Depressive symptoms and all-cause mortality among middle-aged and older people in China and associations with chronic diseases.

Introduction: It remains unclear whether depressive symptoms are associated with increased all-cause mortality and to what extent depressive symptoms are associated with chronic disease and all-cause mortality. The study aims to explore the relationship between depressive symptoms and all-cause mortality, and how depressive symptoms may, in turn, affect all-cause mortality among Chinese middle-aged and older people through chronic diseases. Methods: Data were collected from the China Health and Retirement Longitudinal Study (CHARLS). This cohort study involved 13,855 individuals from Wave 1 (2011) to Wave 6 (2020) of the CHARLS, which is a nationally representative survey that collects information from Chinese residents ages 45 and older to explore intrinsic mechanisms between depressive symptoms and all-cause mortality. The Center for Epidemiological Studies Depression Scale (CES-D-10) was validated through the CHARLS. Covariates included socioeconomic variables, living habits, and self-reported history of chronic diseases. Kaplan-Meier curves depicted mortality rates by depressive symptom levels, with Cox proportional hazards regression models estimating the hazard ratios (HRs) of all-cause mortality. Results: Out of the total 13,855 participants included, the median (Q1, Q3) age was 58.00 (51.00, 63.00) years. Adjusted for all covariates, middle-aged and older adults with depressive symptoms had a higher all-cause mortality rate (HR = 1.20 [95% CI, 1.09-1.33]). An increased rate was observed for 55-64 years old (HR = 1.23 [95% CI, 1.03-1.47]) and more than 65 years old (HR = 1.32 [95% CI, 1.18-1.49]), agricultural Hukou (HR = 1.44, [95% CI, 1.30-1.59]), and nonagricultural workload (HR = 1.81 [95% CI, 1.61-2.03]). Depressive symptoms increased the risks of all-cause mortality among patients with hypertension (HR = 1.19 [95% CI, 1.00-1.40]), diabetes (HR = 1.41[95% CI, 1.02-1.95]), and arthritis (HR = 1.29 [95% CI, 1.09-1.51]). Conclusion: Depressive symptoms raise all-cause mortality risk, particularly in those aged 55 and above, rural household registration (agricultural Hukou), nonagricultural workers, and middle-aged and older people with hypertension, diabetes, and arthritis. Our findings through the longitudinal data collected in this study offer valuable insights for interventions targeting depression, such as early detection, integrated chronic disease care management, and healthy lifestyles; and community support for depressive symptoms may help to reduce mortality in middle-aged and older people.

Association of depressive symptoms and sleep disturbances with survival among US adult cancer survivors.

BACKGROUND: Depression and sleep disturbances are associated with increased risks of various diseases and mortality, but their impacts on mortality in cancer survivors remain unclear. The objective of this study was to characterize the independent and joint associations of depressive symptoms and sleep disturbances with mortality outcomes in cancer survivors. METHODS: This population-based prospective cohort study included cancer survivors aged ≥ 20 years (n = 2947; weighted population, 21,003,811) from the National Health and Nutrition Examination Survey (NHANES) 2007-2018 cycles. Depressive symptoms and sleep disturbances were self-reported. Depressive symptoms were assessed using the Patient Health Questionnaire 9 (PHQ-9). Death outcomes were determined by correlation with National Death Index records through December 31, 2019. Primary outcomes included all-cause, cancer-specific, and noncancer mortality. RESULTS: During the median follow-up of 69 months (interquartile range, 37-109 months), 686 deaths occurred: 240 participants died from cancer, 146 from heart disease, and 300 from other causes. Separate analyses revealed that compared with a PHQ-9 score (0-4), a PHQ-9 score (5-9) was associated with a greater risk of all-cause mortality (hazard ratio [HR], 1.28; 95% CI, 1.03-1.59), and a PHQ-9 score (≥ 10) was associated with greater risk of all-cause mortality (HR, 1.37; 95% CI, 1.04-1.80) and noncancer mortality (HR, 1.45; 95% CI, 1.01-2.10). Single sleep disturbances were not associated with mortality risk. In joint analyses, the combination of a PHQ-9 score ≥ 5 and no sleep disturbances, but not sleep disturbances, was associated with increased risks of all-cause mortality, cancer-specific mortality, and noncancer mortality. Specifically, compared with individuals with a PHQ-9 score of 0-4 and no sleep disturbances, HRs for all-cause mortality and noncancer mortality in individuals with a PHQ-9 score of 5-9 and no sleep disturbances were 1.72 (1.21-2.44) and 1.69 (1.10-2.61), respectively, and 2.61 (1.43-4.78) and 2.77 (1.27-6.07), respectively, in individuals with a PHQ-9 score ≥ 10 and no sleep disturbances; HRs for cancer-specific mortality in individuals with a PHQ-9 score ≥ 5 and no sleep disturbances were 1.95 (1.16-3.27). CONCLUSIONS: Depressive symptoms were linked to a high risk of mortality in cancer survivors. The combination of a PHQ-9 score (≥ 5) and an absence of self-perceived sleep disturbances was associated with greater all-cause mortality, cancer-specific mortality, and noncancer mortality risks, particularly in individuals with a PHQ-9 score (≥ 10).

