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The Emerging Concept of and Treatment Approaches for Autoimmune Psychosis

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Abstract

The etiology of severe mental illnesses (SMIs) of the schizophrenic and affective spectra still appears to be rather obscure. However, a small, emerging subgroup can now be diagnosed as autoimmune psychoses (AP), often presenting as schizophrenia-like psychosis, and can be successfully treated with various immune-modulatory treatments. These recent insights match the longer, previously defined, mild encephalitis hypothesis. Recently published consensus AP diagnostic criteria are comparable with autoimmune encephalitis criteria and are mainly based on the presence of neuronal autoantibodies in cerebrospinal fluid (CSF). Other forms of autoimmune-mediated psychiatric syndromes may present in context with systemic autoimmune diseases and yet unknown underlying causes. The frequent prevalence of minor CSF pathologies and postmortem findings of low-grade neuroinflammatory processes in a considerable subgroup of SMIs remains an intriguing challenge for further etiology-focused research, which should include immunogenetics, the role of infections and of the blood-brain barrier, and potentially, various types of immune-pathology beyond the important paraclinical methods, such as CSF diagnostics and neuroimaging.

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References

  1. Ellul P, Groc L, Tamouza R, Leboyer M. The clinical challenge of autoimmune psychosis: learning from anti-NMDA receptor autoantibodies. Front Psych. 2017;8 https://doi.org/10.3389/fpsyt.2017.00054.

  2. Al-Diwani A, Pollak TA, Langford AE, Lennox BR. Synaptic and neuronal autoantibody-associated psychiatric syndromes: controversies and hypotheses. Front Psych. 2017;8 https://doi.org/10.3389/fpsyt.2017.00013.

  3. Najjar S, Pahlajani S, Sanctis V de, Stern JNH, Najjar A, Chong D. Neurovascular unit dysfunction and blood–brain barrier hyperpermeability contribute to schizophrenia neurobiology: a theoretical integration of clinical and experimental evidence. Front Psych 2017. doi:https://doi.org/10.3389/fpsyt.2017.00083.

  4. Najjar S, Steiner J, Najjar A, Bechter K. A clinical approach to new-onset psychosis associated with immune dysregulation: the concept of autoimmune psychosis. J Neuroinflammation. 2018;15(1):40. https://doi.org/10.1186/s12974-018-1067-y.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Bechter K. Mild encephalitis underlying psychiatric disorders-a reconsideration and hypothesis exemplified on Borna disease. Neurol Psychiatry Brain Res. 2001;9:55–70.

    Google Scholar 

  6. Bechter K. Die milde Enzephalitishypothese--neue Befunde und Studien. Psychiatr Prax 2004;31 Suppl 1:S41–S43. doi:https://doi.org/10.1055/s-2004-828428.

  7. Bechter K. Updating the mild encephalitis hypothesis of schizophrenia. Prog Neuro-Psychopharmacol Biol Psychiatry. 2013;42:71–91. https://doi.org/10.1016/j.pnpbp.2012.06.019.

    Article  CAS  Google Scholar 

  8. Pollak TA, Lennox BR. Time for a change of practice: the real-world value of testing for neuronal autoantibodies in acute first-episode psychosis. BJPsych Open. 2018;4(4):262–4. https://doi.org/10.1192/bjo.2018.27.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Herken J, Prüss H. Red flags: clinical signs for identifying autoimmune encephalitis in psychiatric patients. Front Psych. 2017;8:25. https://doi.org/10.3389/fpsyt.2017.00025. eCollection 2017

    Article  Google Scholar 

  10. Mack A, Pfeiffer C, Schneider EM, Bechter K. Schizophrenia or atypical lupus erythematosus with predominant psychiatric manifestations over 25 years: case analysis and review. Front Psych. 2017;8:131. https://doi.org/10.3389/fpsyt.2017.00131. eCollection 2017

    Article  Google Scholar 

  11. Endres D, Lüngen E, Hasan A, Kluge M, Fröhlich S, Lewerenz J, Bschor T, Haußleiter IS, Juckel G, Then Bergh F, Ettrich B, Kertzscher L, Oviedo-Salcedo T, Handreka R, Lauer M, Winter K, Zumdick N, Drews A, Obrocki J, Yalachkov Y, Bubl A, von Podewils F, Schneider U, Szabo K, Mattern M, Philipsen A, Domschke K, Wandinger KP, Neyazi A, Stich O, Prüss H, Leypoldt F, Tebartz van Elst L. Clinical manifestations and immunomodulatory treatment experiences in psychiatric patients with suspected autoimmune encephalitis: a case series of 91 patients from Germany. Mol Psychiatry. 2022;27(3):1479–89. https://doi.org/10.1038/s41380-021-01396-4. Epub 2022 Jan 19

