Depression not a causal risk factor for disability progression: Study

Physical disability at diagnosis found to be linked to future disease progression

by Lindsey Shapiro, PhD | June 6, 2023

Physical disability, not whether patients are depressed, when they’re diagnosed with multiple sclerosis significantly influences their future disability progression, according to a recent U.K. registry study.

Although patients who were depressed at the time of their diagnosis were more likely to accumulate significant disability and require an aid to walk short distances earlier than those who were not depressed, depression was not found to be an independent risk factor.

The findings "raise the suspicion that depression is not a causal risk factor for future disease progression, but a reflection of prior disease activity and present severity," researchers wrote.

The study, "Early depressive symptoms and disability accrual in Multiple Sclerosis: a UK MS Register study," was published in Scientific Reports.

MS is different for every patient, with symptoms, disease progression, and treatment responses varying significantly from person to person. Understanding which factors contribute to the course of MS — particularly disability accumulation — is critical for identifying novel interventions that can slow disease progression.

Psychiatric conditions, including anxiety and depression, are common in MS. A few studies have suggested that depression may be one factor that contributes to greater disability accumulation in MS, but not all studies agree.

"Clarifying the nature of this association has implications for the management of comorbid [co-existing] depressive symptoms in MS," the researchers wrote.

Therefore, researchers in the U.K. sought to further explore the relationship by analyzing long-term data from a group of MS patients included in the UK MS Register (UKMSR). This is a longitudinal study of MS patients in the U.K. which has collected patient-reported information on demographics, risk factors, and outcomes via an online portal since 2011.

UKMSR participants were included in the analysis if they had a recorded Expanded Disability Status Scale (EDSS) score, a measure of disability status, within five years of their MS diagnosis date (baseline) and again at least six months after that.

All participants had a baseline EDSS score less than 6. Ranging from 0-10, with higher scores reflecting worse disability, a score of 6 reflects a need for a walking aid and is a commonly used cut-off for identifying patients with more severe disability.

Participants also needed at least one recorded score on the Hospital Anxiety and Depression Scale (HADS) before or within six months of their baseline EDSS reading.

Ultimately, from a UKMSR population of more than 23,000 patients, 862 people met the criteria for inclusion. The patients, with a median age of 43 at diagnosis, were mostly women (76.3%) and had relapsing-remitting MS (83.1%).

A total of 134 people reached an EDSS score of at least 6 during the follow-up period. Patients who reached this level of disability were older at diagnosis (48.5 vs. 42 years), more likely to have primary progressive MS (23% vs. 7.6%), and had higher baseline EDSS scores (4.5 vs. 3) than those who didn't reach a score of 6.

Anxiety and depression were common among both groups. Rates of anxiety at baseline did not differ between those who eventually reached an EDSS score of 6 (46.3%) and those who did not (40.9%). However, depression at baseline was significantly more common among those who reached an EDSS score of 6 (43.3% vs. 22.4%).

Ultimately, depression was found to raise, by 2.42 times, the risk of needing a walking aid to walk short distances, even when adjusting for potentially influential factors such as age, sex, and MS subtype.

The findings overall corroborate previous observations linking depression and disability accrual in MS among patients in Sweden and Canada, according to the team.

However, the relationship almost completely disappeared when adjusting for each person's baseline EDSS score, meaning that a person's early disability was significantly involved in the relationship between depression and later disability.

That finding could mean that "depression may simply reflect more advanced disease rather than being an independent predictor of progression," the researchers wrote.

They noted, however, that their analysis was limited by a number of factors, including the use of self-reported EDSS scores in some cases, lack of depression data prior to diagnosis, a relatively young and more recently diagnosed study population, and an inability to account for the effects of disease-modifying treatments on patient outcomes.

While the findings don't overall support a causal role for depression on disability accumulation, "the high prevalence of depressive illness in this cohort underscores the importance of recognising and treating depression in people with MS," the team concluded.