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January 29, 2019; 92 (5) Article

Comorbid anxiety, depression, and cognition in MS and other immune-mediated disorders

View ORCID ProfileChristiane E. Whitehouse, John D. Fisk, Charles N. Bernstein, Lindsay I. Berrigan, James M. Bolton, Lesley A. Graff, Carol A. Hitchon, James J. Marriott, Christine A. Peschken, Jitender Sareen, John R. Walker, Sherry H. Stewart, Ruth Ann Marrie, for the CIHR Team in Defining the Burden and Managing the Effects of Psychiatric Comorbidity in Chronic Immunoinflammatory Disease
First published January 11, 2019, DOI: https://doi.org/10.1212/WNL.0000000000006854
Christiane E. Whitehouse
From the Departments of Psychology and Neuroscience (C.E.W., J.D.F., S.H.S.), Psychiatry (J.D.F.), and Medicine (J.D.F.), Dalhousie University; Nova Scotia Health Authority (J.D.F.), Halifax; Departments of Internal Medicine (C.N.B., J.J.M., C.A.P., C.A.H., R.A.M.), Psychiatry (J.M.B., J.S.), Clinical Health Psychology (L.A.G., J.R.W.), and Community Health Sciences (R.A.M.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg; and Department of Psychology (L.I.B.), St. Francis Xavier University, Antigonish, Canada.
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  • ORCID record for Christiane E. Whitehouse
John D. Fisk
From the Departments of Psychology and Neuroscience (C.E.W., J.D.F., S.H.S.), Psychiatry (J.D.F.), and Medicine (J.D.F.), Dalhousie University; Nova Scotia Health Authority (J.D.F.), Halifax; Departments of Internal Medicine (C.N.B., J.J.M., C.A.P., C.A.H., R.A.M.), Psychiatry (J.M.B., J.S.), Clinical Health Psychology (L.A.G., J.R.W.), and Community Health Sciences (R.A.M.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg; and Department of Psychology (L.I.B.), St. Francis Xavier University, Antigonish, Canada.
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Charles N. Bernstein
From the Departments of Psychology and Neuroscience (C.E.W., J.D.F., S.H.S.), Psychiatry (J.D.F.), and Medicine (J.D.F.), Dalhousie University; Nova Scotia Health Authority (J.D.F.), Halifax; Departments of Internal Medicine (C.N.B., J.J.M., C.A.P., C.A.H., R.A.M.), Psychiatry (J.M.B., J.S.), Clinical Health Psychology (L.A.G., J.R.W.), and Community Health Sciences (R.A.M.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg; and Department of Psychology (L.I.B.), St. Francis Xavier University, Antigonish, Canada.
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Lindsay I. Berrigan
From the Departments of Psychology and Neuroscience (C.E.W., J.D.F., S.H.S.), Psychiatry (J.D.F.), and Medicine (J.D.F.), Dalhousie University; Nova Scotia Health Authority (J.D.F.), Halifax; Departments of Internal Medicine (C.N.B., J.J.M., C.A.P., C.A.H., R.A.M.), Psychiatry (J.M.B., J.S.), Clinical Health Psychology (L.A.G., J.R.W.), and Community Health Sciences (R.A.M.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg; and Department of Psychology (L.I.B.), St. Francis Xavier University, Antigonish, Canada.
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James M. Bolton
From the Departments of Psychology and Neuroscience (C.E.W., J.D.F., S.H.S.), Psychiatry (J.D.F.), and Medicine (J.D.F.), Dalhousie University; Nova Scotia Health Authority (J.D.F.), Halifax; Departments of Internal Medicine (C.N.B., J.J.M., C.A.P., C.A.H., R.A.M.), Psychiatry (J.M.B., J.S.), Clinical Health Psychology (L.A.G., J.R.W.), and Community Health Sciences (R.A.M.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg; and Department of Psychology (L.I.B.), St. Francis Xavier University, Antigonish, Canada.
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Lesley A. Graff
From the Departments of Psychology and Neuroscience (C.E.W., J.D.F., S.H.S.), Psychiatry (J.D.F.), and Medicine (J.D.F.), Dalhousie University; Nova Scotia Health Authority (J.D.F.), Halifax; Departments of Internal Medicine (C.N.B., J.J.M., C.A.P., C.A.H., R.A.M.), Psychiatry (J.M.B., J.S.), Clinical Health Psychology (L.A.G., J.R.W.), and Community Health Sciences (R.A.M.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg; and Department of Psychology (L.I.B.), St. Francis Xavier University, Antigonish, Canada.
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Carol A. Hitchon
From the Departments of Psychology and Neuroscience (C.E.W., J.D.F., S.H.S.), Psychiatry (J.D.F.), and Medicine (J.D.F.), Dalhousie University; Nova Scotia Health Authority (J.D.F.), Halifax; Departments of Internal Medicine (C.N.B., J.J.M., C.A.P., C.A.H., R.A.M.), Psychiatry (J.M.B., J.S.), Clinical Health Psychology (L.A.G., J.R.W.), and Community Health Sciences (R.A.M.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg; and Department of Psychology (L.I.B.), St. Francis Xavier University, Antigonish, Canada.
