Psychiatric Comorbidities Common in MOGAD, MS, and NMOSD: Timing of Onset Differs

Psychiatric conditions are frequently observed in individuals diagnosed with myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD), relapsing-remitting multiple sclerosis (RRMS), and neuromyelitis optica spectrum disorder (NMOSD), but the timing of these comorbidities differs between the diseases, according to research presented at the 2026 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum held February 5-7 in San Diego, California.

A cross-sectional comparison study revealed that while psychiatric symptoms often precede neurological onset in RRMS, patients with MOGAD are more likely to develop these conditions shortly after the onset of neurological disease. The study, led by Moritz Niederschweiberer, MD, a neurologist at Mayo Clinic, underscores the complex interplay between neurological and mental health in these demyelinating diseases.

Anxiety disorder was the most common psychiatric comorbidity across all three patient groups. Specifically, anxiety was observed in 46.3% of patients with MOGAD (n = 119), 48.6% of those with RRMS (n = 125), and 41.4% of patients with NMOSD (n = 24). Importantly, the differences in anxiety prevalence between these groups were not statistically significant.

The study also examined the prevalence of depression, finding a statistically significant difference between MOGAD and RRMS. 47.5% of patients with RRMS (n = 122) had a history of depression, compared with 37.4% of patients with MOGAD (n = 96) (P = .02). Depression was observed in 41.4% of patients with NMOSD (n = 24), though this cohort was smaller.

Researchers reviewed electronic medical records from patients prospectively enrolled between March 2020 and June 2025 at the Center for MS and Autoimmune Neurology at Mayo Clinic. Participants met the 2023 diagnostic criteria for MOGAD, RRMS, and aquaporin-4–IgG–positive NMOSD. The primary aim of the study was to assess the frequency and timing of psychiatric comorbidities across these conditions.

The study included 257 patients with MOGAD and 257 patients with RRMS, matched by sex and age at disease onset, as well as 58 patients with NMOSD. The median age at neurological onset was 35 years (IQR, 25–47) for both MOGAD and RRMS, compared with 47 years (IQR, 37–56) for NMOSD. Women comprised 63.9% of the MOGAD and RRMS cohorts and 89.7% of the NMOSD cohort.

Investigators found that a significantly greater proportion of patients with RRMS experienced the onset of depression or anxiety more than 5 years prior to neurological onset compared with patients with MOGAD (27.2% vs 17.6%; P=.037). Conversely, psychiatric symptoms were significantly more likely to emerge shortly after neurological disease onset in patients with MOGAD. Within the first year following neurological onset, 23.1% of patients with MOGAD (n = 42) developed depression or anxiety, compared with 8.6% of individuals with RRMS (n = 14) (P < .001).

Attention-deficit/hyperactivity disorder (ADHD) occurred less frequently overall and did not differ significantly among the groups, affecting 8.9% of patients with MOGAD (n = 23), 10.1% with RRMS (n = 26; P = .65), and 5.2% with NMOSD (n = 3; P = .44). Insomnia was relatively uncommon but occurred significantly more often in patients with NMOSD (n = 5, 8.6%) than in those with MOGAD (n = 5; 1.9%; P = .009) or RRMS (n = 6; 6.6%; P = .019).

The authors note that psychiatric comorbidities are well-documented in MS and NMOSD, and some studies suggest psychiatric symptoms may precede MS onset, hinting at a potential presymptomatic phase. However, MOGAD is a more recently defined disease, and limited data exists regarding its associated psychiatric burden or how it compares temporally with other inflammatory demyelinating diseases.

This research highlights the importance of considering mental health screening and support for individuals diagnosed with these neurological conditions, recognizing that the timing of psychiatric symptom onset may vary depending on the specific disease process. Further investigation is needed to understand the underlying mechanisms driving these associations and to develop targeted interventions to improve the overall well-being of patients.