Chronic Pain And Depressive Symptoms In Chinese Middle-Aged And Older Adults:A Follow Up Study


 Objective: This study aimed to analyze the effects of chronic pain on the occurrence of depressive symptoms in Chinese middle-aged and older adults, and to provide a scientific basis for reducing the incidence of depressive symptoms, improving the quality of life in middle-aged and older adults, and reducing the disease burden in the aging population.Methods: a prospective study was conducted to select adults aged 45 years or older from the longitudinal study of China Health and elderly care follow-up survey (Charls) (2015 and 2018). Pain was assessed according to the patient's self exposure, and depression was assessed using the Chinese version of the center for epidemiological research Depression Scale (CES-D). Univariate analysis and binary logistic regression model were used for analysis. Results: The 3-year cumulative incidence of depression in chronic pain patients was 52.4% and the annual incidence was 17.5% in the middle-aged and elderly Chinese population. Univariate analysis showed statistically significant differences in the incidence of depressive symptoms between the different genders, age, residence, education level, marriage, self perceived health status, nocturnal sleep time, number of social activities in the past month, smoking, alcohol consumption, impaired ADL and Medicare insurance coverage. This study, after controlling for demographic characteristics, health status and health behaviors, Different pain conditions remained statistically significant for depression in middle-aged and older adults. Compared with middle-aged and older adults without pain, both Unisomatic pain (OR = 1.388) and Multiple somatic pain (OR= 1.869) increased the risk of depression in the middle-aged and older populations. Conclusion: chronic pain is associated with the risk of depressive symptoms in middle-aged and elderly people, and the incidence of depression in middle-aged and elderly people in China is not optimistic.


Introduction
Depression, as one of the most common mental health problems of the middle-aged and elderly, has become an increasingly serious public health problem because of stigma, lack of effective treatment and lack of mental health resources. According to WHO ,it is estimate that about 350 million people suffer from depression every year and more than 800000 people die of suicide [1] . In 2015, depression was estimated to be the third largest cause of disability in the world [2] . Depression has a high prevalence in China [3,4] , and studies have shown that 30% of middle-aged and older Chinese men and 43% of women have depression [5] . Depression has a major impact on middle-aged and older adults in terms of quality of life, ability to live, and how they feel.
Pain, as one of the most common symptoms distressing people, is increasing in prevalence due to the aging population and increasing prevalence of chronic diseases [6,7] . In China, the prevalence of chronic pain in the elderly has reached 35.71% [8] . The results of the global burden of disease study 2016 show a high prominence of pain and pain related disorders as leading causes of disability and disease burden worldwide [9] . In 2011, the report of Institute Of Medicine 2011 (Institute Of Medicine 2011 Report) pointed out that the medical burden of pain exceeds the total cost associated with cardiovascular disease, diabetes and cancer [10] . Pain has a high prevalence in China [8,11,12] and has become an important public health problem.
Acute pain has positive effects, alerting the organism of the potential danger that tissues and organs can be. In chronic pain, where central mechanisms are involved, however, the persistence of pain overrides its biological effectiveness and greatly discourses patient quality of life. Chronic pain can trigger various somatic and mental stresses that increase the risk of developing depression. The association between depression and pain can be explained by common neurobiological pathways as well as physiological contexts. The most frequently implicated neurobiological pathway is the HPA axis. Pain and depression involve many brain regions.In addition to possessing adjacent anatomical locations, these brain regions are co activated in their ontogenetic development. Pain signals pass through the spino thalamic tract to project to the thalamus and parietal cortex. It projects via the thalamus to the amygdala, insula, ventral striatum, hippocampus, as well as to the prefrontal cortex. These pathways are involved in the affective component of pain perception as well as in the pathophysiology of depression [13] Multiple studies have noted depression in approximately 35% of individuals diagnosed with chronic pain [14][15][16] . Comorbid depression in patients with chronic pain causes greater di culties in the treatment of pain and depression, severely affecting patients' quality of life and conferring a greater burden of disease. However, whether pain contributes to the development of depression among Chinese middleaged and elderly is unknown. Therefore, this study uses data from the 2015 and 2018 China health and retirement longitudinal survey(Charls), which are based on community populations, to analyze the effects of chronic pain on the occurrence of depressive symptoms among middle-aged and elderly, and to reduce the incidence of depressive symptoms. Improving the quality of life of middle-aged and elderly and reducing the burden of disease in the aging population provide scienti c evidence. and were aged ≥ 45 years and ≤ 105 years.The sample selected according to the inclusion criteria was 12832, excluding 88 who could not judge the outcome of depressive symptoms in the baseline and follow-up survey, 2085 lost follow-up samples, 285 missing pain variables, and 744 missing other key variables (baseline age, residential address, education level, conscious health status, night sleep time, smoking, drinking, medical insurance). Because cancer or major disability (including physical disability, intellectual disability, blindness, deafness and dumb) in the baseline will have a mixed impact on the research results, this study only selects the population without cancer and major disability at the baseline (excluding 966 people with cancer and major disability at the baseline), and nally includes 8664 people.
Entry criteria: ≥ 45 years of age, free of depressive symptoms (CES-D score < 10) in 2015, free of cancer and other signi cant disabilities and completing the 2018 survey, key variables (2011 gender, age, type of residence, address of residence, level of education, marriage, self perceived health status, night time sleeping, number of social activities in past month, smoking, alcohol consumption, impaired ADL, Medicare and pain conditions; 2015, 2018 depressive symptoms) People without deletions. This project was ethically reviewed by the Peking University Biomedical Ethics Committee, and all subjects interviewed gave written informed consent.