Depressive symptoms and smoking: Effect on mortality in a primary care cohort.

OBJECTIVE: Depressive symptoms have been suggested to increase mortality risk but causality remains unproven. Depressive symptoms increase likelihood of smoking which is thus a potential factor modifying the effect of depressive symptoms on mortality. This study aims to assess if the association of depressive symptoms and all-cause mortality is affected by smoking. METHODS: A prospective cohort study in Finnish primary care setting was conducted among 2557 middle-aged cardiovascular disease (CVD) risk persons identified in a population survey. Baseline depressive symptoms were assessed by Beck's Depression Inventory (BDI) and current smoking by self-report. Data on mortality was obtained from the official statistics. Effect of depressive symptoms and smoking on all-cause mortality after 14-year follow-up was estimated. RESULTS: Compared to non-depressive non-smokers, the adjusted hazard ratio (HR) for all-cause mortality was 3.10 (95% CI 2.02 to 4.73) and 1.60 (95% CI 1.15 to 2.22) among smoking subjects with and without depressive symptoms, respectively. Compared to the general population, relative survival was higher among non-depressive non-smokers and lower among depressive smokers. Relative standardized mortality ratio (SMR) for all-cause mortality was 1.78 (95% CI 1.31 to 2.44) and 3.79 (95% CI 2.54 to 6.66) among non-depressive and depressive smokers, respectively, compared to non-depressive non-smokers. The HR for all-cause mortality and relative SMR of depressive non-smokers were not increased compared to non-depressive non-smokers. CONCLUSION: Current smoking and increased depressive symptoms seem to additively contribute to excess mortality.

Association of composite dietary antioxidant index with depression and all-cause mortality in middle-aged and elderly population.

Current research has shown an increasing acceptance of interventions for depression through dietary modifications. However, whether composite dietary antioxidant index (CDAI) is associated with depression and all-cause mortality in middle-aged and elderly population remains unknown. This study aimed to explore those associations in American middle-aged and elderly population. Weighted logistic regression models and weighted Cox proportional hazard regression models were used to assess the association of CDAI, covariates, depression, and all-cause mortality, respectively. The stability of the results was also determined by a linear trend test based on CDAI quintiles. Restricted cubic spline curves were employed to test for non-linear relationships. In the model adjusted for all covariates, significant associations were found with the ORs (95% CI) for CDAI and depression [0.77 (0.67, 0.89)] and the HRs (95% CI) for CDAI with all-cause mortality[0.91 (0.83, 1.00)]. Upon conducting restricted cubic spline curves, we found that the association between CDAI and depression was linear, whereas the association between CDAI and all-cause mortality was non-linear with an inflection point of -0.19. Statistical significance was only found before the inflection point. In this study of middle-aged and elderly Americans, CDAI was linearly negatively associated with depression and non-linearly negatively associated with all-cause mortality.

The effects of health risk behaviors to excess mortality in the population with depression: A cohort study based on NHANES data.

BACKGROUND: The population with depression had a considerable excess mortality risk. This increased mortality may be attributed to the biological consequences of depression or the substantial prevalence of health risk behaviors (HRBs). This study aimed to quantify the combined effects of four major HRBs - smoking, excessive alcohol use, physical inactivity, and an unhealthy diet - on excess mortality among depressed individuals. METHODS: This study included 35,738 adults from the National Health and Nutrition Examination Survey 2005-06 to 2017-18, with mortality follow-up data censored through 2019. The standardized prevalence of HRBs was calculated for populations with and without depression. Poisson regression models were used to calculate the mortality rate ratio (MRR). Based on model adjusting for socio-demographic factors, the attenuation of MRR was determined after further adjustment for HRBs. RESULTS: A total of 3147 participants were identified as having depression. All HRBs showed a significantly higher prevalence among the population with depression. After adjusting for socio-demographic factors, depression was associated with 1.7 and 1.8 times higher all-cause and cardiovascular disease mortality rate, respectively. Further adjustment for all current HRBs resulted in a 21.9 % reduction in all-cause mortality rate and a 15.4 % decrease in cardiovascular disease mortality rate. LIMITATION: HRBs were reported at a single time point, and we are unable to demonstrate a causal effect. CONCLUSION: At least 1/5 of excess mortality for population with depression was attributable to HRBs. Efforts should be made to address HRBs among population with depression.

