Major depressive disorders accompanying autoimmune diseases – Response to treatment
Introduction
The leading aspect of research into the human brain is to understand its functioning at the molecular, cellular and systemic levels, which may contribute to the comprehension of the pathogenesis of brain diseases. These disorders constitute a cluster of leading health problems around the world. Among them, a depressive disorder (MDD, depression) represents one of the most frequently diagnosed diseases and a major contributing factor to the overall global burden of all diseases (WHO 2018). The number of depressed patients is increasing every year, making depression one of the most common diseases afflicting the human population. According to the World Health Organization, depression affects approximately 350 million people, i.e. approximately 5% of the global population. Moreover, up to 10% of the society in developed countries may suffer from depression (DiLuca and Olesen 2014). It is estimated that by 2020 MDD will have been the second most common cause of disability, directly behind cardiovascular diseases (Poniatowska-Leszczyńska and Małyszczak 2013, WHO 2018). Depression can occur in both sexes; however, women are about twice more likely to suffer from this disease than men (Seedat et al. 2009). Additionally, MDD is one of the most economically burdening diseases in the modern world with over 60% of all costs generated annually by brain diseases (DiLuca and Olesen 2014). Furthermore, mood disorders, including MDD, increase the risk of suicide in relation to the general population (Bachmann 2018, Handley et al. 2018). Almost one million people commit suicide every year, which is the second leading cause of death among people aged 15–29 (Marcus et al. 2012, WHO 2018).
Despite the importance of the problem, knowledge of the pathogenesis of the disease is not complete, which is partly due to its multifactorial nature. However, the role of complex interrelations between genetic, environmental, biological as well as psychosocial factors is emphasized among many processes that may have an impact on the development and progression of the disease (Sullivan 2000, Dowlati et al. 2010). In spite of the availability of many antidepressants, about 30% of all patients do not respond to conventional methods of therapy (Al-Harbi 2012). Therefore, there is a strong need to understand the mechanisms underlying depressive disorders, which may contribute to the development of novel and personalized treatment options. It has been found that MDDs frequently accompany many other medical conditions, for example autoimmune diseases (ADs) caused by inflammation (Dantzer et al. 2008, Dowlati et al. 2010, Lotrich 2012, Alcocer-Gómez et al. 2014). Thus, the role of immune impairment in the course of depression has been studied for the past two decades (Miller and Raison 2015). Nevertheless, the mechanisms underlying this phenomenon remain unclear (Kessler and Bromet 2013). ADs represent a cluster of disorders accompanied by chronic inflammation, which develop as a result of a reduction or loss of immunological tolerance to self-antigens (Anaya 2012). There is a growing body of evidence indicating that several autoimmune diseases are characterized by an increased immune response (Khaibullin et al. 2017). The aim of this paper is to elucidate, based on the available research results and literature, the role of the relationship between the comorbidity of MDD and ADs as well as the reaction to antidepressant treatment under conditions with an altered immune response. We have put forward a hypothesis that inflammation in the course of an autoimmune disease may significantly reduce the chance of a positive response to MDD treatment. In this article, instead of a systematic comprehensive literature review, we provided a meaningful synthesis of available literature data.
Section snippets
Depression and inflammation
Inflammation is characterized by a number of behavioral, autonomic and endocrine changes that affect the balance of physiological processes (Dantzer et al. 2008). Inflammatory processes cause a broad spectrum of symptoms and behavioral changes observed in both illness and depressive disorders. During inflammation, the most important cells are macrophages (Jiang et al. 2014), since they stimulate the immune system to produce prostaglandins and a variety of cytokines (Sokol and Luster 2015). The
The relationship between depression and autoimmune disorders
The association between autoimmunity and mood disorders is probably the result of increased inflammatory activity and has been observed for various autoimmune diseases (Siegmann et al. 2018). Such an association has also been found for depression (Chosidow et al. 2010, Kheirandish et al. 2015, Khaibullin et al. 2017, Muscatello et al. 2017, Marrie et al. 2018). Previously, studies focused on the prevalence of mood disorders, especially depression, in patients suffering from ADs; now, there is a
Inflammation and pharmacotherapy
Psychopharmacological approaches to MDDs include many types of therapies. Several antidepressant drugs are available, which provide different mechanisms of action (Table 1). Most of them usually affect the metabolism of monoamines. It is known that some antidepressants have anti-inflammatory and neuroprotective activity, which may partly be attributed to their ability of downregulation of pro-inflammatory cytokine production and upregulation of the production of anti-inflammatory cytokines (
Impact of anti-inflammatory agents on depressive symptoms
As mentioned above, pro-inflammatory cytokines and other immune agents are upregulated in various autoimmune diseases, while their elevated levels may affect response to antidepressant treatment. These facts have allowed putting forward a hypothesis that co-occurrence of autoimmune diseases in the course of depressive disorders may reduce the chance of a positive response to treatment. Moreover, some piece of evidence shows that this relation is bidirectional, and depression may affect the
Future perspectives
The data collected in this review have shown some promising information. Although autoimmune diseases and depression retain their own individual sets of inflammatory cytokines in their pathogenesis and course of the disease, many alterations in cytokines can be found in both disorders. The research studies evaluating therapy with cytokine inhibitors in patients with depressive disorders without any autoimmune comorbidities are limited. Nonetheless, those studies provide data regarding a
Conclusion
The objective of this review was to evaluate the relationship between an altered immune response in both depressive disorders and autoimmune diseases, and a response to treatment in depression accompanied by autoimmune disorders. Another purpose of this study was to assess the efficacy of cytokine inhibitors in reducing the severity of depressive symptoms in AD patients suffering from MDDs. The factors contributing to the coexistence of depression as well as the ones affecting antidepressant
Acknowledgements
This work was supported by the Polish National Science Centre (No. UMO-2015/19/BNZ7/00410).
References (133)
- et al.
Effect of celecoxib add on treatment on symptoms and serum IL-6 concentrations in patients with major depressive disorder: randomized double-blind placebo-controlled study
J Affect Disord.
(2012) - et al.
Chronic antidepressant treatments resulted in altered expression of genes involved in inflammation in the rat hypothalamus
Eur J Pharmacol.
(2013) - et al.
NLRP3 inflammasome is activated in mononuclear blood cells from patients with major depressive disorder
Brain Behav. Immun.
(2014) Common mechanisms of autoimmune diseases (the autoimmune tautology)
Autoimmunity Reviews
(2012)- et al.
Cytokines in psoriasis
Cytokine.
(2015) - et al.
Lack of clinical therapeutic benefit of antidepressants is associated overall activation of the inflammatory system
J. Affect. Disord.
(2013 May 15) - et al.
Depression, another autoimmune disease from the view of autoantibodies
Med. Hypotheses
(2009) - et al.
Unregulated IL-23/IL-17 immune response in autoimmune diseases
Diabetes Res. Clin. Pract.
(2010) - et al.
The cost of brain diseases: a burden or a challenge?
Neuron
(2014) - et al.
A metaanalysis of cytokines in major depression
Biol. Psychiatry
(2010)