Mortality and the risk of cause-specific death in patients with depression : A nationwide cohort study

Mortality and the risk of cause-specific death in patients with depression : A nationwide cohort study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Mortality and the risk of cause-specific death in patients with depression : A nationwide cohort study Hong Jin Jeon, Hyewon Kim, Se Yun Kim, Kyungdo Han This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8433731/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Depression is associated with premature mortality, yet the magnitude and heterogeneity of cause-specific mortality risks remain incompletely understood at the population level. We conducted a nationwide cohort study using data from the National Health Insurance Sharing Service linked to mortality records from Statistics Korea. A total of 4,611,122 adults aged ≥ 20 years were followed for a mean of 10.2 years. Depression was identified based on clinical diagnoses. Adjusted hazard ratios (aHRs) for all-cause and cause-specific mortality were estimated using Cox proportional hazards models. During follow-up, 231,440 deaths occurred. Individuals with depression exhibited a higher incidence of all-cause mortality compared with those without depression. After adjustment for demographic, clinical, and lifestyle factors, depression was associated with increased all-cause mortality (aHR, 1.09; 95% CI, 1.07–1.11). Cause-specific analyses revealed the greatest risk elevation for suicide (aHR, 2.05; 95% CI, 1.92–2.19). In contrast, depression was associated with a lower risk of cancer-related mortality (aHR, 0.88; 95% CI, 0.86–0.91). In conclusion, depression was associated with heterogeneous patterns of mortality, characterized by markedly elevated suicide risk and a reduced risk of cancer-related death. These findings suggest distinct underlying biological and behavioral pathways linking depression to specific causes of mortality and highlight the need for cause-targeted prevention and intervention strategies. Health sciences/Diseases/Psychiatric disorders/Depression Biological sciences/Neuroscience Figures Figure 1 Figure 2 Figure 3 Introduction Depression is a common mental disorder with a lifetime prevalence of ~ 15% ( 1 ) and is recognized as the leading disease burden worldwide ( 2 ). Depression is particularly common in patients with physical illness, as the risk of depression is approximately seven times higher than in the general population ( 3 ). In general hospital inpatients, although there is considerable heterogeneity between studies, the prevalence of depression has been estimated as 12% with a 95% prediction interval of 4–32% ( 4 ). The link between depression and physical illnesses has been explained by various mechanisms (e.g., therapy-related pathways, behavioral connections, converging biology and psychosocial factors), besides coincidence ( 3 ). Depression is also associated with an increased risk of death. Previous studies have reported that all-cause mortality is increased by 17–60% in patients with depression ( 5 – 7 ). Regarding the cause of death, depression was associated with increased risks of death by cardiovascular diseases, respiratory illness, Parkinson’s disease, and suicide ( 5 , 6 , 8 , 9 ). While previous studies have suggested poor outcomes related to medical illness and the increased risk of mortality in patients with depression, they have limitations in that they were not conducted in populations representative of depressed patients ( 6 ), focused on a single cause-specific death ( 5 , 8 ), had short observation periods ( 6 ), or did not sufficiently consider various potential confounders ( 9 ). Therefore, in this study, we investigated the mortality pattern and analyzed the risk of each cause-specific death in patients with depression using national cohort data. Methods Data Source We used data from the National Health Insurance Sharing Service (NHISS) database provided by South Korea’s National Health Insurance Service (NHIS) ( 10 ). The NHIS is a government organization responsible for operating a mandatory, universal health insurance service that covers the South Korean population of over 50 million. The NHISS database contains data on medical service claims, including admissions, outpatient clinic visits, emergency room visits, pharmaceutical service use, and health screening programs. The general health screening program in South Korea is one of the world’s largest programs aimed at preventing and early intervening in common chronic diseases, and the participation rate is about 70% ( 11 ). Data from Statistics Korea were also used to obtain information on deaths. Statistics Korea is a central government organization that provides annual statistics on causes of death. We requested that Statistics Korea link the cause and date of death of the participants in the dataset extracted from the NHISS. The data from the NHISS and linked data from Statistics Korea were anonymized. The study protocol was approved by the Institutional Review Board of Samsung Medical Center (No. SMC 2024-07-039). Identification of eligible participants Among the people aged 20 years or older who underwent the health screening program in 2012, 4,910,068 were selected after a 40% simple random sampling. Among them, 6,454 individuals with a diagnosis of bipolar disorder (the International Statistical Classification of Diseases and Related Health Problems, 10th revision [ICD-10] codes of F30, F31, and F34.0 as the primary diagnostic code) and 17,522 individuals with a diagnosis of schizophrenia spectrum disorder (ICD-10 codes of F20–29) were excluded. After excluding 274,970 individuals with missing values ​​in the variables, 4,611,122 participants were identified as eligible for the analysis. We followed deaths from the day of the health screening program (index date) until December 2022 ( Supplementary Fig. 1 ). Definition of Depression Depression was identified based on claims made during the year before the index date. The diagnostic codes of F32 and F33 were used to define depression according to the ICD-10. Outcomes The outcome was death. The cause-specific deaths were coded based on the Korean Standard Classification of Diseases and Causes of Death, which is based on the ICD-10. Covariates We identified the participants’ baseline characteristics using data obtained on the day of the health screening program. Low income was defined as less than the bottom 25% of the total premium insurance payment, which is determined by income level and medical aid. Individuals’ smoking status, alcohol consumption (alcohol intake per day > 0 g), and physical activity were identified through answers to a self-questionnaire. Those who performed vigorous-intensity physical activity ≥ 3 days or moderate-intensity physical activity ≥ 5 days per week were considered to engage in regular physical activity ( 12 ). Obesity was defined as a body mass index of ≥ 25 kg/m 2 . In addition, age, sex, previous medical history of diabetes (ICD-10 code of E11, E12, E13, or E14 and one or more prescriptions of antidiabetic medication or fasting glucose level ≥ 126 mg/dL), hypertension (one or more prescription of antihypertensive agents under ICD-10 code of I10–13 or I15 or a systolic/diastolic blood pressure ≥ 140/90 mmHg), dyslipidemia (one or more prescription of anti-hyperlipidemic agents under ICD-10 code of E78 or total cholesterol ≥ 240 mg/dL), and cancer (ICD-10 C code or cancer registration code [V193]). The Charlson Comorbidity Index was calculated by weighting pre-established diagnoses to consider the individuals’ disease burden ( 13 ). Comorbid psychiatric diseases were also defined based on diagnostic codes from the ICD-10: anxiety disorder (F40, F41 as the primary diagnostic code), insomnia (G47.0, F51.0), substance use disorder (F10–19, including alcohol use disorder), obsessive-compulsive disorder (OCD) (F42), posttraumatic stress disorder (PTSD) (F43.1), dementia [Alzheimer’s disease (F00 or G30), vascular dementia (F01), and other dementia (F02, F03, or G31) and prescription of one or more dementia medications, such as donepezil, galantamine, rivastigmine, and memantine], and personality disorder (F60, F61). Statistical analysis Baseline demographic and clinical characteristics were presented as mean ± standard deviation (SD) for continuous variables and numbers with percentages for categorical variables. An analysis of variance and a χ 2 test were used to compare the variables between people with depression and those without depression. The incidence rates of all-cause death and cause-specific death were calculated and presented per 1,000 person-years. Cox proportional hazard regression analyses were conducted to investigate the association between depression and the risk of each cause-specific death. Hazard ratios (HR) and corresponding 95% confidence intervals (CIs) were presented. Model 1 was adjusted for age, sex, and low income; Model 2 was adjusted for smoking, drinking, physical activity, and the Charlson comorbidity index in addition to Model 1; and Model 3 was adjusted for obesity, anxiety disorder, insomnia, substance use disorder, obsessive-compulsive disorder, posttraumatic stress disorder, dementia, diabetes, hypertension, dyslipidemia, and cancer in addition to Model 2. Subgroup analyses were conducted according to sex, age, and CCI. Results Baseline characteristics Table 1 shows the baseline characteristics of the study participants. Among the 4,611,122 participants, 183,851 (4.0%) were identified as having depression. The proportion of females among those with depression was higher than that among those without (63.9 vs. 45.2%, respectively; P < 0.001). The mean age of those with depression was higher (57.9 years; SD, 13.2 years) than that of those without (48.0 years; SD, 13.8 years). Patients with depression tended to have low income, smoke less, drink less alcohol, be obese, have more comorbid psychiatric diseases and physical illnesses than those without depression. Table 1 Baseline characteristics of study subjects All (N = 4,611,122) Depression No (N = 4,427,271) Yes (N = 183,851) P value Sex < 0.001 Male 2,491,920 (54.0) 2,425,579 (54.8) 66,341 (36.1) Female 2,119,202 (46.0) 2,001,692 (45.2) 117,510 (63.9) Age (years) 48.4 ± 13.9 48.0 ± 13.8 57.9 ± 13.2 < 0.001 Age group < 0.001 20–39 1,263,672 (27.4) 1,248,698 (28.2) 14,974 (8.1) 40–64 2,728,980 (59.2) 2,619,515 (59.2) 109,465 (59.5) ≥ 65 618,470 (13.4) 559,058 (12.6) 59,412 (32.3) Low income 856,561 (18.6) 813,955 (18.4) 42,606 (23.2) < 0.001 Lifestyle factors Smoking 1,128,363 (24.5) 1,101,132 (24.9) 27,231 (14.8) < 0.001 Drinking 2,252,456 (48.9) 2,199,893 (49.7) 52,563 (28.6) < 0.001 Regular physical activity 882,065 (19.1) 847,053 (19.1) 35,012 (19.0) 0.342 Obesity 1,528,120 (33.1) 1,465,964 (33.1) 62,156 (33.8) < 0.001 Comorbid psychiatric diseases Anxiety disorder 352,219 (7.6) 277,356 (6.3) 74,863 (40.7) < 0.001 Insomnia 181,393 (3.9) 132,246 (3.0) 49,147 (26.7) < 0.001 Substance use disorder 12,838 (0.3) 7,787 (0.2) 5,051 (2.8) < 0.001 Obsessive-compulsive disorder 2,861 (0.1) 1,584 (0.0) 1,277 (0.7) < 0.001 PTSD 944 (0.0) 444 (0.0) 500 (0.3) < 0.001 Dementia 