A cross-sectional analysis of the association between physical activity, depression, and all-cause mortality in Americans over 50 years old.

Depression is estimated to be the second leading cause of disability in the United States and is associated with a 52% increased risk of death. Lifestyle components may have an important role in depression pathogenesis. The aims of this study were to analyze the association of meeting the physical activity (PA) recommendation guidelines and depression, and to analyze the all-cause mortality risk of the joint association of PA and depression. This cross-sectional study included 7201 participants from the 2007-2014 National Health and Nutrition Examination Survey aged ≥ 50 years and linked to National Death Index records through December 31, 2015. Depression was defined as a score ≥ 10 using the Patient Health Questionnaire (PHQ-9). PA was self-reported, and total PA was used to classify participants as more active (≥ 600 MET-min/week) or less active (< 600 MET-min/week). The odds ratios for depression were examined according to be more active or less active. The hazard ratios (HR) for the association of PA level and depression status with all-cause mortality were examined. Being more active was associated with reduced odds for depression. Compared with less active participants with depression, those who were more active and having depression had HR 0.45 (95% CI 0.22, 0.91, p = 0.026) for all-cause mortality. Being more active is associated with lower odds for depression and seems to be a protective factor against the increased all-cause mortality risk due to depression.

Sex-related differences on the risks of in-hospital and late outcomes after acute aortic dissection: A nationwide population-based cohort study.

OBJECTIVE: The aim of this study is to evaluate the sex-related differences on the risks of perioperative and late outcomes for adult acute aortic dissection (AAD) patients following surgical management. METHODS AND RESULTS: By using Taiwan National Health Insurance Research Database, totally 1,410 female and 3,432 male patients were identified to first-ever receive type A AAD open surgery or type B AAD stenting treatment from 2004 to 2013. We assessed the sex-related difference on outcomes, including in-hospital mortality, all-cause mortality, aortic death, redo aortic surgery, ischemic stroke, and depression during the follow-up period. The analysis was done separately for type A and type B surgeries. RESULTS: On average, female patients diagnosed with AAD were older than males. There was no significant sex difference of in-hospital mortality or all-cause mortality for both type A open and type B stent surgeries. The risk of redo aortic surgery was significantly greater in males than females (7.8% vs. 4%; unadjusted subdistribution hazard ratio [SHR] 0.51, 95% CI 0.38-0.69) for type A open surgery, but not for type B stent surgery. Noticeably, the risk of newly-diagnosed depression was significantly greater in females than males (8% vs. 5.1%; unadjusted SHR 1.6, 95% CI 1.24-2.06) for type A open surgery, but not for type B stent surgery. CONCLUSIONS: No significant sex-related difference was found for the in-hospital mortality or accumulative all-cause mortality. However, there were more redo aortic surgeries for males and more postoperative depression for females in type A AAD population.

Effect of depression on progression to end-stage renal disease or pre-end-stage renal disease death in advanced diabetic nephropathy: A prospective cohort study of the Diabetes Study from the Center of Tokyo Women's Medical University.

AIMS/INTRODUCTION: This study aimed to determine the effect of depression on the progression to end-stage renal disease (ESRD) and pre-ESRD death in patients with advanced diabetic nephropathy. MATERIALS AND METHODS: This single-center prospective cohort study enrolled Japanese patients with type 2 diabetes and advanced diabetic nephropathy. The total Patient Health Questionnaire-9 score was used to evaluate depression at baseline and classified patients into: no, mild and severe depression groups. The outcomes were ESRD, defined as initiation of renal replacement therapy, and pre-ESRD death. The relationship between the severity of depression and these outcomes was analyzed using a competing risks model, defining each outcome as the competing risk of the other outcome. RESULTS: Of the 486 patients with a mean estimated glomerular filtration rate of 37.1 ± 21.1 mL/min/1.73 m2 , 345 were men. During the median follow up of 4.4 years, 164 patients progressed to ESRD and 50 died. The cumulative incidence function of ESRD was significantly higher in the severe depression group (Gray's test, P = 0.003). The ESRD risk increased by 12.4% and 45.1% in patients with mild and severe depression, respectively, compared with those without depression, although these differences did not reach statistical significance in the multivariate subdistribution hazard model (P = 0.450 and 0.161, respectively). The cumulative incidence of death was similar for the study groups. CONCLUSION: Depression potentially has a weak impact on progression to ESRD, however, the presence of comorbidities might have the possibility to reduce the effect of depression on the renal outcome in patients with advanced diabetic nephropathy.

