The Risk for Depression Comorbidity in Patients With COPD

doi:10.1378/chest.08-0965

Chest

Volume 135, Issue 1, January 2009, Pages 108-114

https://doi.org/10.1378/chest.08-0965 Get rights and content

Introduction

Patients with COPD are believed to have a high risk for the development of depression. However, it remains unclear whether or not there is a temporal relation between COPD and depression, and if the higher risk for depression is a result of having a chronic disease, or is specific for COPD. The aim of this study is to compare the risk for physician-diagnosed depression in patients with COPD, patients with diabetes mellitus (DM), and control subjects without chronic conditions.

Methods

The study was a prospective cohort study based on the Continuous Morbidity Registration database. Cox proportional hazards analysis was used to identify the risk of a first episode of depression in patients with COPD compared to patients with DM and matched control subjects without chronic conditions. The following covariates were added to the model: age, the general practice the patient was listed with, socioeconomic status, comorbidity, and gender. All patients with a diagnosis of depression preceding the date of first diagnosis of COPD or DM (dummy date in control subjects) were excluded.

Results

The hazard ratios for a first episode of depression in the COPD group compared to the DM group and healthy controls subjects were 1.80 (95% confidence interval [CI], 1.16 to 2.81) and 1.68 (95% CI, 1.20 to 2.35), respectively.

Discussion

We found a temporal relation between COPD and physician-diagnosed depression. Patients with COPD are more likely to have depression diagnosed than patients with DM and control subjects without chronic conditions.

Section snippets

Materials and Methods

The design of this study was a historical cohort study based on the Continuous Morbidity Registration (CMR) database with a 35-year observation period. Details of the CMR database have been described elsewhere.¹⁶ Briefly, the CMR records since 1971 all new episodes of morbidity presented to general practitioners (GPs) in four general practices in the surroundings of Nijmegen, the Netherlands. The practices have a stable practice population of approximately 12,000 individuals.¹⁷ The turnover of

Results

The flowchart in Figure 1 summarizes the selection procedure of patients and control subjects in the study. Of the patients with COPD, 5.5% were excluded because depression had been diagnosed prior or at the same time of the diagnosis of COPD, or the date of first depression was unknown. For patients with DM, this was also 5.5%.

Table 1 shows the characteristics of the selected COPD, DM, and control groups. Patients with COPD had depression diagnosed almost twice as often by their GP, compared

Discussion

The objective of this study was to determine the incidence of GP-diagnosed initial episodes of depression in patients with COPD, and to compare the risk of depression with patients with DM and with control subjects without chronic conditions. In total, 5.5% of the COPD population and DM group were not selected for this study because depression had been diagnosed at the same time or prior to the diagnosis of COPD or DM. Our study showed that the risk for a depression was approximately 1.7- to

Acknowledgment

The authors thank the GPs and practice nurses of the CMR practices for the collecting of data for so many years. Moreover, we are very grateful to Reinier Akkermans for his help with advanced Cox proportional hazard modeling.

