The association of unipolar depression with thirty-day mortality after hospitalization for infection: A population-based cohort study in Denmark
Introduction
Depression is a highly prevalent psychiatric disorder throughout the world [1]. It is a leading cause of years lived with disability [1], and individuals with depression suffer more chronic medical disease-related sequelae than those without depression [2]. Notably, a recent meta-analysis identified that having a diagnosis of depression is associated with a 71% greater risk for premature all-cause mortality [3]. Importantly, a nationwide cohort study from Denmark identified that unipolar depression is associated with a decreased life expectancy of 14 years in men and 10 years in women [4]. While this study found that depression was strongly associated with increased risk for death due to suicide and accidents [4], the absolute number of deaths attributable to depression was highest for medical diseases [4].
Yet, while depression is known to be associated with increased risk for mortality in patients with chronic diseases such as diabetes and coronary artery disease [5], [6], [7], it remains unclear whether death following acute medical illnesses may explain some of the association between depression and reduced life expectancy. Depression has been found to be associated with increased risk for hospitalization for serious infections [8], but it is unknown if pre-existing depression is a risk factor for death following serious infections. This possibility is important to consider since depression has been shown to be associated with increased levels of inflammatory cytokines [9], a contributing factor in the development of sepsis in the face of infection [10], from which nearly 1/3rd of patients do not survive [11]. Furthermore, a recent study identified that individuals with schizophrenia or bipolar disorder have higher mortality following hospitalization for an infection [12]. Since unipolar depression is more prevalent in the general population than schizophrenia or bipolar disorder [13], [14], and evidence-based depression treatments are being increasingly integrated into general practice settings world-wide [15], [16], identifying depression as a potential risk factor for death following hospitalization for a serious infection could have important public health impact.
The present study utilizes data from a large population-based cohort of Danish adults to determine if pre-existing unipolar depression is associated with increased risk of mortality within 30 days after hospitalization for a serious infection. We hypothesized that pre-existing depression would be associated with a higher relative risk of death when compared to individuals without pre-existing depression.
Section snippets
Population
We conducted a population-based cohort investigation utilizing data from nationwide Danish registries. Our cohort included all living persons aged 15 years or older, residing in Denmark for at least 10 years (to ensure continuous information on depression), and hospitalized for an infection at least once between January 1, 2005 and December 1, 2013. We constructed our cohort using information from two registries: 1) the Danish Civil Registration System [17], which includes data on sex, birth
Results
After excluding 14,709 persons with a diagnosis of schizophrenia, schizoaffective disorder or bipolar disorder and 2457 persons who died on the day of hospitalization (of whom 797 were depressed), 589,688 individuals were hospitalized a total of 703,158 times for an infection during the study period. Of the hospitalizations, 189,817 (27.0%) were among individuals with pre-existing unipolar depression. Table 1 displays the characteristics of our cohort at time of hospitalization for infection by
Discussion
In this population-based cohort study of individuals hospitalized for an infection, we found that having pre-existing unipolar depression was associated with a slightly increased risk of all-cause mortality within 30 days after admission. Notably, this association remained significant even after controlling for medical and substance use comorbidities, suggesting that our findings may be overly conservative since medical and substance use comorbidities could mediate the association of
Disclosures
The authors have no relevant conflicts of interest to disclose.
Funding
This work was supported by an unrestricted grant (grant number: R155-2012-11280) from the Lundbeck Foundation.
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