Mortalidade em transtornos mentais no estudo UK Biobank / Mortality in mental disorders in the UK Biobank study

Introdução - Vasta literatura tem associado transtornos mentais a uma mortalidade aumentada. Porém, poucos estudos sobre o tema identificaram transtornos mentais através de questionários validados. Além disso, pouco se sabe sobre a contribuição de fatores de risco modificáveis para explicar o excesso de mortalidade associado a transtornos mentais. Objetivo - Utilizar dados do UK Biobank, um grande estudo prospectivo que recrutou meio milhão de participantes de meia idade e idosos entre 2006 e 2010, para investigar: (I) a mortalidade relativa e as causas de morte associadas a uma ampla gama de transtornos mentais; (II) padrões de combinações de transtornos mentais e a mortalidade relativa associada a essas combinações; e (III) a contribuição de fatores de risco modificáveis para explicar o excesso de mortalidade associado à depressão. Transtornos mentais foram identificados por variados métodos, incluindo um Questionário de Saúde Mental completado por cerca de 160.000 participantes, diagnósticos registrados durante internações hospitalares obtidos via linkage e diagnósticos autorrelatados. Métodos - Foram obtidas estimativas de mortalidade relativa por todas as causas associadas a diferentes transtornos mentais e suas combinações com modelos de regressão de Cox ajustados por idade (ou idade e sexo). Padrões de combinações de transtornos mentais foram explorados através de mineração de regras de associação. Um método baseado em modelos de regressão de Cox foi utilizado para estimar a porcentagem do excesso de mortalidade associada à depressão explicada por fatores de risco modificáveis. Resultados - A maioria dos transtornos mentais e combinações de transtornos mentais se associaram com maior mortalidade, independentemente do método de identificação. Cerca de 70% da mortalidade em excesso associada à depressão pôde ser explicada por fatores de risco modificáveis. Conclusões - Em uma grande amostra de indivíduos de meia idade e idosos no Reino Unido, transtornos mentais e suas combinações estiveram consistentemente associados a uma maior mortalidade. Em depressão, essa associação parece ser explicada em grande parte pela presença de fatores de risco modificáveis.

Introduction - Extensive literature has associated mental disorders with increased mortality. However, few studies on this topic have identified mental disorders through validated questionnaires. In addition, little is known about the contribution of modifiable risk factors to explain the excess mortality associated with mental disorders. Objective - To use data from the UK Biobank, a large prospective study which recruited half a million middle-aged and elderly participants between 2006 and 2010, to investigate: (I) the relative mortality and causes of death associated with a wide range of mental disorders; (II) patterns of combinations of mental disorders and the relative mortality associated with these combinations; and (III) the contribution of modifiable risk factors to explain the excess mortality associated with depression. Mental disorders were identified by various methods, including a Mental Health Questionnaire completed by approximately 160,000 participants, diagnoses from hospital inpatient records obtained via linkage, and self-reported diagnoses. Methods - The relative all-cause mortality associated with different mental disorders and their combinations was estimated using Cox regression models adjusted for age (or age and sex). Association rule mining was used to explore patterns of combinations of mental disorders. A method based on Cox regression models was used to estimate the percentage of excess mortality associated with depression explained by modifiable risk factors. Results The majority of mental disorders and combinations of mental disorders were associated with higher mortality, regardless of the identification method. Approximately 70% of the excess mortality associated with depression could be explained by modifiable risk factors. Conclusions - In a large sample of middle-aged and elderly individuals in the UK, mental disorders and their combinations were consistently associated with higher mortality. In depression, this association seems to be largely explained by the presence of modifiable risk factors.

Effect of polymorphism rs1799964 in TNF-α gene on survival in depressive patients with chronic heart failure.

