Hostname: page-component-848d4c4894-5nwft Total loading time: 0 Render date: 2024-05-25T14:08:10.762Z Has data issue: false hasContentIssue false
  • English
  • Français

Prevalence of serum anti-neuronal autoantibodies in patients admitted to acute psychiatric care

Published online by Cambridge University Press:  09 September 2016

M. Schou ,
S. G. Sæther ,
K. Borowski ,
B. Teegen ,
D. Kondziella ,
W. Stoecker ,
A. Vaaler  and
S. K. Reitan
M. Schou*
Affiliation:
Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway Department of Psychiatry, St Olavs University Hospital, Trondheim, Norway
S. G. Sæther
Affiliation:
Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway Department of Psychiatry, St Olavs University Hospital, Trondheim, Norway
K. Borowski
Affiliation:
Institute for Experimental Immunology, Euroimmun AG, Lübeck, Germany
B. Teegen
Affiliation:
Institute for Experimental Immunology, Euroimmun AG, Lübeck, Germany
D. Kondziella
Affiliation:
Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway Neurology Department, Rigshospitalet, Copenhagen, Denmark
W. Stoecker
Affiliation:
Institute for Experimental Immunology, Euroimmun AG, Lübeck, Germany
A. Vaaler
Affiliation:
Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway Department of Psychiatry, St Olavs University Hospital, Trondheim, Norway
S. K. Reitan
Affiliation:
Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway Department of Psychiatry, St Olavs University Hospital, Trondheim, Norway
*
*Address for correspondence: M. B. Schou, M.D., Department of Psychiatry, St Olavs Hospital HF avd Østmarka, Postboks 3250 Sluppen, 7006 Trondheim, Norway. (Email: morten.b.schou@ntnu.no)
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Autoimmune encephalitis associated with anti-neuronal antibodies may be challenging to distinguish from primary psychiatric disorders. The significance of anti-neuronal antibodies in psychiatric patients without clear evidence of autoimmune encephalitis is unknown. We investigated the serum prevalence of six anti-neuronal autoantibodies in a cohort of unselected patients admitted to acute psychiatric care.

Method

Serum was drawn from 925 patients admitted to acute psychiatric in-patient care. Psychiatric diagnoses were set according to International Classification of Diseases (ICD)-10 criteria. Antibody analysis was performed with an indirect immunofluorescence test for N-methyl d-aspartate receptor (NMDAR) antibodies and five other anti-neuronal autoantibodies of the immunoglobulin (Ig) classes IgA, IgG and IgM isotype.

Results

Anti-neuronal autoantibodies were found in 11.6% of patients: NMDAR antibodies in 7.6%, contactin-associated protein-like 2 (CASPR2) antibodies in 2.5%, glutamic acid decarboxylase-65 (GAD65) antibodies in 1.9%, and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antibodies in 0.1%. Leucine-rich glioma-inactivated protein-1 (LGI1) and γ-aminobutyric acid B (GABAB) receptor antibodies were not detected. NMDAR antibodies of class IgG were present in five patients only (0.5%). NMDAR antibodies of all Ig classes were equally prevalent in patients with and without psychosis. There were no significant differences in antibody prevalence in the different diagnostic categories, except for a higher odds ratio of being NMDAR antibody positive for patients without a specific psychiatric diagnosis.

Conclusions

NMDAR IgG autoantibodies, which are known to be strongly associated with anti-NMDAR encephalitis, were rarely found. CASPR2 and GAD65 antibodies were more frequently encountered in the present study than previously reported. Further research on the clinical significance of anti-neuronal autoantibodies in patients with acute psychiatric symptoms is needed.

