title: Is it time for immunopsychiatry in psychotic disorders?
abstract: BACKGROUND
  Immune dysregulation is suggested to play an important aetiological role in schizophrenia (SZ) and bipolar disorder (BD) potentially driving neurodevelopmental pathways. Immune dysfunction may precede the onset of psychiatric disorders and parallel the development of multiaxial comorbidity, including suicidal behaviour and metabolic and autoimmune disorders. Depicting the source of the chronic low-grade inflammatory component in SZ and BD is thus a research priority. Strong environmental insults early in life, such as infections, acting on a background of genetic vulnerability, may induce potent and enduring inflammatory responses setting a state of liability to second-hit environmental encounters, namely childhood trauma, drug abuse or additional infectious exposures. The immunogenetic background of susceptibility, suggested to be not only lying within the HLA locus but also implicating inherited deficits of the innate immune system, may amplify the harmful biological effects of infections/psychosocial stress leading to the manifestation of a broad range of psychiatric symptoms.
  
  
  OBJECTIVE
  The present review aims to discuss the following: (i) biological arguments in favour of a chronic low-grade inflammation in SZ and BD and its potential origin in the interaction between the immunogenetic background and environmental infectious insults, and (ii) the consequences of this inflammatory dysfunction by focusing on N-methyl-D-aspartate (NMDA) receptor antibodies and activation of the family of human endogenous retroviruses (HERVs).
  
  
  CONCLUSIONS
  Specific therapeutic approaches targeting immune pathways may lead the way to novel personalized medical interventions, improvement of quality of life and average life expectancy of psychiatric patients, if not even prevent mood episodes and psychotic symptoms.
authors.affiliation: Université Paris-Est, INSERM U955, Laboratoire Psychiatrie Translationnelle, et AP-HP, DHU Pe-PSY, Pole de Psychiatrie et d'addictologie des Hôpitaux Universitaires Henri Mondor, et fondation FondaMental, F-94000, Créteil, France. marion.leboyer@inserm.fr.|Pôle de Psychiatrie, Hôpital Albert Chenevier, 40 rue de Mesly, 94000, Créteil, France. marion.leboyer@inserm.fr.
authors.forename: Marion
authors.initials: M
authors.lastname: Leboyer
authors.affiliation: Université Paris-Est, INSERM U955, Laboratoire Psychiatrie Translationnelle, et AP-HP, DHU Pe-PSY, Pole de Psychiatrie et d'addictologie des Hôpitaux Universitaires Henri Mondor, et fondation FondaMental, F-94000, Créteil, France.|INSERM, U1160, Hôpital Saint Louis, Laboratoire Jean Dausset and LabEx Transplantex, Hôpital Saint Louis, Université Paris Diderot, Sorbonne Paris-Cité, Paris, France.
authors.forename: José
authors.initials: J
authors.lastname: Oliveira
authors.affiliation: INSERM, U1160, Hôpital Saint Louis, Laboratoire Jean Dausset and LabEx Transplantex, Hôpital Saint Louis, Université Paris Diderot, Sorbonne Paris-Cité, Paris, France.
authors.forename: Ryad
authors.initials: R
authors.lastname: Tamouza
authors.affiliation: Université de Bordeaux, CNRS, Interdisciplinary Institute for Neuroscience, UMR 5297, F-33000, Bordeaux, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Groc
mesh_terms: D000818:Animals; D006801:Humans; D007167:Immunotherapy / Q000639:trends*; D007249:Inflammation / Q000276:immunology / Q000523:psychology; D011570:Psychiatry / Q000639:trends*; D011598:Psychoneuroimmunology; D011618:Psychotic Disorders / Q000276:immunology* / Q000628:therapy*
keywords: Bipolar disorder; Gene-environment interactions; HERV-W; Immunogenetics; Immunopsychiatry; NMDA receptor; Schizophrenia