Psychiatric Autoimmunity

N-Methyl-d-Aspartate Receptor IgG and Beyond

Jennifer L. Kruse, Maria Isabel Lapid, Vanda A Lennon, Christopher Jon Klein, Orna O. Toole, Sean J Pittock, Edythe A. Strand, Mark A Frye, Andrew B McKeon

Research output: Contribution to journalArticle

21 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)227-241
Number of pages15
JournalPsychosomatics
Volume56
Issue number3
DOIs
StatePublished - May 1 2015

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Autoimmunity
Psychiatry
N-Methyl-D-Aspartate Receptors
Immunoglobulin G
Encephalitis
Autoantibodies
Inpatients
Healthy Volunteers
Q-Type Calcium Channels
P-Type Calcium Channels
Voltage-Gated Potassium Channels
Nuclear Antigens
Neurotransmitter Receptor
Glutamate Decarboxylase
N-Methylaspartate
aspartic acid receptor
Serum
Ion Channels
Medical Records
Cerebrospinal Fluid

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Applied Psychology
  • Arts and Humanities (miscellaneous)

Cite this

Psychiatric Autoimmunity : N-Methyl-d-Aspartate Receptor IgG and Beyond. / Kruse, Jennifer L.; Lapid, Maria Isabel; Lennon, Vanda A; Klein, Christopher Jon; Toole, Orna O.; Pittock, Sean J; Strand, Edythe A.; Frye, Mark A; McKeon, Andrew B.

In: Psychosomatics, Vol. 56, No. 3, 01.05.2015, p. 227-241.

Research output: Contribution to journalArticle

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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.",
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AU - Lapid, Maria Isabel

AU - Lennon, Vanda A

AU - Klein, Christopher Jon

AU - Toole, Orna O.

AU - Pittock, Sean J

AU - Strand, Edythe A.

AU - Frye, Mark A

AU - McKeon, Andrew B

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N2 - 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.

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