Keywords

AntibodiesautoimmunityN-methyl D-aspartate (NMDA) receptorpsychiatry
Type
Original Articles
Information
Psychological Medicine , Volume 46 , Issue 16 , December 2016 , pp. 3303 - 3313
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

Bagoien, G, Bjorngaard, JH, Ostensen, C, Reitan, SK, Romundstad, P, Morken, G (2013). The effects of motivational interviewing on patients with comorbid substance use admitted to a psychiatric emergency unit – a randomised controlled trial with two year follow-up. BMC Psychiatry 13, 93.Google Scholar
Barry, H, Hardiman, O, Healy, DG, Keogan, M, Moroney, J, Molnar, PP, Cotter, DR, Murphy, KC (2011). Anti-NMDA receptor encephalitis: an important differential diagnosis in psychosis. British Journal of Psychiatry 199, 508–509.CrossRefGoogle ScholarPubMed
Bergink, V, Armangue, T, Titulaer, MJ, Markx, S, Dalmau, J, Kushner, SA (2015). Autoimmune encephalitis in postpartum psychosis. American Journal of Psychiatry 172, 901–908.CrossRefGoogle ScholarPubMed
Busse, S, Busse, M, Brix, B, Probst, C, Genz, A, Bogerts, B, Stoecker, W, Steiner, J (2014). Seroprevalence of N-methyl-d-aspartate glutamate receptor (NMDA-R) autoantibodies in aging subjects without neuropsychiatric disorders and in dementia patients. European Archives of Psychiatry and Clinical Neuroscience 264, 545–550.Google Scholar
Chapman, MR, Vause, HE (2011). Anti-NMDA receptor encephalitis: diagnosis, psychiatric presentation, and treatment. American Journal of Psychiatry 168, 245–251.Google Scholar
Cohen, BJ, McGarvey, EL, Pinkerton, RC, Kryzhanivska, L (2004). Willingness and competence of depressed and schizophrenic inpatients to consent to research. Journal of the American Academy of Psychiatry and the Law 32, 134–143.Google Scholar
Dahm, L, Ott, C, Steiner, J, Stepniak, B, Teegen, B, Saschenbrecker, S, Hammer, C, Borowski, K, Begemann, M, Lemke, S, Rentzsch, K, Probst, C, Martens, H, Wienands, J, Spalletta, G, Weissenborn, K, Stocker, W, Ehrenreich, H (2014). Seroprevalence of autoantibodies against brain antigens in health and disease. Annals of Neurology 76, 82–94.Google Scholar
Dalmau, J, Gleichman, AJ, Hughes, EG, Rossi, JE, Peng, X, Lai, M, Dessain, SK, Rosenfeld, MR, Balice-Gordon, R, Lynch, DR (2008). Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurology 7, 1091–1098.CrossRefGoogle ScholarPubMed
De Witte, LD, Hoffmann, C, Van Mierlo, HC, Titulaer, MJ, Kahn, RS, Martinez-Martinez, P; European Consortium of Autoimmune Mental Disorders (CAIMED) (2015). Absence of N-methyl-d-aspartate receptor IgG autoantibodies in schizophrenia: the importance of cross-validation studies. JAMA Psychiatry 72, 731–733.CrossRefGoogle ScholarPubMed
Dogan Onugoren, M, Deuretzbacher, D, Haensch, CA, Hagedorn, HJ, Halve, S, Isenmann, S, Kramme, C, Lohner, H, Melzer, N, Monotti, R, Presslauer, S, Schabitz, WR, Steffanoni, S, Stoeck, K, Strittmatter, M, Stogbauer, F, Trinka, E, Von Oertzen, TJ, Wiendl, H, Woermann, FG, Bien, CG (2015). Limbic encephalitis due to GABAB and AMPA receptor antibodies: a case series. Journal of Neurology, Neurosurgery, and Psychiatry 86, 965–972.CrossRefGoogle ScholarPubMed