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Depression is frequently reported in patients with Chronic Obstructive Pulmonary Disease (COPD). However, there is little information available on the incidence of depression following a COPD diagnosis.
To determine the incidence of a new diagnosis of depression or antidepressant prescription in people with and without a COPD diagnosis.
A matched cohort study was conducted using The Health Improvement Network database. Patients with confirmed COPD diagnosis were matched to up to four subjects without a COPD diagnosis by age, sex and GP practice. Cox proportional hazards models were used to assess the incidence rates of depression and antidepressant prescription.
44,362 patients with COPD and 124,140 subjects without COPD were included. The incidence rate of depression per 1000 person-years following COPD diagnosis was greater (11.4; 95% CI: 10.9–11.8) compared to subjects without COPD (5.7; 95% CI: 5.5–5.8) (p < 0.001). Patients with COPD were 42% more likely to have an incident depression (adjusted hazard ratio [aHR]: 1.42; 95% CI: 1.32–1.53; p < 0.001), and 40% more likely to be prescribed an antidepressant (aHR: 1.40; 95% CI: 1.35–1.45; p < 0.001). The incidence to either depression or antidepressant prescription was also greater for patients with COPD (aHR: 1.41; 95% CI: 1.36–1.46; p < 0.001). Patients with COPD and worse breathlessness had a higher risk of incident depression compared to patients with less breathlessness.
Healthcare providers managing patients with COPD should be alert to the existence of depression and aware of its symptoms and consequences.
Hypobaric hypoxia exposure in rats differentially alters antidepressant efficacy of the selective serotonin reuptake inhibitors fluoxetine, paroxetine, escitalopram and sertraline
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Treatment-resistant depression, a chronic condition that affects 30% of depressed patients on antidepressants, is highly linked to suicidal behavior. Chronic hypoxia exposure via living at altitude (hypobaric hypoxia) or with chronic hypoxic diseases is demographically linked to increased risk for depression and suicide. We previously demonstrated that housing rats at altitude for a week incrementally increases depression-like behavior in the forced swim test (FST) in females, but not males. In animal models, high altitude exposure reduces brain serotonin, and selective serotonin reuptake inhibitors (SSRIs) can lose efficacy when brain serotonin levels are low. To address whether residence at moderate altitude is detrimental to SSRI function, we examined SSRI efficacy in the FST after a week of housing rats at altitudes of 4500 ft. or 10,000 ft. as compared to at sea level. In females, the tricyclic antidepressant desipramine (positive control) functioned well in all groups, increasing latency to immobility and decreasing immobility, by increasing climbing. However, the SSRIs fluoxetine, paroxetine and escitalopram were ineffective in females in all groups: only paroxetine improved swimming in the FST as expected of a SSRI, while all three unexpectedly reduced climbing. Fluoxetine was also ineffective in male rats. Sertraline was the only SSRI with antidepressant efficacy at altitude in both females and males, increasing swimming, climbing and latency to immobility, and reducing immobility. Hypobaric hypoxia thus appears to be detrimental to efficacy of the SSRIs fluoxetine, paroxetine and escitalopram, but not of sertraline. Unlike the other SSRIs, sertraline can improve both serotonergic and dopaminergic transmission, and may be less impacted by a hypoxia-induced serotonin deficit. A targeted approach may thus be necessary for successful antidepressant treatment in patients with depression who live at altitude or with chronic hypoxic diseases, and that sertraline may be the SSRI of choice for prescription for this population.
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Both diseases generate an elevated global economic and social burden [2]. While the association between COPD and depression should be anticipated because of social isolation of more severe patients, the prevalence of depression in COPD appears to be more frequent than in other chronic disabling diseases [3,4]. However, the relationship between depression and COPD is not linear [5].
Depression is frequently reported in association with COPD. However, the prevalence of depression in these patients ranges largely. This study aimed to systematically review the prevalence of depression in COPD and controls and to explore remaining causes of inter-study variability in the reported prevalence.
A systemic review of the literature and a meta-analysis was performed to evaluate the source of variability in the reported rates of depression in stable COPD. Main eligibility criteria were: controlled studies with a sample size >100, outpatients with COPD diagnosed by spirometry and, use of a validated depression screening instrument.
From 1613 studies identified, eight controlled studies were included in the review. The number of participants in the pooled studies was of 5.552 COPD subjects and 5.211 controls. Using stricter criteria for study selection reduced the variability of the depression prevalence in COPD and controls, which was 27.1% [25.9–28.3] in COPD subjects and 10.0% [9.2–10.8] in the control group. The pooled odds ratio and 95% CI was 3.74 [2.4–5.9]. However, the heterogeneity across studies was high. Possible explanatory factor included sample sizes, COPD/controls ratio, smoker’s/nonsmokers ratio and qualitative differences (source of subjects, instruments to screen depression, COPD severity, smoking status, and comorbidities).
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Although mild hypoxia can elicit beneficial effect through endogenous adaptive responses to subsequent either severe hypoxia or cerebral ischemia (Leconte et al., 2012), chronic hypoxia is deleterious to the brain because it elicits neuronal death ultimately leading to neurological and behavioral disturbances, including anxiety and depression (Bahrke and Shukitt-Hale, 1993; Bartsch and Swenson, 2013; Kanekar et al., 2015; Netzer et al., 2013). For example, people living at high altitude have higher levels of anxiety and depression than those living at sea level (Gamboa et al., 2011), and accumulating clinical investigations have proven anxiety and depression are highly prevalent in patients living with chronic hypoxic disorders such as COPD, SAS, and PAH (Naeije and Vanderpool, 2013; Schneider et al., 2010; Webb et al., 2012; van den Bemt et al., 2009). These data suggest that chronic hypoxia could be a key factor for the induction of anxiety and depression in people living at high altitude or suffering from chronic hypoxic health conditions, the underlying mechanisms of which, however, are not fully understood yet.
This study aims to investigate whether inflammation mediated by NF-κB activation is involved in the induction of anxiety-like behavior in chronic normobaric hypoxia (CNH) exposed rats and to investigate the underlying mechanism. To this end, rats were exposed in a normobaric hypoxic chamber with a fraction of inspired oxygen (FIO₂) of ∼10%, 23 h/d, continues for 2 weeks. Anxiety-like behavior was tested by elevated plus maze and open field, inflammatory response, nucleus translocation of NF-κB, and signaling pathway in hippocampus were examined. CNH induced a significant increase of anxiety- like behavior and inflammation responses, which were ameliorated by NF-κB inhibitor, PDTC pretreatment, suggesting that the anxiogenic effect induced by inflammation is through NF-κB activation. CNH treatment significantly increased nucleus translocation of p65 and p105 in hippocampus, which was suppressed by PDTC pretreatment. In addition, CNH treatment significantly increased Iba-1, iNOS, COX-2, and p-PKA in hippocampus, which were blocked by PDTC pretreatment, suggesting CNH may activate microglia cells in hippocampus through NF-κB pathway. In conclusion, our results illustrate a mechanism that, activation of NF-κB in hippocampus may trigger the proinflammatory response of microglia cells, and iNOS-PKA pathway may involve in anxiogenic effect in CNH exposed rats.

