Psychiatric morbidity during the multiple sclerosis prodrome is associated with future disability

Evidence suggests a prodromal phase in multiple sclerosis (MS) identifiable via healthcare use, including psychiatric symptoms. The association between psychiatric morbidity in this phase and future outcomes remains unclear.

We investigated the association between psychiatric morbidity in the 5-years pre-MS onset and subsequent disability (EDSS) scores.

We identified MS patients who visited an MS clinic in British Columbia, Canada (1991-2018) and linked their clinical and population-based health administrative data. Psychiatric morbidity was identified using physician/hospital visits in the 5-years pre-MS onset. Multivariable generalized linear models examined the association between psychiatric morbidity and subsequent EDSS scores. We explored effect modification by sex, age, and MS course and investigated if high psychiatric-related physician visits (>median) or hospitalizations (measures of "psychiatric morbidity burden") were associated with EDSS scores.

Among 2212 MS patients, 481 (21.7%) had psychiatric morbidity in the 5-years pre-MS onset. Follow-up averaged 5.2 (SD: 4.9) years (first-to-last EDSS assessment). Psychiatric morbidity pre-MS onset was associated with higher post-diagnosis EDSS scores (covariate-adjusted[adj) β = 0.17; 95% confidence interval (CI): 0.03-0.30). Associations were more pronounced in males (adjβ = 0.43; 95% CI: 0.04-0.83), <30 years (adjβ = 0.44; 95% CI: 0.15-0.73), relapsing-onset-MS (adjβ = 0.22; 95% CI: 0.08-0.37) and high psychiatric-related physician visit burden (adjβ = 0.23; 95% CI: 0.05-0.41), or hospitalizations (adjβ = 0.48; 95% CI: 0.002-0.96).

Psychiatric morbidity before MS recognition was associated with increased future disability, particularly in males, younger individuals, relapsing-onset-MS, and high pre-MS onset psychiatric morbidity burden.