Doss, S, Wandinger, KP, Hyman, BT, Panzer, JA, Synofzik, M, Dickerson, B, Mollenhauer, B, Scherzer, CR, Ivinson, AJ, Finke, C, Schöls, L, Müller Vom Hagen, J, Trenkwalder, C, Jahn, H, Höltje, M, Biswal, BB, Harms, L, Ruprecht, K, Buchert, R, Höglinger, GU, Oertel, WH, Unger, MM, Körtvélyessy, P, Bittner, D, Priller, J, Spruth, EJ, Paul, F, Meisel, A, Lynch, DR, Dirnagl, U, Endres, M, Teegen, B, Probst, C, Komorowski, L, Stöcker, W, Dalmau, J, Prüss, H (2014). High prevalence of NMDA receptor IgA/IgM antibodies in different dementia types. Annals of Clinical and Translational Neurology 1, 822–832.CrossRefGoogle ScholarPubMed
Endres, D, Perlov, E, Baumgartner, A, Hottenrott, T, Dersch, R, Stich, O, Tebartz Van Elst, L (2015). Immunological findings in psychotic syndromes: a tertiary care hospital's CSF sample of 180 patients. Frontiers in Human Neuroscience 9, 476.Google Scholar
Hammer, C, Stepniak, B, Schneider, A, Papiol, S, Tantra, M, Begemann, M, Sirén, AL, Pardo, LA, Sperling, S, Mohd Jofrry, S, Gurvich, A, Jensen, N, Ostmeier, K, Lühder, F, Probst, C, Martens, H, Gillis, M, Saher, G, Assogna, F, Spalletta, G, Stöcker, W, Schulz, TF, Nave, KA, Ehrenreich, H (2014). Neuropsychiatric disease relevance of circulating anti-NMDA receptor autoantibodies depends on blood–brain barrier integrity. Molecular Psychiatry 19, 1143–1149.Google Scholar
Höftberger, R, Van Sonderen, A, Leypoldt, F, Houghton, D, Geschwind, M, Gelfand, J, Paredes, M, Sabater, L, Saiz, A, Titulaer, MJ, Graus, F, Dalmau, J (2015). Encephalitis and AMPA receptor antibodies: novel findings in a case series of 22 patients. Neurology 84, 2403–2412.CrossRefGoogle Scholar
Huda, S, Wong, SH, Pettingill, P, O'Connell, D, Vincent, A, Steiger, M (2015). An 11-year retrospective experience of antibodies against the voltage-gated potassium channel (VGKC) complex from a tertiary neurological centre. Journal of Neurology 262, 418–424.Google Scholar
Irani, SR, Alexander, S, Waters, P, Kleopa, KA, Pettingill, P, Zuliani, L, Peles, E, Buckley, C, Lang, B, Vincent, A (2010). Antibodies to Kv1 potassium channel-complex proteins leucine-rich, glioma inactivated 1 protein and contactin-associated protein-2 in limbic encephalitis, Morvan's syndrome and acquired neuromyotonia. Brain 133, 2734–2748.CrossRefGoogle ScholarPubMed
Jørgensen, A, Hansen, BS, Stanislaus, S, Düring, S, Jørgensen, MB, Pinborg, LH, Kondziella, D (2015). Anti-N-methyl-d-aspartate receptor encephalitis is an important differential diagnosis in acute psychiatric disease. Acta Psychiatrica Scandinavica 131, 69–70.Google Scholar
Kawasaki, E (2014). Type 1 diabetes and autoimmunity. Clinical Pediatric Endocrinology 23, 99–105.CrossRefGoogle ScholarPubMed
Kayser, MS, Kohler, CG, Dalmau, J (2010). Psychiatric manifestations of paraneoplastic disorders. American Journal of Psychiatry 167, 1039–1050.Google Scholar
Kayser, MS, Titulaer, MJ, Gresa-Arribas, N, Dalmau, J (2013). Frequency and characteristics of isolated psychiatric episodes in anti-N-methyl-d-aspartate receptor encephalitis. JAMA Neurology 70, 1133–1139.CrossRefGoogle ScholarPubMed
Klein, CJ, Lennon, VA, Aston, PA, McKeon, A, O'Toole, O, Quek, A, Pittock, SJ (2013). Insights from LGI1 and CASPR2 potassium channel complex autoantibody subtyping. JAMA Neurology 70, 229–234.CrossRefGoogle ScholarPubMed
Kohigashi, M, Kitabayashi, Y, Okamura, A, Nakamura, M, Hoshiyama, A, Kunizawa, M, Futori, K, Kitabayashi, M, Narumoto, J, Fukui, K (2013). Relationship between patients’ quality of life and coercion in psychiatric acute wards. Psychiatry Research 208, 88–90.Google Scholar
