Elsevier

Journal of Affective Disorders

Volume 238, 1 October 2018, Pages 491-498
Journal of Affective Disorders

Research paper
Depression and anxiety symptoms are associated with prooxidant-antioxidant balance: A population-based study

https://doi.org/10.1016/j.jad.2018.05.079Get rights and content

Highlights

  • Depression symptoms are associated with elevated serum PAB values; however, this association is stronger in men.

  • Anxiety symptoms are also associated with elevated serum PAB values; however, this association is stronger in men.

  • The weaker association in women may be partly explained by antioxidant and anti-inflammatory properties of estrogen in premenopausal women.

Abstract

Background

Depression and anxiety are significantly associated with systemic inflammation. Moreover, oxidative stress resulting from a disturbance in the prooxidant-antioxidant balance is linked to inflammation-related conditions. Therefore, depression/anxiety symptoms may also be associated with oxidative stress.

Objective

To examine the association between depression/anxiety symptoms and serum prooxidant-antioxidant balance (PAB) in adults who participated in a large population-based, cross-sectional study.

Methods

Serum PAB values were measured in 7516 participants (62% females and 38% males) aged 35–65 years, enrolled in a population-based cohort study. beck depression and anxiety inventories were used to evaluate symptoms of depression and anxiety. Multinomial logistic regression was used to examine the effect of confounders on the status of serum PAB change.

Results

Among men, serum PAB values were increased incrementally from 1.55 ± 0.47 to 1.59 ± 0.47, 1.69 ± 0.38, and 1.68 ± 0.38 in the no or minimal, mild, moderate and severe depression groups, respectively (Ptrend < 0.001). Serum PAB values also increased significantly across these four corresponding groups among women [1.70 ± 0.45, 1.73 ± 0.44, 1.75 ± 0.44, and 1.76 ± 0.40, (Ptrend = 0.005)]. About anxiety, serum PAB values increased significantly across the four groups in men (Ptrend = 0.02) but not in women (Ptrend = 0.2). The adjusted odds ratios for serum PAB values among men with severe depression and anxiety symptoms were 1.75 and 1.27, respectively. Moreover, the adjusted odds ratios for serum PAB values among women with severe depression and anxiety symptoms were 1.40 and 1.17, respectively.

Conclusion

Symptoms of depression and anxiety appear to be associated with higher degrees of oxidative stress, expressed by higher serum PAB values.

Introduction

Depression and anxiety are two of the most common mental disorders and are significantly associated with systemic inflammation upregulation indicated by an increased production of pro-inflammatory cytokines and oxidative biomarkers (Duivis et al., 2013, Tayefi et al., 2017). The homeostatic buffering mechanisms regulating inflammation and oxidation in healthy individuals become dysregulated in untreated depression (Rawdin et al., 2013). In this regard, we have recently shown that depression and anxiety are associated not only with serum level of hs-CRP, but also with hematological inflammatory markers including white blood cell (WBC) count and red cell distribution width (RDW) (Shafiee et al., 2017). Such a heightened inflammatory state is accompanied by increased oxidative stress due to alterations in prooxidant-antioxidant balance (PAB), increased generation of reactive oxygen species (ROS), lipid peroxidation and decreased anti-oxidant defenses (Kawanishi et al., 2006, Valko et al., 2006).

Oxidative stress has been implicated in a variety of pathological conditions and traumatic events, including CVD, autoimmune diseases, traumatic brain injury, and others (Ehsaei et al., 2015, Heitzer et al., 2001, Sahebari et al., 2015). Oxidative stress is defined as a serious disturbance in the prooxidant-antioxidant balance in favor of the prooxidants, in which elevated levels of intracellular ROS such as hydrogen peroxide (H2O2), superoxide radical (O¯) or hydroxyl radical (•OH), contribute to tissue damage (Sies, 1997). Prooxidants are derived either from normal metabolic processes or from external sources such as dietary iron, cigarette smoke, and alcohol (Albano, 2006, Stone et al., 2002, van der Vaart et al., 2004). Antioxidants include the three major lipid-soluble antioxidants (e.g. α-tocopherol and vitamin A), water-soluble antioxidants (e.g. vitamin C, urate, polyphenols, and flavonoids) and the enzymatic antioxidants (e.g. catalase, peroxidase, and superoxide dismutase) (Alamdari et al., 2007). Although various methods have been developed to measure either the total oxidants [e.g. total oxidant status assays (Erel, 2005)] or antioxidants [e.g. the ferric reducing ability of plasma (Benzie and Strain, 1996)], these methods are time-consuming and imprecise due to the need for two separate tests to estimate serum prooxidant-antioxidant balance (PAB) (Alamdari et al., 2007). Therefore, we have previously developed a method in which the balance of oxidants and antioxidants can be measured using 3,3´,5,5´-tetramethylbenzidine (TMB) (Alamdari et al., 2008). The serum PAB assay has the ability to measure the prooxidant burden and the antioxidant capacity simultaneously in one assay to provide a redox index (Alamdari et al., 2008). A high serum PAB value means that the number of oxidants considerably outweigh the number of antioxidants and may reflect a higher oxidative stress state.

