Immune-Inflammatory and Oxidative and Nitrosative Stress Biomarkers of Depression Symptoms in Subjects with Multiple Sclerosis: Increased Peripheral Inflammation but Less Acute Neuroinflammation

Abstract

There is evidence that activated immune-inflammatory and oxidative and nitrosative stress (IO&NS) pathways play a role in the pathophysiology of multiple sclerosis (MS) and depression. This study examines serum levels of interleukin (IL)-1β, IL-4, IL-6, and IL-10; peroxides (LOOH); nitric oxide metabolites (NOx); albumin; ferritin; C-reactive protein (CRP); and tumor necrosis factor (TNF)-β NcoI polymorphism (rs909253) and gadolinium-enhanced magnetic resonance imaging (MRI) scan in MS patients with (n = 42) and without (n = 108) depression and normal controls (n = 249). Depression is scored using the depressive subscale of the Hospital Anxiety and Depression Scale (HADS). The extent of neurological disability is measured using the Expanded Disability Status Scale (EDSS) at the same time of the abovementioned measurements and 5 years earlier. Disease progression is assessed as actual EDSS-EDSS 5 years earlier. Three variables discriminate MS patients with depression from those without depression, i.e., increased IL-6 and lower IL-4 and albumin. Binary logistic regression showed that MS with depression (versus no depression) was characterized by more gastrointestinal symptoms and disease progression, higher serum IL-6, and lower albumin levels. In subjects with MS, the HADS score was significantly predicted by three EDSS symptoms, i.e., pyramidal, gastrointestinal, and visual symptoms. Fifty-eight percent of the variance in the HADS score was predicted by gastrointestinal symptoms, visual symptoms, the TNFB1/B2 genotype, and contrast enhancement (both inversely associated). There were no significant associations between depression in MS and type of MS, duration of illness, age, sex, nicotine dependence, and body mass index. MS with depression is associated with signs of peripheral inflammation, more disability, disease progression, gastrointestinal and visual symptoms, but less contrast enhancement as compared to MS without depression. It is concluded that depression is part of the neurological symptoms of MS and that its expression is primed by peripheral inflammation while acute neuroinflammation and the TNFB1/B2 genotype may be protective.

Residual Effects of Restless Sleep over Depressive Symptoms on Chronic Medical Conditions: Race by Gender Differences

“…Significant evidence has shown dysregulation of homeostatic buffering mechanisms regulating oxidation and inflammation that exist in healthy individuals in the presence of depression, sleep disorder, and CMC (95). Thus, changes in inflammation, oxidative stress and immune function may be the mechanisms that at least in part explain the effect of depression and poor sleep on CMC over time (96–100). It is still not clear if peripheral and central inflammation fully mediate the comorbidities between poor sleep, depression, and CMC (101).…”

Integrating Interleukin-6 into depression diagnosis and treatment

“…In support of this hypothesis, there have been numerous studies in patients with various inflammatory conditions including rheumatoid arthritis (Joaquim and Appenzeller, 2015 Matcham et al., 2015, Ryan and McGuire, 2015), multiple sclerosis (Hoang et al., 2016; Kallaur et al., 2015, Marrie et al., 2015), and psoriasis (Walker et al., 2011 Rabin et al., 2012, McDonough et al., 2014), demonstrating a relationship between inflammation and depressed mood. However, the relationship between depression and inflammation in humans is largely confounded by the likelihood that the symptoms of the disease themselves contribute to mood changes.…”

Inverse association between serum albumin and depressive symptoms among drug-free individuals with a recent suicide attempt

“…Among others, patients with major depressive disorder (MDD) appear to have lower serum albumin levels compared to controls [9][10][11][12][13], increasing with anti-depressant therapy [8]. Lower serum albumin levels have also been linked to more severe depressive symptoms in various cohorts of patients with non-psychiatric diseases like stroke, HIV, multiple sclerosis (MS), chronic kidney disease, hemodialysis patients, hypertension or cancer [10,[12][13][14][15][16][17][18][19][20][21][22]. Interestingly, according to several studies, the negative association between serum albumin and depressive symptoms may be independent of immunological markers like CRP and IL-6 [14][15][16][17][18][19][20][21][22].…”