Study design
The speci c research design and methods are shown in the literature [17] 2.3 Chronic Pain: subjects were self-reported to have had ongoing or intermittent pain lasting for more than 3 months involving two sites and above in the head, neck, shoulders, arms, wrists, ngers, chest, stomach, back, waist, hip, legs, knees, ankles, toes pain was de ned as multisomatic pain, pain at either site was de ned as unisomatic pain, Absence of pain sensation at any site was de ned as no pain.

Depression: the depressive symptoms were measured by the Center for Epidemiologcal Studies
Depression Scale CES-D10 [18] The scale consists of three depressed mood options, ve somatic symptom items, and two positive affect items and is calculated according to the Chinese version of the scale with 0 representing < 1D, 1 representing 1-2D, 2 representing 3-4d, and 3 representing 5-7d added up to a total score of 30, with higher scores indicating more severe depressive symptoms, and a score of ≥ 10 rated as having depressive symptoms [19]

Functional Health and Covariates
In addition, other studies were included on social and demographic characteristics (gender, age, level of education, marriage, type of address and residence) and health status and health-related behaviors (selfrated health, suffering from various chronic diseases, night sleep duration, number of social activities in the past month, smoking, alcohol consumption, ADL, and medical insurance). According to the World Health Organization classi cation method for the age of the middle-aged and elderly, they were divided into three groups 45-60 years, 60-75 years, and ≥ 75 years. The survey subjects were divided into married, unmarried, divorced / widowed / separated based on their marital status. Uneducated, not nished primary school, private home, and primary school graduation were de ned as primary school and below; Junior high school graduate, senior high school graduate, and junior high school graduate are de ned as secondary school, junior college graduate, undergraduate graduate, master's graduate, and doctoral graduation are de ned as junior college and above. The type of address included home dwelling, nursing home or other nursing home, hospital and other, divided into home dwelling and non home dwelling based on the response. The residential address includes the main city area, urban-rural Union area, town central area, town and Town Union area, special area, town central area and village, de ning the main city area and town central area as town, the urban-rural Union area and town and town and village central area as urban-rural Union area, special area as special area, and the town central area and village as rural.
In the process of self-rated health questionnaire survey, the subjects' self-rated health status, including: very good, good, ordinary, bad and very bad. The questionnaire was self-administered with the question "have you ever been told by a physician that you have any of these chronic conditions? "and was categorized into " ≥ 2, 1, 0 " by answering. According to the recommendations of the American National Sleep Foundation [20] , the subjects were divided into three groups: short sleep duration (< 6 h / D), normal sleep duration (6 ~ 9 h / D) and long sleep duration (> 9 h / D). Study subjects were informed of the number of social activities in the past January by asking "have you performed the following social activities in the past month? "and were categorized as " 0 times, 1 time, ≥ 2 times "by answering; According to the question "have you ever smoked", the respondents who answered "no" were judged as non-smoking, the respondents who answered "still smoking or quitting smoking " were judged as smoking. Whether or not they drank in the questionnaire based on the question" in the past 1 year, how often they drank", those who answered "less than 1 time per month or not drank" were judged as not drinking, and those who answered "more than 1 time per month" were judged as drinking. De nition of ADL: Katz [21] ADL assessment scale is used as the assessment tool, which includes 6 items: toilet, eating, dressing, defecation control, getting out of bed and bathing. The evaluation results of each project are divided into three levels: no need for help, partial need for help and complete need for help. Any one of the six items (including partial need for help and complete need for help) is damaged by ADL, and the six items do not need help are intact. The types of medical insurance include: medical insurance for urban employees, medical insurance for urban residents, new rural cooperative medical insurance, medical insurance for urban and rural residents, public medical treatment and medical assistance; Any of the above medical insurance is de ned as medical insurance, otherwise it is de ned as no medical insurance.
2.6 Statistical analysis Statistical analysis of the data was performed in this study using spss26.0 software. Mean ± standard deviation (± s) was used to describe quantitative data that conformed to normal distribution, and rate or constituent ratio was used to describe qualitative data; use χ² Tests to compare differences in rates between two and more groups. The effect of different pain states on depressive symptoms was analyzed by multivariate logistic regression model, and P < 0.05 was considered statistically signi cant.

