Psychiatric Autoimmunity: N-Methyl-D-Aspartate Receptor IgG and Beyond

Psychosomatics. May-Jun 2015;56(3):227-41. doi: 10.1016/j.psym.2015.01.003. Epub 2015 Feb 4.

Abstract

Background: Descriptions of psychiatric autoimmunity beyond N-methyl-D-aspartate (NMDA) receptor encephalitis are sparse.

Objective: To report the autoimmune psychiatric spectrum currently recognized in Mayo Clinic practice.

Methods: Medical record review, testing of stored serum and cerebrospinal fluid for IgGs reactive with synaptic receptors and ion channels, neuronal nuclear and cytoplasmic antigens (including glutamic acid decarboxylase 65-kDa isoform) and case-control comparison were conducted. Patients were categorized into group 1, all adult psychiatric inpatients tested for neural autoantibodies (2002-2011; n = 213), and group 2, all Mayo NMDA receptor IgG-positive patients (2009-2013; n = 13); healthy control subjects were also included (n = 173).

Results: In group 1, at least 1 serum autoantibody (but not NMDA receptor IgG) was detected in 36 of 213 psychiatric inpatients. In total, 12 patients were determined retrospectively to have high-likelihood autoimmune encephalitic diagnoses. The most commonly detected autoantibody specificities were voltage-gated potassium channel ([Kv1] VGKC) complex (6) and calcium channel (P/Q type or N type; 5). Symptoms seen were as follows: depressive (8), anxious (7), psychotic (7), disorganized (5), suicidal (3), manic (1) and catatonic (1). In group 2, among 13 NMDA receptor IgG-positive patients, 12 had encephalitis; their psychiatric symptoms were as follows: depressive (9), catatonic (9), disorganized (8), anxious (8), psychotic (7), manic (6), and suicidal (3). Catatonic symptoms were more common in the 12 NMDA receptor IgG-positive patients than in the 12 group 1 patients with high likelihood of encephalitis (p = 0.002). Antibody positivities were usually low positive in value among healthy controls (12 of 16 vs 3 of 12 group 1 encephalitis cases, p = 0.025). NMDA receptor IgG was not detected in any healthy control subject.

Conclusions: A spectrum of psychiatric autoimmunity beyond NMDA-R IgG may be under-recognized. Diagnosis is facilitated by combining results of comprehensive psychiatric, laboratory, radiologic, and electrophysiologic evaluations.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-N-Methyl-D-Aspartate Receptor Encephalitis / immunology*
  • Anti-N-Methyl-D-Aspartate Receptor Encephalitis / psychology
  • Anxiety Disorders / immunology
  • Anxiety Disorders / psychology
  • Autoantibodies / immunology*
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / psychology
  • Autoimmunity / immunology
  • Bipolar Disorder / immunology
  • Bipolar Disorder / psychology
  • Calcium Channels, N-Type / immunology*
  • Calcium Channels, P-Type / immunology
  • Calcium Channels, Q-Type / immunology
  • Case-Control Studies
  • Catatonia / immunology
  • Catatonia / psychology
  • Depressive Disorder / immunology
  • Depressive Disorder / psychology
  • Female
  • Humans
  • Immunoglobulin G / immunology
  • Male
  • Mental Disorders / immunology*
  • Mental Disorders / psychology
  • Middle Aged
  • Potassium Channels, Voltage-Gated / immunology*
  • Psychotic Disorders / immunology
  • Psychotic Disorders / psychology
  • Receptors, N-Methyl-D-Aspartate / immunology
  • Schizophrenia, Disorganized / immunology
  • Schizophrenia, Disorganized / psychology
  • Suicidal Ideation
  • Young Adult

Substances

  • Autoantibodies
  • Calcium Channels, N-Type
  • Calcium Channels, P-Type
  • Calcium Channels, Q-Type
  • Immunoglobulin G
  • Potassium Channels, Voltage-Gated
  • Receptors, N-Methyl-D-Aspartate