title: Health-related quality of life in multiple sclerosis: Direct and indirect effects of comorbidity.
abstract: OBJECTIVE
  To evaluate the direct and indirect influences of physical comorbidity, symptoms of depression and anxiety, fatigue, and disability on health-related quality of life (HRQoL) in persons with multiple sclerosis (MS).
  
  
  METHODS
  A large (n = 949) sample of adults with MS was recruited from 4 Canadian MS clinics. HRQoL was assessed using the patient-reported Health Utilities Index Mark 3. Expanded Disability Status Scale scores, physical comorbidity, depression, anxiety, and fatigue were evaluated as predictors of HRQoL in a cross-sectional path analysis.
  
  
  RESULTS
  All predictors were significantly associated with HRQoL and together accounted for a large proportion of variance (63%). Overall, disability status most strongly affected HRQoL (β = -0.52) but it was closely followed by depressive symptoms (β = -0.50). The direct associations of physical comorbidity and anxiety with HRQoL were small (β = -0.08 and -0.10, respectively), but these associations were stronger when indirect effects through other variables (depression, fatigue) were also considered (physical comorbidity: β = -0.20; anxiety: β = -0.34).
  
  
  CONCLUSIONS
  Increased disability, depression and anxiety symptoms, fatigue, and physical comorbidity are associated with decreased HRQoL in MS. Disability most strongly diminishes HRQoL and, thus, interventions that reduce disability are expected to yield the most substantial improvement in HRQoL. Yet, interventions targeting other factors amenable to change, particularly depression but also anxiety, fatigue, and physical comorbidities, may all result in meaningful improvements in HRQoL, as well. Our findings point to the importance of further research confirming the efficacy of such interventions.
authors.affiliation: From the Department of Psychology (L.I.B.), St. Francis Xavier University, Antigonish; Department of Psychiatry (L.I.B., J.D.F.), Department of Medicine (J.D.F.), Dalhousie University, Halifax; Departments of Psychiatry and Community Health Sciences (S.B.P.), Cumming School of Medicine, University of Calgary; Division of Neurology, Faculty of Medicine (H.T., K.A.M.), University of British Columbia, Vancouver; Departments of Epidemiology & Biostatistics, Occupational Health, & Medicine (C.W.), McGill University, Montreal; Faculty of Rehabilitation Medicine (S.W.), University of Alberta, Edmonton; and Departments of Internal Medicine (K.M.F., R.A.M.) and Community Health Sciences (R.A.M.), College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada. lberriga@stfx.ca.
authors.forename: Lindsay I
authors.initials: LI
authors.lastname: Berrigan
authors.affiliation: From the Department of Psychology (L.I.B.), St. Francis Xavier University, Antigonish; Department of Psychiatry (L.I.B., J.D.F.), Department of Medicine (J.D.F.), Dalhousie University, Halifax; Departments of Psychiatry and Community Health Sciences (S.B.P.), Cumming School of Medicine, University of Calgary; Division of Neurology, Faculty of Medicine (H.T., K.A.M.), University of British Columbia, Vancouver; Departments of Epidemiology & Biostatistics, Occupational Health, & Medicine (C.W.), McGill University, Montreal; Faculty of Rehabilitation Medicine (S.W.), University of Alberta, Edmonton; and Departments of Internal Medicine (K.M.F., R.A.M.) and Community Health Sciences (R.A.M.), College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada.
authors.forename: John D
authors.initials: JD
authors.lastname: Fisk
authors.affiliation: From the Department of Psychology (L.I.B.), St. Francis Xavier University, Antigonish; Department of Psychiatry (L.I.B., J.D.F.), Department of Medicine (J.D.F.), Dalhousie University, Halifax; Departments of Psychiatry and Community Health Sciences (S.B.P.), Cumming School of Medicine, University of Calgary; Division of Neurology, Faculty of Medicine (H.T., K.A.M.), University of British Columbia, Vancouver; Departments of Epidemiology & Biostatistics, Occupational Health, & Medicine (C.W.), McGill University, Montreal; Faculty of Rehabilitation Medicine (S.W.), University of Alberta, Edmonton; and Departments of Internal Medicine (K.M.F., R.A.M.) and Community Health Sciences (R.A.M.), College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada.
authors.forename: Scott B
authors.initials: SB
authors.lastname: Patten
