title: Psychiatric Autoimmunity: N-Methyl-D-Aspartate Receptor IgG and Beyond.
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.
authors.affiliation: Department of Psychiatry and Psychology, College of Medicine, Mayo Clinic, Rochester, MN.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Kruse
authors.affiliation: Department of Psychiatry and Psychology, College of Medicine, Mayo Clinic, Rochester, MN.
authors.forename: Maria I
authors.initials: MI
authors.lastname: Lapid
authors.affiliation: Laboratory Medicine and Pathology, College of Medicine, Mayo Clinic, Rochester, MN; Department of Neurology, College of Medicine, Mayo Clinic, Rochester, MN; Department of Immunology, College of Medicine, Mayo Clinic, Rochester, MN.
authors.forename: Vanda A
authors.initials: VA
authors.lastname: Lennon
authors.affiliation: Laboratory Medicine and Pathology, College of Medicine, Mayo Clinic, Rochester, MN; Department of Neurology, College of Medicine, Mayo Clinic, Rochester, MN.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Klein
authors.affiliation: Department of Neurology, College of Medicine, Mayo Clinic, Rochester, MN.
authors.forename: Orna O'
authors.initials: OO
authors.lastname: Toole
authors.affiliation: Laboratory Medicine and Pathology, College of Medicine, Mayo Clinic, Rochester, MN; Department of Neurology, College of Medicine, Mayo Clinic, Rochester, MN.
authors.forename: Sean J
authors.initials: SJ
authors.lastname: Pittock
authors.affiliation: Department of Neurology, College of Medicine, Mayo Clinic, Rochester, MN.
authors.forename: Edythe A
authors.initials: EA
authors.lastname: Strand
authors.affiliation: Department of Psychiatry and Psychology, College of Medicine, Mayo Clinic, Rochester, MN.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Frye
authors.affiliation: Laboratory Medicine and Pathology, College of Medicine, Mayo Clinic, Rochester, MN; Department of Neurology, College of Medicine, Mayo Clinic, Rochester, MN. Electronic address: mckeon.andrew@mayo.edu.
authors.forename: Andrew
authors.initials: A
authors.lastname: McKeon
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D060426:Anti-N-Methyl-D-Aspartate Receptor Encephalitis / Q000276:immunology* / Q000523:psychology; D001008:Anxiety Disorders / Q000276:immunology / Q000523:psychology; D001323:Autoantibodies / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology / Q000523:psychology; D015551:Autoimmunity / Q000276:immunology; D001714:Bipolar Disorder / Q000276:immunology / Q000523:psychology; D020864:Calcium Channels, N-Type / Q000276:immunology*; D020865:Calcium Channels, P-Type / Q000276:immunology; D020907:Calcium Channels, Q-Type / Q000276:immunology; D016022:Case-Control Studies; D002389:Catatonia / Q000276:immunology / Q000523:psychology; D003866:Depressive Disorder / Q000276:immunology / Q000523:psychology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D001523:Mental Disorders / Q000276:immunology* / Q000523:psychology; D008875:Middle Aged; D024642:Potassium Channels, Voltage-Gated / Q000276:immunology*; D011618:Psychotic Disorders / Q000276:immunology / Q000523:psychology; D016194:Receptors, N-Methyl-D-Aspartate / Q000276:immunology; D012562:Schizophrenia, Disorganized / Q000276:immunology / Q000523:psychology; D059020:Suicidal Ideation; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D020864:Calcium Channels, N-Type; D020865:Calcium Channels, P-Type; D020907:Calcium Channels, Q-Type; D007074:Immunoglobulin G; D024642:Potassium Channels, Voltage-Gated; D016194:Receptors, N-Methyl-D-Aspartate