Original article| Volume 42, 102054, July 2020

Identifying the relevant determinants of MS related fatigue: The role of the clinical indicators of disease and personality


      • Personality is directly and indirectly associated with fatigue.
      • Temperament and character traits are associated with fatigue.
      • Clinical features are associated with fatigue only when paired with personality


      Background and objective

      Research on the factors contributing to multiple sclerosis (MS) related fatigue are far from conclusive. Some studies put forward that clinical aspects of the disease give rise to this symptom whilst others emphasize the effects of psychological factors on its etiology. This study investigated the relationship between clinical aspects of MS and personality with MS fatigue.


      A total of 201 participants with MS of which 48 (23.9%) males and 153 (76.1%) females took part in this online study. Questionnaires were populated measuring clinical features of the disease (disease duration, type of MS, Expanded Disability Status Scale - EDSS), personality traits, and MS-related fatigue. Data was analyzed by hierarchical regression analyses.


      Personality traits accounted for a greater variance in MS fatigue ( = .482, p < .01) than clinical aspects of the disease, these results were conclusive after controlling for the sociodemographic variables and depression. Temperament explained in total 10.5% variance of fatigue and character an additional 4.0 %. High Harm avoidance (HA) (β = .229, p < .01) and low Self-directedness (SD) (β = −.217, p < .01) directly predicted fatigue. Also, temperament was shown to indirectly affect fatigue, through character. High HA and high Novelty-seeking (NS) through low SD predicted fatigue. The association between clinical features and fatigue was not observed unless paired with personality traits. EDSS in conjunction with HA and Secondary – progressive MS (SPMS) coupled with SD negatively affected fatigue levels.