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Dalmau J. The case for autoimmune neurology. Neurol Neuroimmunol Neuroinflamm. 2017;4:e373. https://doi.org/10.1212/NXI.0000000000000373.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Graus F, Titulaer MJ, Balu R, Benseler S, Bien CG, Cellucci T, Cortese I, Dale RC, Gelfand JM, Geschwind M, Glaser CA, Honnorat J, Höftberger R, Iizuka T, Irani SR, Lancaster E, Leypoldt F, Prüss H, Rae-Grant A, Reindl M, Rosenfeld MR, Rostásy K, Saiz A, Venkatesan A, Vincent A, Wandinger KP, Waters P, Dalmau J. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol. 2016;15(4):391–404. https://doi.org/10.1016/S1474-4422(15)00401-9. Epub 2016 Feb 20

    Article  PubMed  PubMed Central  Google Scholar 

  14. Pollak TA, Lennox BR, Müller S, Benros ME, Prüss H, Tebartz van Elst L, Klein H, Steiner J, Frodl T, Bogerts B, Tian L, Groc L, Hasan A, Baune BT, Endres D, Haroon E, Yolken R, Benedetti F, Halaris A, Meyer JH, Stassen H, Leboyer M, Fuchs D, Otto M, Brown DA, Vincent A, Najjar S, Bechter K. Autoimmune psychosis: an international consensus on an approach to the diagnosis and management of psychosis of suspected autoimmune origin. Lancet Psychiatry. 2020;7(1):93–108. https://doi.org/10.1016/S2215-0366(19)30290-1. Epub 2019 Oct 24

    Article  PubMed  Google Scholar 

  15. Lennox BR, Coles AJ, Vincent A. Antibody-mediated encephalitis: a treatable cause of schizophrenia. Br J Psychiatry. 2012;200(2):92–4. https://doi.org/10.1192/bjp.bp.111.095042.

    Article  PubMed  Google Scholar 

  16. Steiner J, Schiltz K, Bernstein H-G, Bogerts B. Antineuronal antibodies against neurotransmitter receptors and synaptic proteins in schizophrenia: current knowledge and clinical implications. CNS Drugs. 2015;29(3):197–206. https://doi.org/10.1007/s40263-015-0233-3.

    Article  CAS  PubMed  Google Scholar 

  17. Prüss H. Autoantibodies in neurological disease. Nat Rev Immunol. 2021;21(12):798–813. https://doi.org/10.1038/s41577-021-00543-w. Epub 2021 May 11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Cannon TD. Microglial activation and the onset of psychosis. Am J Psychiatry. 2016;173(1):3–4. https://doi.org/10.1176/appi.ajp.2015.15111377.

    Article  PubMed  Google Scholar 

  19. Müller N. Neuroprogression in schizophrenia and psychotic disorders: the possible role of inflammation. Mod Trends Pharmacopsychiatry. 2017;31:1–9. https://doi.org/10.1159/000470802.

    Article  PubMed  Google Scholar 

  20. Drexhage HA. Editorial: activation and de-activation of inflammatory pathways. The disequilibrium of immune-neuro-endocrine networks in psychiatric disorders. Brain Behav Immun. 2019;78:5–6. https://doi.org/10.1016/j.bbi.2019.01.007.

    Article  CAS  PubMed  Google Scholar 

  21. Drexhage RC, Hoogenboezem TH, Versnel MA, Berghout A, Nolen WA, Drexhage HA. The activation of monocyte and T cell networks in patients with bipolar disorder. Brain Behav Immun. 2011;25(6):1206–13. https://doi.org/10.1016/j.bbi.2011.03.013.

    Article  CAS  PubMed  Google Scholar 

  22. Steiner J, Gos T, Bogerts B, Bielau H, Drexhage H, Bernstein H-G. Possible impact of microglial cells and the monocyte-macrophage system on suicidal behavior. CNS Neurol Disord Drug Targets. 2013;12(7):971–9. https://doi.org/10.2174/18715273113129990099.

    Article  CAS  PubMed  Google Scholar 

  23. Black JE, Kodish IM, Grossman AW, Klintsova AY, Orlovskaya D, Vostrikov V, Uranova N, Greenough WT. Pathology of layer V pyramidal neurons in the prefrontal cortex of patients with schizophrenia. Am J Psychiatry. 2004;161(4):742–4. https://doi.org/10.1176/appi.ajp.161.4.742.