Considering the close association between inflammation and oxidative stress, and the fact that depression and anxiety are linked to inflammation (Berk et al., 2013, Duivis et al., 2013), we hypothesized that more severe depression/anxiety symptoms are associated with more oxidative stress reflected by higher values of serum PAB. In this regard, numerous studies have linked increased measures of oxidative stress in depression and anxiety disorders (Hovatta et al., 2010, Yanik et al., 2004). For instance, Sarandol et al. conducted a study on ninety-six patients with a diagnosis of major depressive disorder (MDD) and 54 healthy controls. Plasma malondialdehyde (MDA) and susceptibility of red blood cells (RBC) to oxidation were found to be higher in the MDD group compared with the control group. Moreover, RBC superoxide dismutase (SOD) was significantly elevated in patients with MDD (Sarandol et al., 2007). In another study, the excretion of urinary F2 isoprostane was observed to be significantly higher in patients with depression than in control subjects, even after adjustment for sex, age and body mass index (BMI) (Chung et al., 2013). Irie et al. found a significant positive correlation between depression scores and the 8-hydroxydeoxyguanosine (8-OH-dG) levels in depressed patients. Since 8-OH-dG is a product of oxidative damage to DNA, the authors suggested that clinical depression can be considered as a risk factor for cancer initiation (Irie et al., 2005). Moreover, Yanik and colleagues also investigated the relationship between the potency of oxidative stress and the severity of depression on 21 patients with MDD and 28 healthy controls. The results showed lower total antioxidant potential of plasma (TAOP) and higher oxidative stress index (OSI) in patients with depression than those in control group (Yanik et al., 2004).

Despite these observations, no studies have evaluated the association between depression/anxiety symptoms and oxidative stress using the serum PAB assay. Therefore, the primary objective of the present study was to examine the cross-sectional association between depression/anxiety symptoms and serum PAB values in a large population-based study.

Section snippets

Study population

A total of 7516 subjects [2865 (38%) males and 4651 (62%) females] were derived from a cohort of free living individuals aged 35–65 years from northeastern Iran (Ghayour-Mobarhan et al., 2015). The Mashhad Stroke and Heart Atherosclerotic Disorders (MASHAD) cohort study is a 10-year cohort, which aims to evaluate the impact of various risk factors on the incidence of cardiovascular events among a general urban population (Ghayour-Mobarhan et al., 2015). The first phase of the MASHAD cohort

Results

Among the 7516 individuals, the average age was 47.9 ± 8.1, with 62% being female. The mean age of premenopausal and menopausal women were 42.6 ± 5.1 and 55.2 ± 5.4, respectively (unshown data). Demographic and biochemical characteristics of the study population are presented in Table 1. Participants were stratified into four groups according to their depression and anxiety scores: “no or minimal”, “mild”, “moderate”, and “severe”. As given in Table 1, the number of individuals with no or

Discussion

Our results suggest that higher depression and anxiety symptoms may be associated with altered oxidative stress status, expressed by higher PAB values. However, this association was stronger for depression than in anxiety and in men than in women.

Some previous studies have reported similar association between depression and increased markers of oxidative stress including MDA (Khanzode et al., 2003, Rybka et al., 2013, Talarowska et al., 2012), isoprostanes (Dimopoulos et al., 2008, Milaneschi

Conflict of interest

None.

Authors' contributions

The work presented here was carried out in collaboration between all authors. M.G-M., S.R.A., and G.A.F. defined the research theme. M.A., S.A., and M.M., designed methods and experiments and carried out the laboratory experiments. M.T. and H.E. analysed the data and interpreted the results. M.S., N.M. and H.V. wrote the paper and revised it critically for important intellectual content.

Acknowledgments

The authors acknowledge with grateful appreciation the kind assistance provided by Mashhad University of Medical Sciences (MUMS) and Tabriz University of Medical Sciences (TUMS).

Funding

This work was supported by Mashhad University of Medical Sciences (MUMS) and Tabriz University of Medical Sciences (TUMS) (Grant number: 85134).

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