{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:35:43Z","timestamp":1790699743159,"version":"4.1.0"},"reference-count":114,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T00:00:00Z","timestamp":1757376000000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Depression in people with multiple sclerosis (MS) is two to three times more frequent than in demographically matched people without MS. The MS-depression literature is large and has expanded exponentially over the past few years. This increase in new knowledge is the impetus for assessing whether there is now sufficient evidence to differentiate depression linked to multiple sclerosis from depression alone. Establishing the validity of MS-depression as a distinct diagnosis is important because it would enhance our understanding of the pathogenesis of depression in general, shed light on a clinical course that might diverge from what is expected from depression without MS, and suggest management strategies that may differ from those followed for people with depression alone.<\/jats:p>\n                  <jats:p>A review of the MS-depression literature from January 2018 to December 2024 (generating 114 papers for inclusion in the manuscript) reveals no unique, distinct MS-depression phenomenology. The factors encompassing predictive validity, namely the course of depression, employment, suicide, cognitive impairment and quality of life, are similar in kind but not severity between depressed people with and without MS. The paucity of randomized controlled trial psychotropic data in MS-related depression means it is unclear whether medication plus psychotherapy is the best treatment option for people with MS who are depressed, as it is in general population samples. In terms of construct validity, the posited immune signature of MS depression, namely an increased frequency of circulating CD4+CCR7low central memory T cells with a Th1 predilection, does not appear to be distinct from depression in the general population. There is considerable neuroimaging commonality, particularly in limbic regional involvement. The potential importance of the dopamine-rich ventral tegmental area in a putative MS depression neural circuit suggests a degree of specificity, but the absence of direct comparison between depressed people with and without MS hinders a more definite conclusion. As for personality factors and socio-economic status in depressed people with MS, the findings essentially overlap with the depression literature in the general population. There are, however, a couple of standout constructs suggesting the possibility of two distinct disorders: the equivocal data pertaining to a specific MS genetic diathesis to depression and the absence of a clear sex difference in depressed people with MS. Until these conundrums are explained, one cannot conclude with certainty that depression in people with and without MS is the same disorder. Further research comparing depressed people with and without MS is needed to understand why this difference may exist.<\/jats:p>","DOI":"10.1093\/brain\/awaf319","type":"journal-article","created":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T11:39:23Z","timestamp":1756467563000},"source":"Crossref","is-referenced-by-count":2,"title":["Is multiple sclerosis-related depression different from depression in general? The data for and against"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0132-0909","authenticated-orcid":false,"given":"Anthony","family":"Feinstein","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Sunnybrook Health Sciences Centre , Toronto, ON M4N 3M5 ,","place":["Canada"]},{"name":"Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto , Toronto, ON M5S 1A8 ,","place":["Canada"]},{"name":"Division of Neurology, Department of Medicine, St. Michael\u2019s Hospital , Toronto, ON M5B 1W8 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit","family":"Bar-Or","sequence":"additional","affiliation":[{"name":"Center for Neuroinflammation and Experimental Therapeutics and Department of Neurology, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA 19104 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph H B","family":"Benedict","sequence":"additional","affiliation":[{"name":"Jacobs Comprehensive MS Treatment and Research Center, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York , Buffalo, NY 14203 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5485-0479","authenticated-orcid":false,"given":"Massimo","family":"Filippi","sequence":"additional","affiliation":[{"name":"Neuroimaging Research Unit, Division of Neuroscience, IRCSS San Raffaele Scientific Institute , Milan 20132 ,","place":["Italy"]},{"name":"Neurology Unit, IRCSS San Raffaele Scientific Institute , Milan 20132 ,","place":["Italy"]},{"name":"Neurorehabilitation Unit, IRCSS San Raffaele Scientific Institute , Milan 20132 ,","place":["Italy"]},{"name":"Faculty of Medicine and Surgery, Department of Neurology, Vita-Salute San Raffaele University , Milan 20132 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4340-3232","authenticated-orcid":false,"given":"David E","family":"Freedman","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Sunnybrook Health Sciences Centre , Toronto, ON M4N 3M5 ,","place":["Canada"]},{"name":"Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto , Toronto, ON M5S 1A8 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Kever","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Medicine, St. Michael\u2019s