Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB, Canada
The Role of Inflammation in Depression and Fatigue.
Depression and fatigue are conditions responsible for heavy global societal burden, especially in patients already suffering from chronic diseases. These symptoms have been identified by those affected as some of the most disabling symptoms which affect the quality of life and productivity of the individual. While many factors play a role in the development of depression and fatigue, both have been associated with increased inflammatory activation of the immune system affecting both the periphery and the central nervous system (CNS). This is further supported by the well-described association between diseases that involve immune activation and these symptoms in autoimmune disorders, such as multiple sclerosis and immune system activation in response to infections, like sepsis. Treatments for depression also support this immunopsychiatric link. Antidepressants have been shown to decrease inflammation, while higher levels of baseline inflammation predict lower treatment efficacy for most treatments. Those patients with higher initial immune activation may on the other hand be more responsive to treatments targeting immune pathways, which have been found to be effective in treating depression and fatigue in some cases. These results show strong support for the hypothesis that depression and fatigue are associated with an increased activation of the immune system which may serve as a valid target for treatment. Further studies should focus on the pathways involved in these symptoms and the development of treatments that target those pathways will help us to better understand these conditions and devise more targeted treatments.
University of South-Eastern Norway and University Oslo Metropolitan University
Chronic fatigue and depression due to multiple sclerosis: Immune-inflammatory pathways, tryptophan catabolites and the gut-brain axis as possible shared pathways
Chronic fatigue and major depression (MDD)-like symptoms are common manifestations of multiple sclerosis (MS), both with huge impact on quality of life. Depression can manifest itself as fatigue, and depressive symptoms are often mistaken for fatigue, and vice versa. The two conditions are sometimes difficult to differentiate, and their relationship is unclear. Whether chronic fatigue and depression occur primarily, secondarily or coincidentally with activated immune-inflammatory pathways in MS is still under debate. We have carried out a descriptive review aiming to gain a deeper understanding of the relationship between chronic fatigue and depression in MS, and the shared pathways that underpin both conditions. This review focuses on immune-inflammatory pathways, the kynurenine pathway and the gut-brain axis. It seems likely that proinflammatory cytokines, tryptophan catabolites (the KYN pathway) and the gut-brain axis are involved in the mechanisms causing chronic fatigue and MDD-like symptoms in MS. However, the evidence base is weak, and more research is needed. In order to advance our understanding of the underlying pathological mechanisms, MS-related fatigue and depression should be examined using a longitudinal design and both immune-inflammatory and KYN pathway biomarkers should be measured, relevant clinical characteristics judiciously registered, and self-report instruments for both fatigue and depression should be used.
Neuroepidemiology Unit, Melbourne School of Population & Global Health, The University of Melbourne, Australia
Depression mediates the relationship between fatigue and mental health-related quality of life in multiple sclerosis
Background: Fatigue is among the most prevalent symptoms for people with multiple sclerosis (pwMS) and is significantly detrimental to mental health-related (mental) quality of life (QoL). We examined the role of depression and physical activity as mediators in the fatigue-QoL relationship in pwMS.
Methods: Using baseline cross-sectional data from an international cohort of 2,104 pwMS, characteristics of fatigue and mental QoL, measured by Fatigue Severity Scale and MSQOL-54 respectively, were assessed using linear and log-binomial regression. Structural Equation Models (SEM) were used to explore the mediating roles of depression and physical activity between fatigue and mental QoL.
Results: The median mental QoL score was 71.9/100. The mean fatigue score was 41.5/63, with 65.6% participants having clinically significant fatigue. In the SEM evaluating depression as a mediator of the fatigue-QoL relationship, mental QoL was 14.72 points lower (95% CI: -16.43 -13.01, p<0.001) in participants with clinically significant fatigue, of which depression accounted for 53.0% (-7.80, 95% CI: -9.03 -6.57, p<0.001). In the SEM evaluating physical activity as a mediator of the fatigue-QoL relationship, mental QoL was 10.89 points lower (95% CI: -12.47, -9.32, p<0.001) in participants with clinically significant fatigue, of which the indirect effect via physical activity accounted for only 4.4% (-0.48, 95% CI: -0.81, -0.14, p=0.005).
Conclusion: Depression accounted for the majority of the fatigue-mental QoL relationship when modelled as a mediator, while physical activity had only a minor role. Our findings may inform the development of treatments for reducing the impacts of fatigue and improving mental QoL in pwMS.
Department of Rehabilitation, C.R.R.F. "Mons. L. Novarese", Loc. Trompone, Moncrivello, VC, Italy
Imaging and depression in multiple sclerosis: a historical perspective
Purpose: Patients affected with multiple sclerosis suffer from depression more frequently than the general population. Beyond psychosocial, genetic and immune-inflammatory factors, also the brain damage which is peculiar of multiple sclerosis has been claimed to have a role in the aetiology of depression in those patients. The study of this interesting relation has been implemented with both conventional and advanced magnetic resonance imaging techniques. The aim of this review is to provide a historical perspective on the link between multiple sclerosis-related depression and structural and functional brain damage.
Methods: In this review, the results of the MRI studies regarding multiple sclerosis-related brain damage and the presence of depression are presented.
Results: The findings of the reports reveal a link between brain pathology and depressive symptoms or the diagnosis of depression in multiple sclerosis.
Conclusions: Although a multifactorial aetiology has been theorized for depression and depressive symptoms in patients with multiple sclerosis, this review supports the hypothesis that the structural and functional brain impairment might substantially be amongst those factors. Thus, depression itself might be a symptom with a neuro-biological basis and not only the consequence of the disability derived from the neurological impairment.
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