethics approval and consent to participate

The CHARLS database has been approved by the Institutional Review Board of Peking University (IRB00001052-11015). All participants provided written informed consent and agreed to data sharing after being fully informed of the study-related risks and benefits.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.