Hospital , Toronto, ON M5B 1W8 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8553-0440","authenticated-orcid":false,"given":"Cecilia","family":"Meza","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Sunnybrook Health Sciences Centre , Toronto, ON M4N 3M5 ,","place":["Canada"]},{"name":"Division of Neurology, Department of Medicine, St. Michael\u2019s Hospital , Toronto, ON M5B 1W8 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2358-4320","authenticated-orcid":false,"given":"Maria A","family":"Rocca","sequence":"additional","affiliation":[{"name":"Neuroimaging Research Unit, Division of Neuroscience, IRCSS San Raffaele Scientific Institute , Milan 20132 ,","place":["Italy"]},{"name":"Neurology Unit, IRCSS San Raffaele Scientific Institute , Milan 20132 ,","place":["Italy"]},{"name":"Faculty of Medicine and Surgery, Department of Neurology, Vita-Salute San Raffaele University , Milan 20132 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,9,9]]},"reference":[{"key":"2025111811014765300_awaf319-B1","doi-asserted-by":"crossref","first-page":"1556","DOI":"10.1111\/ene.14314","article-title":"Incident depression in patients diagnosed with multiple sclerosis: A multi-database study","volume":"27","author":"Persson","year":"2020","journal-title":"Eur J Neurol"},{"key":"2025111811014765300_awaf319-B2","doi-asserted-by":"crossref","first-page":"100484","DOI":"10.1016\/j.bbih.2022.100484","article-title":"Prevalence of depression and anxiety in the different clinical forms of multiple sclerosis and associations with disability: A systematic review and meta-analysis","volume":"24","author":"Peres","year":"2022","journal-title":"Brain Behav Immun Health"},{"key":"2025111811014765300_awaf319-B3","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1111\/j.1524-475X.2004.04006.x","article-title":"A process for systematically reviewing the literature: Providing the research evidence for public health nursing interventions","volume":"1","author":"Thomas","year":"2004","journal-title":"Worldviews Evid Based Nurs"},{"key":"2025111811014765300_awaf319-B4","doi-asserted-by":"crossref","DOI":"10.1353\/book.100157","volume-title":"Mind, mood, and memory: The neurobehavioural consequences of multiple sclerosis","author":"Feinstein","year":"2022"},{"key":"2025111811014765300_awaf319-B5","doi-asserted-by":"crossref","first-page":"110402","DOI":"10.1016\/j.jpsychores.2021.110402","article-title":"Major depressive disorder subtypes and depression symptoms in multiple sclerosis: What is different compared to the general population?","volume":"144","author":"Rodgers","year":"2021","journal-title":"J Psychosom Res"},{"key":"2025111811014765300_awaf319-B6","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/j.jpsychires.2024.05.039","article-title":"Examining the influence of episode number and age of onset on individual depressive symptoms across episodes of major depression","volume":"175","author":"Schlechter","year":"2024","journal-title":"J Psychiatr Res"},{"key":"2025111811014765300_awaf319-B7","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1177\/13524585231190771","article-title":"Within-person fluctuations over three years in depression, anxiety, fatigue, and health-related quality of life in multiple sclerosis","volume":"29","author":"Marrie","year":"2023","journal-title":"Mult Scler J"},{"key":"2025111811014765300_awaf319-B8","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/j.ibneur.2024.04.002","article-title":"Longitudinal determinants of employment status in people with relapsing-remitting multiple sclerosis","volume":"16","author":"Van Egmond","year":"2024","journal-title":"IBRO Neurosci Rep"},{"key":"2025111811014765300_awaf319-B9","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1016\/j.apmr.2017.12.028","article-title":"Predictors for employment status in people with multiple sclerosis: A 10-year longitudinal observational study","volume":"99","author":"Forslin","year":"2018","journal-title":"Arch Phys Med Rehabil"},{"key":"2025111811014765300_awaf319-B10","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1177\/1352458517692887","article-title":"Revisiting cognitive reserve and cognition in multiple sclerosis: A closer look at depression","volume":"24","author":"Patel","year":"2018","journal-title":"Mult Scler J"},{"key":"2025111811014765300_awaf319-B11","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1016\/j.apmr.2020.03.013","article-title":"Risk factors for suicide in a national sample of veterans with multiple sclerosis","volume":"101","author":"Kellerman","year":"2020","journal-title":"Arch Phys Med Rehabil"},{"key":"2025111811014765300_awaf319-B12","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1080\/19371918.2020.1810839","article-title":"Prevalence of suicidal ideation in multiple sclerosis patients: Meta-analysis of international studies","volume":"35","author":"Kouchaki","year":"2020","journal-title":"Soc Work Public Health"},{"key":"2025111811014765300_awaf319-B13","first-page":"13","article-title":"Prevalence of suicidal ideation among adults in Canada: Results of the second survey on COVID-19 and mental health","volume":"33","author":"Liu","year":"2022","journal-title":"Health Rep"},{"key":"2025111811014765300_awaf319-B14","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1016\/j.apmr.2020.09.385","article-title":"Depressive symptoms and suicidal ideation in progressive multiple sclerosis compared with relapsing-remitting multiple sclerosis: Results from a cross-sectional