Abstract
Objectives
Depression is a common disease of elderly population, with a global prevalence of more than 20%. Few studies have involved the associations of constipation and overeating with depression, especially in the elderly population. We aimed to address these associations in Chinese oldest-old and centenarians.
Methods
A total of 1863 elderly individuals from 18 regions of Hainan, China, were investigated from July 2014 to December 2016. Health survey, physical examination, and blood analyses were performed through structured questionnaires and standard procedures. The Geriatric Depression Scale (GDS-15) was used to measure depression.
Results
The proportions of elderly individuals with depression, constipation, and overeating were 20.80% (349), 15.14% (254), and 26.52% (445), respectively. The prevalence of constipation and overeating was significantly higher in the elderly group with depression than in those without depression (P < 0.05, all). In the multiple linear regression analyses, higher prevalence of constipation and overeating had positive and significant associations with the GDS-15 (P < 0.05, all). In the multiple logistic regression analyses, constipation (odds ratio [OR]: 2.328; 95% confidence interval [CI]: 1.540–3.521) and overeating (OR: 2.735; 95% CI: 1.920–3.898) had positive and significant associations with depression (P < 0.05, in all).
Conclusions and Implications
This study provides epidemiological evidence that constipation and overeating have positive associations with depression in Chinese oldest-old and centenarians. The interventions for constipation and overeating should be improved to promote prevention and treatment for depression and achieve successful aging and healthy longevity.
Keywords: Centenarians, Constipation, Depression, Oldest-old, Overeating
Centenarians; Constipation; Depression; Oldest-old; Overeating.
1. Introduction
Depression is a common disease of elderly population, with a global prevalence of more than 20% [1, 2]. It is closely related to the decline in cognitive function and life quality in the elderly population. In severe cases, it can lead to suicidal behavior; thus, its prevention is important. Depression is not an inevitable manifestation of aging, but most studies have shown that age and sex (female) is an important risk factor for depression [3, 4]. More importantly, age-related life factors such as living alone, pain, visual impairment, and auditory impairment will further increase the probability of depression in the elderly population [5, 6, 7, 8, 9, 10]. Additionally, improper or long-term use of drugs, such as proton-pump inhibitors, may lead to neuropsychological side effects and promote the development of depression [11, 12]. Previous study has also shown that concomitant use of benzodiazepines with antipsychotics increases the risk of neurological dysfunction in older people [13]. The current risk factors that were discovered can improve our ability to identify older people who are at higher risk of depression, but they are still not comprehensive.
Recently, with the continuous exploration of the gut-brain axis, people have gradually realized close relationships between the intestinal and central nervous system and discovered that normal activities of the intestine play a vital role in the neuroactive potential [14]. Conversely, constipation caused by abnormal gut movements can change the structure of intestinal microbiota, such as bifidobacteria and lactobacilli [15], and induce central nervous system diseases by influencing neurogenesis, α-synuclein, neurotransmitter content, antioxidant defense, and immune regulation [16, 17]. Numerous clinical studies have shown that constipation and overeating are closely related to the occurrence of central neuropathy, and it is a risk factor for Parkinson's and Alzheimer's diseases [18, 19]. However, the clinical research on depression is relatively insufficient compared with the aforementioned diseases. Studies have shown that constipation and overeating are more common in depressed individuals than in non-depressed individuals [20], but there is no clear conclusion on the associations of constipation and overeating with depression, especially in the elderly population.
Therefore, based on the China Hainan Centenarian Cohort Study, the current study aimed to address the associations of constipation and overeating with depression in Chinese oldest-old and centenarians to provide a reference for the prevention and treatment of depression.
2. Material and methods
2.1. Study design and population
According to the age information provided by the Civil Affairs Department of Hainan, the structured questionnaires of 1863 elderly individuals from 18 regions of Hainan, China, were investigated from June 2014 to December 2016. Physical examination and blood analyses were performed through the standard procedures. The research designation and investigation methods have been described in a previous article [21]. Excluding those with incomplete data, 1678 older people were eventually included in the study. All participants provided informed consent, and the protocol (no. 301HNLL-2016-01) was approved by the local ethics committee.
2.2. Depression and overeating
The Geriatric Depression Scale (GDS-15) was used to measure the participants’ depressive symptoms. The scale has a total of 15 dichotomous items, and higher scores indicate more depressive symptoms. The scores >6 (possible range 0–15) indicated depression. Constipation and overeating were determined through a questionnaire answered by the participants and recorded by the investigator. Constipation was when the interval between defecation was more than 3 days. Overeating was determined when feeling fullness after eating.