13,858 (0.3) 8,834 (0.2) 5,024 (2.7) < 0.001 Physical illness Hypertension 1,273,146 (27.6) 1,187,929 (26.8) 85,217 (46.4) < 0.001 Diabetes 466,162 (10.1) 432,584 (9.8) 33,578 (18.3) < 0.001 Dyslipidemia 940,401 (20.4) 876,330 (19.8) 64,071 (34.9) < 0.001 Cancer 69,401 (1.5) 63,996 (1.5) 5,405 (2.9) < 0.001 Charlson comorbidity index < 0.001 0 2,231,628 (48.4) 2,197,352 (49.6) 34,276 (18.6) 1 1,0482,04 (22.7) 1,008,848 (22.8) 39,356 (21.4) 2 625,739 (13.6) 589,935 (13.3) 35,804 (19.5) ≥ 3 705,551 (15.3) 631,136 (14.3) 74,415 (40.5) Mortality in patients with depression The average follow-up period was 10.2 years (SD, 1.2 years). Among those with depression, 23,592 died, with a mortality rate of 13.00 per 1,000 person-years, and among those without depression, 207,848 died, with a mortality rate of 4.61 per 1,000 person-years. In patients with depression, the crude mortality rate was highest due to cancer (3.10 per 1,000 person-years), followed by cardiovascular diseases (2.51 per 1,000 person-years), others (2.29 per 1,000 person-years), and respiratory diseases (1.60 per 1,000 person-years). (Table 2 and Fig. 1 ) The Kaplan-Meier survival curves for all-cause death and suicide are presented in Fig. 2 . Table 2 Hazard ratios and 95% confidence intervals of depression for each cause-specific death Depression N Death Duration (person-year) Incidence rate (per 1,000 person-years) Hazard ratio (95% Confidence intervals) Crude Model 1 Model 2 Model 3 All-cause death No 4,427,271 207,848 45,073,840.8 4.61 1 (Ref.) 1 (Ref.) 1 (Ref.) 1 (Ref.) Yes 183,851 23,592 1,814,687.1 13.00 2.82 (2.78, 2.85) 1.44 (1.42, 1.46) 1.20 (1.18, 1.22) 1.09 (1.07, 1.11) Infectious diseases No 4,427,271 5,169 45,073,840.8 0.11 1 (Ref.) 1 (Ref.) 1 (Ref.) 1 (Ref.) Yes 183,851 785 1,814,687.1 0.43 3.76 (3.49, 4.05) 1.69 (1.57, 1.82) 1.39 (1.28, 1.50) 1.20 (1.10, 1.30) Cancers No 4,427,271 74,419 45,073,840.8 1.65 1 (Ref.) 1 (Ref.) 1 (Ref.) 1 (Ref.) Yes 183,851 5,621 1,814,687.1 3.10 1.88 (1.83, 1.93) 1.03 (1.00, 1.06) 0.81 (0.79, 0.83) 0.88 (0.86, 0.91) Endocrine diseases No 4,427,271 5,876 45,073,840.8 0.13 1 (Ref.) 1 (Ref.) 1 (Ref.) 1 (Ref.) Yes 183,851 974 1,814,687.1 0.54 4.10 (3.83, 4.39) 1.93 (1.81, 2.07) 1.31 (1.22, 1.41) 1.21 (1.12, 1.30) Mental disorders No 4,427,271 1,754 45,073,840.8 0.04 1 (Ref.) 1 (Ref.) 1 (Ref.) 1 (Ref.) Yes 183,851 334 1,814,687.1 0.18 4.73 (4.21, 5.32) 2.07 (1.84, 2.33) 1.96 (1.74, 2.21) 1.26 (1.11, 1.44) Neurological disorders No 4,427,271 6,457 45,073,840.8 0.14 1 (Ref.) 1 (Ref.) 1 (Ref.) 1 (Ref.) Yes 183,851 1,239 1,814,687.1 0.68 4.74 (4.46, 5.04) 2.03 (1.91, 2.16) 1.83 (1.72, 1.95) 1.36 (1.27, 1.45) Cardiovascular diseases No 4,427,271 37,891 45,073,840.8 0.84 1 (Ref.) 1 (Ref.) 1 (Ref.) 1 (Ref.) Yes 183,851 4,548 1,814,687.1 2.51 2.98 (2.89, 3.07) 1.37 (1.33, 1.41) 1.19 (1.15, 1.22) 1.06 (1.02, 1.09) Respiratory diseases No 4,427,271 19,929 45,073,840.8 0.44 1 (Ref.) 1 (Ref.) 1 (Ref.) 1 (Ref.) Yes 183,851 2,911 1,814,687.1 1.60 3.62 (3.48, 3.76) 1.60 (1.54, 1.66) 1.37 (1.31, 1.42) 1.16 (1.12, 1.21) Digestive diseases No 4,427,271 7,584 45,073,840.8 0.17 1 (Ref.) 1 (Ref.) 1 (Ref.) 1 (Ref.) Yes 183,851 943 1,814,687.1 0.52 3.09 (2.89, 3.30) 1.82 (1.70, 1.95) 1.41 (1.31, 1.51) 1.06 (0.98, 1.15) Genitourinary diseases No 4,427,271 4,300 45,073,840.8 0.10 1 (Ref.) 1 (Ref.) 1 (Ref.) 1 (Ref.) Yes 183,851 649 1,814,687.1 0.36 3.74 (3.45, 4.06) 1.59 (1.46, 1.73) 1.13 (1.04, 1.23) 1.04 (0.95, 1.14) Suicide No 4,427,271 10,176 45,073,840.8 0.23 1 (Ref.) 1 (Ref.) 1 (Ref.) 1 (Ref.) Yes 183,851 1,426 1,814,687.1 0.79 3.48 (3.29, 3.68) 3.24 (3.06, 3.43) 3.05 (2.87, 3.23) 2.05 (1.92, 2.19) Others No 4,427,271 34,293 45,073,840.8 0.76 1 (Ref.) 1 (Ref.) 1 (Ref.) 1 (Ref.) Yes 183,851 4,162 1,814,687.1 2.29 3.00 (2.91, 3.10) 1.52 (1.47, 1.57) 1.40 (1.35, 1.45) 1.20 (1.16, 1.24) Model 1: adjusted for age, sex, and low income; Model 2: adjusted for age, sex, low income, smoking, drinking, physical activity, and Charlson comorbidity index; Model 3: adjusted for age, sex, low income, smoking, drinking, physical activity, obesity, and anxiety disorder, insomnia, substance use disorder, obsessive-compulsive disorder, posttraumatic stress disorder, dementia, diabetes, hypertension, dyslipidemia, cancer, and Charlson comorbidity index Risk of cause-specific death in patients with depression Table 2 and Fig. 3 show the risk of cause-specific death in patients with depression compared to those without depression. Compared to those without depression, patients with depression showed an increased risk of all-cause death (adjusted HR [aHR], 1.09; 95% CI, 1.07–1.11) after controlling for covariates. In the fully adjusted model, the cause-specific death with the greatest increased risk in patients with depression was suicide (aHR, 2.05; 95% CI, 1.92–2.19). The following increased risks were observed: neurological disorders (aHR, 1.36; 95% CI, 1.27–1.45), mental disorder (aHR, 1.26; 95% CI, 1.11–1.44), endocrine diseases (aHR, 1.21; 95% CI, 1.12–1.30), infectious diseases (aHR, 1.20; 95% CI, 1.10–1.30), respiratory diseases (aHR, 1.16; 95% CI, 1.12–1.21), and cardiovascular diseases (aHR, 1.06; 95% CI, 1.02–1.09). Compared to those without depression, patients with depression showed a decreased risk of death by cancer (aHR 0.88; 95% CI, 0.86–0.91). Subgroup analyses Supplementary Table 1 shows the results of subgroup analyses according to sex. The risk of death by suicide was found to be greater in females (aHR, 2.31 [95% CI, 2.10–2.54] for females; aHR, 1.90 [95% CI, 1.76–2.06] for males; P for interaction = 0.001). The increased risk of death from digestive diseases was more pronounced in females ( P for interaction = 0.009), and the increased risk of death from neurological disorders was more pronounced in males ( P for interaction = 0.005). The decreased risk of death from cancer was more pronounced in females ( P for interaction < 0.001). Supplementary Table 2 presents the results of the subgroup analyses by age subgroups. Overall, the risk of death in patients with depression was significantly increased in those aged 20–39 years (aHR, 1.97 [95% CI, 1.70–2.29] for 20–39 years; aHR, 1.27 [1.23–1.30] for 40–64 years; aHR 1.04 [95% CI, 1.02–1.05] for ≥ 65 years; P for interaction < 0.001). In particular, the increased risks of death from mental disorders, endocrine diseases, neurological diseases, suicide, genitourinary diseases, and digestive diseases were pronounced in those aged 20–39 years, and the increased risks of death from respiratory diseases, infectious diseases, and cardiovascular diseases were pronounced in those aged 40–64 years. Supplementary Table 3 presents the results of subgroup analyses by CCI. The risk of all-cause death associated with depression was inversely related to comorbidity burden, with the most pronounced increase observed among patients with a CCI of 0 with an aHR of 1.24 (95% CI, 1.18–1.30) ( P for interaction < 0.001). Each cause-specific death showed similar results, with cancers ( P for interaction < 0.001), neurological disorders ( P for interaction < 0.001), digestive diseases (P for interaction < 0.001), and genitourinary diseases ( P for interaction = 0.026) showing this pattern. Discussion In this nationwide cohort study, we followed up deaths among 4,611,122 adults, according to the presence or absence of depression. We presented the risk of depression on all-cause death and cause-specific death after controlling for various potential confounders. We found that the distribution of causes of death was similar between people with and without depression. However, people with depression had a higher risk of all-cause death and several cause-specific deaths, including suicide, and a lower risk of death from cancer, compared to those without depression. The distribution of crude mortality in people with and without depression showed a similar pattern. Despite variations in the classification of causes of death, previous studies have consistently identified cancer, cardiovascular diseases, and respiratory diseases as the most common causes of death in patients with depression ( 9 , 14 ). However, in the regression analysis, the highest cause-specific mortality risk among patients with depression was observed for suicide. Prior studies have reported hazard ratios ranging from 2.1 to 13.2 for the association between depression or mood disorders with suicide, consistent with our findings ( 6 , 9 , 15 ). Depression is a well-established risk factor for suicide, associated not only with suicide deaths but also with suicidal ideation and attempts ( 16 , 17 ). Consequently, suicide prevention among patients with depression represents a critical clinical priority. The finding that suicide was the leading cause of death among patients with depression in our study further underscores this important clinical implication. In addition, the survival curve for suicide among patients with depression showed a gradual and continuous decline, suggesting that the elevated risk of suicide persists across the entire follow-up period without being confined to a specific time window. Besides suicide, depression was associated with an increased risk of death from various physical illnesses. Depression is one of the most common comorbidities of many medical diseases ( 18 ). And, poorer outcomes have frequently been reported in patients with medical disease who have depression. For example, in patients with type 2 diabetes, depression increases the risk of cardiovascular events such as myocardial infarction or ischemic stroke by 18–19%, and the risk of death by 24% ( 19 ). In patients with chronic obstructive pulmonary disease (COPD), the presence of depression was associated with a 36% increased risk of acute exacerbation.