OBJECTIVE: To date, there are no literature reports combining the relationship between depression and chronic heart failure (CHF) in relations to selective nutritional, cardiac and laboratory parameters. The aim of this study was to correlate the rs1799964 genotypes in TNF-α with clinical outcomes of depressive CHF patients. PATIENTS AND METHODS: 94 CHF patients were enrolled to assess depression prevalence and to compare values of cardiac, laboratory and nutritional parameters between depressed and non-depressed patients with different rs1799964 genotypes. RESULTS: Depression was diagnosed in 66 individuals (70.2%). We noted significant reduction of EF% in CC genotype carriers compared to other patients (mean EF%: 36±11 CC vs. 44±14 CT and 46±7 TT; p=0.023) and worse outcomes in NYHA examination (p=0.033). We noticed a significant increase in serum CRP and TNF-α in CC patients (p=0.003 and p<0.001). Compared with T allele carriers, the CHF patients bearing CC genotype were more frequently diagnosed as cachectic (cachexia incidence for CC - 80% vs. 28% for CT and 38.7% for TT; p=0.017). CC genotype of rs1799964 was found as unfavorable factor affecting survival of depressive CHF patients (HR=8.87; p<0.001). CONCLUSIONS: The presence of the CC genotype in patients with depression and CHF can be considered an unfavorable prognostic factor related to the risk of shortening the life expectancy and deteriorating its quality, which is reflected in the severity of inflammation.

Effect of depression on mortality in type 2 diabetes mellitus after 8 years of follow-up. The DIADEMA study.

AIM: To assess the effect of depression on all-cause mortality in patients with type 2 diabetes mellitus (T2DM) followed up during 8 years in primary care in Spain. METHODS: Depression was diagnosed according to MINI 5.0.0 questionnaire, physician-diagnosis or following antidepressant therapy for at least two months in 3923 people with T2DM. We analyzed mortality-rates/10,000 person-years. We compared survival according to baseline depression with Kaplan-Meier estimates and the log-rank test. We performed Cox proportional hazard model analyses. RESULTS: Baseline depression was diagnosed in 22.1% of participants. Mortality was higher in patients with depression (31.9% vs. 26.9%; p = 0.003), who had a significantly poorer survival (median survival = 7.4 vs. 7.8 years, respectively; Log Rank = 15.83; p < 0.001). Depression showed an adjusted mortality hazard ratio (HR) = 1.40 (95%CI:1.20-1.65; p < 0.001). The strongest predictive factors were: age >75 years (HR = 6.04; 95%CI:4.62-7.91; p < 0.001), insulin use (HR = 2.37; 95%CI:1.86-3.00; p < 0.001), lower limb amputation (HR = 1.99; 95%CI:1.28-3.11; p = 0.002), heart failure (HR = 1.94; 95%CI:1.63-2.30; p < 0.001), and male gender (HR = 1.90; 95%CI:1.59-2.27). CONCLUSION: In a Spanish cohort of older T2DM patients, depression was associated with a higher mortality risk. More efforts are needed to minimize the influence of depression on mortality in people with T2DM and to implement measures that allow its early diagnosis and effective treatment.

Combined Effects of Depression and Chronic Disease on the Risk of Mortality: The Korean Longitudinal Study of Aging (2006-2016).

BACKGROUND: The prevalence of depression is much higher in people with chronic disease than in the general population. Depression exacerbates existing physical conditions, resulting in a higher-than-expected death rate from the physical condition itself. In our aging society, the prevalence of multimorbid patients is expected to increase; the resulting mental problems, especially depression, should be considered. Using a large-scale cohort from the Korean Longitudinal Study of Aging (KLoSA), we analyzed the combined effects of depression and chronic disease on all-cause mortality. METHODS: We analyzed 10-year (2006-2016) longitudinal data of 9,819 individuals who took part in the KLoSA, a nationwide survey of people aged 45-79 years. We examined the association between multimorbidity and depression using chi-square test and logistic regression. We used the Cox proportional hazard model to determine the combined effects of multimorbidity and depression on the all-cause mortality risk. RESULTS: During the 10-year follow up, 1,574 people (16.0%) died. The hazard ratio associated with mild depression increased from 1.35 (95% confidence interval [CI], 1.05-1.73) for no chronic disease to 1.25 (95% CI, 0.98-1.60) for 1 chronic disease, and to 2.00 (95% CI, 1.58-2.52) for multimorbidity. The hazard ratio associated with severe depression increased from 1.73 (95% CI, 1.33-2.24) for no chronic disease, to 2.03 (95% CI, 1.60-2.57) for 1 chronic disease, and to 2.94 (95% CI, 2.37-3.65) for multimorbidity. CONCLUSION: Patients with coexisting multimorbidity and depression are at an increased risk of all-cause mortality than those with chronic disease or depression alone.

Pre-existing depression in patients with coronary artery disease undergoing percutaneous coronary intervention.