2.3. Definitions of the study variables
Investigators conducted household interviews after rigorous training and collected data including age, sex, illiteracy, smoking (every week), drinking (every week), the presence of cerebrovascular disease, visual impairment, auditory impairment, dementia, pain, duration of outdoor activities (more than an hour a day), living alone and life satisfaction. A life satisfaction questionnaire was used to assess the state of their life satisfaction. Visual impairment, auditory impairment, and pain were defined based on whether they affected the participant's daily life.
Body mass index (BMI) was computed using the following standard formula: BMI (kg/m2) = weight/height2. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured twice using calibrated desktop sphygmomanometer (Yuwell medical equipment and supply Co., Ltd., Jiangsu, China), and the values used in the analyses were the average of the two measurements. Samples of venous blood were obtained from the participants by professional nurses, and blood specimens were transported within 4 h in cold storage (4 °C) to a clinical laboratory. Total cholesterol (TC), triglyceride (TG), glucose (GLU) and vitamin D3 were determined by enzyme colorimetry using a fully automatic biochemical autoanalyzer (COBAS c702; Roche Products, Ltd.).
2.4. Statistical analyses
The mean ± standard deviation is used to describe continuous variables that were analyzed using the t-test, and number (percentage) is used to describe categorical variables that were analyzed using the chi-square test. Multiple linear and logistic regression analyses were used to evaluate the associations between constipation, overeating, and depression, which were adjusted for age, sex, illiteracy, smoking, drinking, cerebrovascular disease, visual impairment, auditory impairment, dementia, pain, duration of outdoor activities, living alone, life satisfaction, BMI, SBP, DBP, TC, TG, GLU, and vitamin D3. Residual error was normally distributed as shown in p-p plot, and the criteria of multiple normality was met in our analyses. Statistical analyses were performed with SPSS 17.0 software package (IBM Corp.). A P-value <0.05 was considered as statistically significant.
3. Results
In total, 1678 elderly individuals participated in this study. Participants’ mean age was 94.45 ± 9.51 years, ranging between 80 and 116 years, and 71.57% were female. The proportions of elderly individuals with depression, constipation, and overeating were 20.80% (349), 15.14% (254), and 26.52% (445), respectively. As Table 1 shows the prevalence of constipation and overeating in the participants with depression were statistically significantly higher than in those without depression (P < 0.05, all). Compared to participants without depression, those with depression had a statistically significantly older age; female predominance; higher prevalence of illiteracy, cerebrovascular disease, visual impairment, auditory impairment, dementia, and pain; lower prevalence of drinking and outdoor activities; and lower levels of life satisfaction, BMI, TC, TG, and vitamin D3 (P < 0.05, all; Table 1).
Table 1.
Characteristics of all participants with and without depression.
| Characteristic | Total (n = 1678) | With depression (n = 349) | Without depression (n = 1329) | P-value |
|---|---|---|---|---|
| Constipation† | 254 (15.14%) | 98 (28.08%) | 156 (11.74%) | <0.001 |
| Overeating† | 445 (26.52%) | 146 (41.83%) | 299 (22.50%) | <0.001 |
| Age, years∗ | 94.45 ± 9.51 | 98.93 ± 8.02 | 93.3 ± 9.53 | <0.001 |
| Female sex† | 1201 (71.57%) | 298 (85.39%) | 903 (67.95%) | <0.001 |
| Illiteracy† | 1430 (85.2%) | 319 (91.4%) | 981 (73.81%) | <0.001 |
| Smoking† | 94 (5.60%) | 14 (4.01%) | 80 (6.02%) | 0.147 |
| Drinking† | 142 (8.46%) | 19 (5.44%) | 123 (9.26%) | 0.023 |
| Cerebrovascular disease† | 34 (2.03%) | 14 (4.01%) | 20 (1.50%) | 0.003 |
| Visual impairment† | 324 (19.31%) | 91 (26.07%) | 233 (17.53%) | <0.001 |
| Auditory impairment† | 342 (20.38%) | 88 (25.21%) | 254 (19.11%) | 0.012 |
| Dementia† | 277 (16.51%) | 110 (31.52%) | 167 (12.57%) | <0.001 |
| Pain† | 664 (39.57%) | 208 (59.60%) | 456 (34.31%) | <0.001 |
| Outdoor activities >1 h/d† | 617 (36.77%) | 82 (23.50%) | 535 (40.26%) | <0.001 |
| Living alone† | 263 (15.67%) | 58 (16.62%) | 205 (15.43%) | 0.585 |
| Life satisfaction∗ | 22.58 ± 5.65 | 20.455 ± 6.454 | 23.132 ± 5.282 | <0.001 |
| BMI (kg/m2)∗ | 19.57 ± 3.87 | 18.54 ± 4.18 | 19.79 ± 3.77 | <0.001 |
| SBP (mmHg)∗ | 150.24 ± 24.75 | 151.148 ± 25.468 | 150.008 ± 24.571 | 0.455 |
| DBP (mmHg)∗ | 78.37 ± 22.05 | 77.372 ± 13.543 | 78.633 ± 23.754 | 0.354 |
| TC (mg/dL)∗ | 4.86 ± 1.07 | 4.68 ± 1.02 | 4.91 ± 1.08 | 0.001 |
| TG (mg/dL)∗ | 1.21 ± 0.64 | 1.14 ± 0.657 | 1.23 ± 0.639 | 0.025 |
| GLU (mmol/L)∗ | 4.99 ± 1.94 | 5.132 ± 1.597 | 4.959 ± 2.014 | 0.156 |
| Vitamin D3 (ng/mL)∗ | 24.56 ± 9.58 | 22.32 ± 8.8 | 25.16 ± 9.7 | <0.001 |
Notes: ∗ Data are presented as mean ± standard deviation. †Data are presented as number (percentage).