( 20 ) A study analyzing data from the WHO World Health Survey found that depression had the largest effect on worsening mean health scores compared with the other chronic conditions, and that comorbidity of depression and one or more chronic conditions had the lowest health scores of all disease groups ( 21 ). Several mechanisms may underlie the increased mortality from physical illnesses among patients with depression. First, depressive symptoms such as fatigue and diminished motivation may reduce patients’ likelihood of seeking timely medical attention or adhering adequately to prescribed treatments. Second, psychotropic medications used in the management of depressive symptoms may exert adverse effects on physical health, thereby exacerbating comorbid medical conditions. Third, physicians may inadvertently focus predominantly on the patient’s psychiatric symptoms, resulting in the relative neglect of physical health concerns. Finally, physical complaints expressed by depressed individuals may be misattributed to psychosomatic origins, leading to delayed recognition or suboptimal management of underlying medical diseases. However, in this study, patients with depression showed a lower risk of cancer-related death. Previous studies examining the prognostic impact of comorbid depression in cancer patients have shown mixed results: meta-analyses have generally reported that comorbid depression in patients with cancer is associated with worse survival outcomes ( 22 , 23 ). In contrast, a previous study of head and neck cancer patients found that the timing of depression diagnosis and the duration of psychiatric follow-up could affect survival: the “pre-cancer only” group had lower survival, whereas the “post-cancer only” group had higher survival, and the “both before and after cancer” group showed higher survival compared with patients whose treatment was discontinued ( 24 ). Similarly, a study of breast cancer patients found that those diagnosed and treated for depression only before or only after their cancer diagnosis had an increased risk of death, whereas those who maintained depression treatment both before and after diagnosis showed no reduction in survival ( 25 ). These findings suggest that consistent psychiatric treatment after a cancer diagnosis may contribute to improving the prognosis of cancer patients. Recent comprehensive cancer center systems commonly incorporate proactive psychiatric consultation, which facilitates earlier detection and intervention for mental disorders and may thereby contribute to reduced mortality among these patients. This study has the strength of being conducted on a large sample size of over 4.6 million participants. Moreover, in addition to presenting crude mortality in patients with depression, we performed analyses that included various potential confounders that could affect death to elucidate the association between depression and each cause-specific death. However, several methodological issues should be considered when interpreting and generalizing the results of this study. First, selection bias may exist since the study targeted people who participated in the national health screening program in a specific year. People who participate in the program may be more likely to engage in positive health behaviors than those who do not participate, or an individual's prior health status may have influenced their decision to participate in the program. Second, the definition of depression was made solely through diagnostic codes. Even if patients met the clinical criteria for depression, those who did not seek medical care may have been classified as not having depression, which could have influenced the study results. Third, several potential confounders that could affect the association between depression and death, including duration and severity of depression, treatment history, medication use, and access to hospitals, were not included in the analysis. Fourth, the causes of death were classified broadly, and deaths due to individual diseases were not included in the analysis. In particular, among the cause-specific deaths, those classified as deaths from mental disorders are presumed to be suicides. This may have arisen from heterogeneity in physicians’ documentation of cause-of-death codes. Future research is expected to focus on the relationship between depression and individual cause-specific death. Fifth, since this study was conducted among the South Korean population, the results may not be generalizable to other populations. Conclusions In this South Korean nationwide cohort study, we found that the distribution of causes of death was similar between people with and without depression. However, people with depression had a higher risk of all-cause death and several cause-specific deaths, including suicide, and a lower risk of death from cancer, compared to those without depression. Declarations Conflicts of interest No disclosures to report. Authors' contributions Hyewon Kim : Conceptualization, Methodology, Writing – Original Draft, Writing – Review & Editing. Se Yun Kim : Formal analysis, Writing – Review & Editing. Kyungdo Han : Conceptualization, Methodology, Formal analysis, Writing – Review & Editing. Hong Jin Jeon : Conceptualization, Project administration, Methodology, Writing – Review & Editing Acknowledgments This research was supported by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), sponsored by the Ministry of Health & Welfare, Republic of Korea (No. HR21C0885). Availability of data Publicly available datasets were analyzed in this study. This data can be found here: https://nhiss.nhis.or.kr/ . References Pedersen CB, Mors O, Bertelsen A, Waltoft BL, Agerbo E, McGrath JJ, et al. A comprehensive nationwide study of the incidence rate and lifetime risk for treated mental disorders. JAMA Psychiatry. 2014;71(5):573–81. Global, regional, and national burden of 12 mental disorders in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Psychiatry. 2022;9(2):137 – 50. Gold SM, Köhler-Forsberg O, Moss-Morris R, Mehnert A, Miranda JJ, Bullinger M, et al. Comorbid depression in medical diseases. Nat Rev Dis Primers. 2020;6(1):69. Walker J, Burke K, Wanat M, Fisher R, Fielding J, Mulick A, et al. The prevalence of depression in general hospital inpatients: a systematic review and meta-analysis of interview-based studies. Psychol Med. 2018;48(14):2285–98. Meng R, Yu C, Liu N, He M, Lv J, Guo Y, et al. Association of Depression With All-Cause and Cardiovascular Disease Mortality Among Adults in China. JAMA Netw Open. 2020;3(2):e1921043. Zivin K, Yosef M, Miller EM, Valenstein M, Duffy S, Kales HC, et al. Associations between depression and all-cause and cause-specific risk of death: a retrospective cohort study in the Veterans Health Administration. J Psychosom Res. 2015;78(4):324–31. Chesney E, Goodwin GM, Fazel S. Risks of all-cause and suicide mortality in mental disorders: a meta-review. World psychiatry: official journal of the World Psychiatric Association (WPA). 2014;13(2):153–60. Kim H, Jung JH, Han K, Jeon HJ. Risk of suicide and all-cause death in patients with mental disorders: a nationwide cohort study. Mol Psychiatry. 2025;30(7):2831–9. Osler M, Rosenqvist TW, Bjørn-Rozing MP, Jorgensen A, Jorgensen MB, Jørgensen TSH, et al. All-Cause and Cause-Specific Mortality Among Individuals With Major Depression: A Nationwide Danish Matched-Cohort Study. Acta Psychiatrica Scandinavica. 2025;152(1):60–8. Lee J, Lee JS, Park SH, Shin SA, Kim K. Cohort Profile: The National Health Insurance Service-National Sample Cohort (NHIS-NSC), South Korea. International journal of epidemiology. 2017;46(2):e15. Shin DW, Cho J, Park JH, Cho B. National General Health Screening Program in Korea: history, current status, and future direction. Precis Future Med. 2022;6(1):9–31. Pescatello LS, Riebe D, Thompson PD. ACSM's guidelines for exercise testing and prescription: Lippincott Williams & Wilkins; 2014. Sundararajan V, Henderson T, Perry C, Muggivan A, Quan H, Ghali WA. New ICD-10 version of the Charlson comorbidity index predicted in-hospital mortality. Journal of clinical epidemiology. 2004;57(12):1288–94. Alotaibi R, Halbesma N, Wild SH, Jackson CA. Severe depression and all-cause and cause-specific mortality in Scotland: 20 year national cohort study. BJPsych Open. 2024;10(1):e28. Plana-Ripoll O, Pedersen CB, Agerbo E, Holtz Y, Erlangsen A, Canudas-Romo V, et al. A comprehensive analysis of mortality-related health metrics associated with mental disorders: a nationwide, register-based cohort study. Lancet. 2019;394(10211):1827–35. Cai H, Xie XM, Zhang Q, Cui X, Lin JX, Sim K, et al. Prevalence of Suicidality in Major Depressive Disorder: A Systematic Review and Meta-Analysis of Comparative Studies. Front Psychiatry. 2021;12:690130. Turecki G, Brent DA, Gunnell D, O’Connor RC, Oquendo MA, Pirkis J, et al. Suicide and suicide risk. Nature Reviews Disease Primers. 2019;5(1):74. Gold SM, Köhler-Forsberg O, Moss-Morris R, Mehnert A, Miranda JJ, Bullinger M, et al. Comorbid depression in medical diseases. Nature Reviews Disease Primers. 2020;6(1):69. Kim H, Lee KN, Shin DW, Han K, Jeon HJ. Association of comorbid mental disorders with cardiovascular disease risk in patients with type 2 diabetes: A nationwide cohort study. Gen Hosp Psychiatry. 2022;79:33–41. Wu K, Lu L, Chen Y, Peng J, Wu X, Tang G, et al. Associations of anxiety and depression with prognosis in chronic obstructive pulmonary disease: A systematic review and meta-analysis. Pulmonology. 2025;31(1):2438553. Moussavi S, Chatterji S, Verdes E, Tandon A, Patel V, Ustun B. Depression, chronic diseases, and decrements in health: results from the World Health Surveys. The Lancet. 2007;370(9590):851–8. Pinquart M, Duberstein PR. Depression and cancer mortality: a meta-analysis. Psychol Med. 2010;40(11):1797–810. Ungvari Z, Fekete M, Buda A, Lehoczki A, Fekete JT, Varga P, et al. Depression increases cancer mortality by 23–83%: a meta-analysis of 65 studies across five major cancer types. GeroScience. 2025. Huang RW, Chang KP, Marchi F, Loh CYY, Lin YJ, Chang CJ, et al. The impact of depression on survival of head and neck cancer patients: A population-based cohort study. Front Oncol. 2022;12:871915. Lei F, Vanderpool RC, McLouth LE, Romond EH, Chen Q, Durbin EB, et al. Influence of depression on breast cancer treatment and survival: A Kentucky population-based study. Cancer. 2023;129(12):1821–35. Additional Declarations The authors have declared there is NO conflict of interest to disclose Supplementary Files Supplementarymaterial.docx Supplementary material Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8433731","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":569058468,"identity":"52cbcf05-f915-4309-9463-bc962bb84997","order_by":0,"name":"Hong Jin Jeon","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA1klEQVRIiWNgGAWjYBACxhkMCQcSDCR42NgbgFwDC6K0JD74UGAjx8dzAKRFgghrJBiYDWd8SDOWk0iAcAkC5tkNz6R5DA4ntkk+v7rhR4EEA397dwJ+h805kAbRIp1TdrMH6DCJM2c3EPBLAlxL2g0eoBYDiVxitUieSbv5h0gtyYYzDNKM2STYj90m1hZgIBvYyLHx5LDdlgFGEEG/GM7IAUblHwke+fbjz26++WMjx9/eS0BLA08ClMljACbxKgcBeQb2A1Am+wOCqkfBKBgFo2BkAgCY00kylzZb3AAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0002-6126-542X","institution":"Samsung Medical Center","correspondingAuthor":true,"prefix":"","firstName":"Hong","middleName":"Jin","lastName":"Jeon","suffix":""},{"id":569058469,"identity":"f413f2b0-5294-4f09-b8ae-cfbc8a6c9eb9","order_by":1,"name":"Hyewon Kim","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Hyewon","middleName":"","lastName":"Kim","suffix":""},{"id":569058470,"identity":"33206541-81ae-4f0d-816b-ce74df9c4f1e","order_by":2,"name":"Se Yun Kim","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Se","middleName":"Yun","lastName":"Kim","suffix":""},{"id":569058471,"identity":"2dffaaaf-9f39-44f9-b0a4-63274cf33a57","order_by":3,"name":"Kyungdo Han","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Kyungdo","middleName":"","lastName":"Han","suffix":""}],"badges":[],"createdAt":"2025-12-23 12:35:32","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8433731/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8433731/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":102761244,"identity":"b392b77d-5c51-42a5-b14d-85ba67c5b6dd","added_by":"auto","created_at":"2026-02-16 10:36:59","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":127399,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMortality rates of each cause of death in people with/without depression\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"OnlineFigure1.Mortality.png","url":"https://assets-eu.researchsquare.com/files/rs-8433731/v1/e1a8353165fc1bc3cb54b1ac.png"},{"id":102963002,"identity":"da376954-4d77-4f10-8874-d69210aa37ac","added_by":"auto","created_at":"2026-02-19 