The impact of pre-existing depression on mortality in individuals with established coronary artery disease (CAD) remains unclear. We evaluate the clinical implications of pre-existing depression in patients who underwent percutaneous coronary intervention (PCI). Based on National Health Insurance claims data in Korea, patients without a known history of CAD who underwent PCI between 2013 and 2017 were enrolled. The study population was divided into patients with angina (n = 50,256) or acute myocardial infarction (AMI; n = 40,049). The primary endpoint, defined as all-cause death, was compared between the non-depression and depression groups using propensity score matching analysis. After propensity score matching, there were 4262 and 2346 matched pairs of patients with angina and AMI, respectively. During the follow-up period, there was no significant difference in the incidence of all-cause death in the angina (hazard ratio [HR] of depression, 1.013; 95% confidence interval [CI] 0.893-1.151) and AMI (HR, 0.991; 95% CI 0.865-1.136) groups. However, angina patients less than 65 years of age with depression had higher all-cause mortality (HR, 1.769; 95% CI 1.240-2.525). In Korean patients undergoing PCI, pre-existing depression is not associated with poorer clinical outcomes. However, in younger patients with angina, depression is associated with higher all-cause mortality.

Personalised support of brain tumour patients during radiotherapy based on psychological profile and quality of life.

PURPOSE: Psychological distress in primary malignant brain tumour (PMBT) patients is associated with poorer outcomes. Radiotherapy (RT) often induces side effects that significantly influence patients' quality of life (QoL), with potential impact on survival. We evaluated distress, anxiety, depression, and QoL over time to identify patients with difficulties in these areas who required more intense psychological support. METHODS: Psychological questionnaires-Distress Thermometer (DT), Hospital Anxiety and Depression Scale (HADS), and Functional Assessment of Cancer Therapy (FACT-G and FACT-Br)-were completed at the beginning (T0), in the middle (T1), directly after RT (T2), and 3 months after RT (T3). We personalised the psychological support provided for each patient with a minimum of three sessions ('typical' schedule) and a maximum of eight sessions ('intensive' schedule), depending on the patients' psychological profiles, clinical evaluations, and requests. Patients' survival was evaluated in the glioblastoma multiforme (GBM) patients, with an explorative intent. RESULTS: Fifty-nine consecutive PMBT patients receiving post-operative RT were included. For patients who were reported as 'not distressed' at T0, no statistically significant changes were noted. In contrast, patients who were 'distressed' at T0 showed statistically significant improvements in DT, HADS, FACT-G, and FACT-Br scores over time. 'Not distressed' patients required less psychological sessions over the study duration than 'distressed' patients. Interestingly, 'not distressed' GBM patients survived longer than 'distressed' GBM patients. CONCLUSIONS: Increased psychological support improved distress, mood, and QoL for patients identified as 'distressed', whereas psychological well-being was maintained with typical psychological support in patients who were identified as being 'not distressed'. These results encourage a standardisation of psychological support for all RT patients.

Safety of antidepressants in a primary care cohort of adults with obesity and depression.

BACKGROUND: Obesity, depressive disorders and antidepressant drugs are associated with increased mortality, cardiovascular disease, diabetes, fractures and falls. We explored outcomes associated with the most commonly prescribed antidepressants in overweight or obese people with depression. METHODS AND FINDINGS: We identified a cohort of overweight or obese adults (≥18 years) in primary care from the UK Clinical Practice Research Datalink, linked with hospital and mortality data, between 1 January 2000 and 31 December 2016 who developed incident depression to January 2019. Cox proportional hazards models and 99% confidence intervals were used to estimate hazard ratios (HR) for mortality, cardiovascular disease, diabetes, and falls/fractures associated with exposure to selective serotonin reuptake inhibitors (SSRIs), tricyclic (TCA)/other, combination antidepressants, citalopram, fluoxetine, sertraline, amitriptyline and mirtazapine, adjusting for potential confounding variables. In 519,513 adults, 32,350 (9.2 per 1,000 years) displayed incident depression and 21,436 (66.3%) were prescribed ≥1 antidepressant. Compared with no antidepressants, all antidepressant classes were associated with increased relative risks of cardiovascular disorders [SSRI HR: 1.32 (1.14-1.53), TCA/Other HR: 1.26 (1.01-1.58)], and diabetes (any type) [SSRI HR: 1.28 (1.10-1.49), TCA/Other: 1.52 (1.19-1.94)]. All commonly prescribed antidepressants except citalopram were associated with increased mortality compared with no antidepressants. However, prescription ≥1 year of ≥40mg citalopram was associated with increased mortality and falls/fractures and ≥1 year 100mg sertraline with increased falls/fractures. CONCLUSIONS: In overweight/obese people with depression, antidepressants may be overall and differentially associated with increased risks of some adverse outcomes. Further research is required to exclude indication bias and residual confounding.

Depression but not non-persistence to antidiabetic drugs is associated with mortality in type 2 diabetes: A nested case-control study.

