Hostname: page-component-586b7cd67f-dlnhk Total loading time: 0 Render date: 2024-11-27T21:52:20.140Z Has data issue: false hasContentIssue false
  • English
  • Français

Schizophrenia among patients with systemic lupus erythematosus: population-based cross-sectional study

Published online by Cambridge University Press:  26 July 2016

S. Tiosano Open the ORCID record for S. Tiosano [Opens in a new window] ,
A. Farhi ,
A. Watad ,
N. Grysman ,
R. Stryjer ,
H. Amital ,
D. Comaneshter ,
A. D. Cohen  and
D. Amital
S. Tiosano
Affiliation:
Department of Medicine ‘B’, Sheba Medical Center, Tel-Hashomer, Israel Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
A. Farhi
Affiliation:
Department of Medicine ‘B’, Sheba Medical Center, Tel-Hashomer, Israel Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
A. Watad
Affiliation:
Department of Medicine ‘B’, Sheba Medical Center, Tel-Hashomer, Israel Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
N. Grysman
Affiliation:
Department of Medicine ‘B’, Sheba Medical Center, Tel-Hashomer, Israel Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
R. Stryjer
Affiliation:
Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel Beer-Yaakov Mental Health Center, Israel
H. Amital*
Affiliation:
Department of Medicine ‘B’, Sheba Medical Center, Tel-Hashomer, Israel Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
D. Comaneshter
Affiliation:
Chief Physician's Office, Clalit Health Services Tel Aviv, Tel-Aviv, Israel
A. D. Cohen
Affiliation:
Chief Physician's Office, Clalit Health Services Tel Aviv, Tel-Aviv, Israel Faculty of Health Sciences, Siaal Research Center for Family Medicine and Primary Care, Ben Gurion University of the Negev, Beer Sheva, Israel
D. Amital
Affiliation:
Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel Beer-Yaakov Mental Health Center, Israel
*
*Address for correspondence: H. Amital, Department of Medicine ‘B’, Sheba Medical Center, Tel-Hashomer, 5262100, Israel. (Email: [email protected])
Get access Rights & Permissions [Opens in a new window]

Abstract

Aims.

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease involving multiple organs, including the central nervous system. Evidence of immune dysfunction exists also in schizophrenia, a psychiatric illness involving chronic or recurrent psychosis. The aim of our study was to investigate if there is an epidemiological association between SLE and schizophrenia.

Method.

A cross-sectional study was conducted comparing patients with SLE with age and gender-matched controls regarding the proportion of patients with comorbid schizophrenia. χ2- and t-tests were used for univariate analysis, and interaction of schizophrenia with SLE across strata of covariates was checked. A logistic regression model was used for multivariate analysis. The study was performed utilising the medical database of Clalit Health Services in Israel.

Results.

The study included 5018 patients with SLE and 25 090 controls. SLE patients had a female predominance, and a higher proportion of smoking compared with age and sex-matched controls. In multivariate analysis, SLE was found to be independently associated with schizophrenia while controlling for age, gender, socioeconomic status (SES) and smoking (OR 1.33, p = 0.042).

Conclusions.

We found a positive association between SLE and schizophrenia across patients of different age, gender and SES. This association can contribute to understanding the pathophysiology of the two disorders and may also have clinical implications for earlier as well as better diagnosis and treatment.