04:12:43","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":126508,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eKaplan-Meier survival curves representing time to all-cause death and suicide in people with/without depression\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"OnlineFigure2.KMcurve.png","url":"https://assets-eu.researchsquare.com/files/rs-8433731/v1/d952b445770df33b9031c462.png"},{"id":102761246,"identity":"70a28aff-20da-460e-ab18-a7d4dbe4d515","added_by":"auto","created_at":"2026-02-16 10:36:59","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":83992,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eForest plots showing the hazard ratios and corresponding 95% confidence intervals of each cause of death in patients with depression\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCI, confidence interval\u003c/p\u003e\n\u003cp\u003eAdjusted for age, sex, low income, smoking, drinking, physical activity, obesity, anxiety disorder, insomnia, substance use disorder, obsessive-compulsive disorder, posttraumatic stress disorder, dementia, diabetes, hypertension, dyslipidemia, cancer, and the Charlson comorbidity index\u003c/p\u003e","description":"","filename":"OnlineFigure3.Forestplot.png","url":"https://assets-eu.researchsquare.com/files/rs-8433731/v1/699f6f9874410e201bd07967.png"},{"id":105734789,"identity":"509108b0-90da-406b-9bce-7776d23cac8c","added_by":"auto","created_at":"2026-03-30 11:47:35","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1663709,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8433731/v1/f5baa6ea-d64b-47d8-8bc2-249adb0a880a.pdf"},{"id":102761247,"identity":"a12b9d2e-6b87-4b99-8d83-c664dee36678","added_by":"auto","created_at":"2026-02-16 10:36:59","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":176165,"visible":true,"origin":"","legend":"Supplementary material","description":"","filename":"Supplementarymaterial.docx","url":"https://assets-eu.researchsquare.com/files/rs-8433731/v1/0df2d493fc9cd5dd847a8b4a.docx"}],"financialInterests":"The authors have declared there is \u003cb\u003eNO\u003c/b\u003e conflict of interest to disclose","formattedTitle":"Mortality and the risk of cause-specific death in patients with depression\r\n: A nationwide cohort study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eDepression is a common mental disorder with a lifetime prevalence of ~\u0026thinsp;15% (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) and is recognized as the leading disease burden worldwide (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Depression is particularly common in patients with physical illness, as the risk of depression is approximately seven times higher than in the general population (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). In general hospital inpatients, although there is considerable heterogeneity between studies, the prevalence of depression has been estimated as 12% with a 95% prediction interval of 4\u0026ndash;32% (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). The link between depression and physical illnesses has been explained by various mechanisms (e.g., therapy-related pathways, behavioral connections, converging biology and psychosocial factors), besides coincidence (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eDepression is also associated with an increased risk of death. Previous studies have reported that all-cause mortality is increased by 17\u0026ndash;60% in patients with depression (\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Regarding the cause of death, depression was associated with increased risks of death by cardiovascular diseases, respiratory illness, Parkinson\u0026rsquo;s disease, and suicide (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eWhile previous studies have suggested poor outcomes related to medical illness and the increased risk of mortality in patients with depression, they have limitations in that they were not conducted in populations representative of depressed patients (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e), focused on a single cause-specific death (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e), had short observation periods (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e), or did not sufficiently consider various potential confounders (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Therefore, in this study, we investigated the mortality pattern and analyzed the risk of each cause-specific death in patients with depression using national cohort data.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eData Source\u003c/h2\u003e \u003cp\u003eWe used data from the National Health Insurance Sharing Service (NHISS) database provided by South Korea\u0026rsquo;s National Health Insurance Service (NHIS) (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). The NHIS is a government organization responsible for operating a mandatory, universal health insurance service that covers the South Korean population of over 50\u0026nbsp;million. The NHISS database contains data on medical service claims, including admissions, outpatient clinic visits, emergency room visits, pharmaceutical service use, and health screening programs. The general health screening program in South Korea is one of the world\u0026rsquo;s largest programs aimed at preventing and early intervening in common chronic diseases, and the participation rate is about 70% (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eData from Statistics Korea were also used to obtain information on deaths. Statistics Korea is a central government organization that provides annual statistics on causes of death. We requested that Statistics Korea link the cause and date of death of the participants in the dataset extracted from the NHISS.\u003c/p\u003e \u003cp\u003eThe data from the NHISS and linked data from Statistics Korea were anonymized. The study protocol was approved by the Institutional Review Board of Samsung Medical Center (No. SMC 2024-07-039).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eIdentification of eligible participants\u003c/h3\u003e\n\u003cp\u003eAmong the people aged 20 years or older who underwent the health screening program in 2012, 4,910,068 were selected after a 40% simple random sampling. Among them, 6,454 individuals with a diagnosis of bipolar disorder (the International Statistical Classification of Diseases and Related Health Problems, 10th revision [ICD-10] codes of F30, F31, and F34.0 as the primary diagnostic code) and 17,522 individuals with a diagnosis of schizophrenia spectrum disorder (ICD-10 codes of F20\u0026ndash;29) were excluded. After excluding 274,970 individuals with missing values ​​in the variables, 4,611,122 participants were identified as eligible for the analysis. We followed deaths from the day of the health screening program (index date) until December 2022 (\u003cb\u003eSupplementary Fig.\u0026nbsp;1\u003c/b\u003e).\u003c/p\u003e\n\u003ch3\u003eDefinition of Depression\u003c/h3\u003e\n\u003cp\u003eDepression was identified based on claims made during the year before the index date. The diagnostic codes of F32 and F33 were used to define depression according to the ICD-10.\u003c/p\u003e\n\u003ch3\u003eOutcomes\u003c/h3\u003e\n\u003cp\u003eThe outcome was death. The cause-specific deaths were coded based on the Korean Standard Classification of Diseases and Causes of Death, which is based on the ICD-10.\u003c/p\u003e\n\u003ch3\u003eCovariates\u003c/h3\u003e\n\u003cp\u003eWe identified the participants\u0026rsquo; baseline characteristics using data obtained on the day of the health screening program. Low income was defined as less than the bottom 25% of the total premium insurance payment, which is determined by income level and medical aid. Individuals\u0026rsquo; smoking status, alcohol consumption (alcohol intake per day\u0026thinsp;\u0026gt;\u0026thinsp;0 g), and physical activity were identified through answers to a self-questionnaire. Those who performed vigorous-intensity physical activity\u0026thinsp;\u0026ge;\u0026thinsp;3 days or moderate-intensity physical activity\u0026thinsp;\u0026ge;\u0026thinsp;5 days per week were considered to engage in regular physical activity (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Obesity was defined as a body mass index of \u0026ge;\u0026thinsp;25 kg/m\u003csup\u003e2\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn addition, age, sex, previous medical history of diabetes (ICD-10 code of E11, E12, E13, or E14 and one or more prescriptions of antidiabetic medication or fasting glucose level\u0026thinsp;\u0026ge;\u0026thinsp;126 mg/dL), hypertension (one or more prescription of antihypertensive agents under ICD-10 code of I10\u0026ndash;13 or I15 or a systolic/diastolic blood pressure\u0026thinsp;\u0026ge;\u0026thinsp;140/90 mmHg), dyslipidemia (one or more prescription of anti-hyperlipidemic agents under ICD-10 code of E78 or total cholesterol\u0026thinsp;\u0026ge;\u0026thinsp;240 mg/dL), and cancer (ICD-10 C code or cancer registration code [V193]). The Charlson Comorbidity Index was calculated by weighting pre-established diagnoses to consider the individuals\u0026rsquo; disease burden (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Comorbid psychiatric diseases were also defined based on diagnostic codes from the ICD-10: anxiety disorder (F40, F41 as the primary diagnostic code), insomnia (G47.0, F51.0), substance use disorder (F10\u0026ndash;19, including alcohol use disorder), obsessive-compulsive disorder (OCD) (F42), posttraumatic stress disorder (PTSD) (F43.1), dementia [Alzheimer\u0026rsquo;s disease (F00 or G30), vascular dementia (F01), and other dementia (F02, F03, or G31) and prescription of one or more dementia medications, such as donepezil, galantamine, rivastigmine, and memantine], and personality disorder (F60, F61).\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eBaseline demographic and clinical characteristics were presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD) for continuous variables and numbers with percentages for categorical variables. An analysis of variance and a χ\u003csup\u003e2\u003c/sup\u003e test were used to compare the variables between people with depression and those without depression. The incidence rates of all-cause death and cause-specific death were calculated and presented per 1,000 person-years.\u003c/p\u003e \u003cp\u003eCox proportional hazard regression analyses were conducted to investigate the association between depression and the risk of each cause-specific death. Hazard ratios (HR) and corresponding 95% confidence intervals (CIs) were presented. Model 1 was adjusted for age, sex, and low income; Model 2 was adjusted for smoking, drinking, physical activity, and the Charlson comorbidity index in addition to Model 1; and Model 3 was adjusted for obesity, anxiety disorder, insomnia, substance use disorder, obsessive-compulsive disorder, posttraumatic stress disorder, dementia, diabetes, hypertension, dyslipidemia, and cancer in addition to Model 2.