Depression Linked to Neuro Dysfunction, Brain Lesions in MS

Deborah Brauser

May 12, 2020

Depression is associated with decreased neurologic function and new brain lesions in patients with multiple sclerosis (MS), new research suggests.

In an observational study of more than 2500 patients with relapsing-remitting MS (RRMS), participants with self-reported depression were more likely to have worse scores on neuroperformance measures, such as processing speed tests, than their peers without depression.

At baseline, the group with depression also had greater odds of having at least one new contrast-enhancing lesion (CEL) on MRI.

"Our results suggest that depression is not merely a reactive symptom but indicates increased risk of future MS disease activity," the investigators note.

Dr Jenny Feng

Lead author Jenny Feng, MD, clinical associate at Cleveland Clinic Mellen Center for MS Treatment and Research, Ohio, added that depression should be routinely screened for in all patients with MS, something done routinely at her center.

"Every single patient that comes through the door with newly diagnosed MS we refer to neuropsychology to screen for depression; and if there is depression, then we actively manage it because it does have an effect" on patients, she told Medscape Medical News.

"Depression isn't just a neuropsychiatric disease," Feng added. As shown in their study, "it may have effects on MS, especially with regards to performance in neurological function testing."

The research is presented on AAN.com as part of the American Academy of Neurology (AAN) 2020 Science Highlights. Because of the COVID-19 pandemic, the AAN had to cancel its 2020 annual meeting.

Associations Have Been "Unclear"

Although inflammatory, psychosocial, and neurodegenerative factors "have been hypothesized as etiologies" for why depression is commonly found in patients with MS, the full association between depression and MS disease activity "is not clear," the investigators note.

For the current study, they assessed data from the Partners-Advancing-Technology-and-Health-Solutions (MS-PATHS) database, an ongoing collaborative network of seven MS centers in the United States and three in Europe.

MS disease history and MRI data were examined, as well as 12-month scores on neuroperformance tests measuring processing speed (Symbol Digit Modalities Test), walking speed (Timed 25-Foot Walk), and manual dexterity (Nine-Hole Peg Test).

Patient-reported outcomes (PROs), as measured with the Quality of Life in Neurological Disorders (Neuro-QoL) and patient-determined disease steps, were also assessed. Depression was defined as a depression T score at baseline greater than "the 50th percentile" on the Neuro-QoL.

In the patient sample, 1333 of the participants with RRMS were classified as "not depressed" (73.7% women; mean age, 45.6 years; disease duration, 13.7 years) while 1172 were "depressed" (78.4% women; mean age, 45.9 years; disease duration, 14.3 years).

"To balance for baseline variances in the observational cohort between group with depression and group without depression, propensity score analysis was used to adjust for potential confounding factors," the investigators report.

Worse Performance

After adjusting for baseline covariates, results showed that the depressed patients performed worse on the walking speed test (0.48; 95% CI, 0.038 - 0.918) and processing speed test (–1.899; 95% CI, –3.548 to –0.250).

The depressed group also had increased odds at baseline of having new CELs (odds ratio, 5.89; 95% CI, 2.236 - 15.517). This demonstrated an "association of depression and neuro-inflammatory activity" in the central nervous system, the investigators note.

At 12 months, processing speed continued to be worse in the depressed group (–1.68; 95% CI, –3.254 to –0.105).

There were trends, albeit insignificant, for decreased walking speed scores at 12 months and for decreased manual dexterity scores at both baseline and at 12 months for the participants who were depressed.

Interestingly, there were "no significant differences in PROs at month 12, despite worsening neuroperformance," the investigators report.

"This means that patients themselves may not even realize that they were getting worse," Feng said.

Underpowered Study?

Further results showed nonsignificant trends for increased T2 lesion volume and white matter fraction and decreased brain volume, gray matter fraction, and cortical gray matter volume at baseline and at 12 months in the depressed group.

The researchers note that study limitations include the unavailability of information on treatment compliance for depression or date of depression onset.

Feng added that because this was an observational study, other missing data included depression status for some patients at year 1 and some MRI metrics.

"So this may have been underpowered to detect some of the results. The power may have been inadequate to detect all changes," she said.

The investigators write that future research should assess larger sample sizes with longer follow-ups and should use more advanced MRI measures, such as diffusion tensor imaging or functional MRI.

In addition, they will continue examining data from MS-PATHS. "With the newest data cut, we have new patients that we can analyze. So perhaps that can provide sufficient power to detect [more MRI] changes," Feng said.

Unusual, Intriguing Findings

Dr Mark Freedman

Commenting on the study for Medscape Medical News, Mark Freedman, MD, professor of neurology at the University of Ottawa and director of the Multiple Sclerosis Research Clinic at the Ottawa Hospital Research Institute in Canada, noted that he "wasn't terribly surprised" by the overall findings.

"We've known for years that patients who are depressed don't do as well on our performance methods," said Freedman, who was not involved with the research.

However, the current investigators "took a huge number of patients in this multicenter study and started using some of the statistical methods we've seen in the use of real-world evidence," he noted.

"So you're looking at some outcome measures and you have to ask yourself, 'Why would it influence that?' and 'Did it happen by chance or not?' And you ask why it is that depressed people might actually have more lesions on their MRI, which is something that is unusual," Freedman said.

"When you start to look at this, even when you're trying to standardize things for the differences that we know of, there are some stuff that comes out as intriguing. In general, I think those depressed patients did worse on several outcome measures that one would say, 'That's somewhat surprising.' That's why this group was very careful to not conclude absolutely that depression drives this disease. But it was consistently trending in the direction that it looks like there was more inflammatory activity in these people," he said.

He echoed the investigators' note that drug adherence and which depression treatment was used wasn't controlled for; and he added that depression in the study was not based on receiving a diagnosis of clinical depression but on self-report.

Still, the patients classified as depressed "did worse. They didn't walk as fast, which was interesting; and we know that cognitive performance is often dampened because of poor concentration. But how do you get worse MRIs? This study is raising a question and [the researchers] conclude that it may be that depression might be an independent factor" for that outcome, Freedman said.

"It might be that you could get more out of a particular [MS] medicine if you pay attention to depression; and if that's the investigators' conclusion, and I think it is, then I certainly agree with it."

Freedman noted that instead of a blanket recommendation that all patients with MS should be screened for depression, he think clinicians, especially those at smaller centers, should focus on what's best for treating all aspects of an individual patient.

"Don't try to manage them if you're not going to manage the entire picture. Looking at depression and mood and other things is very important. And if you have the capacity for an official screening, I think it's wonderful; but not everybody does," he said.

Feng and Freedman have disclosed no relevant financial relationships. Freedman is currently a member of the Medscape Neurology Advisory Board.

American Academy of Neurology (AAN) 2020 Annual Meeting: Abstract S54.007

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