survey","volume":"102","author":"Knowles","year":"2021","journal-title":"Arch Phys Med Rehabil"},{"key":"2025111811014765300_awaf319-B15","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1111\/ane.13559","article-title":"Standardized mortality ratios in multiple sclerosis: Systematic review with meta-analysis","volume":"145","author":"Smyrke","year":"2022","journal-title":"Acta Neurol Scand"},{"key":"2025111811014765300_awaf319-B16","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.msard.2019.06.012","article-title":"Association between suicide and multiple sclerosis: An updated meta-analysis","volume":"34","author":"Shen","year":"2019","journal-title":"Mult Scler Relat Disord"},{"key":"2025111811014765300_awaf319-B17","doi-asserted-by":"crossref","first-page":"e041249","DOI":"10.1136\/bmjopen-2020-041249","article-title":"Quality of life in adults with multiple sclerosis: A systematic review","volume":"10","author":"Gil-Gonz\u00e1lez","year":"2020","journal-title":"BMJ Open"},{"key":"2025111811014765300_awaf319-B18","doi-asserted-by":"crossref","first-page":"e668","DOI":"10.1016\/S2589-7500(23)00109-7","article-title":"Internet-delivered cognitive behavioral therapy programme to reduce depressive symptoms in patients with multiple sclerosis: A multicentre randomized controlled phase 3 trial","volume":"5","author":"Gold","year":"2023","journal-title":"Lancet Digit Health"},{"issue":"Suppl 1","key":"2025111811014765300_awaf319-B19","first-page":"118","article-title":"Depression but not physical activity mediates the fatigue-mental quality of life relationship in multiple sclerosis","volume":"25","author":"Fidao","year":"2019","journal-title":"Mult Scler J"},{"key":"2025111811014765300_awaf319-B20","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1136\/bmjspcare-2020-002604","article-title":"Global, regional, and national quality of life in patients with multiple sclerosis: A global systematic review and meta-analysis","volume":"12","author":"Pashazadeh Kan","year":"2020","journal-title":"BMJ Support Palliat Care"},{"key":"2025111811014765300_awaf319-B21","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1080\/13854046.2023.2192963","article-title":"The relationship between depression and cognitive performance in multiple sclerosis: A meta-analysis","volume":"38","author":"Altieri","year":"2024","journal-title":"Clin Neuropsychol"},{"key":"2025111811014765300_awaf319-B22","doi-asserted-by":"crossref","first-page":"4885","DOI":"10.1007\/s00415-024-12409-x","article-title":"The influence of depression and anxiety on cognition in people with multiple sclerosis: A cross-sectional analysis","volume":"271","author":"Freedman","year":"2024","journal-title":"J Neurol"},{"key":"2025111811014765300_awaf319-B23","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1177\/1352458518770086","article-title":"The link between depression and performance on the symbol digit modalities test: Mechanisms and clinical significance","volume":"25","author":"Patel","year":"2019","journal-title":"Mult Scler J"},{"key":"2025111811014765300_awaf319-B24","doi-asserted-by":"crossref","first-page":"103427","DOI":"10.1016\/j.msard.2021.103427","article-title":"Correlation of the symbol digit modalities test with the quality of life and depression in Japanese patients with multiple sclerosis","volume":"57","author":"Niino","year":"2022","journal-title":"Mult Scler Relat Disord"},{"key":"2025111811014765300_awaf319-B25","doi-asserted-by":"crossref","first-page":"2147","DOI":"10.1007\/s13760-022-02127-4","article-title":"The relation between the symbol digit modalities test, fatigue, depression, and anxiety symptoms in a Belgian MS cohort","volume":"123","author":"Borrelli","year":"2023","journal-title":"Acta Neurol Belg"},{"key":"2025111811014765300_awaf319-B26","doi-asserted-by":"crossref","first-page":"102593","DOI":"10.1016\/j.msard.2020.102593","article-title":"Comorbidity effect on processing speed test and MRI measures in multiple sclerosis patients","volume":"46","author":"Abbatemarco","year":"2020","journal-title":"Mult Scler Relat Disord"},{"key":"2025111811014765300_awaf319-B27","doi-asserted-by":"crossref","first-page":"1632","DOI":"10.1177\/13524585231198746","article-title":"Depression symptoms and cognition in multiple sclerosis: Longitudinal evidence of a specific link to executive control","volume":"29","author":"Anderson","year":"2023","journal-title":"Mult Scler J"},{"key":"2025111811014765300_awaf319-B28","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1177\/1352458520958359","article-title":"Depression and cognitive function in early multiple sclerosis: Multitasking is more sensitive than traditional assessments","volume":"27","author":"Glukhovsky","year":"2020","journal-title":"Mult Scler J"},{"key":"2025111811014765300_awaf319-B29","doi-asserted-by":"crossref","first-page":"1771","DOI":"10.1177\/1352458520979304","article-title":"Depression in multiple sclerosis across the adult lifespan","volume":"27","author":"Chan","year":"2021","journal-title":"Mult Scler J"},{"key":"2025111811014765300_awaf319-B30","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1111\/jnp.12283","article-title":"Investigating the association of mood and fatigue with objective and subjective cognitive impairment in multiple sclerosis","volume":"16","author":"Davenport","year":"2022","journal-title":"J Neuropsychol"},{"key":"2025111811014765300_awaf319-B31","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1007\/s11136-021-02927-w","article-title":"Does