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James J. Marriott
From the Departments of Psychology and Neuroscience (C.E.W., J.D.F., S.H.S.), Psychiatry (J.D.F.), and Medicine (J.D.F.), Dalhousie University; Nova Scotia Health Authority (J.D.F.), Halifax; Departments of Internal Medicine (C.N.B., J.J.M., C.A.P., C.A.H., R.A.M.), Psychiatry (J.M.B., J.S.), Clinical Health Psychology (L.A.G., J.R.W.), and Community Health Sciences (R.A.M.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg; and Department of Psychology (L.I.B.), St. Francis Xavier University, Antigonish, Canada.
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Christine A. Peschken
From the Departments of Psychology and Neuroscience (C.E.W., J.D.F., S.H.S.), Psychiatry (J.D.F.), and Medicine (J.D.F.), Dalhousie University; Nova Scotia Health Authority (J.D.F.), Halifax; Departments of Internal Medicine (C.N.B., J.J.M., C.A.P., C.A.H., R.A.M.), Psychiatry (J.M.B., J.S.), Clinical Health Psychology (L.A.G., J.R.W.), and Community Health Sciences (R.A.M.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg; and Department of Psychology (L.I.B.), St. Francis Xavier University, Antigonish, Canada.
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Jitender Sareen
From the Departments of Psychology and Neuroscience (C.E.W., J.D.F., S.H.S.), Psychiatry (J.D.F.), and Medicine (J.D.F.), Dalhousie University; Nova Scotia Health Authority (J.D.F.), Halifax; Departments of Internal Medicine (C.N.B., J.J.M., C.A.P., C.A.H., R.A.M.), Psychiatry (J.M.B., J.S.), Clinical Health Psychology (L.A.G., J.R.W.), and Community Health Sciences (R.A.M.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg; and Department of Psychology (L.I.B.), St. Francis Xavier University, Antigonish, Canada.
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John R. Walker
From the Departments of Psychology and Neuroscience (C.E.W., J.D.F., S.H.S.), Psychiatry (J.D.F.), and Medicine (J.D.F.), Dalhousie University; Nova Scotia Health Authority (J.D.F.), Halifax; Departments of Internal Medicine (C.N.B., J.J.M., C.A.P., C.A.H., R.A.M.), Psychiatry (J.M.B., J.S.), Clinical Health Psychology (L.A.G., J.R.W.), and Community Health Sciences (R.A.M.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg; and Department of Psychology (L.I.B.), St. Francis Xavier University, Antigonish, Canada.
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Sherry H. Stewart
From the Departments of Psychology and Neuroscience (C.E.W., J.D.F., S.H.S.), Psychiatry (J.D.F.), and Medicine (J.D.F.), Dalhousie University; Nova Scotia Health Authority (J.D.F.), Halifax; Departments of Internal Medicine (C.N.B., J.J.M., C.A.P., C.A.H., R.A.M.), Psychiatry (J.M.B., J.S.), Clinical Health Psychology (L.A.G., J.R.W.), and Community Health Sciences (R.A.M.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg; and Department of Psychology (L.I.B.), St. Francis Xavier University, Antigonish, Canada.
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Ruth Ann Marrie
From the Departments of Psychology and Neuroscience (C.E.W., J.D.F., S.H.S.), Psychiatry (J.D.F.), and Medicine (J.D.F.), Dalhousie University; Nova Scotia Health Authority (J.D.F.), Halifax; Departments of Internal Medicine (C.N.B., J.J.M., C.A.P., C.A.H., R.A.M.), Psychiatry (J.M.B., J.S.), Clinical Health Psychology (L.A.G., J.R.W.), and Community Health Sciences (R.A.M.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg; and Department of Psychology (L.I.B.), St. Francis Xavier University, Antigonish, Canada.
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From the Departments of Psychology and Neuroscience (C.E.W., J.D.F., S.H.S.), Psychiatry (J.D.F.), and Medicine (J.D.F.), Dalhousie University; Nova Scotia Health Authority (J.D.F.), Halifax; Departments of Internal Medicine (C.N.B., J.J.M., C.A.P., C.A.H., R.A.M.), Psychiatry (J.M.B., J.S.), Clinical Health Psychology (L.A.G., J.R.W.), and Community Health Sciences (R.A.M.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg; and Department of Psychology (L.I.B.), St. Francis Xavier University, Antigonish, Canada.
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Comorbid anxiety, depression, and cognition in MS and other immune-mediated disorders
Christiane E. Whitehouse, John D. Fisk, Charles N. Bernstein, Lindsay I. Berrigan, James M. Bolton, Lesley A. Graff, Carol A. Hitchon, James J. Marriott, Christine A. Peschken, Jitender Sareen, John R. Walker, Sherry H. Stewart, Ruth Ann Marrie, for the CIHR Team in Defining the Burden and Managing the Effects of Psychiatric Comorbidity in Chronic Immunoinflammatory Disease
Neurology Jan 2019, 92 (5) e406-e417; DOI: 10.1212/WNL.0000000000006854

