The burden of psychiatric morbidity in Multiple Sclerosis, AQP4-antibody NMOSD and MOGAD before and after neurological diagnosis

BACKGROUND: Psychiatric comorbidities are common in Multiple Sclerosis (MS) and are increasingly recognised in Aquaporin-4-Antibody Neuromyelitis Optica Spectrum Disorders (AQP4-Ab NMOSD) and Myelin Oligodendrocyte Glycoprotein-Antibody Associated Disease (MOGAD). However, it is unclear if these psychiatric comorbidities predate neurological diagnosis or classical neurological symptoms that are conventionally used to establish the onset of these central nervous system inflammatory demyelinating diseases. We sought to: (1) assess the frequency and incidence of psychiatrist-diagnosed psychiatric disorders before and after formal MS, AQP4-Ab NMOSD, and MOGAD diagnosis, and (2) identify potential factors associated with the presence of pre-existing psychiatric morbidity and depression severity at the first clinical visit for MS patients.

METHODS: A retrospective observational study was performed on MS, AQP4-Ab NMOSD, and MOGAD patients seen at the National Neuroscience Institute (NNI) Singapore. Individuals with psychiatrist-diagnosed psychiatric disorders before and after neurological diagnosis were identified. Demographic, clinical data, and Patient Health Questionnaire (PHQ)-9 score at first clinic visit were collected and analysed.

RESULTS: Three hundred and ninety-nine patients (249 MS, 102 AQP4-Ab NMOSD, 48 MOGAD) were included. A higher proportion of MS patients (13/249, 5.2%) had psychiatric disorders before neurological diagnosis, compared to AQP4-Ab NMOSD (1/102, 1.0%) and MOGAD (0/48, 0.0%) (p = 0.054). Within MS patients, univariate logistic regression revealed that age, sex, race, MS subtype, initial MRI lesion load, and interval between classical MS symptom onset to MS diagnosis were not associated with pre-existing psychiatric disorders. Mean PHQ-9 score for MS patients at their first MS consult was 4.4 (cut-off for no/minimal depression is ≤4); no clinical factors were predictive of higher PHQ-9 scores on univariate linear regression. The proportion of MS patients (29/236, 12.2%) who developed psychiatric illness after neurological diagnosis was not different from AQP4-Ab NMOSD (9/101, 8.9%) (p > 0.999), while this was significantly higher compared to MOGAD (0/48, 0.0%) (p = 0.021). The incidence rate of psychiatric diseases after neurological diagnosis, accounting for follow up time, was also similar between MS and AQP4-Ab NMOSD (incidence rate ratio 1.2; 95% confidence interval 0.54 - 2.8; p = 0.689).

CONCLUSION: There is a significant psychiatric burden prior to MS diagnosis compared to AQP4-Ab NMOSD and MOGAD. The increased frequency of psychiatric comorbidity after NMOSD diagnosis merits further study to investigate the determinants of this phenomenon.