depression in multiple sclerosis mediate effects of cognitive functioning on quality of life?","volume":"31","author":"Crouch","year":"2021","journal-title":"Qual Life Res"},{"key":"2025111811014765300_awaf319-B32","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/1471-244X-14-5","article-title":"Cognitive behavioural therapy for the treatment of depression in people with multiple sclerosis: A systematic review and meta-analysis","volume":"14","author":"Hind","year":"2014","journal-title":"BMC Psychiatry"},{"key":"2025111811014765300_awaf319-B33","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1136\/jnnp-2018-320165","article-title":"Mindfulness-based interventions for mental well-being among people with multiple sclerosis: A systematic review and meta-analysis of randomised controlled trials","volume":"90","author":"Simpson","year":"2019","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"2025111811014765300_awaf319-B34","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/S2215-0366(14)00049-2","article-title":"An online programme to reduce depression in patients with multiple sclerosis: A randomised controlled trial","volume":"2","author":"Fischer","year":"2015","journal-title":"Lancet Psychiatry"},{"key":"2025111811014765300_awaf319-B35","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1001\/jama.2024.5756","article-title":"Management of depression in adults: A review","volume":"332","author":"Simon","year":"2024","journal-title":"JAMA"},{"key":"2025111811014765300_awaf319-B36","first-page":"CD007295","article-title":"Pharmacologic treatment of depression in multiple sclerosis","volume":"2","author":"Koch","year":"2011","journal-title":"Cochrane Database Syst Rev"},{"key":"2025111811014765300_awaf319-B37","doi-asserted-by":"crossref","first-page":"2080","DOI":"10.1080\/10803548.2021.1954793","article-title":"Unemployment associated with major depression disorder and depressive symptoms: A systematic review and meta-analysis","volume":"28","author":"Amiri","year":"2022","journal-title":"Int J Occup Saf Ergon"},{"key":"2025111811014765300_awaf319-B38","doi-asserted-by":"crossref","first-page":"2299","DOI":"10.1016\/S0140-6736(18)31948-2","article-title":"Depression","volume":"392","author":"Malhi","year":"2018","journal-title":"Lancet"},{"key":"2025111811014765300_awaf319-B39","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1017\/S1092852918001207","article-title":"Cognitive impairment in major depressive disorder","volume":"24","author":"Pan","year":"2019","journal-title":"CNS Spectr"},{"key":"2025111811014765300_awaf319-B40","doi-asserted-by":"crossref","first-page":"2028","DOI":"10.3390\/ijerph15092028","article-title":"Suicide risk and mental disorders","volume":"15","author":"Br\u00e5dvik","year":"2018","journal-title":"Int J Environ Res Public Health"},{"key":"2025111811014765300_awaf319-B41","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.msard.2018.09.018","article-title":"How does cognition relate to employment in multiple sclerosis? A systematic review","volume":"26","author":"Clemens","year":"2018","journal-title":"Mult Scler Relat Disord"},{"key":"2025111811014765300_awaf319-B42","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1001\/jamaneurol.2020.4920","article-title":"Identifying the distinct cognitive phenotypes in multiple sclerosis","volume":"78","author":"De Meo","year":"2021","journal-title":"JAMA Neurol"},{"key":"2025111811014765300_awaf319-B43","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/s11910-019-0992-1","article-title":"Depression and suicidality in multiple sclerosis: Red flags, management strategies, and ethical considerations","volume":"19","author":"Kalb","year":"2019","journal-title":"Curr Neurol Neurosci Rep"},{"key":"2025111811014765300_awaf319-B44","doi-asserted-by":"crossref","first-page":"1799","DOI":"10.1177\/1352458521996601","article-title":"Depression and multiple sclerosis: A bidirectional Mendelian randomization study","volume":"27","author":"Binzer","year":"2021","journal-title":"Mult Scler J"},{"key":"2025111811014765300_awaf319-B45","doi-asserted-by":"crossref","first-page":"2077","DOI":"10.1177\/1352458521993075","article-title":"Mendelian randomization provides no evidence for a causal role in the bidirectional relationship between depression and multiple sclerosis","volume":"27","author":"Harroud","year":"2021","journal-title":"Mult Scler"},{"key":"2025111811014765300_awaf319-B46","doi-asserted-by":"crossref","first-page":"105866","DOI":"10.1016\/j.msard.2024.105866","article-title":"Evidence of symptom specificity for depression in multiple sclerosis: A two-sample Mendelian randomization study","volume":"91","author":"Hu","year":"2024","journal-title":"Mult Scler Relat Disord"},{"key":"2025111811014765300_awaf319-B47","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1038\/s41380-021-01413-6","article-title":"Genetic heterogeneity and subtypes of major depression","volume":"27","author":"Nguyen","year":"2022","journal-title":"Mol Psychiatry"},{"key":"2025111811014765300_awaf319-B48","first-page":"e522","article-title":"Polygenicity of comorbid depression in multiple sclerosis","volume":"101","author":"Kowalak","year":"2023","journal-title":"Neurology"},{"key":"2025111811014765300_awaf319-B49","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1177\/1352458518770021","article-title":"Polymorphism in the serotonin transporter gene polymorphisms (5-HTTLPR) modifies the association between significant life