AIMS: To measure the effect of depression on mortality of individuals newly treated with antidiabetic drugs, accounting for non-persistence to treatment. METHODS: We conducted a nested case-control study within a cohort of newly treated individuals with diabetes. Using Quebec administrative data, we identified all-cause, diabetes-related, cardiovascular-related and major cardiovascular event deaths during a maximum follow-up of eight years. Each case was matched with up to 10 controls by age, sex, follow-up, and comorbidity index. We used conditional logistic regressions to estimate the effect of depression on mortality, adjusting for non-persistence to antidiabetic drug treatment, and other variables. RESULTS: We retrieved 13,558 deaths, of which 3,652 were related to cardiovascular diseases, 2,112 to major cardiovascular events, and 311 to diabetes. Depression was associated with an increased risk of all-cause and cardiovascular-related deaths, with adjusted odds ratios (ORs) ranging from 1.32 (95% CI: 1.21-1.45) to 1.72 (95% CI: 1.57-1.88) depending on the model, but not with diabetes-related mortality. CONCLUSION: Depression is independently associated with all-cause and cardiovascular-related mortality in individuals with type 2 diabetes, even when adjusting for non-persistence to antidiabetic drug treatment. Identifying risk factors for depression and implementing a screening and proper treatment for depression may help reducing mortality.

Association of Posttraumatic Stress and Depressive Symptoms With Mortality in Women.

Importance: Consistent evidence has found associations between posttraumatic stress disorder (PTSD) and increased risk of chronic disease and greater prevalence of health risk factors. However, the association between PTSD and all-cause mortality has not been thoroughly investigated in civilians. Objective: To investigate the association between PTSD symptoms, with or without comorbid depressive symptoms, and risk of death. Design, Setting, and Participants: This prospective cohort study was conducted using data on female US nurses in the Nurses' Health Study II followed up from 2008 to 2017. Women who responded to a 2008 questionnaire querying PTSD and depressive symptoms were included. Data were analyzed from September 2018 to November 2020. Exposures: Symptoms of PTSD, measured using the short screening scale for Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) PTSD, and depression symptoms, measured using the Center for Epidemiologic Studies Depression Scale-10 in 2008. Main Outcomes and Measures: All-cause mortality was determined via National Death Index, US Postal Service, or report of participant's family. The hypothesis being tested was formulated after data collection. Trauma exposure and PTSD symptoms were jointly coded as no trauma exposure (reference), trauma and no PTSD symptoms, 1 to 3 PTSD symptoms (subclinical), 4 to 5 PTSD symptoms (moderate), and 6 to 7 PTSD symptoms (high). Results: Among 51 602 women (50 137 [97.2%] White individuals), the mean (range) age was 53.3 (43-64) years at study baseline in 2008. PTSD and probable depression were comorbid; of 4019 women with high PTSD symptoms, 2093 women (52.1%) had probable depression, while of 10 105 women with no trauma exposure, 1215 women (12.0%) had probable depression. Women with high PTSD symptoms and probable depression were at nearly 4-fold greater risk of death compared with women with no trauma exposure and no depression (hazard ratio [HR], 3.80; 95% CI, 2.65-5.45; P < .001). After adjustment for health factors, women with these conditions had a more than 3-fold increased risk (HR, 3.11; 95% CI, 2.16-4.47, P < .001). Women with subclinical PTSD symptoms without probable depression had increased risk of death compared with women with no trauma exposure and no depression (HR, 1.43; 95% CI, 1.06-1.93; P = .02). Among 7565 women with PTSD symptoms and probable depression, 109 deaths (1.4%) occurred for which we obtained cause of death information, compared with 124 such deaths (0.6% ) among 22 215 women with no depression or PTSD symptoms. Women with PTSD symptoms and probable depression, compared with women with no PTSD or depression, had higher rates of death from cardiovascular disease (17 women [0.22%] vs 11 women [0.05%]; P < .001), diabetes (4 women [0.05%] vs 0 women; P < .001), unintentional injury (7 women [0.09%] vs 7 women [0.03%]; P = .03), suicide (9 women [0.12%] vs 1 woman [<0.01%]; P < .001), and other causes of death (14 women [0.19%] vs 17 women [0.08%]; P = .01). Conclusions and Relevance: These findings suggest that at midlife, women with high PTSD symptoms and co-occurring probable depression are at increased risk of death compared with women without these disorders. Treatment of PTSD and depression in women with symptoms of both disorders and efforts to improve their health behaviors may reduce their increased risk of mortality.

Depression and survival of breast cancer patients: A protocol for systematic review and meta-analysis.

