Depressive disorders (DD) are the second cause of disability worldwide. DD affect predominantly working age individuals, recurring in 75% of cases. DD pathophysiology is intricate and multi-factorial. Several inflammatory diseases have been linked to mood disorders. Amidst these conditions is multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system, characterized by frequent exacerbations and progressive functional loss.

To review the current knowledge on DD and MS as comorbidities and the underlying pathophysiologic mechanisms.

We performed a bibliographic search in Pubmed–publications released in the last 5 years, written in English, Portuguese and Spanish, containing the keywords depression, inflammatory disorders, multiple sclerosis.

The inflammatory hypothesis of depression provides a strong foundation to explain its close link with multiple sclerosis. The incidence and prevalence of DD is significantly higher in MS, especially in men. Functional imaging studies have shown that depressive symptoms are closely linked to the extension of inflammatory lesions, especially on the frontal and parietal regions, with particular emphasis to those affecting the grey matter. On the one hand, the clinical course and response to treatment of MS may be hindered by DD; on the other hand, the evolution of MS lesions leads to fluctuations in mood, with significant improvement of DD with successful MS treatment, independently of physical improvement.

There appears to be a biological link between DD and MS, with a bidirectional interference in the clinical course, prognosis and treatment response. Thus, both conditions must be correctly identified and treated.

The authors have not supplied their declaration of competing interest.