Oxidative stress and neuroinflammation should be both considered in the occurrence of fatigue and depression in multiple sclerosis

Abstract

Oxidative stress and neuroinflammation have a role in the pathogenesis of multiple sclerosis (MS) and in depression. Fatigue is the most disabling symptom in patients with MS and could also be a part of depressive symptomatology. In this study, we measured the serum levels of uric acid (UA) as a marker of oxidative stress and C-reactive protein (CRP) as an inflammatory marker, in 98 patients with MS in relapse and remitting phase of illness and 35 healthy subjects. Degree of depressive symptomatology and fatigue were assessed with Beck's Depression Inventory (BDI) and Fatigue Severity Scale (FSS). Further, we examined the possible correlation of these biomarkers with symptoms of depression and fatigue. Relapse and remitting MS had a lower serum UA levels than controls (236.97 ± 9.25 µmol/L vs. 268.27 ± 0.09 µmol/L vs. 314.82 ± 11.02 µmol/L; p = 0.000), while sera levels of CRP were higher in relapse than remitting patients (4.46 ± 0.40 mg/L vs. 1.01 ± 0.38 mg/L; p = 0.000). Patients in relapse had higher BDI scores (15.68 ± 16.62 vs. 8.36 ± 7.10; p = 0.045). Decreased UA levels showed weak negative correlation with the presence of sadness and disturbed daily activities, higher CRP levels positively correlated with severe depression and the correlation between depression and fatigue was also observed (p < 0.05). It is possible that decreased UA levels lead to sadness, disturbed daily activities and severe disability. Every attack of CRP elevation in relapse could additionally precipitate the depression onset. The clinicians must pay special attention to early detection of fatigue because it could precede depression and improve further treatment.

Possible Reduction of Cardiac Risk after Supplementation with Epigallocatechin Gallate and Increase of Ketone Bodies in the Blood in Patients with Multiple Sclerosis. A Pilot Study

“…These anthropometric changes are observed through an increase in body mass index (BMI) and, especially, waist circumference [4] where fat accumulates around the abdomen [5]. A rise in body fat is positively correlated with concentrations of C-reactive protein (CRP) [6], which is linked to the disease's progression [7]. In addition, metabolic alterations alongside fat accumulation, especially in the abdominal area, increase oxidative stress [8].…”

Increased Oxidative Stress Toxicity and Lowered Antioxidant Defenses in Temporal Lobe Epilepsy and Mesial Temporal Sclerosis: Associations with Psychiatric Comorbidities

“…These findings contrast our a priori hypothesis that both comorbidities are accompanied by increased oxidative stress toxicity which would reflect cumulative effects of increased levels in both TLE and affective disorders. Moreover, comorbidities between depression and neuroinflammatory disorders including multiple sclerosis and stroke are associated not only with increased morbidity and mortality but also with increased inflammatory and oxidative stress biomarkers [77][78][79]. Therefore, our findings could indicate that depression and anxiety disorder due to TLE have a different pathophysiology than major depression and anxiety disorders such as GAD [26,27].…”

On elucidation of the role of mitochondria dysfunction and oxidative stress in multiple sclerosis

“…246 Evidence suggests that fatigue is a key feature of mitochondrial disease 247 and mitochondria bioenergetics is altered in patients with chronic fatigue syndrome. 248 Also, OS and neuroinflammation play a critical role in the occurrence of fatigue in MS. 80 HPA-axis dysfunction has been implicated in MS. 249 Research indicates that mitochondria DNA damage is strongly associated with HPA-axis alteration and negative feedback. 250 Evidence suggests that mitochondria play a role in HPA axis and influence the body's response to psychological stress both at the cellular and global levels.…”

“…Also, OS plays a central role in psychiatric disorders [74][75][76][77][78][79] . Indeed, evidence suggests that it contributes to depression in MS. 80…”

“…Evidence suggests that fatigue is a key feature of mitochondrial disease and mitochondria bioenergetics is altered in patients with chronic fatigue syndrome . Also, OS and neuroinflammation play a critical role in the occurrence of fatigue in MS . HPA‐axis dysfunction has been implicated in MS .…”