events and depression in people with multiple sclerosis","volume":"25","author":"Saul","year":"2019","journal-title":"Mult Scler J"},{"key":"2025111811014765300_awaf319-B50","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1177\/1352458520921073","article-title":"Predicting self-reported depression after the onset of multiple sclerosis using genetic and non-genetic factors","volume":"27","author":"Wang","year":"2021","journal-title":"Mult Scler J"},{"key":"2025111811014765300_awaf319-B51","doi-asserted-by":"crossref","first-page":"102537","DOI":"10.1016\/j.msard.2020.102537","article-title":"Depression in multiple sclerosis patients associated with risk variant near NEGR1","volume":"46","author":"Brugger","year":"2020","journal-title":"Mult Scler Relat Disord"},{"key":"2025111811014765300_awaf319-B52","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1177\/1352458512436596","article-title":"High body mass index before age 20 is associated with increased risk for multiple sclerosis in both men and women","volume":"18","author":"Hedstr\u00f6m","year":"2012","journal-title":"Mult Scler"},{"key":"2025111811014765300_awaf319-B53","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1093\/ije\/dyy223","article-title":"Using genetics to understand the causal influence of higher BMI on depression","volume":"48","author":"Tyrrell","year":"2019","journal-title":"Int J Epidemiol"},{"key":"2025111811014765300_awaf319-B54","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1037\/0003-066X.48.1.26","article-title":"The structure of phenotypic personality traits","volume":"48","author":"Goldberg","year":"1993","journal-title":"Am Psychol"},{"key":"2025111811014765300_awaf319-B55","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1177\/1073191110368482","article-title":"The NEO-FFI in multiple sclerosis: Internal consistency, factorial validity, and correspondence between self and informant reports","volume":"18","author":"Schwartz","year":"2011","journal-title":"Assessment"},{"key":"2025111811014765300_awaf319-B56","doi-asserted-by":"crossref","first-page":"e02596","DOI":"10.1002\/brb3.2596","article-title":"Personality traits of patients with multiple sclerosis and their correlation with anxiety and depression levels: A cross-sectional case-control study","volume":"12","author":"Ghahremani","year":"2022","journal-title":"Brain Behav"},{"key":"2025111811014765300_awaf319-B57","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1093\/arclin\/acx104","article-title":"Personality and primary emotional traits: Disentangling multiple sclerosis-related fatigue and depression","volume":"33","author":"Sindermann","year":"2018","journal-title":"Arch Clin Neuropsychol"},{"key":"2025111811014765300_awaf319-B58","doi-asserted-by":"crossref","first-page":"2526","DOI":"10.1017\/S0033291719002629","article-title":"Genetic stratification of depression by neuroticism: Revisiting a diagnostic tradition","volume":"50","author":"Adams","year":"2019","journal-title":"Psychol Med"},{"key":"2025111811014765300_awaf319-B59","doi-asserted-by":"crossref","first-page":"103648","DOI":"10.1016\/j.msard.2022.103648","article-title":"Association of personality traits with physical function, cognition, and mood in multiple sclerosis","volume":"59","author":"Kever","year":"2022","journal-title":"Mult Scler Relat Disord"},{"key":"2025111811014765300_awaf319-B60","doi-asserted-by":"crossref","first-page":"120145","DOI":"10.1016\/j.jns.2022.120145","article-title":"Is there a multiple sclerosis personality? Personality characteristics in newly diagnosed multiple sclerosis and association with mood and cognition","volume":"434","author":"Chu","year":"2022","journal-title":"J Neurol Sci"},{"key":"2025111811014765300_awaf319-B61","doi-asserted-by":"crossref","first-page":"105138","DOI":"10.1016\/j.msard.2023.105138","article-title":"The influence of personality in persons with MS","volume":"81","author":"Bonf\u00e1-Araujo","year":"2024","journal-title":"Mult Scler Relat Disord"},{"key":"2025111811014765300_awaf319-B62","doi-asserted-by":"crossref","first-page":"102560","DOI":"10.1016\/j.msard.2020.102560","article-title":"How personality traits affect functional outcomes in patients with multiple sclerosis: A scoping review on a poorly understood topic","volume":"46","author":"Maggio","year":"2020","journal-title":"Mult Scler Relat Disord"},{"key":"2025111811014765300_awaf319-B63","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1080\/13548506.2016.1164321","article-title":"Personality in multiple sclerosis (MS): Impact on health, psychological well-being, coping, and overall quality of life","volume":"22","author":"Strober","year":"2016","journal-title":"Psychol Health Med"},{"key":"2025111811014765300_awaf319-B64","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1177\/1352458518820272","article-title":"Trait conscientiousness predicts rate of longitudinal SDMT decline in multiple sclerosis","volume":"26","author":"Fuchs","year":"2020","journal-title":"Mult Scler J"},{"key":"2025111811014765300_awaf319-B65","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1177\/1352458519858605","article-title":"Trait conscientiousness predicts rate of brain atrophy in multiple sclerosis","volume":"26","author":"Fuchs","year":"2020","journal-title":"Mult Scler J"},{"key":"2025111811014765300_awaf319-B66","doi-asserted-by":"crossref","first-page":"45","DOI":"10.7224\/1537-2073.2021-005","article-title":"Preliminary support of a behavioral intervention for trait