What Causes Depression and Anxiety in Multiple Sclerosis?

The obvious answer — the response to an unpredictable and potentially disabling disease. But how to explain the fact that levels of depression and anxiety are higher in MS than in rheumatoid arthritis patients with the same level of physical disability. Or that depression, insomnia, fatigue, and cognitive impairment can occur before onset of typical MS symptoms.

The observations support the “inflammatory hypothesis,” meaning that major depression is related to immune system activation. Pro-inflammatory cytokines play a central role in the communication between the immune system and the central nervous system.

A new study shows that in genetically predisposed people, levels of a particular cytokine (IL-1b) are higher than in controls and so is their risk of depression. Antidepressants have been demonstrated to normalize upregulated cytokine levels. In animal models, IL-1b injection produces depressive-like behaviors. An anti-inflammatory drug (anakinra) used to treat rheumatoid arthritis improves mood.

In MS patients, the odds of having depressive symptoms were lower in those on a disease modifying treatment. It is unclear if this association reflects a positive direct anti-inflammatory effect or an indirect effect due to a positive impact on disease course.

In MS then, it is important not only to screen for and treat depression, but also to use an effective disease modifying therapy.

Adapted from the article by Ferreira et al in Multiple Sclerosis and Related Disorders, 2021.

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