\u003c/p\u003e \u003cp\u003eSubgroup analyses were conducted according to sex, age, and CCI.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eBaseline characteristics\u003c/h2\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows the baseline characteristics of the study participants. Among the 4,611,122 participants, 183,851 (4.0%) were identified as having depression. The proportion of females among those with depression was higher than that among those without (63.9 \u003cem\u003evs.\u003c/em\u003e 45.2%, respectively; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The mean age of those with depression was higher (57.9 years; SD, 13.2 years) than that of those without (48.0 years; SD, 13.8 years). Patients with depression tended to have low income, smoke less, drink less alcohol, be obese, have more comorbid psychiatric diseases and physical illnesses than those without depression.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline characteristics of study subjects\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eAll\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;4,611,122)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003eDepression\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;4,427,271)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;183,851)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2,491,920 (54.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2,425,579 (54.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e66,341 (36.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2,119,202 (46.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2,001,692 (45.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e117,510 (63.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e48.4\u0026thinsp;\u0026plusmn;\u0026thinsp;13.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e48.0\u0026thinsp;\u0026plusmn;\u0026thinsp;13.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e57.9\u0026thinsp;\u0026plusmn;\u0026thinsp;13.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eAge group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e20\u0026ndash;39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1,263,672 (27.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1,248,698 (28.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e14,974 (8.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e40\u0026ndash;64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2,728,980 (59.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2,619,515 (59.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e109,465 (59.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e618,470 (13.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e559,058 (12.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e59,412 (32.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eLow income\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e856,561 (18.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e813,955 (18.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e42,606 (23.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eLifestyle factors\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eSmoking\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1,128,363 (24.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1,101,132 (24.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e27,231 (14.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eDrinking\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2,252,456 (48.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2,199,893 (49.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e52,563 (28.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eRegular physical activity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e882,065 (19.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e847,053 (19.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e35,012 (19.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.342\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eObesity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1,528,120 (33.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1,465,964 (33.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e62,156 (33.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eComorbid psychiatric diseases\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eAnxiety disorder\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e352,219 (7.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e277,356 (6.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e74,863 (40.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eInsomnia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e181,393 (3.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e132,246 (3.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e49,147 (26.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eSubstance use disorder\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12,838 (0.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7,787 (0.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5,051 (2.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eObsessive-compulsive disorder\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2,861 (0.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1,584 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1,277 (0.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003ePTSD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e944 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e444 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e500 (0.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eDementia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13,858 (0.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8,834 (0.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5,024 (2.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003ePhysical illness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1,273,146 (27.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1,187,929 (26.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e85,217 (46.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eDiabetes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e466,162 (10.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e432,584 (9.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e33,578 (18.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eDyslipidemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e940,401 (20.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e876,330 (19.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e64,071 (34.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eCancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e69,401 (1.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e63,996 (1.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5,405 (2.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eCharlson comorbidity index\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2,231,628 (48.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2,197,352 (49.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e34,276 (18.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1,0482,04 (22.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1,008,848 (22.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e39,356 (21.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e625,739 (13.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e589,935 (13.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e35,804 (19.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e705,551 (15.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e631,136 (14.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e74,415 (40.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eMortality in patients with depression\u003c/h2\u003e \u003cp\u003eThe average follow-up period was 10.2 years (SD, 1.2 years). Among those with depression, 23,592 died, with a mortality rate of 13.00 per 1,000 person-years, and among those without depression, 207,848 died, with a mortality rate of 4.61 per 1,000 person-years.\u003c/p\u003e \u003cp\u003eIn patients with depression, the crude mortality rate was highest due to cancer (3.10 per 1,000 person-years), followed by cardiovascular diseases (2.51 per 1,000 person-years), others (2.29 per 1,000 person-years), and respiratory diseases (1.60 per 1,000 person-years). (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) The Kaplan-Meier survival curves for all-cause death and suicide are presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eHazard ratios and 95% confidence intervals of depression for each cause-specific death\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"11\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eDepression\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eDeath\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eDuration (person-year)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eIncidence rate\u003c/p\u003e \u003cp\u003e(per 1,000 person-years)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c11\" namest=\"c8\"\u003e \u003cp\u003eHazard ratio (95% Confidence intervals)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eCrude\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eModel 1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eModel 2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003eModel 3\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"11\" nameend=\"c11\" namest=\"c1\"\u003e \u003cp\u003eAll-cause death\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4,427,271\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e207,848\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e45,073,840.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1 (Ref.)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1 (Ref.)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1 (Ref.)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e1 (Ref.)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e183,851\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e23,592\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1,814,687.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e13.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2.82 (2.78, 2.85)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1.44 (1.42, 1.46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1.20 (1.18, 1.22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e1.09 (1.07, 1.11)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"11\" nameend=\"c11\" namest=\"c1\"\u003e \u003cp\u003eInfectious diseases\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4,427,271\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5,169\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e45,073,840.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1 (Ref.)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1 (Ref.)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1 (Ref.)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e1 (Ref.)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e183,851\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e785\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1,814,687.