Patients with different types of arthritis may be at risk for major depression: results from the National Health and Nutrition Examination Survey 2007–2018

Introduction

Arthritis refers to the infections in and around the joints. It is a common clinical chronic systemic inflammatory disease, which is characterized by redness, swelling, heat and pain. Arthritis is a common chronic disabling disease in America. According to the research based on the National Health Interview Survey database, about 22.7 percent of adults in the United States have been diagnosed with arthritis by doctors, and 9.8 percent have limited activities, such as difficulty in dressing or going to the toilet, due to arthritis. Arthritis is a common disease not only in the United States but around the world. There are currently 355 million people suffering from arthritis in the worldwide. It is estimated that by 2040, adults diagnosed with arthritis account for 25.9% of all American adults (1). Arthritis can lead to severe joint pain and dysfunction, resulting in limited movement and decreased quality of life. Arthritis and its limited activity will remain a serious problem in clinical and public health systems.

The most common form of arthritis is osteoarthritis, but arthritis also includes rheumatoid arthritis (RA), psoriatic arthritis (PsA), gout, etc. Osteoarthritis, also known as degenerative arthritis, is a degenerative change, mainly manifested by the degenerative damage of articular cartilage, and the reactive hyperplasia of joint edge and subchondral bone, mainly in the elderly. It is most common among middle-aged and elderly people. While RA, PsA and other types of arthritis are more common inflammatory arthritis, whose pathological manifestations are primarily synovitis and vasculitis. Because of severe joint pain and limited activity, arthritis has a great impact on patients’ mental health. A multicenter cross-sectional study showed that patients with knee osteoarthritis were more likely to be depressed, and 10.4% of these depressed patients suffer from moderate to severe depression (2). Baerwald et al. (3) found that the risk of depression in patients with RA was significantly higher than that of the general population. Depression has adverse effects on the treatment of RA, such as reducing the remission rate and increasing mortality rate. A meta-analysis found that patients with PsA were generally depressed and anxious, with a higher incidence of depression (4), Matcham and his colleagues (5) found that the prevalence rate of major depression among patients with PsA is about 16.8%. Ryu et al. (6) found that RA and degenerative arthritis may have a greater impact on the risk of major depression than other diseases. According to survey statistics, Major Depressive Disorder (MDD) affects about 6% of adults worldwide every year, and is the second major factor contributing to the burden of chronic disease. In addition, the possibility of suicide among MDD patients is almost 20 times of that in general population. Clinical studies have shown that arthritis patients are more likely to suffer from major depression. However, few large sample studies have confirmed this correlation, and there is a lack of cross-sectional comparisons between different types of arthritis and major depression risks.

This study aims to explore the relationship between arthritis and major depression, as well as the relationship between different types of arthritis and major depression risk through a nationally representative population-based cohort study.

We present the following article in accordance with the STROBE reporting checklist (available at http://dx.doi.org/10.21037/apm-21-279).

Methods

Study design

The data used in this study comes from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018. NHANES is a national cross-sectional survey which collects nationally representative health and nutrition data, and uses complex and multi-stage probability samples of American civilians and non-institutionalized population to determine the prevalence and risk factors of major diseases in the American population (7). The study was conducted by doctors and experienced medical staff using open online data, including questionnaires, physical examinations and laboratory data (http://www.cdc.gov). In addition, our study conformed to the provisions of the Declaration of Helsinki (as revised in 2013).

Study population

The history of arthritis was investigated in 35,162 adults (≥18 years old). Participants who answer “no” or “don’t know”, or those who have at most one missing answer to Patient Health Questionnaire-9 (PHQ-9) questions, will be excluded from our analysis (n=3,702). Participants who lack information or have a “no” or “unknown” response to arthritis history will also be excluded (n=1,822). The missing value of other variables is 3,648. The final sample size included in the analysis was 25,990, of which 7,049 admitted to having arthritis history and 18,941 did not. Figure 1 presented a flow chart of the 2007–2018 NHANES survey.

Figure 1 Flowchart of the study sample.

Measurements and variables

Definition of primary exposure

The history of arthritis is determined by a questionnaire, in which the patient answers the question “have any doctors or other health experts told you that you have arthritis?” with “yes” or “no”. If the answer is “yes”, the patient will be further urged to answer “what type of arthritis is this?” “osteoarthritis, degenerative arthritis, rheumatoid arthritis, psoriatic arthritis or other?”.

PHQ-9 is a simple and effective self-rating scale for depression, which is based on Diagnostic and Statistical Manual of Mental Diseases formulated by American Psychiatric Society (DSM)-IV. It has good reliability and validity in assisting the diagnosis of depression and evaluating the severity of symptoms. PHQ-9 scores each of the nine DSM-IV criteria as “0” (not at all) to “3” (nearly every day) (8). Participants can chose “not at all” (score of 0), “several days a week” (score of 1), “more than half the days” (score of 2), or “nearly every day” (score of 3) to answer the following nine questions. The total score of PHQ-9 is 27, and a PHQ-9 score ≥10 had a sensitivity of 88% and a specificity of 88% for major depression (8).