authors.affiliation: From the Department of Psychology (L.I.B.), St. Francis Xavier University, Antigonish; Department of Psychiatry (L.I.B., J.D.F.), Department of Medicine (J.D.F.), Dalhousie University, Halifax; Departments of Psychiatry and Community Health Sciences (S.B.P.), Cumming School of Medicine, University of Calgary; Division of Neurology, Faculty of Medicine (H.T., K.A.M.), University of British Columbia, Vancouver; Departments of Epidemiology & Biostatistics, Occupational Health, & Medicine (C.W.), McGill University, Montreal; Faculty of Rehabilitation Medicine (S.W.), University of Alberta, Edmonton; and Departments of Internal Medicine (K.M.F., R.A.M.) and Community Health Sciences (R.A.M.), College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada.
authors.forename: Helen
authors.initials: H
authors.lastname: Tremlett
authors.affiliation: From the Department of Psychology (L.I.B.), St. Francis Xavier University, Antigonish; Department of Psychiatry (L.I.B., J.D.F.), Department of Medicine (J.D.F.), Dalhousie University, Halifax; Departments of Psychiatry and Community Health Sciences (S.B.P.), Cumming School of Medicine, University of Calgary; Division of Neurology, Faculty of Medicine (H.T., K.A.M.), University of British Columbia, Vancouver; Departments of Epidemiology & Biostatistics, Occupational Health, & Medicine (C.W.), McGill University, Montreal; Faculty of Rehabilitation Medicine (S.W.), University of Alberta, Edmonton; and Departments of Internal Medicine (K.M.F., R.A.M.) and Community Health Sciences (R.A.M.), College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada.
authors.forename: Christina
authors.initials: C
authors.lastname: Wolfson
authors.affiliation: From the Department of Psychology (L.I.B.), St. Francis Xavier University, Antigonish; Department of Psychiatry (L.I.B., J.D.F.), Department of Medicine (J.D.F.), Dalhousie University, Halifax; Departments of Psychiatry and Community Health Sciences (S.B.P.), Cumming School of Medicine, University of Calgary; Division of Neurology, Faculty of Medicine (H.T., K.A.M.), University of British Columbia, Vancouver; Departments of Epidemiology & Biostatistics, Occupational Health, & Medicine (C.W.), McGill University, Montreal; Faculty of Rehabilitation Medicine (S.W.), University of Alberta, Edmonton; and Departments of Internal Medicine (K.M.F., R.A.M.) and Community Health Sciences (R.A.M.), College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada.
authors.forename: Sharon
authors.initials: S
authors.lastname: Warren
authors.affiliation: From the Department of Psychology (L.I.B.), St. Francis Xavier University, Antigonish; Department of Psychiatry (L.I.B., J.D.F.), Department of Medicine (J.D.F.), Dalhousie University, Halifax; Departments of Psychiatry and Community Health Sciences (S.B.P.), Cumming School of Medicine, University of Calgary; Division of Neurology, Faculty of Medicine (H.T., K.A.M.), University of British Columbia, Vancouver; Departments of Epidemiology & Biostatistics, Occupational Health, & Medicine (C.W.), McGill University, Montreal; Faculty of Rehabilitation Medicine (S.W.), University of Alberta, Edmonton; and Departments of Internal Medicine (K.M.F., R.A.M.) and Community Health Sciences (R.A.M.), College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada.
authors.forename: Kirsten M
authors.initials: KM
authors.lastname: Fiest
authors.affiliation: From the Department of Psychology (L.I.B.), St. Francis Xavier University, Antigonish; Department of Psychiatry (L.I.B., J.D.F.), Department of Medicine (J.D.F.), Dalhousie University, Halifax; Departments of Psychiatry and Community Health Sciences (S.B.P.), Cumming School of Medicine, University of Calgary; Division of Neurology, Faculty of Medicine (H.T., K.A.M.), University of British Columbia, Vancouver; Departments of Epidemiology & Biostatistics, Occupational Health, & Medicine (C.W.), McGill University, Montreal; Faculty of Rehabilitation Medicine (S.W.), University of Alberta, Edmonton; and Departments of Internal Medicine (K.M.F., R.A.M.) and Community Health Sciences (R.A.M.), College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada.
authors.forename: Kyla A
authors.initials: KA
authors.lastname: McKay
authors.affiliation: From the Department of Psychology (L.I.B.), St. Francis Xavier University, Antigonish; Department of Psychiatry (L.I.B., J.D.F.), Department of Medicine (J.D.F.), Dalhousie University, Halifax; Departments of Psychiatry and Community Health Sciences (S.B.P.), Cumming School of Medicine, University of Calgary; Division of Neurology, Faculty of Medicine (H.T., K.A.M.), University of British Columbia, Vancouver; Departments of Epidemiology & Biostatistics, Occupational Health, & Medicine (C.W.), McGill University, Montreal; Faculty of Rehabilitation Medicine (S.W.), University of Alberta, Edmonton; and Departments of Internal Medicine (K.M.F., R.A.M.) and Community Health Sciences (R.A.M.), College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada.
authors.forename: Ruth Ann
authors.initials: RA
authors.lastname: Marrie