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3.76 (3.49, 4.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1.69 (1.57, 1.82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1.39 (1.28, 1.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e1.20 (1.10, 1.30)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"11\" nameend=\"c11\" namest=\"c1\"\u003e \u003cp\u003eCancers\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4,427,271\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e74,419\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e45,073,840.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1 (Ref.)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1 (Ref.)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1 (Ref.)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e1 (Ref.)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e183,851\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5,621\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1,814,687.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.88 (1.83, 1.93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1.03 (1.00, 1.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.81 (0.79, 0.83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.88 (0.86, 0.91)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"11\" nameend=\"c11\" namest=\"c1\"\u003e \u003cp\u003eEndocrine diseases\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4,427,271\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5,876\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e45,073,840.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1 (Ref.)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1 (Ref.)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1 (Ref.)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e1 (Ref.)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e183,851\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e974\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1,814,687.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e4.10 (3.83, 4.39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1.93 (1.81, 2.07)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1.31 (1.22, 1.41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e1.21 (1.12, 1.30)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"11\" nameend=\"c11\" namest=\"c1\"\u003e \u003cp\u003eMental disorders\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4,427,271\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1,754\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e45,073,840.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1 (Ref.)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1 (Ref.)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1 (Ref.)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e1 (Ref.)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e183,851\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e334\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1,814,687.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e4.73 (4.21, 5.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e2.07 (1.84, 2.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1.96 (1.74, 2.21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e1.26 (1.11, 1.44)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"11\" nameend=\"c11\" namest=\"c1\"\u003e \u003cp\u003eNeurological disorders\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4,427,271\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6,457\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e45,073,840.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1 (Ref.)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1 (Ref.)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1 (Ref.)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e1 (Ref.)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e183,851\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1,239\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1,814,687.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e4.74 (4.46, 5.04)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e2.03 (1.91, 2.16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1.83 (1.72, 1.95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e1.36 (1.27, 1.45)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"11\" nameend=\"c11\" namest=\"c1\"\u003e \u003cp\u003eCardiovascular diseases\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4,427,271\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e37,891\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e45,073,840.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1 (Ref.)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1 (Ref.)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1 (Ref.)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e1 (Ref.)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e183,851\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4,548\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1,814,687.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2.98 (2.89, 3.07)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1.37 (1.33, 1.41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1.19 (1.15, 1.22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e1.06 (1.02, 1.09)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"11\" nameend=\"c11\" namest=\"c1\"\u003e \u003cp\u003eRespiratory diseases\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4,427,271\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e19,929\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e45,073,840.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1 (Ref.)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1 (Ref.)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1 (Ref.)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e1 (Ref.)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e183,851\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2,911\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1,814,687.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3.62 (3.48, 3.76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1.60 (1.54, 1.66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1.37 (1.31, 1.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e1.16 (1.12, 1.21)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"11\" nameend=\"c11\" namest=\"c1\"\u003e \u003cp\u003eDigestive diseases\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4,427,271\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7,584\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e45,073,840.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1 (Ref.)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1 (Ref.)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1 (Ref.)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e1 (Ref.)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e183,851\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e943\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1,814,687.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3.09 (2.89, 3.30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1.82 (1.70, 1.95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1.41 (1.31, 1.51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e1.06 (0.98, 1.15)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"11\" nameend=\"c11\" namest=\"c1\"\u003e \u003cp\u003eGenitourinary diseases\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4,427,271\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4,300\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e45,073,840.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1 (Ref.)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1 (Ref.)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1 (Ref.)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e1 (Ref.)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e183,851\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e649\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1,814,687.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3.74 (3.45, 4.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1.59 (1.46, 1.73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1.13 (1.04, 1.23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e1.04 (0.95, 1.14)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"11\" nameend=\"c11\" namest=\"c1\"\u003e \u003cp\u003eSuicide\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4,427,271\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10,176\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e45,073,840.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1 (Ref.)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1 (Ref.)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1 (Ref.)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e1 (Ref.)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e183,851\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1,426\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1,814,687.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3.48 (3.29, 3.68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e3.24 (3.06, 3.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e3.05 (2.87, 3.23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e2.05 (1.92, 2.19)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"11\" nameend=\"c11\" namest=\"c1\"\u003e \u003cp\u003eOthers\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4,427,271\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e34,293\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e45,073,840.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1 (Ref.)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1 (Ref.)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1 (Ref.)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e1 (Ref.)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e183,851\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4,162\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1,814,687.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3.00 (2.91, 3.10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1.52 (1.47, 1.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1.40 (1.35, 1.