Keywords

Autoimmune diseaseautoimmunitypsychosisSLESchizophrenia
Type
Original Articles
Information
Epidemiology and Psychiatric Sciences , Volume 26 , Issue 4 , August 2017 , pp. 424 - 429
Copyright
Copyright © Cambridge University Press 2016 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Adams, DD, Knight, JG, Ebringer, A (2012). The autoimmune model of schizophrenia. ISRN Psychiatry 2012, 758072.CrossRefGoogle ScholarPubMed
Asano, NMJ, Coriolano, M das GW de S, Asano, BJ, Lins, OG (2013). Psychiatric comorbidities in patients with systemic lupus erythematosus: a systematic review of the last 10 years. Revista Brasileira De Reumatologia 53, 431–437.Google ScholarPubMed
Benros, ME, Mortensen, PB, Eaton, WW (2012). Autoimmune diseases and infections as risk factors for schizophrenia. Annals of the New York Academy of Sciences 1262, 56–66.CrossRefGoogle ScholarPubMed
Bieber, V, Cohen, AD, Freud, T, Agmon-Levin, N, Gertel, S, Amital, H (2013). Autoimmune smoke and fire-coexisting rheumatoid arthritis and chronic obstructive pulmonary disease: a cross-sectional analysis. Immunologic Research 56, 261–266.CrossRefGoogle ScholarPubMed
Dickinson, D, Bellack, AS, Gold, JM (2007). Social/communication skills, cognition, and vocational functioning in schizophrenia. Schizophrenia Bulletin 33, 1213–1220.CrossRefGoogle ScholarPubMed
Farhi, A, Cohen, AD, Shovman, O, Comaneshter, D, Amital, H, Amital, D (2016). Bipolar disorder associated with rheumatoid arthritis: a case–control study. Journal of Affective Disorders 189, 287–289.CrossRefGoogle ScholarPubMed
Goldsmith, C-AW, Rogers, DP (2008). The case for autoimmunity in the etiology of schizophrenia. Pharmacotherapy 28, 730–741.CrossRefGoogle ScholarPubMed
Guy, A, Tiosano, S, Comaneshter, D, Tekes-Manova, D, Shovman, O, Cohen, AD, Amital, H (2016). Aortic aneurysm association with SLE – a case–control study. Lupus 25, 959–963.CrossRefGoogle ScholarPubMed
Hanly, JG, Su, L, Urowitz, MB, Romero-Diaz, J, Gordon, C, Bae, S-C, Bernatsky, S, Clarke, AE, Wallace, DJ, Merrill, JT, Isenberg, DA, Rahman, A, Ginzler, EM, Petri, M, Bruce, IN, Dooley, MA, Fortin, P, Gladman, DD, Sanchez-Guerrero, J, Steinsson, K, Ramsey-Goldman, R, Khamashta, MA, Aranow, C, Alarcón, GS, Fessler, BJ, Manzi, S, Nived, O, Sturfelt, GK, Zoma, AA, van Vollenhoven, RF, Ramos-Casals, M, Ruiz-Irastorza, G, Lim, SS, Kalunian, KC, Inanc, M, Kamen, DL, Peschken, CA, Jacobsen, S, Askanase, A, Theriault, C, Thompson, K, Farewell, V (2015). Mood disorders in systemic lupus erythematosus: results from an international inception cohort study. Arthritis and Rheumatology (Hoboken, NJ) 67, 1837–1847.CrossRefGoogle ScholarPubMed
Ho, RC, Thiaghu, C, Ong, H, Lu, Y, Ho, CS, Tam, WW, Zhang, MW (2016). A meta-analysis of serum and cerebrospinal fluid autoantibodies in neuropsychiatric systemic lupus erythematosus. Autoimmunity Reviews 15, 124–138.CrossRefGoogle ScholarPubMed
Houri Levi, E, Watad, A, Whitby, A, Tiosano, S, Comaneshter, D, Cohen, AD, Amital, H (2016). Coexistence of ischemic heart disease and rheumatoid arthritis patients – a case control study. Autoimmunity Reviews 15, 393–396.CrossRefGoogle ScholarPubMed