Abbreviations: BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; TC, total cholesterol; TG, triglyceride; GLU, glucose.
In the multiple linear regression analyses, older age; higher prevalence of constipation, overeating, illiteracy, dementia, pain, and living alone; higher levels of DBP; and lower levels of life satisfaction, had positive and statistically significant associations with the GDS-15 (P < 0.05, all; Table 2). In the multiple logistic regression analyses, constipation (odds ratio [OR]: 2.328; 95% confidence interval [CI]: 1.540–3.521) and overeating (OR: 2.735; 95% CI: 1.920–3.898) had positive and statistically significant associations with depression (P < 0.05, all; Table 3). Moreover, participants who were older, female and illiterate, had statistically significant higher prevalence of dementia, pain and living alone, higher levels of DBP, and lower levels of life satisfaction tended to have more depression (P < 0.05, all).
Table 2.
Multiple linear regression analyses between constipation, overeating, and GDS-15.
| Variable | Beta | 95% confidence interval | P-value |
|---|---|---|---|
| Constipation | |||
| Crude Model | 1.528 | 1.127–1.928 | <0.001 |
| Model 1 | 1.134 | 0.741–1.528 | <0.001 |
| Model 2 | 0.827 | 0.380–1.273 | <0.001 |
| Model 3 | 0.848 | 0.403–1.294 | 0.001 |
| Overeating | |||
| Crude Model | 1.351 | 1.027–1.675 | 0.001 |
| Model 1 | 1.015 | 0.695–1.335 | <0.001 |
| Model 2 | 1.125 | 0.777–1.473 | <0.001 |
| Model 3 | 1.324 | 0.981–1.667 | <0.001 |
Crude model: none adjusted.
Model 1: adjusted for age and sex.
Model 2: model 1 plus body mass index, systolic blood pressure, diastolic blood pressure, total cholesterol, triglyceride, and glucose.
Model 3: model 2 plus illiteracy, cerebrovascular disease, smoking, drinking, visual impairment, auditory impairment, dementia, pain, outdoor activities, living alone, life satisfaction, and vitamin D3.
Table 3.
Multiple logistic regression analyses between constipation, overeating, and depression.
| Variable | Odds ratio | 95% confidence interval | P-value |
|---|---|---|---|
| Constipation | |||
| Crude Model | 2.936 | 2.203–3.912 | <0.001 |
| Model 1 | 2.324 | 1.721–3.138 | <0.001 |
| Model 2 | 2.112 | 1.451–3.074 | <0.001 |
| Model 3 | 2.328 | 1.540–3.521 | <0.001 |
| Overeating | |||
| Crude Model | 2.478 | 1.932–3.177 | <0.001 |
| Model 1 | 1.998 | 1.540–2.593 | <0.001 |
| Model 2 | 2.270 | 1.656–3.111 | <0.001 |
| Model 3 | 2.735 | 1.920–3.898 | <0.001 |
Crude model: none adjusted.
Model 1: adjusted for age and sex.
Model 2: model 1 plus body mass index, systolic blood pressure, diastolic blood pressure, total cholesterol, triglyceride, and glucose.
Model 3: model 2 plus illiteracy, cerebrovascular disease, smoking, drinking, visual impairment, auditory impairment, dementia, pain, outdoor activities, living alone, life satisfaction, and vitamin D3.
4. Discussion
In this study, higher prevalence of overeating and constipation had positive and significant associations with depression in Chinese oldest-old and centenarians. These associations remained unchanged after adjusting for demographic characteristics and potential confounders. Based on this large sample study, we provided the evidence of the associations between overeating, constipation, and depression among the elderly population.