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Abstract

Objective To determine whether anxiety and depression are associated with cognition in multiple sclerosis (MS), and whether these associations are similar in other immune-mediated inflammatory diseases (IMID; including inflammatory bowel disease [IBD] and rheumatoid arthritis [RA]) and in anxious/depressed individuals (ANX/DEP) without an IMID.

Methods Participants (MS: n = 255; IBD: n = 247; RA: n = 154; ANX/DEP: n = 308) completed a structured psychiatric interview, the Hospital Anxiety and Depression Scale, and cognitive testing, including the Symbol Digit Modalities Test, the California Verbal Learning Test, and Letter Number Sequencing test. Test scores were converted to age-, sex-, and education-adjusted z scores. We evaluated associations of anxiety and depression with the cognitive z scores using multivariate linear models, adjusting for disease cohort.

Results All cohorts exhibited higher rates of impairment (i.e., z less than or equal to −1.5) in the domains of processing speed, verbal learning, and delayed recall memory relative to general population norms. Higher levels of anxiety symptoms were associated with slower processing speed, lower verbal learning, and lower working memory performance (all p < 0.001); higher levels of depression symptoms were associated with slower processing speed. These associations did not differ across cohorts.

Conclusion Anxiety and depression are associated with lower cognitive function in MS, with a similar pattern observed in persons with other IMID, including IBD and RA, and persons without an IMID. Managing symptoms of anxiety and of depression in MS, as well as other IMIDs, is important to mitigate their effect on cognition.

Glossary

ANCOVA=
analysis of covariance;
ANOVA=
analysis of variance;
ANX/DEP=
individuals with anxiety and depressive disorders;
CVLT-II=
California Verbal Learning Test, Second Edition;
DSM-IV=
Diagnostic and Statistical Manual of Mental Disorders, 4th edition;
HADS=
Hospital Anxiety and Depression Scale;
HADS-A=
Hospital Anxiety and Depression Scale–anxiety;
HADS-D=
Hospital Anxiety and Depression Scale–depression;
IBD=
inflammatory bowel disease;
IMID=
immune-mediated inflammatory disease;
LNS=
Letter Number Sequencing;
MANOVA=
multivariate analysis of variance;
MDD=
major depressive disorder;
MS=
multiple sclerosis;
RA=
rheumatoid arthritis;
SCID-IV=
Structured Clinical Interview for DSM-IV;
SDMT=
Symbol Digit Modalities Test;
WTAR=
Wechsler Test of Adult Reading

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • The CIHR Team coinvestigators are listed in Appendix 2 at the end of the article.

  • Editorial page 211

  • CME Course: NPub.org/cmelist

  • Received May 23, 2018.
  • Accepted in final form September 27, 2018.
  • © 2019 American Academy of Neurology
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Letters: Rapid online correspondence

  • Authors’ reply to Dr. Golan
    • Ruth Ann Marrie, Neurologist, University of Manitoba
    • Christiane Whitehouse, Graduate student, Dalhousie University
    • John Fisk, Neuropsychologist, Dalhousie University
    Submitted February 21, 2019
  • Anxiety and cognition association in immune-mediated inflammatory diseases may be confounded by disease severity
    • Daniel Golan, Senior Neurologist, Department of Neurology & Multiple Sclerosis Center, Lady Davis Carmel Medical Center (Haifa, Israel)
    Submitted January 25, 2019
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