Inês, L, Silva, C, Galindo, M, López-Longo, FJ, Terroso, G, Romão, VC, Rúa-Figueroa, I, Santos, MJ, Pego-Reigosa, JM, Nero, P, Cerqueira, M, Duarte, C, Miranda, LC, Bernardes, M, Gonçalves, MJ, Mouriño-Rodriguez, C, Araújo, F, Raposo, A, Barcelos, A, Couto, M, Abreu, P, Otón-Sanchez, T, Macieira, C, Ramos, F, Branco, JC, Silva, JAP, Canhão, H, Calvo-Alén, J, Rheumatic Diseases Registry of the Portuguese Society of Rheumatology, & Registry of Systemic Lupus Erythematosus Patients of the Spanish Society of Rheumatology (2015). Classification of systemic lupus erythematosus: systemic lupus international collaborating clinics versus American college of rheumatology criteria. A comparative study of 2,055 patients from a real-life, international systemic lupus erythematosus cohort. Arthritis Care and Research 67, 1180–1185.CrossRefGoogle Scholar
Jones, AL, Mowry, BJ, Pender, MP, Greer, JM (2005). Immune dysregulation and self-reactivity in schizophrenia: do some cases of schizophrenia have an autoimmune basis? Immunology and Cell Biology 83, 9–17.CrossRefGoogle ScholarPubMed
Jones, AL, Holliday, EG, Mowry, BJ, McLean, DE, McGrath, JJ, Pender, MP, Greer, JM (2009). CTLA-4 single-nucleotide polymorphisms in a Caucasian population with schizophrenia. Brain Behavior and Immunity 23, 347–350.CrossRefGoogle Scholar
Jones, AL, Mowry, BJ, McLean, DE, Mantzioris, BX, Pender, MP, Greer, JM (2014). Elevated levels of autoantibodies targeting the M1 muscarinic acetylcholine receptor and neurofilament medium in sera from subgroups of patients with schizophrenia. Journal of Neuroimmunology 269, 68–75.CrossRefGoogle ScholarPubMed
Laskaris, LE, Di Biase, MA, Everall, I, Chana, G, Christopoulos, A, Skafidas, E, Cropley, VL, Pantelis, C (2016). Microglial activation and progressive brain changes in schizophrenia. British Journal of Pharmacology 173, 666–680.CrossRefGoogle ScholarPubMed
Levite, M (2014). Glutamate receptor antibodies in neurological diseases: anti-AMPA-GluR3 antibodies, anti-NMDA-NR1 antibodies, anti-NMDA-NR2A/B antibodies, anti-mGluR1 antibodies or anti-mGluR5 antibodies are present in subpopulations of patients with either: epilepsy, encephalitis, cerebellar ataxia, systemic lupus erythematosus (SLE) and neuropsychiatric SLE, Sjogren's syndrome, schizophrenia, mania or stroke. These autoimmune anti-glutamate receptor antibodies can bind neurons in few brain regions, activate glutamate receptors, decrease glutamate receptor's expression, impair glutamate-induced signaling and function, activate blood brain barrier endothelial cells, kill neurons, damage the brain, induce behavioral/psychiatric/cognitive abnormalities and ataxia in animal models, and can be removed or silenced in some patients by immunotherapy. Journal of Neural Transmission (Vienna, Austria: 1996) 121, 1029–1075.CrossRefGoogle ScholarPubMed
