Review articleExamining the role of neuroinflammation in major depression
Introduction
The prevalence of mental health disorders continues to rise worldwide, such that it is estimated that 1 in 4 individuals will be affected by a mental health disorder at some point in their lifetime (World Health Organization, 2011). Research has found that the most prevalent mental health disorders are depressive and anxiety disorders (Kessler et al., 2012), both of which hinder an individual’s functioning on multiple domains.
Depression is estimated to significantly impact 350 million people worldwide and it is projected to become the primary cause of global disease burden by 2030 (World Health Organization, 2012). Furthermore, the Global Burden of Disease Study found that depressive disorders were the second leading cause of Years Lived with Disability (YLDs) and the leading cause of Disability Adjusted Life Years (DALYs) globally (Ferrari et al., 2013). Depressive disorders, according to the Diagnostic and Statistical Manual of Mental Disorders (DSM IV) (American Psychiatric Association, 2000), include Major Depressive Disorder (MDD) and Dysthymia. MDD is characterized by Major Depressive Episodes (MDE) that are symptomatic almost all day, every day for periods of at very least 2 weeks, whereas dysthymia is described as a milder but more chronic form of depression lasting for at least 2 years (Ferrari et al., 2013). Changes with the DSM-5 (American Psychiatric Association, 2013), have included the insertion of Persistent Depressive Disorder (that includes both Dysthymia, and chronic and unremitted Major Depressive Disorder), as well as including a variety of specifiers, such as “with anxious distress,” in which the presence of anxiety symptoms suggests potentially higher risks of complications in diagnosis, as well as a higher likelihood of chronicity (Lamers et al., 2011).
With medical comorbidities being very common in MDD, growing interest has been placed on the role of the immune system and inflammation and its relation to psychiatric disorders. Although it has generally been said that genetic and environmental factors may play a significant role in the cause of depression (Lesch, 2004), recent research has focused on the role of cytokines and immune biomarkers (Felger and Lotrich, 2013) as predictors of the disorder. The present commentary will review the current scientific literature in regard to immune mediated theories in depression.
Section snippets
Methods
The present review is aimed at evaluating and interpreting literature regarding depressive disorders and the role of the immune system, specifically, HPA activity and a variety of inflammatory cytokines. A PubMed, MEDLINE, and PsycINFO literature search was performed for the past decade (2004 to 2014), for clinical studies in depressed patients assessing the role of the immune system. Keywords for this review included: major depression, immune system, inflammation, cytokines, TNF, interleukin,
The immune system and cytokines
The role of cytokines can be understood simply as hormonal messengers responsible for most of the biological effects in the immune system. They can be functionally divided into two groups: those that are proinflammatory and those, which are essentially anti-inflammatory, but may also promote allergic or autoimmune responses.
Lymphocytes (the primary cells of the immune response) are of two types, the T and B lymphocytes, both of which specifically tailor their responses to each pathogenic insult
Cortisol and the HPA axis
Major Depressive Disorder (MDD) is a severely debilitating disorder that imposes a significant burden on one’s quality of life. MDD is often comorbid with both psychiatric illnesses (Kessler et al., 2012), as well as medical illnesses including metabolic syndrome (Park et al., 2014), cancer, diabetes and cardiovascular diseases (Benton et al., 2007). Individuals with MDD are at an increased risk of developing coronary artery disease, as well as of having poorer outcomes when suffering with
C-reactive protein in depression
C-reactive Protein (CRP) has been utilized as a biomarker for detecting inflammation, in which levels exceeding 10 mg/L are considered to predict inflammatory states (Pepys and Hirschfield, 2003, Nordestgaard, 2009), and is a significant predictor of coronary heart disease (Tracy et al., 1997, Koenig et al., 1999, Ridker et al., 2000, Danesh et al., 2004). Given the relationship between depressive disorders, inflammatory disease, and cardiac disease, researchers have begun investigating the
Inflammatory response to antidepressant treatment
Various studies have been conducted in MDD patients to specifically examine the effect of antidepressant treatment on the HPA axis, as well as on cytokine activity (see Table 6). Fluoxetine response was evaluated in 20 premenopausal females with MDD in a study in which they were administered 750 mg of metyrapone on 2 separate intervals, followed by 20 mg of fluoxetine for a 4 week period; nonresponders (50% or less decrease in HAM-D scores) at week 4 were increased to 40 mg for the final two weeks
Conclusion
Depressive disorders continue to increase in prevalence globally and cause substantial impairments in an individual’s functioning, as well as significant economic burden. It is therefore essential to comprehensively understand the mechanisms that contribute to these disorders in order to develop efficacious treatment strategies. Research focused on neuroimmunology has provided important information, specifically in regard to HPA activity, as well as inflammatory and anti-inflammatory properties.
Conflict of interest
Dr. Katzman has participated on advisory boards and/or similar committees for GlaxoSmithKline Inc., Wyeth Pharmaceuticals, Lundbeck Canada Inc., Eli Lilly, Organon, AstraZeneca, Janssen-Ortho Inc., Shire, Bristol-Myers Squibb, Pfizer, Biovail, Genuine Health, Boehringer Ingelheim, and Solvay; has received research funding from CIHR, Sick Kids Foundation, Centre for Addiction and Mental Health Foundation, Canadian Psychiatric Research Foundation, Canadian Foundation for Innovation,
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