Krishnamoorthy, ES, Trimble, MR, Blumer, D (2007). The classification of neuropsychiatric disorders in epilepsy: a proposal by the ILAE Commission on Psychobiology of Epilepsy. Epilepsy and Behavior 10, 349–353.CrossRefGoogle ScholarPubMed
Malter, MP, Helmstaedter, C, Urbach, H, Vincent, A, Bien, CG (2010). Antibodies to glutamic acid decarboxylase define a form of limbic encephalitis. Annals of Neurology 67, 470–478.CrossRefGoogle ScholarPubMed
Manto, M, Honnorat, J, Hampe, CS, Guerra-Narbona, R, López-Ramos, JC, Delgado-García, JM, Saitow, F, Suzuki, H, Yanagawa, Y, Mizusawa, H, Mitoma, H (2015). Disease-specific monoclonal antibodies targeting glutamate decarboxylase impair GABAergic neurotransmission and affect motor learning and behavioral functions. Frontiers in Behavioral Neuroscience 9, 78.Google Scholar
Mordal, J, Medhus, S, Holm, B, Morland, J, Bramness, JG (2013). Influence of drugs of abuse and alcohol upon patients admitted to acute psychiatric wards: physician's assessment compared to blood drug concentrations. Journal of Clinical Psychopharmacology 33, 415–419.Google Scholar
Padmos, RC, Bekris, L, Knijff, EM, Tiemeier, H, Kupka, RW, Cohen, D, Nolen, WA, Lernmark, A, Drexhage, HA (2004). A high prevalence of organ-specific autoimmunity in patients with bipolar disorder. Biological Psychiatry 56, 476–482.Google Scholar
Paterson, RW, Zandi, MS, Armstrong, R, Vincent, A, Schott, JM (2014). Clinical relevance of positive voltage-gated potassium channel (VGKC)-complex antibodies: experience from a tertiary referral centre. Journal of Neurology, Neurosurgery, and Psychiatry 85, 625–630.CrossRefGoogle ScholarPubMed
Pathmanandavel, K, Starling, J, Merheb, V, Ramanathan, S, Sinmaz, N, Dale, RC, Brilot, F (2015). Antibodies to surface dopamine-2 receptor and N-methyl-d-aspartate receptor in the first episode of acute psychosis in children. Biological Psychiatry 77, 537–547.Google Scholar
Pollak, TA, McCormack, R, Peakman, M, Nicholson, TR, David, AS (2014). Prevalence of anti-N-methyl-d-aspartate (NMDA) receptor [corrected] antibodies in patients with schizophrenia and related psychoses: a systematic review and meta-analysis. Psychological Medicine 44, 2475–2487.Google Scholar
Probst, C, Saschenbrecker, S, Stoecker, W, Komorowski, L (2014). Anti-neuronal autoantibodies: current diagnostic challenges. Multiple Sclerosis and Related Disorders 3, 303–320.Google Scholar
Prüss, H, Finke, C, Höltje, M, Hofmann, J, Klingbeil, C, Probst, C, Borowski, K, Ahnert-Hilger, G, Harms, L, Schwab, JM, Ploner, CJ, Komorowski, L, Stoecker, W, Dalmau, J, Wandinger, KP (2012 a). N-methyl-d-aspartate receptor antibodies in herpes simplex encephalitis. Annals of Neurology 72, 902–911.Google Scholar
Prüss, H, Höltje, M, Maier, N, Gomez, A, Buchert, R, Harms, L, Ahnert-Hilger, G, Schmitz, D, Terborg, C, Kopp, U, Klingbeil, C, Probst, C, Kohler, S, Schwab, JM, Stoecker, W, Dalmau, J, Wandinger, KP (2012 b). IgA NMDA receptor antibodies are markers of synaptic immunity in slow cognitive impairment. Neurology 78, 1743–1753.Google Scholar
Somers, KJ, Lennon, VA, Rundell, JR, Pittock, SJ, Drubach, DA, Trenerry, MR, Lachance, DH, Klein, CJ, Aston, PA, McKeon, A (2011). Psychiatric manifestations of voltage-gated potassium-channel complex autoimmunity. Journal of Neuropsychiatry and Clinical Neurosciences 23, 425–433.CrossRefGoogle ScholarPubMed