Petri, M, Orbai, A-M, Alarcón, GS, Gordon, C, Merrill, JT, Fortin, PR, Bruce, IN, Isenberg, D, Wallace, DJ, Nived, O, Sturfelt, G, Ramsey-Goldman, R, Bae, S-C, Hanly, JG, Sánchez-Guerrero, J, Clarke, A, Aranow, C, Manzi, S, Urowitz, M, Gladman, D, Kalunian, K, Costner, M, Werth, VP, Zoma, A, Bernatsky, S, Ruiz-Irastorza, G, Khamashta, MA, Jacobsen, S, Buyon, JP, Maddison, P, Dooley, MA, van Vollenhoven, RF, Ginzler, E, Stoll, T, Peschken, C, Jorizzo, JL, Callen, JP, Lim, SS, Fessler, BJ, Inanc, M, Kamen, DL, Rahman, A, Steinsson, K, Franks, AG, Sigler, L, Hameed, S, Fang, H, Pham, N, Brey, R, Weisman, MH, McGwin, G, Magder, LS (2012). Derivation and validation of the systemic lupus international collaborating clinics classification criteria for systemic lupus erythematosus. Arthritis and Rheumatism 64, 2677–2686.CrossRefGoogle ScholarPubMed
Réus, GZ, Fries, GR, Stertz, L, Badawy, M, Passos, IC, Barichello, T, Kapczinski, F, Quevedo, J (2015). The role of inflammation and microglial activation in the pathophysiology of psychiatric disorders. Neuroscience 300, 141–154.CrossRefGoogle Scholar
Rogers, DP, Goldsmith, C-AW (2009). Treatment of schizophrenia in the 21st Century: beyond the neurotransmitter hypothesis. Expert Review of Neurotherapeutics 9, 47–54.CrossRefGoogle ScholarPubMed
Somers, EC, Marder, W, Cagnoli, P, Lewis, EE, DeGuire, P, Gordon, C, Helmick, CG, Wang, L, Wing, JJ, Dhar, JP, Leisen, J, Shaltis, D, McCune, WJ (2014). Population-based incidence and prevalence of systemic lupus erythematosus: the Michigan Lupus Epidemiology and Surveillance program. Arthritis and Rheumatology (Hoboken, NJ) 66, 369–378.CrossRefGoogle ScholarPubMed
Strous, RD, Shoenfeld, Y (2006). Schizophrenia, autoimmunity and immune system dysregulation: a comprehensive model updated and revisited. Journal of Autoimmunity 27, 71–80.CrossRefGoogle ScholarPubMed
Tandon, R, Keshavan, MS, Nasrallah, HA (2008). Schizophrenia, ‘just the facts’ what we know in 2008. 2. Epidemiology and etiology. Schizophrenia Research 102, 1–18.CrossRefGoogle ScholarPubMed
Urowitz, MB, Gladman, DD, Ibañez, D, Sanchez-Guerrero, J, Romero-Diaz, J, Gordon, C, Bae, S-C, Clarke, AE, Bernatsky, S, Fortin, PR, Hanly, JG, Isenberg, D, Rahman, A, Wallace, DJ, Ginzler, E, Petri, M, Bruce, IN, Merrill, JT, Nived, O, Sturfelt, G, Dooley, MA, Alarcón, GS, Fessler, B, Steinsson, K, Ramsey-Goldman, R, Zoma, A, Khamashta, M, Manzi, S, van Vollenhoven, R, Ramos-Casals, M, Aranow, C, Stoll, T (2014). American College of Rheumatology criteria at inception, and accrual over 5 years in the SLICC inception cohort. Journal of Rheumatology 41, 875–880.CrossRefGoogle ScholarPubMed
Watad, A, Cohen, AD, Comaneshter, D, Tekes-Manova, D, Amital, H (2016 a). Hyperthyroidism association with SLE, lessons from real-life data – a case–control study. Autoimmunity 49, 17–20.CrossRefGoogle ScholarPubMed
Watad, A, Mahroum, N, Whitby, A, Gertel, S, Comaneshter, D, Cohen, AD, Amital, H (2016 b). Hypothyroidism among SLE patients: case–control study. Autoimmunity Reviews 15, 484–486.CrossRefGoogle ScholarPubMed
Wolfe, F, Walitt, BT, Katz, RS, Häuser, W (2014). Symptoms, the nature of fibromyalgia, and diagnostic and statistical manual 5 (DSM-5) defined mental illness in patients with rheumatoid arthritis and fibromyalgia. PLoS ONE 9, e88740.CrossRefGoogle ScholarPubMed
Zardi, EM, Taccone, A, Marigliano, B, Margiotta, DPE, Afeltra, A (2014). Neuropsychiatric systemic lupus erythematosus: tools for the diagnosis. Autoimmunity Reviews 13, 831–839.CrossRefGoogle ScholarPubMed