Assessment of covariates

The relationship between arthritis and depression was studied from three aspects: demographic data, healthy lifestyle, and medical history. Information on gender, age, race, education, poverty-to-income ratio (PIR), and marriage was obtained by experienced interviewers using CAPI system to conduct household population questionnaire. Body mass index (BMI) was obtained from the examination data. Race was divided into “black”, “Mexican”, “Hispanic” or “others” and “whites”. Education was divided into “college and above” or “high school graduation” and “below high school”. PIR was divided into “PIR ≥5” and “PIR <5”. Marriage was divided into “living with partner”, “living alone” and “married”.

Healthy lifestyle was determined by investigating recreational activities and smoking habits. Moderate recreational activities were reflected in the following questionnaire: in a typical week, did you have any moderate-intensity sports, fitness or recreational activities, which led to a slight increase in breathing or heart rate, such as walking fast, cycling, swimming or playing volleyball continuously for at least 10 minutes? The patient’s answer to the question was “yes” or “no”. Those who answered the question “have you smoked at least 100 cigarettes in your life?” as “yes” were determined to be smokers. Variables related to medical history, such as coronary heart disease, stroke, cancer or malignant tumor, diabetes and hypertension, etc. were collected from specific personal questions, and the patients were asked whether they had been diagnosed by doctors.

Statistical analysis

Continuous variables are represented by means and standard errors (SE), while percentages are used to represent classified variables. For continuous data, if normal distribution and homogeneity of variance are satisfied, t-test is used to compare between groups; otherwise, nonparametric test is used. Chi-square test is used for comparison between different types of data sets. A multivariate logistic regression models was constructed to test the relationship between depression and arthritis. In order to discuss the relationship between different conditions, three models are established in the following order. The first model (Model 1) is adjusted according to gender, age, race, BMI, PIR, education and marriage. The second model (Model 2) has made additional adjustments for moderate recreational activities and smoking. The third model (Model 3) was further adjusted according to the history of coronary heart disease, stroke, malignant tumor, diabetes and hypertension. The results are expressed by odds ratios (OR) and corresponding 95% confidence intervals (CI). R3.6.2 is used to analyze research data. All statistical tests are double-tailed, and the significance level is set as α=0.05.

Results

Characteristics of study population

Table 1 show the characteristics of the study population. Our final data included 25,990 patients (average age 49.3 years, male 49.1%). Among all depression patients, 2,327 patients have major depression and other 23,663 patients have not yet reached the level of major depression. And there are 1,045 patients suffering from both major depression and arthritis. There are obvious differences in clinical features of major depression. Compared with patients without major depression, patients with major depression are more likely to be female, Hispanics, smokers, less educated, less recreational activities, PIR <5, patients with coronary heart disease, stroke, malignant tumor, diabetes and hypertension. Patients with major depression also have higher BMI. There is no significant difference in age between patients with and without major depression. In univariate analyses, arthritis is significantly related to major depression (25.4% vs. 44.9%; P<0.001).

Table 1 Characteristics of study participants based on depression status (n=25,990)
Full table

Association between depression arthritis

Table 2 show the relationship between major depression and arthritis. When the model is adjusted for other covariates, arthritis can be determined as a risk factor of major depression from OR value. When the model is only adjusted for gender, age, race, BMI, PIR, education and marriage (Model 1), the OR value is the highest among the three models (OR =2.72, 95% CI, 2.45–3.02, P<0.001). When the model was adjusted for moderate recreational activities and smoking, the OR value decreased (Model 2) (OR =2.51, 95% CI, 2.26–2.80, P<0.001), but remained statistically significant. When the model is further adjusted for all covariates, the OR value is the lowest (Model 3). Participants with arthritis were 2.30 times more likely to suffer from major depression than normal people (OR =2.30, 95% CI, 2.06–2.56, P<0.001).

Table 2 Multinomial logit regression analysis of depression (PHQ score ≥10) and arthritis
Full table

Subgroup analysis

The results of subgroup analysis are shown in Table 3 and Figure 2. In order to determine which type of arthritis has the greatest influence on major depression, we further divide arthritis into “osteoarthritis or degenerative arthritis”, “rheumatoid arthritis”, “psoriatic arthritis” and “other arthritis” (the control group were all other patients without arthritis). “Psoriatic arthritis” showed the highest OR value in all three models (Model 1 =2.89, Model 2 =2.69, Model 3 =2.49). This significant correlation exists in all models, which suggests that PsA may have the greatest influence on patients with depression.

Table 3 Multinomial logit regression analysis of depression (PHQ score ≥10) and different types of arthritis
Full table

Figure 2 Forest plot of suburb analysis.

Discussion

At present, the treatment of arthritis mainly focuses on drugs and lifestyle changes (9). However, it is difficult for patients to change their lifestyle, because the psychological characteristics of arthritis-related complications, such as depression, may lead to poor compliance with dietary counseling and exercise prevention measures (10). Depression is also related to poor compliance with medical advice for general chronic diseases (11) and rheumatological treatment. In order to address the impact of depression on the management of arthritis, it is reasonable to actively screen and treat arthritis patients with depression in time.

