Relationship between chronic diseases and depression: the mediating effect of pain

The occurrence of chronic diseases is a predominant challenge in global public health [1, 2]. According to the 2019 study conducted by the Global Burden of Disease, chronic diseases, such as hypertension and diabetes, are included in the top five death risks in the world and are responsible for approximately 20 and 10% of global deaths, respectively [3]. According to the World Health Organization, 40.5 million (71%) of the 56.9 million global deaths in 2016 were due to noncommunicable diseases [4]. At present, the situation of chronic diseases in China is serious, and the prevalence of chronic diseases is increasing. In 2016, 230 million elderly people in China who were over the age of 60 years accounted for 16.7% of the total population, and the proportion of elderly people who were suffering from chronic diseases accounted for more than 65% of the elderly population [5]. In the USA, chronic diseases are the main cause of poor health, disability, and death and account for most healthcare expenditures. Approximately 60% of adults meet the criteria for multimorbidity in America, with a remarkable increase over the last three decades [6]. Half of the adults in Canada have at least one chronic disease, and a quarter have frequently occurring diseases [7]. These statistics show that chronic diseases have become the main cause of death and disease burden.

Patients with chronic diseases may experience negative emotions, such as depression. Many scholars have conducted related theoretical or empirical studies on the psychological status of patients with chronic diseases. The estimated prevalence of depression in patients with chronic diseases is ranges from 9.3 to 25% [8]. Patients with chronic diseases such as hypertension, coronary heart disease, and diabetes have a high incidence of depression; depression and the cardiovascular risk are strongly correlated [9]. People with multimorbid conditions are twice as likely to be depressed as people without multimorbidity [10]. Related studies have confirmed that many patients with chronic diseases have mental disorders, such as depression, because of the long-term nature of the disease and its impact on quality of life [11‐13]. Patients with chronic diseases suffer from pain for many years and may even have physical dysfunction, which leads to a lower quality of life and lower ability for social and role adaptation than normal and subsequently leads to their denial of self-worth, a sense of powerlessness toward life, and the occurrence of depression [14].

In addition to depression, chronic diseases are also attributed to negative physical effects, such as pain. Chronic pain is the most common symptom of chronic diseases, such as rheumatic arthritis [15]. Chronic pain is experienced by 80% of patients with rheumatoid arthritis within 5 years of onset [16]. The most common types of pain in elderly adults are low back pain or neck pain, musculoskeletal pain, peripheral neuropathic pain, and chronic joint pain [17]. Approximately one- third of patients with chronic lung disease and coronary heart disease have chronic pain [18].

Patients who often suffer from pain are prone to depression and negative psychology. A 12-year longitudinal study on aging in Amsterdam concluded using covariate-adjusted Cox regression models concluded that the risk of developing depressive symptoms is substantial in nondepressed participants with elevated pain at baseline [19]. Depression and chronic pain are highly prevalent in elderly populations. Approximately 13% of the elderly population suffers simultaneously from pain and depression [20]. Clinical studies have revealed that chronic pain, a stress state, often induces depression, and up to 85% of patients with chronic pain are affected by severe depression [21‐24]. Patients who are constantly in pain are more likely to develop muscle soreness, which may lead to irritability and restlessness and subsequently lead to anxiety or depression [25, 26]. Pain negatively affects the sleep duration, which also leads to an increased risk of depression [27]. People with chronic pain experience negative effects, such as loss of function, decreased quality of life, and depression [28]. The risk of depression increases remarkably as the pain level increases [29, 30].

Factors such as sex, age, and marital status may also have important effects on the relationship among chronic diseases, pain, and depression. Age, sex, marital status, and chronic diseases are related [31‐35]. Sex is also associated with some chronic conditions [36]. Older age is a common factor associated with the four main chronic diseases, namely, hypertension, diabetes mellitus, chronic obstructive pulmonary disease, and stroke [36]. Age, sex, and marital status are associated with pain [37‐41]. Women have lower pain thresholds and tolerance, and are more likely to experience more severe pain and unpleasant feelings than men [42‐47]. Aging reduces pain sensitivity and pain intensity [37, 48]. Sex, age, and marital status are also associated with depressive symptoms [49‐53].

