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June 11, 2020/Neurosciences/Research

New Study Indicates Neurological Function Deteriorates Quicker in Depressed MS Patients

Depressed patients also have increased odds for new brain lesions on MRI

MS Woman Wheelchair

Multiple sclerosis (MS) patients with more severe depression show greater worsening in neurological function, relapses and MRI lesion activity over 12 months of follow-up compared with their less depressed counterparts, according to a large real-world observational cohort study. The findings were published as an abstract in Neurology and presented by Cleveland Clinic researchers as part of the American Academy of Neurology’s 2020 Science Highlights in lieu of its canceled in-person annual meeting.


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“Depression is common in people with MS and has been shown to have inflammatory underpinnings,” says the study’s lead author, Jenny Feng, MD, a fellow in Cleveland Clinic’s Mellen Center for Multiple Sclerosis Treatment and Research. “Our standard practice is to screen every patient with newly diagnosed MS for depression. If they show signs of depression, we actively manage it in order to limit its effect on their MS. Our results from this study indicate that depression can negatively affect aspects of neuroperformance and increase odds of having at least one new contrast-enhancing lesion on MRI in patients with MS.”

Study at a glance

The study included 2,505 patients from the Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS) database, a registry of patients from 10 MS centers, including Cleveland Clinic’s Mellen Center. Demographic and clinical data, MRI metrics, neuroperformance test scores and patient-reported outcomes were obtained at baseline and routine 12-month follow-up.

Patients were compared in terms of depression severity at baseline. Depression T-score > 45 on the Quality of Life in Neurological Disorders (Neuro-QoL™) instrument was considered more severe. Propensity score weighting was used to adjust for baseline variances between patients with more severe depression (n = 1,172) and those with less severe depression (n = 1,333).

After adjustment for baseline covariates, the analysis showed that, compared with their less depressed counterparts, patients with more severe baseline depression had the following baseline features:

  • Worse processing speed test score (effect estimate = –1.899; 95% CI: –3.548 to –0.250)
  • Slower walking speed test time (effect estimate = 0.478 s; 95% CI: 0.038s to 0.918 s)
  • Greater odds of ≥ 1 new contrast-enhancing lesion (OR = 5.891; 95% CI: 2.236 to 15.517)

At 12-month follow-up, patients with more severe baseline depression continued to have worse processing speed (effect estimate = –1.680; 95% CI: –3.254 to –0.105).

Depressed patients may not notice functional decline

One of the more surprising findings from the study was that even as measured neuroperformance decreased, patient-reported outcomes remained relatively similar by month 12. “Even as more severely depressed patients’ functional performance diminished, they didn’t recognize the decline,” says Dr. Feng. “This demonstrates that depression has contributory roles in the MS disease course, in addition to being a reactive phenomenon. Recognizing the potential long-term effects of depression and initiating appropriate treatment is important in optimizing MS treatment.”

Related: Suicide in Patients with Multiple Sclerosis: Guidance on Red Flags and Prevention


This study was not without limitations, however. “Because this was an observational study, first-year depression status for some patients was missing, along with a few MRI metrics,” notes senior author Daniel Ontaneda, MD, PhD, a staff neurologist in the Mellen Center. Treatment compliance for depression, along with the date of depression onset, were also unavailable, he adds, and these limitations may have led to underpowered results.

In order to overcome these limitations, the authors suggest that future research should focus on including an even larger sample size, extending follow-up over longer periods and incorporating different advanced MRI metrics.

“In this large real-world observational cohort, MS patients with more severe depression at baseline showed more worsening in neurological function and MRI lesion activity at baseline and over the next year compared to less depressed patients,” the authors conclude.

“When treating MS, it’s important to take a holistic approach towards patient care because of the compounding effects of other comorbidities, such as depression, on MS disease activity, disability and quality of life.” Dr. Feng observes. “This study reinforces that notion and reiterates the importance of mental health screening and counseling among MS patients.”


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