    Article  PubMed  Google Scholar 

  24. Cai HQ, Catts VS, Webster MJ, Galletly C, Liu D, O'Donnell M, Weickert TW, Weickert CS. Increased macrophages and changed brain endothelial cell gene expression in the frontal cortex of people with schizophrenia displaying inflammation. Mol Psychiatry. 2020;25(4):761–75. https://doi.org/10.1038/s41380-018-0235-x. Epub 2018 Sep 13

    Article  CAS  PubMed  Google Scholar 

  25. Laskaris L, Zalesky A, Weickert CS, Di Biase MA, Chana G, Baune BT, Bousman C, Nelson B, McGorry P, Everall I, Pantelis C, Cropley V. Investigation of peripheral complement factors across stages of psychosis. Schizophr Res. 2019;204:30–7. https://doi.org/10.1016/j.schres.2018.11.035. Epub 2018 Dec 6

    Article  PubMed  Google Scholar 

  26. Maxeiner H-G, Rojewski MT, Schmitt A, Tumani H, Bechter K, Schmitt M. Flow cytometric analysis of T cell subsets in paired samples of cerebrospinal fluid and peripheral blood from patients with neurological and psychiatric disorders. Brain Behav Immun. 2009;23(1):134–42. https://doi.org/10.1016/j.bbi.2008.08.003.

    Article  CAS  PubMed  Google Scholar 

  27. Kuehne LK, Reiber H, Bechter K, Hagberg L, Fuchs D. Cerebrospinal fluid neopterin is brain-derived and not associated with blood-CSF barrier dysfunction in non-inflammatory affective and schizophrenic spectrum disorders. J Psychiatr Res. 2013;47(10):1417–22. https://doi.org/10.1016/j.jpsychires.2013.05.027.

    Article  PubMed  Google Scholar 

  28. Endres D, Meixensberger S, Dersch R, Feige B, Stich O, Venhoff N, Matysik M, Maier SJ, Michel M, Runge K, Nickel K, Urbach H, Domschke K, Prüss H, Tebartz van Elst L. Cerebrospinal fluid, antineuronal autoantibody, EEG, and MRI findings from 992 patients with schizophreniform and affective psychosis. Transl. Psychiatry. 2020;10(1):279. https://doi.org/10.1038/s41398-020-00967-3.

    Article  CAS  Google Scholar 

  29. Zetterberg H, Jakobsson J, Redsäter M, Andreasson U, Pålsson E, Ekman CJ, Sellgren C, Johansson AG, Blennow K, Landén M. Blood-cerebrospinal fluid barrier dysfunction in patients with bipolar disorder in relation to antipsychotic treatment. Psychiatry Res. 2014;217(3):143–6. https://doi.org/10.1016/j.psychres.2014.03.045. Epub 2014 Apr 5

    Article  CAS  PubMed  Google Scholar 

  30. Bechter K, Reiber H, Herzog S, Fuchs D, Tumani H, Maxeiner HG. Cerebrospinal fluid analysis in affective and schizophrenic spectrum disorders: identification of subgroups with immune responses and blood-CSF barrier dysfunction. J Psychiatr Res. 2010;44(5):321–30. https://doi.org/10.1016/j.jpsychires.2009.08.008.

    Article  CAS  PubMed  Google Scholar 

  31. Bechter K. CSF diagnostics in psychiatry – present status – future projects. Neurol Psychiatry Brain Res. 2016;22(2):69–74. https://doi.org/10.1016/j.npbr.2016.01.008.

    Article  Google Scholar 

  32. Andreassen OA, Harbo HF, Wang Y, Thompson WK, Schork AJ, Mattingsdal M, Zuber V, Bettella F, Ripke S, Kelsoe JR, Kendler KS, O’Donovan MC, Sklar P, Psychiatric Genomics Consortium (PGC) Bipolar Disorder and Schizophrenia Work Groups; International Multiple Sclerosis Genetics Consortium (IMSGC), McEvoy LK, Desikan RS, Lie BA, Djurovic S, Dale AM. Genetic pleiotropy between multiple sclerosis and schizophrenia but not bipolar disorder: differential involvement of immune-related gene loci. Mol Psychiatry. 2015;20(2):207–14. https://doi.org/10.1038/mp.2013.195. Epub 2014 Jan 28

    Article  CAS  PubMed  Google Scholar 

  33. Moises HW, Wollschläger D, Binder H. Functional genomics indicate that schizophrenia may be an adult vascular-ischemic disorder. Transl Psychiatry. 2015;5(8):e616. https://doi.org/10.1038/tp.2015.103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Meyer U. New serological evidence points toward an infectious route to bipolar disorder. Am J Psychiatry. 2014;171(5):485–8. https://doi.org/10.1176/appi.ajp.2014.14010095.

