Mood Disorders in Systemic Lupus Erythematousus (SLE): Results from an International, Inception Cohort Study

John G. Hanly for the Systemic Lupus International Collaborating Clinics¹, Li Su², Murray Urowitz³, Juanita Romero-Diaz⁴, Caroline Gordon⁵, Sang-Cheol Bae⁶, Sasha R Bernatsky⁷, Ann E. Clarke⁸, Daniel J. Wallace⁹, Joan T. Merrill¹⁰, David A. Isenberg¹¹, Anisur Rahman¹², Ellen M. Ginzler¹³, Paul Fortin¹⁴, Dafna D. Gladman¹⁵, Jorge Sanchez-Guerrero¹⁶, Michelle Petri¹⁷, Ian Bruce¹⁸, Mary Anne Dooley¹⁹, Rosalind Ramsey-Goldman²⁰, Cynthia Aranow²¹, Graciela S. Alarcon²², Barri J. Fessler²³, Kristján Steinsson²⁴, Ola Nived²⁵, Gunnar K. Sturfelt²⁵, Susan Manzi²⁶, Munther A. Khamashta²⁷, Ronald F. van Vollenhoven²⁸, Asad Zoma²⁹, Manuel Ramos-Casals³⁰, Guillermo Ruiz-Irastorza³¹, S. Sam Lim³², Thomas Stoll³³, Murat Inanc³⁴, Kenneth C. Kalunian³⁵, Diane L. Kamen³⁶, Peter Maddison³⁷, Christine A. Peschken³⁸, Søren Jacobsen³⁹, Anca Askanase⁴⁰, Jill P. Buyon⁴¹, Chris Theriault⁴², Kara Thompson⁴² and Vernon Farewell², ¹Division of Rheumatology, Dalhousie University and Capital Health, Nova Scotia, Canada, Halifax, NS, Canada, ²MRC Biostatistics Unit, Institute of Public Health, University Forvie Site, Cambridge, United Kingdom, ³Medicine, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital and University of Toronto, Toronto, ON, Canada, ⁴Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutricion, Mexico city, Mexico, ⁵Rheumatology Research Group, School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom, ⁶Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea, ⁷Division of Rheumatology and Clinical Epidemiology, McGill University, Montreal, Quebec, QC, Canada, ⁸Division of Rheumatology, University of Calgary, Alberta, Calgary, AB, Canada, ⁹Rheumatology, Cedars-Sinai/David Geffen School of Medicine at UCLA, Los Angeles, CA, ¹⁰Department of Clinical Pharmacology, Oklahoma Medical Research Foundation, Oklahoma City, OK, ¹¹Centre for Rheumatology Research, Rayne Building, 4th Floor, Centre for Rheumatology, Department of Medicine, University College London, London, United Kingdom, ¹²Centre for Rheumatology Research, University College London, London, United Kingdom, ¹³Rheumatology, SUNY-Downstate Medical Center, Brooklyn, NY, ¹⁴Medicine, Division of Rheumatology, Centre Hospitalier Universitaire de Quebec et Universite Laval, Quebec, QC, Canada, ¹⁵University of Toronto, Toronto Western Hospital, Toronto, ON, Canada, ¹⁶Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital and University of Toronto, Toronto, ON, Canada, ¹⁷Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, ¹⁸Kellgren Centre for Rheum, Arthritis Research UK Epidemiology Unit, Institution of Inflammation and Repair, University of Manchester, NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospitals, Manchester Academic Health Sciences Centre, Manchester, United Kingdom, ¹⁹Thurston Arthritis Research Center, University of North Carolina, Chapel Hill, NC, ²⁰Rheumatology, Northwestern University and Feinberg School of Medicine, Chicago, IL, ²¹Feinstein Institute for Medical Research, Mahasset, NY, ²²Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, ²³Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, ²⁴Centre for Rheumatology Research, Landspital University Hospital, Reykjavik, Iceland, ²⁵Department of Rheumatology, University Hospital Lund, Lund, Sweden, ²⁶Division of Rheumatology, University of Pittsburgh School of Medicine, Pittsburgh, PA, ²⁷Lupus Research Unit, The Rayne Institute, St Thomas Hospital, Kings College London School of Medicine, London, United Kingdom, ²⁸Unit for clinical therapy research (ClinTrid), Karolinska Institute, Stockholm, Sweden, ²⁹Lanarkshire Centre for Rheumatology, Hairmyres Hospital, East Kilbride, United Kingdom, ³⁰Josep Font Autoimmune Diseases Laboratory, IDIBAPS, Department of Autoimmune Diseases, Hospital Clinic, Barcelona, Spain, ³¹Autoimmune Diseases Research Unit, Department of Internal Medicine, BioCruces Health Research Institute, Hospital Universitario Cruces, University of the Basque Country, Barakaldo, Spain, ³²Emory University School of Medicine, Division of Rheumatology, Atlanta, GA, ³³Kantonsspital Geissbergstr, Schaffhausen, Switzerland, ³⁴Rheumatology, Division of Rheumatology, Department of Internal Medicine, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey, ³⁵UCSD School of Medicine, La Jolla, CA, ³⁶Department of Medicine, Division of Rheumatology, Medical University of South Carolina, Charleston, SC, ³⁷Ysbyty Gwynedd Bangor, North Wales, United Kingdom, ³⁸University of Manitoba, Canada, Winnipeg, MB, Canada, ³⁹Department of Rheumatology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark, ⁴⁰Columbia University Medical Center, New York, NY, ⁴¹Department of Medicine, Division of Rheumatology, New York University School of Medicine, New York, NY, ⁴²Department of Medicine, Queen Elizabeth II Health Sciences Centre and Dalhousie University, Halifax, NS, Canada