Previous studies on chronic diseases have shown that chronic diseases directly lead to depression. Patients with chronic disease are affected by pain [15, 16, 18]. Patients who often suffer from pain have a higher incidence of depression than those who do not experience chronic pain [19]. Thus, studies are needed to verify whether pain exerts a mediating effect on the relationship between chronic disease and depression. This study used national survey data from middle-aged and elderly people to (1) explore the mediating effect of pain on the relationship between chronic disease and depression and (2) analyze the effects of demographic factors, such as sex, age, and marital status, on the relationships among chronic disease, pain, and depression.

As shown in Table 2, among the 15,213 survey subjects, 18.16% had no chronic diseases, 26.60% had one chronic disease, and 55.24% had two or more chronic diseases. In addition, 33.90% had a tendency toward depression, 30.21% had moderate to severe pain, and 74.06% of the people with pain took measures to relieve pain. The incidence of depression was related to sex, age, education level, marital status, urbanity, current working status, chronic disease, and degree of pain in the comparison of the characteristics of the groups with and without depression. Participants who are female, middle-aged, less educated, unmarried, living in rural areas, working, suffering from a variety of chronic diseases, and suffering from severe pain had a higher incidence of depression. Insurance status and depression occurrence were not statistically significantly associated with depression. The participants with self-reported pain did not display substantial differences in the occurrence of depression, regardless of whether measures were taken to relieve pain.

Table 3 shows that in the patients with self-reported pain, chronic diseases and the degree of pain (with mild pain as the reference) were significantly related (odds ratio [OR] = 3.697, P < 0.001, confidence interval [CI] = 2.919–4.681). People with more chronic diseases had higher pain levels and were more likely to take measures to reduce pain. Sex, age, education, and urbanity were related to the degree of pain. Sex, age, and education were risk factors, whereas urbanity was a protective factor. Chronic diseases and pain measures were significantly positively correlated (OR = 1.693, P < 0.001, CI = 1.335–2.148). Sex was related to taking measures to reduce pain; namely, women were more likely to take measures to reduce pain than men.

Table 4 illustrates that the number of chronic diseases and depression were substantially related to the pain level. Patients with more chronic diseases had a higher incidence of depression in the same pain state. Patients with more severe pain had a higher incidence of depression in the same chronic disease state. The number of chronic diseases was positively correlated with the incidence of depression regardless of whether measures were taken to relieve pain.

Table 5 displays the mediating effect of pain on the relationship between chronic diseases and depression, as determined using the binary regression analysis. In Model 1 shown in Table 5, sociodemographic characteristics, namely, sex, age, education, marital status, urbanity, current working status, and insurance situation, were controlled in the full sample, and the relationship between chronic diseases and depression was analyzed. Chronic diseases were significantly associated with depression (OR = 2.777, P < 0.001, CI = 2.497–3.090). The number of chronic diseases in patients was positively correlated with the incidence of depression. The incidence of depression was higher in patients with chronic diseases than in those without chronic diseases, and the incidence of depression in patients with more chronic diseases was higher than that in patients with one chronic disease. Sex, age, education, marital status, urbanity, and insurance status were related to depression. Among these variables, urbanity was a protective factor, and the remaining variables were risk factors.

Model 3 used pain samples to further control whether measures were taken to reduce pain. No remarkable association between measures taken to reduce pain and depression occurrence was observed. Therefore, the effect of this mediating variable on depression should be verified. Chronic diseases and the degree of pain were still remarkably related to the occurrence of depression. Sex, education, marital status, urbanity, and employment were associated with depression. The incidence of depression was generally higher in patients who were female, less educated, unmarried, living in rural areas, and working.