    Article  PubMed  Google Scholar 

  35. Prüss H. Postviral autoimmune encephalitis: manifestations in children and adults. Curr Opin Neurol. 2017;30(3):327–33. https://doi.org/10.1097/WCO.0000000000000445.

    Article  CAS  PubMed  Google Scholar 

  36. Thienemann M, Murphy T, Leckman J, Shaw R, Williams K, Kapphahn C, Frankovich J, Geller D, Bernstein G, Chang K, Elia J, Swedo S. Management of pediatric acute-onset neuropsychiatric syndrome: part I-psychiatric and behavioral interventions. J Child Adolesc Psychopharmacol. 2017;27(7):566–73. https://doi.org/10.1089/cap.2016.0145.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Spartz EJ, Freeman GM, Brown K, Farhadian B, Thienemann M, Frankovich J. Course of neuropsychiatric symptoms after introduction and removal of nonsteroidal anti-inflammatory drugs: a pediatric observational study. J Child Adolesc Psychopharmacol. 2017;27(7):652–9. https://doi.org/10.1089/cap.2016.0179.

    Article  CAS  PubMed  Google Scholar 

  38. Venkatesan A, Tunkel AR, Bloch KC, Lauring AS, Sejvar J, Bitnun A, et al. Case definitions, diagnostic algorithms, and priorities in encephalitis: consensus statement of the international encephalitis consortium. Clin Infect Dis. 2013;57(8):1114–28. https://doi.org/10.1093/cid/cit458.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Banks WA. The blood-brain barrier in neuroimmunology: Tales of separation and assimilation. Brain Behav Immun. 2015;44:1–8. https://doi.org/10.1016/j.bbi.2014.08.007.

    Article  CAS  PubMed  Google Scholar 

  40. Galea I, Perry VH. The blood-brain interface: a culture change. Brain Behav Immun. 2018;68:11–6. https://doi.org/10.1016/j.bbi.2017.10.014. Epub 2017 Oct 26

    Article  PubMed  Google Scholar 

  41. Endres D, von Zedtwitz K, Matteit I, Bünger I, Foverskov-Rasmussen H, Runge K, Feige B, Schlump A, Maier S, Nickel K, Berger B, Schiele MA, Cunningham JL, Domschke K, Prüss H, Tebartz van Elst L. Spectrum of novel anti-central nervous system autoantibodies in the cerebrospinal fluid of 119 patients with schizophreniform and affective disorders. Biol Psychiatry. 2022;92(4):261–74. https://doi.org/10.1016/j.biopsych.2022.02.010. Epub 2022 Feb 19

    Article  CAS  PubMed  Google Scholar 

  42. Duong SL, Prüss H. Molecular disease mechanisms of human antineuronal monoclonal autoantibodies. Trends Mol Med. 2022;S1471-4914(22):00259–3. https://doi.org/10.1016/j.molmed.2022.09.011.

    Article  CAS  Google Scholar 

  43. Endres D, Pollak TA, Bechter K, Denzel D, Pitsch K, Nickel K, Runge K, Pankratz B, Klatzmann D, Tamouza R, Mallet L, Leboyer M, Prüss H, Voderholzer U, Cunningham JL, ECNP Network Immuno-NeuroPsychiatry, Domschke K, Tebartz van Elst L, Schiele MA. Immunological causes of obsessive-compulsive disorder: is it time for the concept of an “autoimmune OCD” subtype? Transl. Psychiatry. 2022;12(1):5. https://doi.org/10.1038/s41398-021-01700-4.

    Article  Google Scholar 

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Authors and Affiliations

  1. Clinic for Psychiatry and Psychotherapy II, Ulm University, Bezirkskrankenhaus Günzburg, Günzburg, Germany

    Karl Bechter

  2. Department of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

    Dominique Endres

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  1. Karl Bechter
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Correspondence to Karl Bechter .

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Editors and Affiliations

  1. International Institute for Brain Health, Zagreb, Croatia

    Vida Demarin

  2. Department of Neuroscience, Università di Padova, Padova, Padova, Italy

    Leontino Battistin

  3. Department of Neurology, Sveti Duh University Hospital, Zagreb, Croatia

    Hrvoje Budinčević

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Bechter, K., Endres, D. (2023). The Emerging Concept of and Treatment Approaches for Autoimmune Psychosis. In: Demarin, V., Battistin, L., Budinčević, H. (eds) Mind, Brain and Education. Springer, Cham. https://doi.org/10.1007/978-3-031-33013-1_8

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