conscientiousness in multiple sclerosis","volume":"24","author":"Fuchs","year":"2022","journal-title":"Int J MS Care"},{"key":"2025111811014765300_awaf319-B67","doi-asserted-by":"crossref","first-page":"102010","DOI":"10.1016\/j.msard.2020.102010","article-title":"Socioeconomic status and race are correlated with affective symptoms in multiple sclerosis","volume":"41","author":"Wang","year":"2020","journal-title":"Mult Scler Relat Disord"},{"issue":"3_suppl","key":"2025111811014765300_awaf319-B68","first-page":"451","article-title":"Relationship between socioeconomic status and depression in patients with multiple sclerosis [poster presentation]","volume":"29","author":"Rubin","year":"2023","journal-title":"Mult Scler J"},{"key":"2025111811014765300_awaf319-B69","doi-asserted-by":"crossref","first-page":"103451","DOI":"10.1016\/j.msard.2021.103451","article-title":"The impact of socioeconomic status on mental health and health-seeking behaviour across race and ethnicity in a large multiple sclerosis cohort","volume":"58","author":"Pimentel Maldonado","year":"2022","journal-title":"Mult Scler Relat Disord"},{"key":"2025111811014765300_awaf319-B70","author":"Amin"},{"key":"2025111811014765300_awaf319-B71","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1007\/s10072-022-06517-7","article-title":"The economic impact of comorbidity in multiple sclerosis","volume":"44","author":"Ponzio","year":"2022","journal-title":"Neurol Sci"},{"key":"2025111811014765300_awaf319-B72","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/s12991-023-00486-7","article-title":"Sex difference in incidence of major depressive disorder: An analysis from the global burden of disease study 2019","volume":"22","author":"Li","year":"2023","journal-title":"Ann Gen Psychiatry"},{"key":"2025111811014765300_awaf319-B73","doi-asserted-by":"crossref","first-page":"102884","DOI":"10.1016\/j.msard.2021.102884","article-title":"Differences in symptoms of depression between females and males with relapsing-remitting multiple sclerosis","volume":"51","author":"Mayo","year":"2021","journal-title":"Mult Scler Relat Disord"},{"key":"2025111811014765300_awaf319-B74","doi-asserted-by":"crossref","first-page":"17562864231197309","DOI":"10.1177\/17562864231197309","article-title":"Factors associated with depressive mood at the onset of multiple sclerosis: An analysis of 781 patients of the German NationMS cohort","volume":"16","author":"Salmen","year":"2023","journal-title":"Ther Adv Neurol Disord"},{"key":"2025111811014765300_awaf319-B75","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.msard.2019.02.014","article-title":"Associations of demographic and clinical factors with depression over 2.5 years in an international prospective cohort of people living with MS","volume":"30","author":"Simpson","year":"2019","journal-title":"Mult Scler Relat Disord"},{"key":"2025111811014765300_awaf319-B76","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1038\/s41582-019-0174-4","article-title":"Immunoneuropsychiatry\u2014Novel perspectives on brain disorders","volume":"15","author":"Pape","year":"2019","journal-title":"Nat Rev Neurol"},{"key":"2025111811014765300_awaf319-B77","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1124\/pharmrev.120.000043","article-title":"Aiding and abetting anhedonia: Impact of inflammation on the brain and pharmacological implications","volume":"73","author":"Lucido","year":"2021","journal-title":"Pharmacol Rev"},{"key":"2025111811014765300_awaf319-B78","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1038\/s41380-019-0471-8","article-title":"Effects of immunomodulatory drugs on depressive symptoms: A mega-analysis of randomized placebo-controlled clinical trials in inflammatory disorders","volume":"25","author":"Wittenberg","year":"2020","journal-title":"Mol Psychiatry"},{"key":"2025111811014765300_awaf319-B79","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1016\/j.biopsych.2018.12.020","article-title":"Longitudinal association between depression and inflammatory markers: Results from The Netherlands study of depression and anxiety","volume":"85","author":"Lamers","year":"2019","journal-title":"Biol Psychiatry"},{"key":"2025111811014765300_awaf319-B80","doi-asserted-by":"crossref","first-page":"100108","DOI":"10.1016\/j.bbih.2020.100108","article-title":"Immune dysregulation in depression: Evidence from genome-wide association","volume":"7","author":"Tubbs","year":"2020","journal-title":"Brain Behav Immun Health"},{"key":"2025111811014765300_awaf319-B81","doi-asserted-by":"crossref","first-page":"6102","DOI":"10.1038\/s41467-022-33885-7","article-title":"Genetic variants associated with psychiatric disorders are enriched at epigenetically active sites in lymphoid cells","volume":"13","author":"Lynall","year":"2022","journal-title":"Nat Commun"},{"key":"2025111811014765300_awaf319-B82","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1038\/s41573-021-00368-1","article-title":"Immune targets for therapeutic development in depression: Towards precision medicine","volume":"21","author":"Drevets","year":"2022","journal-title":"Nat Rev Drug Discov"},{"key":"2025111811014765300_awaf319-B83","doi-asserted-by":"crossref","first-page":"423","DOI":"10.3390\/cells13050423","article-title":"Role of inflammatory mechanisms in major depressive disorder: From etiology to potential pharmacological targets","volume":"13","author":"Kouba","year":"2024","journal-title":"Cells"},{"key":"2025111811014765300_awaf319-B84","doi-asserted-by":"crossref","first-page":"458","DOI":"10.3389\/fpsyt.2019.00458","article-title":"Low-grade