Psychiatric Disorders Linked to Progression in MS

Deborah Brauser

October 27, 2017

PARIS — Psychiatric disorders in patients with multiple sclerosis (MS) are associated with MS progression, especially in women, new research suggests.

A cohort study of more than 2300 patients with adult-onset MS showed that those with psychiatric comorbidities had scores on the Expanded Disability Status Scale (EDSS) that averaged 3 points higher over a 10-year follow-up period than those without the comorbidities, signifying greater MS disability progression.

Dr Kyla A. McKay

In addition, the association with MS progression was significant in women but not men, and for depression but not anxiety or bipolar disorder.

"I was expecting an effect but I really had no idea of the strength of that effect," Kyla A. McKay, PhD, a postdoctoral fellow at Karolinska Institute, Stockholm, Sweden, told Medscape Medical News.

"At first glance, a 3-point difference on the EDSS doesn't appear that significant, but it's actually clinically meaningful. That's like 3 additional years of MS progression for someone with psychiatric comorbidities," added Dr McKay.

She presented her findings here at the 7th Joint European Committee for Treatment and Research in Multiple Sclerosis-Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2017 meeting.

Beyond Prevalence Rates

Dr McKay noted that while working as a research coordinator in the clinical trials group at the University of British Columbia, she first started noticing the prevalence of psychiatric conditions in patients with MS.

"Even when these patients in the trials were quickly given treatment options and seen quite frequently by an extensive team, they weren't really given psychiatric treatment and counselling support," said Dr McKay, adding that this is what led her to pursue a PhD assessing mental health in MS.

"I wanted to go beyond just looking at the prevalence of these disorders because we've already established that depression, anxiety, and bipolar disorder occur at high rates in MS. I was interested in what the impact of that was, and I think that piece of the puzzle has been missing for a long time," she said.

"Does having psychiatric comorbidity actually influence longer-term disability progression? Because that's such a challenging question to answer, there hasn't really been a lot of work into it so far."  

In their study, the investigators prospectively assessed linked clinical and population-based health administrative databases in Canada and examined information for 2312 incident cases of MS (75.7% women; mean age at MS onset, 36.9 years).

They also used a validated algorithm of codes from the ninth and tenth editions of the International Classification of Diseases for depression, anxiety, or bipolar disorder during hospital and physician visits.

During a mean follow-up of 10.5 years, the following were seen:

  • 35.8% of the participants had any mood or anxiety disorder;

  • 37% had depression;

  • 22.1% had anxiety; and

  • 5.1% had bipolar disorder.

In the full study group and in women, after adjustment for a wide variety of confounders (including disease duration, age at MS onset, and disease-modifying therapy), there was a significant link between having any mood or anxiety disorder and greater disability on the EDSS.

Table 1. Association Between Mood/Anxiety Disorder and Disability by Group

Group β-Coefficient (95% Confidence Interval) P Value
All 0.28 (0.12 - 0.44) <.001
Women 0.31 (0.13 - 0.49) < .001
Men 0.22 (–0.09 to 0.53) .17 (not significant)


"Among all patients, the association was driven predominantly by the effect of depression" (adjusted β = 0.24; P = .001), write the investigators.

There was also a nonsignificant trend for bipolar disorder (adjusted β =  0.29; P = .08). Anxiety had a low β  estimate for MS progression of 0.11 (P = .21).

Dr McKay noted that the bipolar finding may have been due to the low number of participants who had the disorder.

"The estimate was high, so I imagine there is an effect. We just didn't have enough people in our cohort to see a statistical difference," she said.

"With anxiety, I was surprised with what we found; but if you look into the literature, you see kind of a similar pattern." In fact, one past study looking at mortality risk factors in MS showed that depression increased risk, "while anxiety actually had a protective effect," said Dr McKay.

She noted that the investigators also conducted a complementary analysis, which was run in one province alone and included dispensed prescription data. This analysis " allowed us to use a more sensitive definition" of psychiatric disorder. These results showed that the association between any mood or anxiety disorder and greater disability was significant for all three groups.

Table 2. Amended Model: Effect of Mood/Anxiety Disorder on Disability

Group Adjusted β (95% Confidence Interval) P Value
All 0.42 (0.17 - 0.67) < .001
Women 0.51 (0.06 - 0.96) .01
Men 0.41 (0.10 - 0.72) .01


Dr McKay noted that the link between psychiatric conditions and EDSS may reflect both biological and psychosocial factors.

"Previous, cross-sectional research has shown that persons with MS and major depression had more T2-weighted lesions on MRI, as well as greater brain atrophy, compared with persons without depression," she said.

"This relationship could also reflect maladaptive coping strategies and poor health behaviors, which could alter the course of MS. For example, depressed patients are more likely to smoke, which is a known factor for MS disability."

During the postpresentation question-and-answer session, an audience member noted that a past study showed depression occurred early in the disease process, which seems to differ from the current findings.

Dr McKay answered that they also saw depression "quite early," but it increased over time. They also saw anxiety at the beginning, which then lessened. "Early in the disease, people are quite anxious, which I think is a reaction to the diagnosis typically. Then, over time, depression becomes more prevalent."

Good First Step?

Session co-chair Charlotte Teunissen, PhD, professor of neurochemistry at VU University Medical Center, Amsterdam, the Netherlands, told Medscape Medical News that "I really liked this," but she started out with some questions.

Dr Charlotte Teunissen

"Based on the original abstract, I was hoping there might be an explanation for what they found, and I'm glad she provided a possible explanation for the link with depression and progression of MS," said Dr Teunissen.

"I think it's due to inflammation, which is shared in depression and anxiety disorders and MS," she added.

For the future, Dr Teunissen said she'd propose that researchers looked into measures of neurofilament light chains, which is also elevated in patients with depression and in those with MS.

Overall, "this was a good study, but I think it's worrying that so many MS patients develop psychiatric disorders — although you can understand why it happens. But I think there may be some good news also, because depression is something you can treat," she said.

"If you treat depression and that leads to reduced disease progression, that would be very promising."

The study was funded by the Canadian Institutes of Health Research. Dr McKay has received research funding from the Canadian Institutes of Health Research.

7th Joint European Committee for Treatment and Research in Multiple Sclerosis-Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2017. Parallel Session 3, oral presentation 103. Presented October 26, 2017.

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