Steiner, J, Teegen, B, Schiltz, K, Bernstein, HG, Stoecker, W, Bogerts, B (2014). Prevalence of N-methyl-d-aspartate receptor autoantibodies in the peripheral blood: healthy control samples revisited. JAMA Psychiatry 71, 838–839.CrossRefGoogle ScholarPubMed
Steiner, J, Walter, M, Glanz, W, Sarnyai, Z, Bernstein, HG, Vielhaber, S, Kastner, A, Skalej, M, Jordan, W, Schiltz, K, Klingbeil, C, Wandinger, KP, Bogerts, B, Stoecker, W (2013). Increased prevalence of diverse N-methyl-d-aspartate glutamate receptor antibodies in patients with an initial diagnosis of schizophrenia: specific relevance of IgG NR1a antibodies for distinction from N-methyl-d-aspartate glutamate receptor encephalitis. JAMA Psychiatry 70, 271–278.Google Scholar
Tidswell, J, Kleinig, T, Ash, D, Thompson, P, Galletly, C (2013). Early recognition of anti-N-methyl d-aspartate (NMDA) receptor encephalitis presenting as acute psychosis. Australasian Psychiatry 21, 596–599.Google Scholar
Vaaler, AE, Morken, G, Iversen, VC, Kondziella, D, Linaker, OM (2010). Acute unstable depressive syndrome (AUDS) is associated more frequently with epilepsy than major depression. BMC Neurology 10, 67.Google Scholar
Van Mierlo, HC, Titulaer, MJ, Kromkamp, M, Van De Kraats, R, Van Veelen, NM, Palmen, SJ, Kahn, RS, De Witte, LD (2015). Early recognition of anti-N-methyl-d-aspartate receptor encephalitis in psychiatric patients. Acta Psychiatrica Scandinavica 132, 312–313.Google Scholar
Waters, P, Reindl, M, Saiz, A, Schanda, K, Tuller, F, Kral, V, Nytrova, P, Sobek, O, Nielsen, HH, Barington, T, Lillevang, ST, Illes, Z, Rentzsch, K, Berthele, A, Berki, T, Granieri, L, Bertolotto, A, Giometto, B, Zuliani, L, Hamann, D, Van Pelt, ED, Hintzen, R, Höftberger, R, Costa, C, Comabella, M, Montalban, X, Tintoré, M, Siva, A, Altintas, A, Deniz, G, Woodhall, M, Palace, J, Paul, F, Hartung, HP, Aktas, O, Jarius, S, Wildemann, B, Vedeler, C, Ruiz, A, Leite, MI, Trillenberg, P, Probst, M, Saschenbrecker, S, Vincent, A, Marignier, R (2016). Multicentre comparison of a diagnostic assay: aquaporin-4 antibodies in neuromyelitis optica. Journal of Neurology, Neurosurgery, and Psychiatry 87, 1005–1015.CrossRefGoogle ScholarPubMed
World Health Organization (1993). The ICD-10 Classification of Mental and Behavioural Disorders: Diagnostic Criteria for Research. World Health Organization: Geneva, Switzerland.Google Scholar
Zandi, MS, Deakin, JB, Morris, K, Buckley, C, Jacobson, L, Scoriels, L, Cox, AL, Coles, AJ, Jones, PB, Vincent, A, Lennox, BR (2014). Immunotherapy for patients with acute psychosis and serum N-methyl d-aspartate receptor (NMDAR) antibodies: a description of a treated case series. Schizophrenia Research 160, 193–195.Google Scholar
Zandi, MS, Irani, SR, Lang, B, Waters, P, Jones, PB, McKenna, P, Coles, AJ, Vincent, A, Lennox, BR (2011). Disease-relevant autoantibodies in first episode schizophrenia. Journal of Neurology 258, 686–688.Google Scholar
Supplementary material: Image

Schou supplementary material

Figure S1

Download Schou supplementary material(Image)
Image 317.2 KB
Supplementary material: File

Schou supplementary material

Tables S1A-S1B

Download Schou supplementary material(File)
File 36.4 KB
Supplementary material: File

Schou supplementary material

Table S2

Download Schou supplementary material(File)
File 54.3 KB