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e1.20 (1.16, 1.24)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"11\"\u003eModel 1: adjusted for age, sex, and low income; Model 2: adjusted for age, sex, low income, smoking, drinking, physical activity, and Charlson comorbidity index; Model 3: adjusted for age, sex, low income, smoking, drinking, physical activity, obesity, and anxiety disorder, insomnia, substance use disorder, obsessive-compulsive disorder, posttraumatic stress disorder, dementia, diabetes, hypertension, dyslipidemia, cancer, and Charlson comorbidity index\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eRisk of cause-specific death in patients with depression\u003c/h2\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e show the risk of cause-specific death in patients with depression compared to those without depression. Compared to those without depression, patients with depression showed an increased risk of all-cause death (adjusted HR [aHR], 1.09; 95% CI, 1.07\u0026ndash;1.11) after controlling for covariates. In the fully adjusted model, the cause-specific death with the greatest increased risk in patients with depression was suicide (aHR, 2.05; 95% CI, 1.92\u0026ndash;2.19). The following increased risks were observed: neurological disorders (aHR, 1.36; 95% CI, 1.27\u0026ndash;1.45), mental disorder (aHR, 1.26; 95% CI, 1.11\u0026ndash;1.44), endocrine diseases (aHR, 1.21; 95% CI, 1.12\u0026ndash;1.30), infectious diseases (aHR, 1.20; 95% CI, 1.10\u0026ndash;1.30), respiratory diseases (aHR, 1.16; 95% CI, 1.12\u0026ndash;1.21), and cardiovascular diseases (aHR, 1.06; 95% CI, 1.02\u0026ndash;1.09). Compared to those without depression, patients with depression showed a decreased risk of death by cancer (aHR 0.88; 95% CI, 0.86\u0026ndash;0.91).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eSubgroup analyses\u003c/h2\u003e \u003cp\u003e \u003cb\u003eSupplementary Table\u0026nbsp;1\u003c/b\u003e shows the results of subgroup analyses according to sex. The risk of death by suicide was found to be greater in females (aHR, 2.31 [95% CI, 2.10\u0026ndash;2.54] for females; aHR, 1.90 [95% CI, 1.76\u0026ndash;2.06] for males; \u003cem\u003eP\u003c/em\u003e for interaction\u0026thinsp;=\u0026thinsp;0.001). The increased risk of death from digestive diseases was more pronounced in females (\u003cem\u003eP\u003c/em\u003e for interaction\u0026thinsp;=\u0026thinsp;0.009), and the increased risk of death from neurological disorders was more pronounced in males (\u003cem\u003eP\u003c/em\u003e for interaction\u0026thinsp;=\u0026thinsp;0.005). The decreased risk of death from cancer was more pronounced in females (\u003cem\u003eP\u003c/em\u003e for interaction\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003e \u003cb\u003eSupplementary Table\u0026nbsp;2\u003c/b\u003e presents the results of the subgroup analyses by age subgroups. Overall, the risk of death in patients with depression was significantly increased in those aged 20\u0026ndash;39 years (aHR, 1.97 [95% CI, 1.70\u0026ndash;2.29] for 20\u0026ndash;39 years; aHR, 1.27 [1.23\u0026ndash;1.30] for 40\u0026ndash;64 years; aHR 1.04 [95% CI, 1.02\u0026ndash;1.05] for \u0026ge;\u0026thinsp;65 years; \u003cem\u003eP\u003c/em\u003e for interaction\u0026thinsp;\u0026lt;\u0026thinsp;0.001). In particular, the increased risks of death from mental disorders, endocrine diseases, neurological diseases, suicide, genitourinary diseases, and digestive diseases were pronounced in those aged 20\u0026ndash;39 years, and the increased risks of death from respiratory diseases, infectious diseases, and cardiovascular diseases were pronounced in those aged 40\u0026ndash;64 years.\u003c/p\u003e \u003cp\u003e \u003cb\u003eSupplementary Table\u0026nbsp;3\u003c/b\u003e presents the results of subgroup analyses by CCI. The risk of all-cause death associated with depression was inversely related to comorbidity burden, with the most pronounced increase observed among patients with a CCI of 0 with an aHR of 1.24 (95% CI, 1.18\u0026ndash;1.30) (\u003cem\u003eP\u003c/em\u003e for interaction\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Each cause-specific death showed similar results, with cancers (\u003cem\u003eP\u003c/em\u003e for interaction\u0026thinsp;\u0026lt;\u0026thinsp;0.001), neurological disorders (\u003cem\u003eP\u003c/em\u003e for interaction\u0026thinsp;\u0026lt;\u0026thinsp;0.001), digestive diseases (P for interaction\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and genitourinary diseases (\u003cem\u003eP\u003c/em\u003e for interaction\u0026thinsp;=\u0026thinsp;0.026) showing this pattern.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this nationwide cohort study, we followed up deaths among 4,611,122 adults, according to the presence or absence of depression. We presented the risk of depression on all-cause death and cause-specific death after controlling for various potential confounders. We found that the distribution of causes of death was similar between people with and without depression. However, people with depression had a higher risk of all-cause death and several cause-specific deaths, including suicide, and a lower risk of death from cancer, compared to those without depression.\u003c/p\u003e \u003cp\u003eThe distribution of crude mortality in people with and without depression showed a similar pattern. Despite variations in the classification of causes of death, previous studies have consistently identified cancer, cardiovascular diseases, and respiratory diseases as the most common causes of death in patients with depression (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). However, in the regression analysis, the highest cause-specific mortality risk among patients with depression was observed for suicide. Prior studies have reported hazard ratios ranging from 2.1 to 13.2 for the association between depression or mood disorders with suicide, consistent with our findings (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). Depression is a well-established risk factor for suicide, associated not only with suicide deaths but also with suicidal ideation and attempts (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). Consequently, suicide prevention among patients with depression represents a critical clinical priority. The finding that suicide was the leading cause of death among patients with depression in our study further underscores this important clinical implication. In addition, the survival curve for suicide among patients with depression showed a gradual and continuous decline, suggesting that the elevated risk of suicide persists across the entire follow-up period without being confined to a specific time window.\u003c/p\u003e \u003cp\u003eBesides suicide, depression was associated with an increased risk of death from various physical illnesses. Depression is one of the most common comorbidities of many medical diseases (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). And, poorer outcomes have frequently been reported in patients with medical disease who have depression. For example, in patients with type 2 diabetes, depression increases the risk of cardiovascular events such as myocardial infarction or ischemic stroke by 18\u0026ndash;19%, and the risk of death by 24% (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). In patients with chronic obstructive pulmonary disease (COPD), the presence of depression was associated with a 36% increased risk of acute exacerbation.(\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e) A study analyzing data from the WHO World Health Survey found that depression had the largest effect on worsening mean health scores compared with the other chronic conditions, and that comorbidity of depression and one or more chronic conditions had the lowest health scores of all disease groups (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eSeveral mechanisms may underlie the increased mortality from physical illnesses among patients with depression. First, depressive symptoms such as fatigue and diminished motivation may reduce patients\u0026rsquo; likelihood of seeking timely medical attention or adhering adequately to prescribed treatments. Second, psychotropic medications used in the management of depressive symptoms may exert adverse effects on physical health, thereby exacerbating comorbid medical conditions. Third, physicians may inadvertently focus predominantly on the patient\u0026rsquo;s psychiatric symptoms, resulting in the relative neglect of physical health concerns. Finally, physical complaints expressed by depressed individuals may be misattributed to psychosomatic origins, leading to delayed recognition or suboptimal management of underlying medical diseases.\u003c/p\u003e \u003cp\u003eHowever, in this study, patients with depression showed a lower risk of cancer-related death. Previous studies examining the prognostic impact of comorbid depression in cancer patients have shown mixed results: meta-analyses have generally reported that comorbid depression in patients with cancer is associated with worse survival outcomes (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). In contrast, a previous study of head and neck cancer patients found that the timing of depression diagnosis and the duration of psychiatric follow-up could affect survival: the \u0026ldquo;pre-cancer only\u0026rdquo; group had lower survival, whereas the \u0026ldquo;post-cancer only\u0026rdquo; group had higher survival, and the \u0026ldquo;both before and after cancer\u0026rdquo; group showed higher survival compared with patients whose treatment was discontinued (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). Similarly, a study of breast cancer patients found that those diagnosed and treated for depression only before or only after their cancer diagnosis had an increased risk of death, whereas those who maintained depression treatment both before and after diagnosis showed no reduction in survival (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). These findings suggest that consistent psychiatric treatment after a cancer diagnosis may contribute to improving the prognosis of cancer patients. Recent comprehensive cancer center systems commonly incorporate proactive psychiatric consultation, which facilitates earlier detection and intervention for mental disorders and may thereby contribute to reduced mortality among these patients.\u003c/p\u003e \u003cp\u003eThis study has the strength of being conducted on a large sample size of over 4.6\u0026nbsp;million participants. Moreover, in addition to presenting crude mortality in patients with depression, we performed analyses that included various potential confounders that could affect death to elucidate the association between depression and each cause-specific death. However, several methodological issues should be considered when interpreting and generalizing the results of this study. First, selection bias may exist since the study targeted people who participated in the national health screening program in a specific year. People who participate in the program may be more likely to engage in positive health behaviors than those who do not participate, or an individual's prior health status may have influenced their decision to participate in the program. Second, the definition of depression was made solely through diagnostic codes. Even if patients met the clinical criteria for depression, those who did not seek medical care may have been classified as not having depression, which could have influenced the study results. Third, several potential confounders that could affect the association between depression and death, including duration and severity of depression, treatment history, medication use, and access to hospitals, were not included in the analysis. Fourth, the causes of death were classified broadly, and deaths due to individual diseases were not included in the analysis. In particular, among the cause-specific deaths, those classified as deaths from mental disorders are presumed to be suicides. This may have arisen from heterogeneity in physicians\u0026rsquo; documentation of cause-of-death codes. Future research is expected to focus on the relationship between depression and individual cause-specific death. Fifth, since this study was conducted among the South Korean population, the results may not be generalizable to other populations.