According to these three models, patients with more chronic diseases were more likely to develop depression (OR = 2.777, P < 0.001, CI = 2.497–3.090), and the overall effect was significant. Patients with more chronic conditions had more severe pain (OR = 3.697, P < 0.001, CI = 2.919–4.681) and were more willing to take steps to reduce their pain (OR = 1.693, P < 0.001, CI = 1.335–2.148). Therefore, the independent variable (chronic disease) affected the two intermediate variables (pain severity and taking measures to reduce pain). Model 3 validates that taking measures to reduce pain and the incidence of depression were not considerably associated. Hence, the mediating effect of the degree of pain was considered. However, when the mediating variable (pain severity) was considered, the effect of chronic disease on depression decreased (OR = 1.777, P < 0.001, CI = 1.587–1.989). Therefore, mediating variables may produce partial mediating effects.

A Sobel test was carried out to further verify the mediating effect of pain severity (Fig. 1). According to the results, the mediating effect of pain severity was significant (t = 7.989, SE = 0.125, P < 0.001). The independent variable (chronic disease) affected the mediating variable (pain severity), and the mediating variable affected the dependent variable (depression). The direct effect (c’) of the independent variable (chronic disease) on the dependent variable (depression) was weakened when mediated by the mediating variable (pain severity). a1 = 1.307 and b1 = 1.860 for indirect effects, and a1b1 = 2.43 for the total effects.

The results of the study suggest that chronic diseases directly affect the occurrence and risk of depression through the mediating effect of pain severity. The degree of pain exerts a partial mediating effect on chronic diseases and depression. Patients with more chronic diseases had more severe pain and a greater risk of depression than patients with fewer chronic diseases. We used cross-sectional data in our research, but previous studies have shown that cross-sectional data may not be able to judge causality [54]. Therefore, chronic diseases may lead to depression, and depression may also lead to chronic diseases. Among the studies on the relationship between chronic diseases and depression, some studies have found that chronic diseases cause depression. For example, depression and the cardiovascular risk are strongly correlated, many patients with chronic diseases have mental disorders [8‐10]. And some studies show that depression increases the risk of chronic diseases or aggravates the condition of patients with chronic diseases. For example, patients with major depression are at an increased risk for developing cardiovascular disease, depression mainly affects those with chronic medical illnesses, worsens the outcomes of many medical illnesses [55‐57]. Although some studies may show that patients with depression are more likely to have chronic diseases, chronic diseases and pain caused depression in our study. Additionally, sex, education, marital status, place of residence, and work status were substantially associated with depression. Among people with chronic diseases and pain, people with the following characteristics were more likely to develop depression: women, people with lower education levels, unmarried people, people living in rural areas, and working people. We speculate that the direct effect of chronic diseases on depression may be due to physical dysfunction, social dysfunction, and the economic burden.

Many patients with chronic diseases have physical dysfunction, which adversely impacts daily life activities and leads to a decrease in quality of life. For example, patients with osteoporosis are prone to fracture and thus unable to carry out normal activities due to the gradual increase in bone fragility; hence, their daily activities are decreased [58]. Older people are prone to feelings of pain, anxiety, and even despair when they encounter difficulties in daily life [59]. Some patients with chronic diseases even must receive care from family members, which leads to an increased psychological burden and produces feelings of inferiority.

People with chronic diseases experience more negative life events than healthy people. Chronic diseases exert a negative effect on family relationships and social interactions and lead to more negative life events and stressful emotions [60]. One study found that negative life events are positively associated with depressive symptoms [61]. People with chronic diseases who experience more negative life events tend to have more severe depressive symptoms. According to stress theory, mental health tends to be poor when a person is stimulated by stress.

Another possible explanation is that patients with chronic diseases have a large amount of long-term medical expenses, which imposes a substantial burden on family and personal economies. Patients with chronic diseases who are unable to care for themselves require care from family members. Thus, the labor time of family members and the economic income of the family will be reduced, and the economic burden of the family will increase [62]. However, in Chinese tradition, most middle-aged and elderly people are expected to take care of their children or grandchildren. As a result, chronically ill elderly people who require care may see themselves as a burden on other family members, which may lead to feelings of despair [63].