Incidence of depression
There were 2887 individuals who developed depression, the 3-year cumulative incidence rate was 33.3%, the average annual incidence rate was: 11.1%, and the age of onset of depression was 58.33 ± 7.603.
There were statistically signi cant differences in the incidence of depressive symptoms between the different genders, ages, residential addresses, educational levels, marriage, self perceived health status, nocturnal sleep time, number of social activities in the past month, smoking, alcohol consumption, impaired ADL and Medicare. The details of these analyses are shown in table 1.

Association between pain and depression
As the number of painful sites increased, the incidence of depression increased compared with no pain. The details of these analyses are shown in table 2. With the occurrence or not of depression as the dependent variable 0=no 1=yes , and the variables that were statistically signi cant in univariate analysis were used as the independent variables. By constructing logistic regression analysis models with stepwise inclusion of control variables, the effects of different pain conditions on the occurrence of depression in middle-aged and older adults were explored separately. Only pain related variables were included in model 1, and the results showed that the middle-aged and older adults whose pain conditions were unipolar and multiple somatic pain had a higher risk of depression (P < 0.05). Model 2, after adjusting for demographic characteristics on the basis of model 1, still showed a statistically signi cant association between pain status and the occurrence of depressive symptoms (P < 0.05), but the or decreased compared with the unadjusted values before. Model 3 further adjusted the factors such as health status and health behavior on the basis of model two, and the results showed that the or values were further reduced compared with model 2, the risk of older people developing depression among those with monomodular pain was 1.388 times higher than that among those without pain, and the risk of older people developing depression among those with multiple somatic pain was 1.869 times higher than that among those without pain. Pain status remained statistically signi cant (P < 0.05) for the occurrence of depression in middle-aged and older adults. The details of these analyses are shown in table 3.