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn this South Korean nationwide cohort study, we found that the distribution of causes of death was similar between people with and without depression. However, people with depression had a higher risk of all-cause death and several cause-specific deaths, including suicide, and a lower risk of death from cancer, compared to those without depression.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eConflicts of interest\u003c/h2\u003e \u003cp\u003eNo disclosures to report.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eAuthors' contributions\u003c/h2\u003e \u003cp\u003e \u003cb\u003eHyewon Kim\u003c/b\u003e: Conceptualization, Methodology, Writing \u0026ndash; Original Draft, Writing \u0026ndash; Review \u0026amp; Editing. \u003cb\u003eSe Yun Kim\u003c/b\u003e: Formal analysis, Writing \u0026ndash; Review \u0026amp; Editing. \u003cb\u003eKyungdo Han\u003c/b\u003e: Conceptualization, Methodology, Formal analysis, Writing \u0026ndash; Review \u0026amp; Editing. \u003cb\u003eHong Jin Jeon\u003c/b\u003e: Conceptualization, Project administration, Methodology, Writing \u0026ndash; Review \u0026amp; Editing\u003c/p\u003e\u003ch2\u003eAcknowledgments\u003c/h2\u003e \u003cp\u003eThis research was supported by the Korea Health Technology R\u0026amp;D Project through the Korea Health Industry Development Institute (KHIDI), sponsored by the Ministry of Health \u0026amp; Welfare, Republic of Korea (No. HR21C0885).\u003c/p\u003e\u003ch2\u003eAvailability of data\u003c/h2\u003e \u003cp\u003ePublicly available datasets were analyzed in this study. This data can be found here: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://nhiss.nhis.or.kr/\u003c/span\u003e\u003cspan address=\"https://nhiss.nhis.or.kr/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003ePedersen CB, Mors O, Bertelsen A, Waltoft BL, Agerbo E, McGrath JJ, et al. A comprehensive nationwide study of the incidence rate and lifetime risk for treated mental disorders. JAMA Psychiatry. 2014;71(5):573\u0026ndash;81.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGlobal, regional, and national burden of 12 mental disorders in 204 countries and territories, 1990\u0026ndash;2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Psychiatry. 2022;9(2):137\u0026thinsp;\u0026ndash;\u0026thinsp;50.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGold SM, K\u0026ouml;hler-Forsberg O, Moss-Morris R, Mehnert A, Miranda JJ, Bullinger M, et al. Comorbid depression in medical diseases. Nat Rev Dis Primers. 2020;6(1):69.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWalker J, Burke K, Wanat M, Fisher R, Fielding J, Mulick A, et al. The prevalence of depression in general hospital inpatients: a systematic review and meta-analysis of interview-based studies. Psychol Med. 2018;48(14):2285\u0026ndash;98.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMeng R, Yu C, Liu N, He M, Lv J, Guo Y, et al. Association of Depression With All-Cause and Cardiovascular Disease Mortality Among Adults in China. JAMA Netw Open. 2020;3(2):e1921043.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZivin K, Yosef M, Miller EM, Valenstein M, Duffy S, Kales HC, et al. Associations between depression and all-cause and cause-specific risk of death: a retrospective cohort study in the Veterans Health Administration. J Psychosom Res. 2015;78(4):324\u0026ndash;31.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChesney E, Goodwin GM, Fazel S. Risks of all-cause and suicide mortality in mental disorders: a meta-review. World psychiatry: official journal of the World Psychiatric Association (WPA). 2014;13(2):153\u0026ndash;60.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim H, Jung JH, Han K, Jeon HJ. Risk of suicide and all-cause death in patients with mental disorders: a nationwide cohort study. Mol Psychiatry. 2025;30(7):2831\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOsler M, Rosenqvist TW, Bj\u0026oslash;rn-Rozing MP, Jorgensen A, Jorgensen MB, J\u0026oslash;rgensen TSH, et al. All-Cause and Cause-Specific Mortality Among Individuals With Major Depression: A Nationwide Danish Matched-Cohort Study. Acta Psychiatrica Scandinavica. 2025;152(1):60\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLee J, Lee JS, Park SH, Shin SA, Kim K. Cohort Profile: The National Health Insurance Service-National Sample Cohort (NHIS-NSC), South Korea. International journal of epidemiology. 2017;46(2):e15.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShin DW, Cho J, Park JH, Cho B. National General Health Screening Program in Korea: history, current status, and future direction. Precis Future Med. 2022;6(1):9\u0026ndash;31.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePescatello LS, Riebe D, Thompson PD. ACSM's guidelines for exercise testing and prescription: Lippincott Williams \u0026amp; Wilkins; 2014.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSundararajan V, Henderson T, Perry C, Muggivan A, Quan H, Ghali WA. New ICD-10 version of the Charlson comorbidity index predicted in-hospital mortality. Journal of clinical epidemiology. 2004;57(12):1288\u0026ndash;94.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlotaibi R, Halbesma N, Wild SH, Jackson CA. Severe depression and all-cause and cause-specific mortality in Scotland: 20 year national cohort study. BJPsych Open. 2024;10(1):e28.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePlana-Ripoll O, Pedersen CB, Agerbo E, Holtz Y, Erlangsen A, Canudas-Romo V, et al. A comprehensive analysis of mortality-related health metrics associated with mental disorders: a nationwide, register-based cohort study. Lancet. 2019;394(10211):1827\u0026ndash;35.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCai H, Xie XM, Zhang Q, Cui X, Lin JX, Sim K, et al. Prevalence of Suicidality in Major Depressive Disorder: A Systematic Review and Meta-Analysis of Comparative Studies. Front Psychiatry. 2021;12:690130.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTurecki G, Brent DA, Gunnell D, O\u0026rsquo;Connor RC, Oquendo MA, Pirkis J, et al. Suicide and suicide risk. Nature Reviews Disease Primers. 2019;5(1):74.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGold SM, K\u0026ouml;hler-Forsberg O, Moss-Morris R, Mehnert A, Miranda JJ, Bullinger M, et al. Comorbid depression in medical diseases. Nature Reviews Disease Primers. 2020;6(1):69.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim H, Lee KN, Shin DW, Han K, Jeon HJ. Association of comorbid mental disorders with cardiovascular disease risk in patients with type 2 diabetes: A nationwide cohort study. Gen Hosp Psychiatry. 2022;79:33\u0026ndash;41.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWu K, Lu L, Chen Y, Peng J, Wu X, Tang G, et al. Associations of anxiety and depression with prognosis in chronic obstructive pulmonary disease: A systematic review and meta-analysis. Pulmonology. 2025;31(1):2438553.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMoussavi S, Chatterji S, Verdes E, Tandon A, Patel V, Ustun B. Depression, chronic diseases, and decrements in health: results from the World Health Surveys. The Lancet. 2007;370(9590):851\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePinquart M, Duberstein PR. Depression and cancer mortality: a meta-analysis. Psychol Med. 2010;40(11):1797\u0026ndash;810.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eUngvari Z, Fekete M, Buda A, Lehoczki A, Fekete JT, Varga P, et al. Depression increases cancer mortality by 23\u0026ndash;83%: a meta-analysis of 65 studies across five major cancer types. GeroScience. 2025.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHuang RW, Chang KP, Marchi F, Loh CYY, Lin YJ, Chang CJ, et al. The impact of depression on survival of head and neck cancer patients: A population-based cohort study. Front Oncol. 2022;12:871915.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLei F, Vanderpool RC, McLouth LE, Romond EH, Chen Q, Durbin EB, et al. Influence of depression on breast cancer treatment and survival: A Kentucky population-based study. Cancer. 2023;129(12):1821\u0026ndash;35.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-8433731/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8433731/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eDepression is associated with premature mortality, yet the magnitude and heterogeneity of cause-specific mortality risks remain incompletely understood at the population level. We conducted a nationwide cohort study using data from the National Health Insurance Sharing Service linked to mortality records from Statistics Korea. A total of 4,611,122 adults aged\u0026thinsp;\u0026ge;\u0026thinsp;20 years were followed for a mean of 10.2 years. Depression was identified based on clinical diagnoses. Adjusted hazard ratios (aHRs) for all-cause and cause-specific mortality were estimated using Cox proportional hazards models. During follow-up, 231,440 deaths occurred. Individuals with depression exhibited a higher incidence of all-cause mortality compared with those without depression. After adjustment for demographic, clinical, and lifestyle factors, depression was associated with increased all-cause mortality (aHR, 1.09; 95% CI, 1.07\u0026ndash;1.11). Cause-specific analyses revealed the greatest risk elevation for suicide (aHR, 2.05; 95% CI, 1.92\u0026ndash;2.19). In contrast, depression was associated with a lower risk of cancer-related mortality (aHR, 0.88; 95% CI, 0.86\u0026ndash;0.91). In conclusion, depression was associated with heterogeneous patterns of mortality, characterized by markedly elevated suicide risk and a reduced risk of cancer-related death. These findings suggest distinct underlying biological and behavioral pathways linking depression to specific causes of mortality and highlight the need for cause-targeted prevention and intervention strategies.\u003c/p\u003e","manuscriptTitle":"Mortality and the risk of cause-specific death in patients with depression\n: A nationwide cohort study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-16 10:36:54","doi":"10.21203/rs.3.rs-8433731/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f6d1bd22-a5e2-40f9-aa7f-768a03cb6bb0","owner":[],"postedDate":"February 16th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":60548972,"name":"Health sciences/Diseases/Psychiatric disorders/Depression"},{"id":60548973,"name":"Biological sciences/Neuroscience"}],"tags":[],"updatedAt":"2026-03-30T11:44:56+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-16 10:36:54","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8433731","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8433731","identity":"rs-8433731","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}