In addition, we established three models from three aspects: demographic data, healthy lifestyle and medical history. The results showed that arthritis was an influential factor of major depression in all three models. Although previous studies have found the impacts of RA or degenerative arthritis on depression, compared with other diseases (2-4,6), there is still a lack of comparison between different types of arthritis. By subdividing arthritis patients into degenerative arthritis, RA, PsA and other types of arthritis, we found that PsA has the greatest influence on major depressive symptoms. The same results appear in all three models. Previous studies have shown that psoriasis increases the risk of depression (12), and our results further complement the relationship between psoriasis-related diseases and major depression.

Our study found that patient with PsA had the highest risk of major depression in all three models. Meta-analysis shows that PsA patients have higher incidence of depression than the general population (4). PsA is a kind of inflammatory arthritis related to psoriasis, with a prevalence rate of 0.3–1% in the general population worldwide and 6–42% in psoriasis patients (13). Patients are usually accompanied by Systemic Psoriatic Disease, including skin, joint and gastrointestinal injuries (14). Any worsening injury on the skin will bring shame to the patient, because it is the most obvious organ to be seen. Skin lesions caused by PsA will affect the appearance of patients and reduce self-acceptance and self-esteem. The typical skin lesions of PsA are hair, limbs, genitals, etc., which lead to severe humiliation of patients, especially during sexual contact. Previous studies have shown that arthritis patients are more likely to be depressed than the general population (15), and their depressive symptoms are aggravated with their sense of shame (16). PsA is also very erosive to joints, and about 20% of patients will develop destructive arthritis. Chronic pain, swelling, deformity and bone fusion caused by arthritis will seriously damage the self-care and mental health of patients. In addition, previous studies have revealed that psoriasis and depression shared many common causes. For example, the decrease of brain-derived neuropathy factor (BDNF) and vitamin D3 (17-19), the increase of inflammatory cytokines and the change of melatonin level (18-20). In addition, in patients with PsA, the hypothalamic-pituitary-adrenal (HPA) axis is overactive, triggering cell-mediated autoimmunity and chronic inflammation. Studies have shown that the HPA axis is also related to mental stress, and an overactive HPA is commonly seen in depression. These may explain the pathogenesis behind the higher risk of depression in patients with PsA. PsA is incurable and recurrent, which can only be controlled by early diagnosis and timely treatments. PsA, which is a recurring, long-term painful and multi-system failure, will increase the psychological burden of patients.

The complex two-way relationship between arthritis and depression has not been fully elucidated (21). However, there is evidence to support a correlation between depression and arthritis. Some pro-inflammatory cytokines such as IL-6 and tumor necrosis factor-alpha (TNFα) are overexpressed in arthritis, so targeting these cytokines can be used as one of the treatment methods for arthritis. And pro-inflammatory cytokines are also risk factors for the development of mental health diseases such as depression. In particular, depression will further aggravate and impair physiological responses, including effective coping behaviors, such as dysregulation of inflammation in patients with arthritis (22). Therefore, the existence of pro-inflammatory cytokines may be one of the reasonable explanations between depression and arthritis. Antidepressant therapy while treating arthritis may improve arthritis.

Since the bidirectional relationship between depression and arthritis subtypes is still unclear, further prospective cohort studies are needed to confirm our results. However, this study is still meaningful. For example, the reliability of self-reporting of various arthritis has been proved to be a satisfactory factor (21,22). We collected and analyzed many high-quality data and questionnaires (PHQ-9) by trained personnel, and controlled many variables at the same time. Regardless of race/ethnicity, this abundant information will greatly extend our understanding. To our knowledge, this is the first time to use a nationally representative cohort to study the relationship between arthritis and depression.

However, there are still some limitations in this study. Firstly, major depression was self-assessed by PHQ-9, which may not be used as a standard to diagnose clinically related depression, this may result in high error rates, because not every patient knows exactly the diagnosis, better would be a Doppler check by medical report. Secondly, cross-sectional design is not considered to be able to infer the causal relationship between depression and arthritis. Finally, some potential confounding variables, such as the course of depression, were not included in the data set, which might interfere with the results to some extent.

Conclusions

Although previous studies have shown that there is a certain relationship between some types of arthritis and major depression, there is still a lack of systematic and large-scale cross-sectional studies, especially a lack of comparison between arthritis subgroups related to major depression. This study focused on the above correlation, and found that patients with PsA had a higher incidence of major depression than those with other types of arthritis. Our study suggests that all arthritis patients, especially PsA patients, may benefit from depression screening. Proper screening and timely treatment of depression have positive effects on the treatment and prognosis of arthritis.

Acknowledgments

Funding: This work was supported by National Natural Science Foundation of China (81774219) and Capital Foundation of Medical Development (2020-1-2121).

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at http://dx.doi.org/10.21037/apm-21-279

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/apm-21-279). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013).

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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