Autoimmune neuropsychiatric disorders manifesting with psychosis
José Maria Cabrera-Maqueda, Jesús Planagumà, Mar Guasp, Josep Dalmau
José Maria Cabrera-Maqueda, Jesús Planagumà, Mar Guasp, Josep Dalmau
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Review

Autoimmune neuropsychiatric disorders manifesting with psychosis

Abstract

The increasing recognition of a new category of encephalitides that occur in association with antibodies against neuronal surface proteins has prompted the use of terms like “autoimmune psychosis” and “autoimmune psychiatric disorders.” However, although psychosis and other psychiatric symptoms can occur in autoimmune encephalitides and systemic autoimmune diseases, evidence for a distinct psychiatric entity beyond these conditions is lacking. A particularly defining condition is anti-NMDA receptor encephalitis, which has been central to promoting concepts such as autoimmune psychosis and autoimmune psychiatric disorders. While anti-NMDA receptor encephalitis can resemble primary psychiatric conditions, certain clinical features often suggest the specific diagnosis. This Review traces the development of the autoimmune psychosis concept and examines the implications of framing it as a separate entity. We discuss leading theories of psychosis and the convergence of the NMDA receptor hypofunction/glutamate hypothesis with anti-NMDA receptor encephalitis mechanisms. The interest generated by such disorders has driven uncontrolled antibody testing in psychiatric populations, often neglecting pretest probability and favoring prevalence over diagnostic specificity. Finally, we highlight the main limitations of current approaches and propose directions for future research.

Authors

José Maria Cabrera-Maqueda, Jesús Planagumà, Mar Guasp, Josep Dalmau

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Figure 3

Tests and samples used in studies of neuronal autoantibodies.

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Tests and samples used in studies of neuronal autoantibodies. (A and B) ...
(A and B) Number of studies examining neuronal autoantibodies in patients with psychiatric disorders (A) or first episode of psychosis (B), categorized by the techniques used: cell-based assay (CBA), tissue-based assay (TBA), or live immunocytochemistry on cultured neurons (LN). (C and D) Number of tests (CBA and/or TBA) performed and corresponding diagnoses in patients with psychiatric disorders and NMDAR antibodies in serum (C) or CSF (D). (E and F) Number of tests (CBA and/or TBA) performed and corresponding diagnoses in patients with first episode of psychosis and NMDAR antibodies in serum (E) or CSF (F). No studies reporting NMDAR antibodies in patients with psychiatric disorders or first episode of psychosis have systematically used the three indicated techniques. Notably, all individuals with NMDAR antibodies detected in CSF, regardless of whether they were initially diagnosed with a psychiatric disorder or first episode of psychosis, were ultimately found to have anti-NMDAR encephalitis and were mostly treated with immunotherapy. In contrast, patients with NMDAR antibodies only in serum (either not tested in CSF or CSF negative), without clinical or paraclinical features of anti-NMDAR encephalitis, typically exhibited symptoms similar to antibody-negative individuals and usually received standard psychiatric care. NMDARE, anti-NMDA receptor encephalitis.