BACKGROUND: Breast cancer is the most common malignancy in women worldwide. Compared with other malignant tumors, breast cancer patients have a higher incidence of depression and other psychiatric symptoms. The purpose of this meta-analysis was to determine the association between long-term survival and depression in patients with breast cancer. METHODS: This review will include cohort studies only. Multiple databases will be searched by 2 independent reviewers, including PubMed, EMBASE, the Cochrane Library, and PsycINFO. The language of studies should be English and Chinese, published from inception to the September 2020. Two independent reviewers will carry out literature screening, research selection and data extraction. Revman5.3 software will be used to generate funnel map, assess heterogeneity, make the subgroup analysis and complete sensitivity analysis. RESULTS: This review will summarize the available evidence to determine the association between depression and survival in breast cancer patients. CONCLUSION: The results of this study will provide reference for the development of comprehensive treatment for breast cancer, and will promote further research. PROSPERO REGISTRATION NUMBER: CRD42020202200.

Depressive and anxiety disorders worsen the prognosis of glioblastoma.

Glioblastoma multiforme (GBM) is one of the most malignant tumors. Depressive and anxiety disorders may co-exist with GBM. We investigated whether depression and anxiety influenced the outcomes of GBM. The Patient Health Questionnaire 9-item (PHQ-9) and Generalized Anxiety Disorder 7-item (GAD-7) scales were used to investigate the mental condition of GBM patients in our department, and the overall survival times of these patients were monitored. The scores on both scales were higher in GBM patients than in healthy controls. For each scale, GBM patients were divided into high- and low-score groups based on the average score. The prognosis was poorer for GBM patients in the high-score groups than for those in the low-score groups. Moreover, magnetic resonance imaging revealed that tumor necrosis was more prevalent among high-scored GBM patients. Cellular experiments were performed on primary GBM cells from patients with either high or low scores on both scales. Sphere formation, EdU and wound healing assays revealed greater proliferation and invasion capacities in GBM cells from patients with high scores on both scales. Western blotting assay revealed significantly different expression of epithelial and mesenchymal markers between the two groups. Thus, our analysis revealed a clinically important correlation between depression/anxiety and GBM prognosis.

Mortality risk of antipsychotic augmentation for adult depression.

IMPORTANCE: Randomized controlled trials have demonstrated increased all-cause mortality in elderly patients with dementia treated with newer antipsychotics. It is unknown whether this risk generalizes to non-elderly adults using newer antipsychotics as augmentation treatment for depression. OBJECTIVE: This study examined all-cause mortality risk of newer antipsychotic augmentation for adult depression. DESIGN: Population-based new-user/active comparator cohort study. SETTING: National healthcare claims data from the US Medicaid program from 2001-2010 linked to the National Death Index. PARTICIPANTS: Non-elderly adults (25-64 years) diagnosed with depression who after ≥3 months of antidepressant monotherapy initiated either augmentation with a newer antipsychotic or with a second antidepressant. Patients with alternative indications for antipsychotic medications, such as schizophrenia, psychotic depression, or bipolar disorder, were excluded. EXPOSURE: Augmentation treatment for depression with a newer antipsychotic or with a second antidepressant. MAIN OUTCOME: All-cause mortality during study follow-up ascertained from the National Death Index. RESULTS: The analytic cohort included 39,582 patients (female = 78.5%, mean age = 44.5 years) who initiated augmentation with a newer antipsychotic (n = 22,410; 40% = quetiapine, 21% = risperidone, 17% = aripiprazole, 16% = olanzapine) or with a second antidepressant (n = 17,172). The median chlorpromazine equivalent starting dose for all newer antipsychotics was 68mg/d, increasing to 100 mg/d during follow-up. Altogether, 153 patients died during 13,328 person-years of follow-up (newer antipsychotic augmentation: n = 105, follow-up = 7,601 person-years, mortality rate = 138.1/10,000 person-years; antidepressant augmentation: n = 48, follow-up = 5,727 person-years, mortality rate = 83.8/10,000 person-years). An adjusted hazard ratio of 1.45 (95% confidence interval, 1.02 to 2.06) indicated increased all-cause mortality risk for newer antipsychotic augmentation compared to antidepressant augmentation (risk difference = 37.7 (95%CI, 1.7 to 88.8) per 10,000 person-years). Results were robust across several sensitivity analyses. CONCLUSION: Augmentation with newer antipsychotics in non-elderly patients with depression was associated with increased mortality risk compared with adding a second antidepressant. Though these findings require replication and cannot prove causality, physicians managing adults with depression should be aware of this potential for increased mortality associated with newer antipsychotic augmentation.