The mediating effect of pain on the relationship between chronic disease and depression may be because pain is one of the symptoms of chronic disease. Chronic diseases, such as arthritis, rheumatism, and gastrointestinal diseases, are often accompanied by pain symptoms [64]. Chronic diseases are long-course diseases. Therefore, the pain caused by chronic diseases is also long term. Pain caused by physical discomfort results in a decrease in the quality of life of patients and results in irritability, restlessness, and other negative emotions, which all lead to the occurrence of depression [28]. Patients with multiple chronic diseases may experience a greater degree of pain. Patients may feel uneasy, powerless, irritable, and other negative emotions after the long-term accumulation of pain, which results in a substantial increase in the risk of depression.

Among people with chronic diseases and pain, individuals with the following characteristics are more likely to become depressed: women, people with lower education levels, unmarried people, people living in rural areas, and working people. The potential explanations are described below. Women with chronic diseases and pain are more likely to be depressed, possibly because women have a lower tolerance for pain than men. A study on pain conducted in Maine, USA, found that women have a lower pain threshold and tolerance and are more likely to experience more intense pain and unpleasant feelings than men [46, 47]. In addition, people of different sexes experience pain differently because of hormonal and genetic factors [39]. Older women with lower education levels and older women in rural areas usually have a lower socioeconomic status and receive less social support, which increases the risk factors for depression [65, 66]. Moreover, residents of rural areas have limited living environments and material resources, and thus they are unable to obtain complete treatment when suffering from chronic diseases and pain. Therefore, they suffer physically and psychologically [40]. On the one hand, unmarried people may lack the supervision of a partner and may have lower adherence to medication for a chronic illness. On the other hand, unmarried people lack the mental support from their partners and are more prone to depression when suffering from chronic diseases and pain [67, 68]. People with jobs are more likely to suffer from depression than those without jobs. One of the reasons is that people with jobs may suffer from an irregular diet due to busy work and become prone to chronic diseases, such as chronic gastritis and shoulder and neck pain [41]. Another possible explanation is that people with jobs may suffer pressure from work, family, and society, which may increase the psychological burden. Working people are more prone to depression due to the dual effects of physical discomfort and psychological stress.

The current study has some limitations. First, pain and depression were not analyzed in participants with different chronic diseases because of data limitations. Detailed information on the severity of chronic diseases was not included. Only the associations of the number of chronic diseases and pain with depression were emphasized. Therefore, the different effects of different chronic diseases on depression may be overlooked. Further studies on individuals with different chronic diseases should be conducted in the future. Second, chronic diseases were not verified from medical records; therefore, the study may be subject to recall bias. Patients may conceal diseases or report diseases that have been self-diagnosed but not recorded by medical institutions, leading to underreporting or overreporting. Third, we used cross-sectional data, which are unable to predict a causal relationship between chronic diseases and depression. Evidence suggests that cross-sectional approaches to mediation generate substantially biased estimates of longitudinal parameters in the special case of complete mediation [54, 69]. The results of our study may also suggest that individuals who are depressed are more likely to experience chronic diseases and pain. However, in our study, pain was added as a mediating variable between chronic diseases and depression to explore their relationship. Hence, pain is not necessarily related to time. The pain caused by chronic diseases may be temporary and could be relieved in a timely manner through drug intervention. Therefore, the use of cross-sectional data might achieve our research goals. In future studies, we will consider the use of longitudinal data for the mediation analysis.

The effect of chronic diseases on the psychological status of middle-aged and elderly people can be partially predicted by determining their pain severity. This study emphasizes that depression might be avoided in some patients with chronic diseases by relieving pain, ameliorating the disability and economic burden caused by chronic diseases. Therefore, measures that reduce pain should be considered in the future treatment of patients with both chronic diseases and depression.