The Clinical Challenge of Autoimmune Psychosis: Learning from Anti-NMDA Receptor Autoantibodies

Steiner

et al. 2018

J Neuroinflammation

Growing data point to the overlap between psychosis and pathological processes associated with immunological dysregulation as well as inflammation. Notably, the recent discovery of antibodies against synaptic and neuronal cell membrane proteins such as anti-N-methyl-d-aspartate receptor provides more direct evidence of the etiological connection between autoimmunity and subsequent hazard of psychosis. Here, we advocate the use of term “autoimmune psychosis,” as this term suggests that autoimmune disorders can masquerade as drug-resistant primary psychosis, and this subtype of psychosis has anatomical and immunological footprints in the brain, despite the frequent absence of structural abnormalities on conventional brain MRI. Furthermore, this term might serve as a reminder not to overlook appropriate neurological workup such as neuroimaging and EEG testing, as well as CSF analysis, for cases with acute or subacute atypical onset of neuropsychiatric presentations including those dominated by acute psychotic symptoms. We propose etiologically and serologically oriented subclassification as well as multi-modal diagnostic approach to address some of the challenges inherent to early diagnosis of patients presenting with atypical and refractory new-onset psychotic symptoms of autoimmune origin. This is particularly relevant to the diagnosis of seronegative but probable autoimmune psychosis (SPAP) that might masquerade as antipsychotic drug-resistant primary psychotic disorder. This distinction is therapeutically important as autoimmune-related psychotic symptomatology can frequently respond well to timely treatment with proper immune modulatory therapies.

Section: Antibodies Against Neurotransmitter Receptors and Synaptic Pmentioning

confidence: 63%

Section: Antibodies Against Neurotransmitter Receptors and Synaptic Pmentioning

confidence: 99%

Section: Antibodies Against Neurotransmitter Receptors and Synaptic Pmentioning

confidence: 99%

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A clinical approach to new-onset psychosis associated with immune dysregulation: the concept of autoimmune psychosis

Steiner

et al. 2018

J Neuroinflammation

Eur Arch Psychiatry Clin Neurosci

“…Autoimmune psychosis (AP): AP describes a syndrome with predominant psychoses and a probable autoimmune pathophysiology [21,61,67]. Initially, a distinction among the following groups was suggested: (1) psychoses with detection of classical antineuronal Abs, (2) psychoses associated with systemic inflammatory and autoimmune diseases, and (3) Ab-negative AP [61].…”

Section: Box 1: Different Nomenclature [6 22]mentioning

confidence: 99%

Autoimmune encephalitis as a differential diagnosis of schizophreniform psychosis: clinical symptomatology, pathophysiology, diagnostic approach, and therapeutic considerations

Endres

Leypoldt

Bechter

et al. 2020

Primary schizophreniform psychoses are thought to be caused by complex gene-environment interactions. Secondary forms are based on a clearly identifiable organic cause, in terms of either an etiological or a relevant pathogenetic factor. The secondary or "symptomatic" forms of psychosis have reentered the focus stimulated by the discovery of autoantibody (Ab)associated autoimmune encephalitides (AEs), such as anti-NMDA-R encephalitis, which can at least initially mimic variants of primary psychosis. These newly described secondary, immune-mediated schizophreniform psychoses typically present with the acute onset of polymorphic psychotic symptoms. Over the course of the disease, other neurological phenomena, such as epileptic seizures, movement disorders, or reduced levels of consciousness, usually arise. Typical clinical signs for AEs are the acute onset of paranoid hallucinatory symptoms, atypical polymorphic presentation, psychotic episodes in the context of previous AE, and additional neurological and medical symptoms such as catatonia, seizure, dyskinesia, and autonomic instability. Predominant psychotic courses of AEs have also been described casuistically. The term autoimmune psychosis (AP) was recently suggested for these patients. Paraclinical alterations that can be observed in patients with AE/AP are inflammatory cerebrospinal fluid (CSF) pathologies, focal or generalized electroencephalographic slowing or epileptic activity, and/or suspicious "encephalitic" imaging findings. The antibody analyses in these patients include the testing of the most frequently found Abs against cell surface antigens (

“…Vaccine-induced GRA mediated GR dysfunction can explain a wide variety of disorders including autism (42), attention deficit hyperactivity (43,44), epilepsy (45,46), schizophrenia (47,48), autoimmune encephalitis (17,(49)(50)(51)(52), and psychosis (17,47,48,52,53).…”

Section: Neuropsychiatric Disordersmentioning

confidence: 99%

Role of NMDA receptor autoimmunity induced by food protein containing vaccines, in the etiology of autism, type 1 diabetes, neuropsychiatric and neurodegenerative disorders

2019

IJPR

Vaccines contain numerous animal and plant proteins (soy, peanut, sesame, maize, wheat, etc.). Vaccine excipients are derived from plant or animal sources. The mechanism of animal protein induced autoimmunity was previously described. Following a report associating maternal gluten intake to type 1 diabetes in the offspring, plant proteins were investigated. The Pandemrix vaccine induced narcolepsy due to molecular mimicry between a H1N1 nucleoprotein peptide in the vaccine and the human hypocretin receptor 2. The BLASTP match score for this peptide was used as a baseline. BLASTP showed strong sequence alignment between gliadin, a wheat protein, and the human ionotropic N-methyl-D-aspartate receptor (NMDAR). Analyzing further, strong sequence alignment was found between soy, peanut, sesame, maize, wheat and human glutamate receptors (GR), both ionotropic and metabotropic. There are reports of boosted wheat allergy and de novo synthesis of NMDAR antibodies following immunization. Once immunized with plant derived antigens, antibody levels will be increased by dietary exposure to these antigens. GR are expressed in the brain, heart, pancreas and the T cells of the immune system. Vaccine induced GR antibodies (GRA) disrupt or destroy GR thus precipitating numerous disorders. This explains the epidemic of food intolerances and food associated immune mediated disorders. Intestinal barrier disruption has been proposed as a cause for food associated autoimmune disorders. However, intestinal barrier disruption may itself be the result of GRA. GRA also disrupt the bloodbrain barrier. This allows other anti-brain antibodies access to their targets. Vaccine-induced GRA can therefore explain a wide variety of disorders including autism, type 1 diabetes, attention deficit hyperactivity, epilepsy, schizophrenia, autoimmune encephalitis, Huntington's, Parkinson's, dementia, cancer and allergies. The ultimate solution is to immediately remove all non-target proteins from all vaccines.