inflammation as a predictor of antidepressant and anti-inflammatory therapy response in MDD patients: A systematic review of the literature in combination with an analysis of experimental data collected in the EU-MOODINFLAME consortium","volume":"10","author":"Arteaga-Henr\u00edquez","year":"2019","journal-title":"Front Psychiatry"},{"key":"2025111811014765300_awaf319-B85","doi-asserted-by":"crossref","first-page":"106005","DOI":"10.1016\/j.nbd.2023.106005","article-title":"Neuro-immune crosstalk in depressive symptoms of multiple sclerosis","volume":"177","author":"Wang","year":"2023","journal-title":"Neurobiol Dis"},{"issue":"Suppl 2","key":"2025111811014765300_awaf319-B86","first-page":"828","article-title":"Characterization of cytokine profiles in multiple sclerosis patients with comorbid depression [poster presentation]","volume":"25","author":"Andlauer","year":"2019","journal-title":"Mult Scler J"},{"issue":"Suppl 1","key":"2025111811014765300_awaf319-B87","first-page":"S511","article-title":"CSF IFN-GAMMA levels are associated with depressive symptoms severity in multiple sclerosis","volume":"43","author":"Sperandei","year":"2022","journal-title":"Neurol Sci"},{"key":"2025111811014765300_awaf319-B88","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.bbi.2021.11.022","article-title":"Immune signature of multiple sclerosis-associated depression","volume":"100","author":"Brasanac","year":"2022","journal-title":"Brain Behav Immun"},{"key":"2025111811014765300_awaf319-B89","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1007\/s00018-022-04315-0","article-title":"Major depression favors the expansion of Th17-like cells and decreases the proportion of CD39+ Treg cell subsets in response to myelin antigen in multiple sclerosis patients","volume":"79","author":"do Sacramento","year":"2022","journal-title":"Cell Mol Life Sci"},{"key":"2025111811014765300_awaf319-B90","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.3390\/brainsci13071073","article-title":"Mood symptoms and chronic fatigue syndrome due to relapsing-remitting multiple sclerosis are associated with immune activation and aberrations in the erythron","volume":"13","author":"Almulla","year":"2023","journal-title":"Brain Sci"},{"key":"2025111811014765300_awaf319-B91","doi-asserted-by":"crossref","first-page":"4113","DOI":"10.1038\/s41380-022-01715-3","article-title":"Functional connectivity in reward circuitry and symptoms of anhedonia as therapeutic targets in depression with high inflammation: Evidence from a dopamine challenge study","volume":"27","author":"Bekhbat","year":"2022","journal-title":"Mol Psychiatry"},{"key":"2025111811014765300_awaf319-B92","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.bbi.2021.02.030","article-title":"The distinct roles of monoamines in multiple sclerosis: A bridge between the immune and nervous systems?","volume":"94","author":"Carandini","year":"2021","journal-title":"Brain Behav Immun"},{"key":"2025111811014765300_awaf319-B93","doi-asserted-by":"crossref","first-page":"5971","DOI":"10.1007\/s12035-021-02507-6","article-title":"Dopaminergic receptors as neuroimmune mediators in experimental autoimmune encephalomyelitis","volume":"58","author":"Gon\u00e7alves","year":"2021","journal-title":"Mol Neurobiol"},{"key":"2025111811014765300_awaf319-B94","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1177\/1352458520972279","article-title":"Fatigue, depression, and pain in multiple sclerosis: How neuroinflammation translates into dysfunctional reward processing and anhedonic symptoms","volume":"28","author":"Heitmann","year":"2022","journal-title":"Mult Scler J"},{"key":"2025111811014765300_awaf319-B95","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.msard.2018.09.008","article-title":"Adverse psychiatric effects of disease-modifying therapies in multiple sclerosis: A systematic review","volume":"26","author":"Gasim","year":"2018","journal-title":"Mult Scler Relat Disord"},{"issue":"2_suppl","key":"2025111811014765300_awaf319-B96","first-page":"131","article-title":"Initiation of higher-efficacy disease-modifying therapy is associated with a reduction in depressive symptom severity in a large population of people with multiple sclerosis [poster presentation]","volume":"25","author":"Fitzgerald","year":"2019","journal-title":"Mult Scler J"},{"key":"2025111811014765300_awaf319-B97","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1038\/s44220-022-00002-y","article-title":"Lesion network localization of depression in multiple sclerosis","volume":"1","author":"Siddiqi","year":"2023","journal-title":"Nat Ment Health"},{"key":"2025111811014765300_awaf319-B98","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1016\/j.biopsych.2023.11.010","article-title":"Mapping the relationship of white matter lesions to depression in multiple sclerosis","volume":"95","author":"Baller","year":"2024","journal-title":"Biol Psychiatry"},{"key":"2025111811014765300_awaf319-B99","doi-asserted-by":"crossref","first-page":"178","DOI":"10.7224\/1537-2073.2020-015","article-title":"Relationship between interpersonal depressive symptoms and reduced amygdala volume in people with multiple sclerosis","volume":"23","author":"Haines","year":"2020","journal-title":"Int J MS Care"},{"key":"2025111811014765300_awaf319-B100","doi-asserted-by":"crossref","first-page":"e01514","DOI":"10.1002\/brb3.1514","article-title":"Diffusion tensor imaging tractography