title: Autoantibodies to central nervous system neuronal surface antigens: psychiatric symptoms and psychopharmacological implications.
abstract: BACKGROUND
  Autoantibodies to central nervous system (CNS) neuronal surface antigens have been described in association with autoimmune encephalopathies which prominently feature psychiatric symptoms in addition to neurological symptoms. The potential role of these autoantibodies in primary psychiatric diseases such as schizophrenia or bipolar affective disorder is of increasing interest.
  
  
  OBJECTIVE
  We aimed to review the nature of psychiatric symptoms associated with neuronal surface autoantibodies, in the context of autoimmune encephalopathies as well as primary psychiatric disorders, and to review the mechanisms of action of these autoantibodies from a psychopharmacological perspective.
  
  
  RESULTS
  The functional effects of the autoantibodies on their target antigens are described; their clinical expression is at least in part mediated by their effects on neuronal receptor function, primarily at the synapse, usually resulting in receptor hypofunction. The psychiatric effects of the antibodies are related to known functions of the receptor target or its complexed proteins, with reference to supportive genetic and pharmacological evidence where relevant. Evidence for a causal role of these autoantibodies in primary psychiatric disease is increasing but remains controversial; relevant methodological controversies are outlined. Non-receptor-based mechanisms of autoantibody action, including neuroinflammatory mechanisms, and therapeutic implications are discussed.
  
  
  CONCLUSIONS
  An analysis of the autoantibodies from a psychopharmacological perspective, as endogenous, bioactive, highly specific, receptor-targeting molecules, provides a valuable opportunity to understand the neurobiological basis of associated psychiatric symptoms. Potentially, new treatment strategies will emerge from the improving understanding of antibody-antigen interaction within the CNS.
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's Health Partners, King's College London, De Crespigny Park, Denmark Hill, London, SE5 8AF, UK. thomas.pollak@kcl.ac.uk.
authors.forename: T A
authors.identifier: http://orcid.org/0000-0002-6171-0810
authors.initials: TA
authors.lastname: Pollak
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's Health Partners, King's College London, De Crespigny Park, Denmark Hill, London, SE5 8AF, UK.
authors.forename: K
authors.initials: K
authors.lastname: Beck
authors.affiliation: Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, UK.
authors.forename: S R
authors.initials: SR
authors.lastname: Irani
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's Health Partners, King's College London, De Crespigny Park, Denmark Hill, London, SE5 8AF, UK.
authors.forename: O D
authors.initials: OD
authors.lastname: Howes
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's Health Partners, King's College London, De Crespigny Park, Denmark Hill, London, SE5 8AF, UK.
authors.forename: A S
authors.initials: AS
authors.lastname: David
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's Health Partners, King's College London, De Crespigny Park, Denmark Hill, London, SE5 8AF, UK.
authors.forename: P K
authors.initials: PK
authors.lastname: McGuire
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D002490:Central Nervous System / Q000276:immunology*; D006801:Humans; D001523:Mental Disorders / Q000276:immunology* / Q000523:psychology*; D009474:Neurons / Q000276:immunology*; D011600:Psychopharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000276:immunology
chemical_list: D000954:Antigens, Surface; D001323:Autoantibodies; D016194:Receptors, N-Methyl-D-Aspartate
keywords: Antibody; GABA receptor; Immunoreactivity; Inflammation; Limbic system; NMDA receptor; Potassium channel; Receptor