Discussion
The incidence rate of incidence rate incidence of depression in 3 years is 33.3% and the annual incidence rate is 11.1%. The cumulative incidence rate of depression in 3 years is 52.4%, and the annual incidence rate is 17.5%. Both signi cantly higher than the US depression incidence (1.51/100 person years) investigated by BF grant et al [22] in 2008 and the Dutch depression incidence (8.86%) investigated by Ron de Graaf et al [23] in 2012. The incidence rate of depression is high in middle-aged and old people in China, and the mental health status is not optimistic.
Epidemiological studies have shown that chronic pain increases the risk of depression by 2.5 to 4.1 times [24,25] . After controlling demographic characteristics, health status and health behavior, this study found that different pain status still had statistical signi cance for middle-aged and elderly depression. Compared with the middle-aged and elderly people without pain, single body pain and multi body pain will increase the risk of depression in the middle-aged and elderly people. Nicassio et al. [26] showed that the two-year follow-up of 242 patients with rheumatoid arthritis showed that pain may exacerbate sleep problems, and both pain and sleep disorders alone increase the risk of depression. Dohrenwend and others [27] studied more than 100 chronic facial pain patients and a similar group of painless subjects. The results showed that chronic muscle facial pain was one of the causes of the incidence rate of depression in these patients. In addition, the link between pain and depression is not limited to the middle-aged and elderly. Rethelyi et al. [28] found that the incidence of depression was signi cantly higher in pain subjects after a cross-sectional health survey of 3615 young Hungarian women aged 15-24 years. The incidence of major depression increased linearly with the increase of pain severity. The study of Currie et al. [29] showed that after adjusting demographic variables, logistic regression analysis showed that back pain was the strongest predictor of severe depression.
Relevant studies have shown that pain and depression have a common neurobiological pathway [13] . The occurrence and development of pain and depression involve the same brain structure, the same neural circuit and the activation of the same neurochemicals. Klaenberg et al. [30] showed that the signs of increased central hyperexcitability were uniform in patients without pain. It is suggested that the common mechanism of depressive disorder and chronic pain is consistent with the hypothesis of non pain related mechanism of central hyperexcitability in depression, for example, by inhibiting the function of serotonin.
In this study, chronic pain was used as the measurement index. Chronic pain is not only a physical symptom, but also has harmful emotional factors [31] . According to the International Association for pain research, it is de ned as unpleasant sensory and emotional experiences associated with actual or potential tissue damage [32] . There is a strong correlation between chronic pain and depression. Various physical pain symptoms will increase the possibility of depression. When the severity of depression increases, the severity of pain also increases. And the occurrence of depression becomes very complex due to psychological, social and physical health reasons. The middle-aged and elderly people who have been in a state of pain for a long time are accompanied by negative and unpleasant emotional reactions.
There is a close relationship between physical health and mental health. Physical discomfort will not only bring serious pain and suffering and heavy economic burden to the middle-aged and elderly people, but also reduce the social participation of the middle-aged and elderly people and have a great impact on their mental health. Similarly, patients with severe depressive disorder have an increased probability of pain [33] . The two affect each other, creating a vicious circle. The comorbidity of pain and depression reduces the overall e cacy of susceptible people, making them have to receive longer treatment, endure more serious symptoms, and reduce the possibility of complete remission.
In conclusion, pain is related to the risk of depressive symptoms in middle-aged and elderly people, and the incidence of depression in middle-aged and elderly people in China is not optimistic. As the most populous country in the world, the challenge of population aging is severe and urgent. Therefore, health-related interventions related to effective and sustainable primary and secondary interventions deserve more research attention. We should take the middle-aged and elderly people with pain, especially the middle-aged and elderly people with multiple body pain, as the key prevention and treatment object of depressive symptoms, actively improve the physical condition of pain patients, pay close attention to the mental health condition of pain middle-aged and elderly people, and strengthen the mental health guidance for middle-aged and elderly people. At the same time, this suggests that when pain occurs, we can't think it is a simple physical problem. We also need to pay attention to the impact of physical health on people's mental health, which may be of great signi cance to improve the quality of life of middleaged and elderly people and reduce the risk of depression.
This study still has some limitations. The pain information in this study comes from the self-report of the middle-aged and elderly. Although a large sample size can reduce the degree of recall bias, it is inevitable; Depression is investigated by CES-D scale, not the gold standard method for diagnosing depression, which has a certain deviation from the real level. And many studies have shown that there is a two-way correlation between pain and depression. In this study, we did not investigate the effect of depression on pain because it was beyond the scope of our study. The relationship and interaction between depression and pain still need to be further studied.

Acknowledgments
The authors would like to thank the National School of Development at Peking University for providing the CHARLS data.

Funding
This research did not receive any speci c grant from funding agencies in the public, commercial, or notfor-pro t sectors.

Availability of data and materials
The datasets used during the current study are available from the website of China Health and Retirement Longitudinal Study (http://charls.pku.edu.cn/pages/data/111/zh-cn.html) and can be accessed by registering to access the study data.The datasets analyzed during the current study are available from the corresponding author upon reasonable request.

Competing interests
The authors declare that there is no con ict of interest.