Physical status is closely related to healthy life of elderly population. As one study found, body fat was positively associated with poorer health-related life quality and depression [22], while lower extremity muscle strength was negatively associated with depression [23]. In recent years, with high-protein diet trend, gastrointestinal symptoms such as constipation, as an unhealthy physical state, are an important manifestation of aging and have a high prevalence in the elderly population [24, 25, 26]. The evidence provided by previous studies has shown that constipation may be related to depressive symptoms. Dore et al. revealed that constipation is related to an increased risk of depression in a representative sample of elderly population from Northern Sardinia aged from 65 to 94 years [27]. Chang et al. reported that constipation was significantly and positively correlated with depression in patients with Parkinson's disease [28]. Rajindrajith et al. found that compared to teenagers without functional constipation, those with functional constipation were more likely to have isolated psychological problems, such as depression and social problems, with a negative impact on their health-related life quality [29]. Additionally, previous research has indicated that a high proportion of individuals with depression meet the criteria for overeating, and are also at an increased risk of weight gain and chronic disease [30]. Consistent with previous studies, our study showed that constipation and overeating were significantly associated with depression after full adjustment.
The mechanism by which constipation influences neurological function has not been clearly understood, but evidence is accumulating to support the view that it may be related to the microecological-gut-brain axis [31, 32]. Gut microbes are capable of producing most of the neurotransmitters found in the human brain, such as 5-hydroxytryptamine, norepinephrine, and diaminobenzoic acid [33, 34, 35]. Israelyan et al. reported that mice with a variant of tryptophan hydroxylase have significant depression-like behaviors and gastrointestinal motor function defects. The administration of slow-release formulation of 5-hydroxytryptophan can restore the development of the enteric nervous system and reverse abnormal behavior, indicating that the deficiency of neurotransmitters, such as 5-hydroxytryptamine, may be a key link in constipation leading to emotional disorders [36]. Through fecal metabolomics and network pharmacology, Liu et al. discovered that choline, betaine, and glycine were significantly associated with constipation and depression [37].
Meanwhile, the association between depression and overeating may be related to neuroendocrine abnormalities. Previous study [30] has found that dopamine levels correlated positively with disordered eating behaviors in females, and negatively in males. The results provide evidence that depressogenic overeating and weight gain are associated with dopamine levels. Animal studies have also shown that corticosterone basal levels were significantly elevated in binge-eating rats with depressive-like behaviors while corticosterone increase to acute stress was attenuated [38]. These findings also provide some potential targets and ideas for early prevention and treatment of depression and overeating [39].
5. Conclusions and Implications
The current study provides epidemiological evidence that constipation and overeating have positive associations with depression in Chinese oldest-old and centenarians. Based on these findings, the interventions for constipation and overeating should be improved to promote prevention and treatment for depression and achieve successful aging and healthy longevity.
Declarations
Author contribution statement
Zhigao Sun; Xin Su; Xiaoqian Zhao; Yao Yao; Yali Zhao; Pei Zhang; Zhirui Li; Shihui Fu: Conceived and designed the experiments; Performed the experiments; Analyzed and interpreted the data; Contributed reagents, materials, analysis tools or data; Wrote the paper.
Funding statement
This work was supported by grants from the National Natural Science Foundation of China (81900357, 81941021, 81903392, 81901252, 82001476, 81802804, 81801251), the Military Medical Science and Technology Youth Incubation Program (20QNPY110, 19QNP060), the Excellent Youth Incubation Program of Chinese People’s Liberation Army General Hospital (2020-YQPY-007), the Natural Science Foundation of Hainan Province (821QN389, 821MS112, 822MS198, 820MS126, 820QN383), the National Key R&D Program of China (2018YFC2000400), the National S&T Resource Sharing Service Platform Project of China (YCZYPT[2018]07), the Specific Research Fund of Innovation Platform for Academicians of Hainan Province (YSPTZX202216), the Medical Big Data R&D Project of Chinese People’s Liberation Army General Hospital (MBD2018030), the China Postdoctoral Science Foundation Funded Project (2019M650359, 2020M682816, 2021T140298), the Heatstroke Treatment and Research Center of Chinese People's Liberation Army, the Simulation Training for Treatment of Heat Stroke, and the Major Science and Technology Programme of Hainan Province (ZDKJ2019012).
Data availability statement
Data will be made available on request.
Declaration of interest’s statement
The authors declare no conflict of interest.
Additional information
Supplementary content related to this article has been published online at [URL].
Acknowledgements
We appreciate all the staff of CHCCS for their continued cooperation and contribution in field work.
Contributor Information
Yali Zhao, Email: zhaoyl301@163.com.
Pei Zhang, Email: peizhang301@126.com.
Zhirui Li, Email: lzr860514@163.com.
Shihui Fu, Email: fushihui@301hospital.com.cn, xiaoxiao0915@126.com.
Appendix A. Supplementary data
The following is the supplementary data related to this article:
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Data Availability Statement
Data will be made available on request.