      Personality traits directly and indirectly predicted MS-related fatigue. Furthermore, the impact of clinical indicators of disease on fatigue would not be observed unless these features occurred together with particular personality traits.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Multiple Sclerosis and Related Disorders
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Krupp L.B.
        Fatigue in multiple sclerosis: definition, pathophysiology and treatment.
        CNS Drugs. 2003; 17: 225-234
        • Braley T.J
        • Chervin R.D.
        Fatigue in multiple sclerosis: mechanisms, evaluation and treatment.
        Sleep. 2010; 33: 1061-1070
        • Chaudhuri A
        • Behan P.O
        Fatigue and basal ganglia.
        J. Neurol. Sci. 2000; 179: 34-42
        • Melanson M
        • Grossberndt A
        • Klowak M
        • et al.
        Fatigue and cognition in patients with relapsing multiple sclerosis treated with interferon beta.
        Int. J. Neurosci. 2010; 120: 631-640
        • Putzki N
        • Yaldizli O
        • Tettenborn B
        • Diener H.C
        Multiple sclerosis associated fatigue during natalizumab treatment.
        J. Neurol. Sci. 2009; 285: 109-113
        • Cantor F
        Central and peripheral fatigue: exemplified by multiple sclerosis and myasthenia gravis.
        PM. R. 2010; 2: 399-405
        • Iriarte J
        • Subira M.L
        • Castro P
        Modalities of fatigue in Multiple sclerosis: correlation with clinical and biological factors.
        Mult. Scler. 2000; 6: 124-130
        • Mills R.J
        • Young C.A.
        The relationship between fatigue and other clinical features of multiple sclerosis.
        Mult. Scler. 2010; 17: 406-412
        • Šabanagić-Hajrić S
        • Suljic E
        • Kučukalić A
        Fatigue during multiple sclerosis relapse and its relationship to depression and neurological disability.
        Psychiatr. Danub. 2015; 27: 406-412
        • Bergamaschi R
        • Romani A
        • Versino M
        • et al.
        Clinical aspects of fatigue in multiple sclerosis.
        Funct. Neurol. 1997; 12: 247-251
        • Colosimo C
        • Millefiorini E
        • Grasso M.G
        • et al.
        Fatigue in MS is associated with specific clinical features.
        Acta Neurol. Scand. 1995; 92: 353-355
        • Ghajarzadeh M
        • Jalilian R
        • Eskandari G
        • et al.
        Fatigue in multiple sclerosis: relationship with disease duration, physical disability, disease pattern, age and sex.
        Acta Neurol. Belg. 2013; 113: 411-414
        • Lerdal A
        • Celius E.G
        • Krupp L
        • et al.
        A prospective study of patterns of fatigue in multiple sclerosis.
        Eur. J. Neurol. 2007; 14: 1338-1343
        • Mainero C
        • Faroni J
        • Gasperini C
        • et al.
        Fatigue and magnetic resonance imagiing activity in multiple sclerosis.
        J. Neurol. 1999; 246: 454-458
        • Vercoulen J.H
        • Hommes O.R
        • Swanink C.M
        • et al.
        The Measurement of Fatigue in Patients with Multiple Sclerosis. A multidimensional comparison with patients with chronic fatigue syndrome and healthy subjects.
        Arch. Neurol. 1996; 53: 642-649
        • Krupp L.B
        • Alvarez L.A
        • LaRocca N.G
        • et al.
        Fatigue in multiple sclerosis.
        Arch Neurol. 1988; 45: 435-437
        • Kroencke D.C
        • Lynch S.G
        • Denney D.R
        Fatigue in multiple sclerosis: relationship to depression, disability, and disease pattern.
        Mult. Scler. 2000; 6: 131-136
        • Hadjimichael O
        • Vollmer T
        • Oleen - Burkey M
        North American Research Committee on Multiple Sclerosis. Fatigue characteristics in multiple sclerosis: the North American Research Committee on Multiple Sclerosis (NARCOMS) survey.
        Health Qual. Life Outcomes. 2008; 6: 100
        • Kandler C
        • Bleidorn W.
        The Genetic and Environmental Contributions to Personality Differences and Development.
        in: Wright JD The International Encyclopedia of Social and Behavioral Sciences. 2nd ed. Elsevier Science, 2015: 884-890
        • Schreiber H
        • Lang M
        • Kiltz K
        • et al.
        Is personality profile a relevant determinant of fatigue in multiple sclerosis?.
        Front Neurol. 2015; 6: 1-7
        • Merkelbach S
        • König J
        • Sittinger H
        Personality traits in multiple sclerosis (MS) patients with and without fatigue experience.
        Acta Neurol. Scand. 2003; 107: 195-201
        • Penner I.K
        • Bechtel N
        • Raselli C
        • et al.
        Fatigue in multiple sclerosis: relation to depression, physical impairment, personality and action control.
        Mult. Scler. 2007; 13: 1161-1167
        • Kiltz K
        • Lang M
        • Flachenecker P
        • et al.
        Physical, cognitive and psychological dimensions of fatigue in patients with relapsing – remitting multiple sclerosis - a multi –center study.
        Mult. Scler. 2009; 15: 131-150
        • Christodoulou C
        • Deluca J
        • Johnson S.K
        • et al.
        Examination of Cloninger's basic dimensions of personality in fatiguing illness: chronic fatigue syndrome and multiple sclerosis.
        J. Psychosom. Res. 1999; 47: 597-607
        • Gazioglu S
        • Cakmak V.A
        • Ozkorumak E
        • et al.
        Personality traits of patients with multiple sclerosis and their relationship with clinical characteristics.
        J. Nerv. Ment. Dis. 2014; 202: 408-411
        • Cloninger C.R.
        The Temperament and Character Inventory-Revised (TCI-R).
        Center for Psychobiology of Personality, Washington University, St. Louis, Missouri1999
        • Kurtzke J.F.
        Rating neurologic impairment in multiple sclerosis: An expanded disability status scale (EDSS).
        Neurology. 1983; 33: 1444-1452
        • Zigmond A.S
        • Snaith R.P.
        The Hospital Anxiety and Depression Scale.
        Acta Psychiatr. Scand. 1983; 67: 361-370
        • Fisk J.D
        • Pontefract A
        • Ritvo P.G
        • et al.
        The impact of fatigue on patients with multiple sclerosis.
        Can. J. Neurol. Sci. 1994; 21: 9-14
        • Baron R.M
        • Kenny D.A.
        The Moderator-Mediator Variable Distinction in Social Psychological Research: Conceptual, Strategic, and Statistical Considerations.
        J. Pers. Soc. Psychol. 1986; 51: 173-182
        • Pardini M
        • Capello E
        • Krueger F
        • et al.
        Reward responsiveness and fatigue in multiple sclerosis.
        Mult. Scler. 2013; 19: 233-240
        • Cloninger C.R
        • Przybeck T.R
        • Svrakic D.M
        • Wetzel R.D.
        The Temperament and Character Inventory (TCI): A Guide to Its Development and Use.
        Center for Psychobiology of Personality, St. Louis, Missouri1994 (Washington University)
        • Cloninger C.R
        • Svrakić D.M
        • Przybeck T.R
        A Psychobiological Model of Temperament and Character.
        Arch. Gen. Psychiatry. 1993; 50: 975-990
        • Van der Werf S.P
        • Evers A
        • Jongen P.J
        • Bleijenberg G
        The role of helplessness as mediator between neurological disability, emotional instability, experienced fatigue and depression.
        Mult. Scler. 2003; 9: 89-94
        • Hyphanthis T.N
        • Christou K
        • Kontoudaki S
        • et al.
        Disability status, disease parameters, defense styles, and ego strength associated with psychiatric complications of multiple sclerosis.
        Int. J. Psychiatry Med. 2008; 38: 307-327
        • Manjaly Z.M
        • Harrison N.A
        • Critchley H.D
        • et al.
        Pathophysiology and cognitive mechanisms of fatigue in multiple sclerosis.
        J. Neurol. Neurosurg. Psychiatry. 2019; 90: 642-651
        • Newland P
        • Starkweather A
        • Sorenson M
        Central fatigue in multiple sclerosis: a review of the literature.
        J. Spinal. Cord. Med. 2016; 39: 386-399