RESIDENT: Anti-Neuronal Cell Surface Antibodies in Treatment Resistant Schizophrenia

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Presenting Author(s): Dr. Mark Colijn

Co-Author(s): Zahinoor Ismail

Date and time: 23 Mar 2019 from 14:30 to 14:50

Location: Hawthorn C  Floor Map


  1. To provide an overview of the relationship between autoimmunity and schizophrenia;
  2. To highlight the relevance of screening for anti-neuronal antibodies in treatment resistant schizophrenia;
  3. To discuss the clinical implications of such research, and future directions.

Literature References

  1. Khandaker GM, Cousins L, Deakin J, Lennox BR, Yolken R, Jones PB. Inflammation and immunity in schizophrenia: implications for
    pathophysiology and treatment. Lancet Psychiatry. 2015;2(3):258-70. doi: 10.1016/S2215-0366(14)00122-9. PubMed PMID: 26359903;
    PubMed Central PMCID: PMCPMC4595998.
  2. Hao Q, Wang D, Guo L, Zhang B. Clinical characterization of autoimmune encephalitis and psychosis. Compr Psychiatry. 2017;74:9-
    14. doi: 10.1016/j.comppsych.2016.12.006. PubMed PMID: 28081431.
  3. Ezeoke A, Mellor A, Buckley P, Miller B. A systematic, quantitative review of blood autoantibodies in schizophrenia. Schizophr Res.
    2013;150(1):245-51. doi: 10.1016/j.schres.2013.07.029. PubMed PMID: 23953827.
  4. Pearlman DM, Najjar S. Meta-analysis of the association between N-methyl-d-aspartate receptor antibodies and schizophrenia,
    schizoaffective disorder, bipolar disorder, and major depressive disorder. Schizophr Res. 2014;157(1-3):249-58. doi:
    10.1016/j.schres.2014.05.001. PubMed PMID: 24882425.
  5. Pollak TA, McCormack R, Peakman M, Nicholson TR, David AS. Prevalence of anti-N-methyl-D-aspartate (NMDA) receptor
    [corrected] antibodies in patients with schizophrenia and related psychoses: a systematic review and meta-analysis. Psychol Med.
    2014;44(12):2475-87. doi: 10.1017/S003329171300295X. PubMed PMID: 24330811.
  6. Grain R, Lally J, Stubbs B, Malik S, LeMince A, Nicholson TR, et al. Autoantibodies against voltage-gated potassium channel and
    glutamic acid decarboxylase in psychosis: A systematic review, meta-analysis, and case series. Psychiatry Clin Neurosci.
    2017;71(10):678-89. doi: 10.1111/pcn.12543. PubMed PMID: 28573688.


Schizophrenia is a phenotypically heterogenous, and poorly understood disorder. While its aetiology is likely multifactorial, immune
system dysfunction has increasingly been implicated in its development. As psychotic symptoms occur frequently and prominently in
autoimmune encephalitis (AE), and given that psychosis may be the first clinical manifestation of the illness, concerns exist that AE may
be misdiagnosed as schizophrenia in a small subset of individuals. Although there is some evidence to suggest that misdiagnosis may
occur in rare cases, the majority of existing studies have primarily included a first episode sample, and have relied exclusively on serum
testing, rather than on CSF testing (which is both more sensitive and specific), making interpretation of the results difficult. This pilot
study is designed to cross sectionally determine the prevalence of anti-neuronal cell surface antibodies commonly implicated in AE, in
both the serum and CSF of 75 treatment resistant schizophrenia patients; a likely enriched population with respect to the presence of
such antibodies. A neurological control group is included for comparison. This study has significant clinical implications, as positive
results should alert psychiatrists to the possibility that a small subset of patients with treatment resistant schizophrenia may actually
have AE. Moreover, phenotypic characterization of positive cases may allow for improved identification of such patients. This is clinically
important as it may allow such individuals to receive more appropriate/effective immune related treatments, such as steroids, IVIG, or
plasmapheresis, and prevent them from continually being unnecessarily exposed to the adverse effects of antipsychotic medications.

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