Table 13.

Included references

Author, year	Symptom or disorder category	MS population	Diagnostic assessment tools	Main findings	Comments
Wijnands et al. 2019 [15]a	Depression	n = 13951 Age: 43.0 ± 6.7 Gender (n): 10156 Canada	ICD-10	The administrative and clinical cohorts included 13,951/66,940 and 3202/16,006 people with and without MS (cases/controls). Compared to controls, in the 5 years before the first demyelinating claim or symptom onset, cases had more physician and hospital encounters (per ICD-10 chapter and per physician specialty) for the nervous, sensory, musculoskeletal, and genitourinary systems. Cases had more psychiatrist and urologist encounters, and higher proportions of musculoskeletal, genitourinary or hormonal-related prescriptions (1.1–1.5 times higher). However, cases had fewer pregnancy-related encounters than controls	Phenotyping the prodrome 5 years before clinical recognition of MS is feasible
Sparaco et al. 2019 [79]b	Depression, anxiety, bipolar disorder, QoL	NA	BDI-II, CMDI, HADS, CES-D, PHQ-9, PROMIS, HDRS,	Epidemiological and clinical aspects of psychiatric syndromes in MS as well as self-report diagnostic scales and radiological correlates of psychiatric syndromes in MS are described. Moreover, some radiological studies about primary psychiatric disorders are reported to underline how gray matter atrophy, white matter abnormalities and corpus callosum involvement in these diseases, as features in common with MS, may explain the more frequent occurrence of psychiatric syndromes in MS than in the general population	None
Erlangsen et al. 2020 [53]a	QoL	n = 31136 Age: NA Female (n): NA Denmark	ICD-10	There was a significantly higher rate of suicide among those with a diagnosed neurological disorder (includes MS) than all other persons. People diagnosed with MS had an adjusted IRR of 1.7 (95% CI, 1.6–1.7). Diagnosis of a neurological disorder was associated with a small but statistically significant increased risk of death by suicide	The retrospective cohort study included persons in Denmark from 1980 through 2016
Fidao et al. 2021 [54]a	Depression, QoL	n = 2104 Age: 45.6 ± 10.5 Female (n): 1728 Australia	MSQOL-54, MHC-SF	The median mental QoL score was 71.9/100. The mean fatigue score was 41.5/63, with 65.6% participants having clinically significant fatigue. In the SEM evaluating depression as a mediator of the fatigue-QoL relationship, mental QoL was 14.72 points lower in participants with clinically significant fatigue, of which depression accounted for 53.0%. In the SEM evaluating physical activity as a mediator of the fatigue-QoL relationship, mental QoL was 10.89 points lower in participants with clinically significant fatigue, of which the indirect effect via physical activity accounted for only 4.4%. Depression accounted for the majority of the fatigue-mental QoL relationship when modelled as a mediator, while physical activity had only a minor role	Findings may inform the development of treatments for reducing the impacts of fatigue and improving mental QoL in patients with MS
Filser et al. 2021 [80]a	Depression, anxiety	n = 314 Age: 48.4 ± 10.8 Female (n): 232 Germany	MeSyMS	MeSyMS revealed an excellent internal consistency. Compared to control subjects, MS patients showed significant mental health problems in all three dimensions (depression, anxiety, and social and emotional health problems). In comparison to the subscales (depression and anxiety), the dimension of social and emotional health problems revealed the highest accuracy and turned out to be the only scale that reliably differentiated between the groups	Social and emotional health problems turned out to be the most important aspect when identifying disease-related mental health symptoms in MS

The selected studies are sorted chronologically by year and alphabetically by author name. Types of articles: ^aEmpirical article; ^bReview article; Definition papers were not included in the table. n = sample size; age: mean ± standard deviation; NA = Not applicable/reported

Abbreviations: BDI (-I/-II) Beck Depression Inventory, CES-D (-10) Center for Epidemiologic Studies Depression Scale (10-item scale, identical to the CES-D), CMDI Chicago Multiscale Depression Inventory, HADS (-A/-D) Hospital Anxiety and Depression Scale (-Anxiety Scale/-Depression Scale), HDRS Hamilton Depression Rating Scale, ICD-9/-10 International Classification of Disease, MeSyMS Mental symptoms in MS, MHC-SF Mental Health Continuum Short Form, MS Multiple Sclerosis, MSQOL-54 Multiple Sclerosis Quality of Life-54, PHQ-2/-9 Patient Health Questionnaire, PROMIS-D-8 Patient Reported Outcome Measurement Information System Depression 8-item bank, QoL quality of life