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: depression, neuropsychiatric disorders and systemic lupus erythematosus (SLE)

Session Information

Title: Systemic Lupus Erythematosus - Clinical Aspects and Treatment: Epidemiology, Women's Health, Cardiovascular and CNS

Session Type: Abstract Submissions (ACR)

Background/Purpose: Neuropsychiatric (NP) events in patients with SLE include mood disorders. We determined the frequency, characteristics, clinical and autoantibody associations of mood disorders in a large, multi-ethnic/racial, inception cohort of SLE patients.

Methods: A prospective study of new onset SLE patients was performed by an international network of 32 academic centers in 11 countries. Patients were evaluated at enrollment and annually for up to 14 years. Data were collected at each assessment on demographic and clinical manifestations, medications, SLE disease activity index-2000 (SLEDAI-2K) and Systemic Lupus International Collaborating Clinics (SLICC)/ACR damage index (SDI). Nervous system events were recorded using the ACR case definitions for 19 NP syndromes. These include mood disorders, determined by clinical judgment (based on Diagnostic and Statistical Manual, DSM-IV, criteria) and consisting of: (i) major depressive-like episode, (ii) mood disorder with depressive features, (iii) mood disorder with manic features and (iv) mood disorder with mixed features. Lupus anticoagulant, IgG autoantibodies to cardiolipin, β₂-glycoprotein I, ribosomal P and NMDA glutamate receptor 2 were measured at enrollment. Pre-defined rules determined the attribution of NP events to SLE and non-SLE causes. Cox regression was used to examine the associations of various factors with the occurrence of first mood disorder and first SLE-attributed mood disorder.

Results: Of 1,827 SLE patients, 88.9% were female, 48.9% Caucasian with mean±SD age 35.1±13.3 years. At enrollment, mean SLE duration was 5.6±4.8 months, SLEDAI-2K was 5.3±5.4, SDI was 0.31±0.74. The mean follow-up was 4.73±3.45 years. Over the study 863 (47.2%) patients had 1,627 NP events of which 503 (30.9%) were attributed to SLE. Mood disorders were the second most frequent NP event: 232 patients experienced 256 mood disorders of which 98/256 (38.3%) were attributed to SLE. The predominant mood disorders were major depressive-like episodes [134/256 (52.3%)], followed by mood disorder with depressive features [114/256 (44.5%)] and the remaining two mood disorders accounted for only 8/256 (0.03%) events. The estimated cumulative incidence of any mood disorder and any SLE-attributed mood disorder after 10 years was 17.7% (95%CI=[15.1%,20.2%]) and 7.9% (95%CI=[6.0%,9.9%]), respectively. A total of 110/256 (43.0%) mood disorders occurred in isolation without other concurrent NP events. Multivariate regression revealed a greater risk of mood disorder in patients with other concurrent NP events (p≤0.01) and a lower risk with Asian race/ethnicity (p=0.01) and immunosuppressive drugs taken in the absence of antidepressants (p=0.003). No association was found between mood disorders and SLEDAI-2K, SDI scores or lupus autoantibodies, whether or not the analysis was confined to mood disorders attributed to SLE.

Conclusion: Mood disorders are the second most frequent NP event in SLE patients and about one third are attributable to lupus. The lack of association of most mood disorders with global SLE disease activity, cumulative organ damage and lupus autoantibodies emphasize their multifactorial etiology and a role for non-lupus specific therapies.

Disclosure:

J. G. Hanly for the Systemic Lupus International Collaborating Clinics,
None;

L. Su,
None;

M. Urowitz,
None;

J. Romero-Diaz,
None;

C. Gordon,
None;

S. C. Bae,
None;

S. R Bernatsky,
None;

A. E. Clarke,
None;

D. J. Wallace,
None;

J. T. Merrill,
None;

D. A. Isenberg,
None;

A. Rahman,
None;

E. M. Ginzler,
None;

P. Fortin,
None;

D. D. Gladman,
None;

J. Sanchez-Guerrero,
None;

M. Petri,
None;

I. Bruce,
None;

M. A. Dooley,
None;

R. Ramsey-Goldman,
None;

C. Aranow,
None;

G. S. Alarcon,
None;

B. J. Fessler,
None;

K. Steinsson,
None;

O. Nived,
None;

G. K. Sturfelt,
None;

S. Manzi,
None;

M. A. Khamashta,
None;

R. F. van Vollenhoven,
None;

A. Zoma,
None;

M. Ramos-Casals,
None;

G. Ruiz-Irastorza,
None;

S. S. Lim,
None;

T. Stoll,
None;

M. Inanc,
None;

K. C. Kalunian,
None;

D. L. Kamen,
None;

P. Maddison,
None;

C. A. Peschken,
None;

S. Jacobsen,
None;

A. Askanase,
None;

J. P. Buyon,
None;

C. Theriault,
None;

K. Thompson,
None;

V. Farewell,
None.

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