Comorbidity between depression and asthma via immune-inflammatory pathways: A meta-analysis

Abstract

Background

Depression is often present in patients with asthma and vice versa. In this review, we aimed to summarize reports on the comorbidity of depression and asthma, and to seek evidence that the biological mechanisms of allergy may have an important role linking asthma and depression.

Method

To explore the relationship and pathway underpinning this comorbidity, we reviewed medical articles and undertook a meta-analysis of epidemiological studies on (i) incidence of asthma in patients with depression; (ii) morbidity of depression in patients with asthma; (iii) concentration of cytokines in depressed subjects.

Results

High level of comorbidity of asthma and depression was consistently demonstrated in 10 studies of patients with asthma and four studies of patients with depression. In search of biological connection of the two illnesses, thirty-eight studies were included for Meta-analyses examining differences in allergy related cytokines between patients with depression and non-depressive subjects. In people with depression, concentration of monocytes related cytokines such as IL-1 (1.56 ng/mL, 95% CI: 0.00–3.12, p=0.05) was significantly higher than that in non-depressive control subjects. At the same time, some other inflammatory factors including IL-4 (5.77 pg/mL, 95% CI: 2.34–9.21, p=0.00010), IL-6 (1.44 ng/mL, 95% CI: 1.05–1.82, p<0.00001) and TNF-α(3.01 ng/mL, 95% CI: 1.76–4.26, p<0.00001) were extremely significantly higher in depressed people compared with the controls. There was no significant differences of the T cell related cytokine levels, IFN-γ (−0.16 ng/mL, 95% CI: −0.85–7.73, p=0.97), accompanied with IL-10 (0.67 ng/mL, 95% CI: −0.84–2.18, p=0.38) between depressive and non-depressive groups.

Conclusions

The varying levels of certain cytokines play an important role in arousing and remitting asthma and depression. That suggests inflammatory response could be a common pathway adjusting both depression and asthma.

Introduction

Asthma is a common chronic disease affecting >300 million people worldwide (Bateman et al., 2008). It has been reported that about 7–10% children and 5% adults suffers from asthma at various severity (Woolcock and Peat 1997). Asthma is a complex and multifaceted illness characterized mainly by bronchial hypersensitivity and airway inflammation, resulting in bronchoconstriction, airway remodeling and airway obstruction (Melissa and Richard 2009). It is known that several types of cells (such as macrophages, mast cells, monocytes, neutrophils, and natural killer cells) and mediators, especially Th1 and Th2 cytokines, play important parts in the inflammatory response. If individuals are exposed to an allergen or irritant, the balance between Th1 and Th2 cells is to break and certain types of inflammatory cells (e.g., mast cells) are activated (Pleung et al., 1988), leading to the over-expression of Th2 related cytokines and reduction of Th1 related cytokines. Cytokines released from activated pulmonary mast cells can act locally on to the airway surface (e.g., mucosa), bronchial smooth muscles, and vessels to cause bronchoconstriction or airway stenosis. Bronchoconstriction would lead to breathlessness (Pleung et al., 1988).

Depression is the most common mental disorder, and is increasingly recognized as a public health and social problem worldwide. A total of 4–20% of the general population would suffer this disorder some time during their lifetime (Bakish 2001). Depression causes significant physical and psychological difficulties, and affects people׳s thoughts, emotions, self-awareness, interpersonal relationships, work productivity, physical functioning and overall life satisfaction (Murray and Lopez 1996). Numerous studies have indicated that depression as well other mentally ill conditions are closely associated with physical status (Richardson et al., 2006). In the early 1990s, depression was reported for the first time being an illness characterized by cell-mediated immune activation (Maes, 1993). This observation developed into a novel hypothesis that inflammation and cell-mediated immune activation may be key factors in depression. That inflammatory triggers “neuraxes” conveying metabolic, gastro-intestinal and cardiovascular information to brain and subsequently drive depressive-like behaviors (Maes et al., 1993). Recent evidence suggests that depression is an inflammatory disorder because of the increased production of interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-αin people with depression (Maes, 2011, Dowlati et al., 2010).

Evidence has shown that individuals with asthma have twice the risk of developing depressive symptoms as compared with those who do not have asthma (Melissa and Richard 2009). Psychological stress and negative emotions can provoke the increase of inflammatory markers (Maes, 1993), and that remission from depression is associated with improvement in asthma symptoms (Loerbroks et al., 2010). Considering the role of inflammatory responses in asthma and depression, ongoing inflammation in the allergic process is very likely to be the “bridge” that connects them. Cytokines modulate inflammatory responses, and the processes they govern may be shared by asthma and depression. In the present review, we aimed to summarize reports on the comorbidity of depression and asthma, and to seek evidence that the biological mechanisms of cell-mediated immunity may have an important role linking asthma and depression.