reveals altered fornix in all diagnostic subtypes of multiple sclerosis","volume":"10","author":"Vald\u00e9s Cabrera","year":"2020","journal-title":"Brain Behav"},{"key":"2025111811014765300_awaf319-B101","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1007\/s12311-019-01096-4","article-title":"Selective cerebellar atrophy associates with depression and fatigue in the early phases of relapse-onset multiple sclerosis","volume":"19","author":"Lazzarotto","year":"2020","journal-title":"Cerebellum"},{"key":"2025111811014765300_awaf319-B102","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1177\/1352458518767051","article-title":"Fronto-limbic disconnection in patients with multiple sclerosis and depression","volume":"25","author":"van Geest","year":"2019","journal-title":"Mult Scler J"},{"key":"2025111811014765300_awaf319-B103","doi-asserted-by":"crossref","first-page":"fcac152","DOI":"10.1093\/braincomms\/fcac152","article-title":"Prefrontal-amygdala emotion regulation and depression in multiple sclerosis","volume":"4","author":"Meyer-Arndt","year":"2022","journal-title":"Brain Commun"},{"key":"2025111811014765300_awaf319-B104","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1177\/13524585221148144","article-title":"Deep gray matter substructure volumes and depressive symptoms in a large multiple sclerosis cohort","volume":"29","author":"Hu","year":"2023","journal-title":"Mult Scler J"},{"key":"2025111811014765300_awaf319-B105","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1007\/s00415-020-10110-3","article-title":"Diagnosis of depression in multiple sclerosis is predicted by frontal-parietal white matter tract disruption","volume":"268","author":"Ashton","year":"2021","journal-title":"J Neurol"},{"key":"2025111811014765300_awaf319-B106","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1007\/s00234-023-03174-1","article-title":"Distinct hemodynamic and functional connectivity features of fatigue in clinically isolated syndrome and multiple sclerosis: Accounting for the confounding effect of concurrent depression symptoms","volume":"65","author":"Antypa","year":"2023","journal-title":"Neuroradiology"},{"key":"2025111811014765300_awaf319-B107","doi-asserted-by":"crossref","first-page":"719088","DOI":"10.3389\/fneur.2021.719088","article-title":"C-reactive protein levels and gadolinium-enhancing lesions are associated with the degree of depressive symptoms in newly diagnosed multiple sclerosis","volume":"12","author":"Yalachkov","year":"2021","journal-title":"Front Neurol"},{"key":"2025111811014765300_awaf319-B108","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1136\/jnnp-2022-330109","article-title":"Monoaminergic network abnormalities: A marker for multiple sclerosis-related fatigue and depression","volume":"94","author":"Carotenuto","year":"2023","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"2025111811014765300_awaf319-B109","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.1038\/s41380-023-01943-1","article-title":"Correspondence among gray matter atrophy and atlas-based neurotransmitter maps is clinically relevant in multiple sclerosis","volume":"28","author":"Fiore","year":"2023","journal-title":"Mol Psychiatry"},{"key":"2025111811014765300_awaf319-B110","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1007\/s00415-023-12138-7","article-title":"Monoaminergic network dysfunction and development of depression in multiple sclerosis: A longitudinal investigation","volume":"271","author":"Mistri","year":"2023","journal-title":"J Neurol"},{"key":"2025111811014765300_awaf319-B111","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/S2215-0366(16)30263-2","article-title":"Why is depression more common among women than among men?","volume":"4","author":"Kuehner","year":"2017","journal-title":"Lancet Psychiatry"},{"key":"2025111811014765300_awaf319-B112","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1111\/jon.13011","article-title":"Functional MRI in major depressive disorder: A review of findings, limitations, and future prospects","volume":"32","author":"Pilmeyer","year":"2022","journal-title":"J Neuroimaging"},{"key":"2025111811014765300_awaf319-B113","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1111\/cns.12835","article-title":"Brain structure alterations in depression: Psychoradiological evidence","volume":"24","author":"Zhang","year":"2018","journal-title":"CNS Neurosci Ther"},{"key":"2025111811014765300_awaf319-B114","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1093\/aje\/kwf182","article-title":"Socioeconomic inequalities in depression: A meta-analysis","volume":"157","author":"Lorant","year":"2003","journal-title":"Am J Epidemiol"}],"container-title":["Brain"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/brain\/advance-article-pdf\/doi\/10.1093\/brain\/awaf319\/64232961\/awaf319.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/brain\/advance-article-pdf\/doi\/10.1093\/brain\/awaf319\/64232961\/awaf319.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T16:02:09Z","timestamp":1763481729000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/brain\/advance-article\/doi\/10.1093\/brain\/awaf319\/8250186"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,9]]},"references-count":114,"URL":"https:\/\/doi.org\/10.1093\/brain\/awaf319","relation":{},"ISSN":["0006-8950","1460-2156"],"issn-type":[{"value":"0006-8950","type":"print"},{"value":"1460-2156","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,9]]},"article-number":"awaf319"}}