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: Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).

¹: Ms. van den Bemt has no conflicts of interest to disclose.

²: Dr. Schermer received grant money for research in the field of respiratory medicine from noncommercial organizations (Radboud University Nijmegen Medical Centre, the Netherlands Organization for Health Research and Development [ZonMw], and the Dutch Asthma Foundation), and from several pharmaceutical companies (Boehringer Ingelheim, AstraZeneca, and GlaxoSmithKline);

³: Mr. Bor, Dr. Smink, and Dr. van Weel-Baumgarten have no conflicts of interest to disclose.

⁴: Dr. van Weel's Department of General Practice, Radboud University Nijmegen Medical Centre, has received financial support for research from the university and unrestricted grants for research and education from the pharmaceutical industry.

View full text

Chest

Original ResearchCOPDThe Risk for Depression Comorbidity in Patients With COPD

Introduction

Methods

Results

Discussion

Section snippets

Materials and Methods

Results

Discussion

Acknowledgment

J Affect Disord

Am J Geriatr Psychiatry

J Affect Disord

J Clin Epidemiol

Lancet

J Clin Epidemiol

J Clin Epidemiol

J Clin Epidemiol

J Psychosom Res

Depression and cardiac mortality: results from a community-based longitudinal study

Arch Gen Psychiatry

Richtlijn ketenzorg COPD

Prevalence of depression in patients with chronic obstructive pulmonary disease: a systematic review

Thorax

Risk of depression in patients with chronic obstructive pulmonary disease and its determinants

Thorax

Depression and anxiety in elderly outpatients with chronic obstructive pulmonary disease: prevalence, and validation of the BASDEC screening questionnaire

Int J Geriatr Psychiatry

Associations of depressive symptoms with gender, body mass index and dyspnea in primary care COPD patients

Fam Pract

Chronic bronchitis, cigarette smoking, and the subsequent onset of depression and anxiety: results from a prospective population-based cohort study

Psychosom Med

Original Research
COPD
The Risk for Depression Comorbidity in Patients With COPD