“Depression is the most frequent comorbidity for people with MS, affecting more than 20% of this patient population,” explains Raffaele Palladino, MD, PhD. “In addition, depression is associated with poorer health behaviors (ie, diet, physical activity) and cardiovascular risk management, which can negatively affect MS as well as other aspects of health. Therefore, it is important to assess whether the association between depression, vascular disease, and mortality differs in people with MS compared with the general population.”

For a paper published in Neurology, Dr. Palladino and colleagues performed a population-based, retrospective, matched cohort study from January 1, 1987, through September 30, 2018, of people with MS (n = 12,251) and matched controls without MS (n = 72,572), stratified by depression status, using the Clinical Practice Research Datalink (CPRD) database. Time-varying Cox proportional hazard regression models were employed to assess the relationship between MS, depression, and time to incident vascular disease and mortality. Analyses were also stratified by sex.

Increased Risk of Incident Vascular Disease & Mortality

“We found that people with MS who have depression have an increased risk for incident vascular disease and mortality, compared with matched controls,” Dr. Palladino says. “At baseline, 21% of people with

MS (n = 2,535) and 9% of controls (n = 2,535) had depression. In both cohorts, people with depression were more likely to be female and were younger than those without depression. More than 40% of those with depression were also smokers in both the MS and control groups. However, the vascular risk at index year was higher for those without depression; 7.7% of the people with MS without depression had diabetes at index year and 6% of them were taking antihypertensive medications, although the difference was not significant for the latter when comparing with controls without depression.” The researchers found that the incidence of all-cause mortality per 100,000 person-years was 2.53 (95% CI, 2.42-2.64) in controls without depression, 3.59 (95% CI, 3.18-4.05) in controls with depression, 10.58 (95% CI, 9.99-11.21) in people with MS without depression, and 10.30 (95% CI, 9.17-11.57) in people with MS and depression (Figure).

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Compared with controls without depression, the 10-year hazard of all-cause mortality was 1.8-fold greater in controls with depression (HR, 1.75; 95% CI, 1.59-1.91), 3.9-fold greater in people with MS without depression (HR, 3.88; 95% CI, 3.66-4.10), and 5.4-fold greater in people with MS and depression (HR, 5.43; 95% CI, 4.88-5.96). “Depression was also associated with a two-fold increased risk for cardiovascular disease mortality in persons with and without MS as compared to controls without depression overall and in women,” Dr. Palladino says. “The associations were weaker in men; men with MS and depression did not have increased cardiovascular mortality.”

Mental Health Screening for People With MS

Although the combination of depression and MS has a synergistic effect on mortality, the reason behind this is still unclear, according to Dr. Palladino. “Several factors may play a role,” he says. “Depression is associated with inflammation and immune dysregulation, as well as dysregulation of the hypothalamic pituitary axis. People with psychiatric disorders may not be managing their cardiovascular risk factors as well as those without psychiatric disorders.”

Dr. Palladino and colleagues point out that these findings support their previous work, which showed an overall 30% increased hazard of any macrovascular disease compared with a matched control population, and underscore the importance of identifying depression in people with MS. “It is extremely important to assess vascular risk and screen for mental health disorders in people with MS in order to reduce the risk and manage the conditions promptly,” Dr. Palladino concludes. “Additional studies should be conducted to evaluate whether effectively treating depression in people with MS reduces the vascular risk and therefore, reduces disability progression and mortality.”