TOPLINE:

In people with primary progressive multiple sclerosis (PPMS), depressive symptoms measured using the Hospital Anxiety and Depression Scale (HADS) predicted subsequent neurologic disability progression.

METHODOLOGY:

• Researchers conducted a prospective cohort study to determine whether baseline symptoms of depression and anxiety, measured using the HADS, could predict subsequent neurologic disability progression in patients with PPMS.
• The study included 111 adults with PPMS from clinical centres in Netherlands who completed the HADS questionnaire within 1 month of the baseline clinical visit and had at least 1 year of follow-up assessment; 62 of these participants completed 2-year follow-up.
• Disability progression was assessed at 1 and 2 years using three endpoints: Expanded Disability Status Scale (EDSS) progression; three-variable composite endpoint progression (EDSS, timed 25-foot walk [T25FW] test, or Arm Function in Multiple Sclerosis Questionnaire [AMSQ]); and five-variable composite endpoint progression (EDSS, T25FW test, AMSQ, Symbol Digit Modalities Test, or Patient-Determined Disease Steps scale).

TAKEAWAY:

• At 1 year, higher total HADS scores predicted progression on the five-variable composite endpoint (odds ratio [OR], 3.10; P = .05), with a modest predictive accuracy (area under the receiver operating characteristic curve [AUC], 0.59; 95% CI, 0.47-0.70).
• At 2 years, higher total HADS scores were associated with substantially increased odds of EDSS progression (OR, 11.63) and five-variable composite endpoint progression (OR, 5.56; P < .05 for both).
• HADS depression scores consistently predicted disability progression across all three endpoints (OR, 7.20-9.46; P < .05 for all), with the strongest discriminative performance observed for the five-variable composite endpoint (AUC, 0.67; 95% CI, 0.50-0.80).
• Notably, two depression-related HADS items — "I feel cheerful" and "I feel as
  if I am slowed down" — were important predictors of disability progression, achieving a similar predictive accuracy as the full HADS questionnaire.

IN PRACTICE:

"Whilst these findings support the potential use of HADS for risk stratification and prioritisation of monitoring, their application to guide treatment decisions requires further investigation in independent cohorts," the authors wrote.

SOURCE:

This study was led by Romy A.M. Klein Kranenbarg, Department of Neurology, MS Centre, Albert Schweitzer Hospital, Dordrecht, Netherlands. It was published online on March 05, 2026, in the Journal of Neurology.

LIMITATIONS:

The study included only a subset of participants due to incomplete HADS data and limited follow-up in some cases, reducing statistical power. Incomplete progression data may have led to the misclassification of some individuals as non-progressors. Mood symptoms were assessed using the HADS rather than structured neuropsychiatric interviews.

DISCLOSURES:

This study received support from Stichting BeterKeten, the Dutch National MS Foundation, and the Albert Schweitzer Hospital. One author declared receiving research support and lecture and/or consultancy fees from various pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.