Abstract
Fatigue and depression are common conditions diagnosed in people with multiple sclerosis (MS). Fatigue defined as subjective lack of physical and/or mental energy is present in 35–97% of people with MS, who classify it as one of the most serious symptoms interfering with daily activities and influencing the quality of life. Depression is diagnosed in about 50% of people with MS. Since fatigue and depression frequently coexists, it may be quite hard to differentiate them. Primary fatigue and primary depression in MS are caused by inflammatory, oxidative/nitrosative, and neurodegenerative processes leading to demyelination, axonal damage, and brain atrophy. In people with MS and comorbid fatigue and/or depression there is reported increased serum and cerebrospinal fluid concentration of inflammatory mediators such as tumor necrosis factor, interleukins (IL-1a, IL-1b, IL-6), interferon γ and neopterin. Moreover, the brain atrophy of prefrontal, frontal, parietotemporal regions, thalamus, and basal ganglia was observed in people with MS with fatigue and/or depression. The secondary fatigue and secondary depression in people with MS may be caused by emotional factors, sleep disorders, pain, the coexistence of other diseases, and the use of medications. In some studies, the use of disease-modifying therapies positively influenced fatigue, probably by reducing the inflammatory response, which proves that fatigue and depression are closely related to immunological factors. In this mini-review, the pathogenesis, methods of evaluation and differentiation, and possible therapies for fatigue and depression in MS are discussed.
Highlights
Fatigue and depression are very common conditions diagnosed in people with multiple sclerosis (MS)
Anhedonia is caused by deficiency of neurotransmitters such as dopamine and serotonin, which leads to impairment in the functioning of mesocorticolimbic pathways projecting from the midbrain to the basal ganglia, the limbic system, and the prefrontal cortex
The proinflammatory cytokines in people with MS induce sickness behavior by disruption of dopamine and serotonin neurotransmission in mesocorticolimbic pathways connecting the midbrain with the basal ganglia, the limbic system, and the prefrontal cortex leading to dysfunctional reward processing and anhedonia [16, 18, 19, 26, 27]
Summary
Fatigue and depression are very common conditions diagnosed in people with multiple sclerosis (MS). Recent studies have identified a strong correlation between fatigue and depression These conditions jointly affect more than half of people with MS [15]. The leading and common symptom of cognitive fatigue and depression is anhedonia defined as decreased motivation, a lack of positive affect, and the reduced ability to experience pleasure [14, 16–18]. Anhedonia is caused by deficiency of neurotransmitters such as dopamine and serotonin, which leads to impairment in the functioning of mesocorticolimbic pathways projecting from the midbrain to the basal ganglia, the limbic system, and the prefrontal cortex It results in disrupting the brain’s reward and valence system [16, 18]. In the present mini-review, we provide and discuss the latest information on the pathogenesis, methods of evaluation and differentiation, and possible therapies for fatigue and depression in MS
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