News of the group:
–Congratulations to Marion LEBOYER who wins the Inserm Grand Prix 2021!
(December 7, 2021)
Immuno-inflammation in major psychiatric disorders
Major psychiatric disorders (depression, bipolar, schizophrenia, autism…) are all underpinned by immune dysfunctions affecting the vast majority of immune processes (Berk, Leboyer and Sommer, 2021). They are thought to result from complex gene and environment interactions along a lifelong pathway including successive events such as early infections, auto-immune conditions, severe stress, unhealthy life style…. We believe that dissecting the different steps of this pathway could improve understanding of psychiatric conditions and help the discovery of biomarkers essential for stratification of patient subgroups, the ultimate goal being the identification of targets for immune-based treatments (Pape et al, 2019).
We have contributed to the demonstration of an immuno-genetically determined inefficient anti-infectious responses by showing several associations between functionally relevant polymorphisms located in genes encoding major innate sensors and the risk to develop bipolar disorders (Oliveira et al, 2017). We then refined pivotal GWAS-based observation strongly implicating the major histocompatibility complex (MHC) in the development of psychiatric disorders. We reported correlations between classical Human Leukocyte Antigen (HLA) haplotypes and bipolar disorders, schizophrenia and autism spectrum disorders (rev in Tamouza et al, 2021). In addition, we also uncovered an association between the immunomodulatory non-classical HLA molecules i.e. HLA-G and HLA-E and bipolar disorders and schizophrenia leading to the description of the dual implication of the MHC/HLA in the risk to develop psychiatric disorders. Finally, we focused our attention towards the implication of the C4 complement cluster, also located in the MHC region and recently demonstrated to be strongly associated with the risk to develop to schizophrenia (Mariaselvam et al, 2021).
Among the consequences of the low grade inflammation following persistent infections, we demonstrated the reactivation of Human Endogenous Retroviral W elements (HERV-W) reflected both at DNA, RNA and protein levels, both in schizophrenia and bipolar disorders (Tamouza et al, 2021). We then described its precise mechanism of action in psychosis (Johanson et al, 2020).
We described the new concept of auto-immune psychosis (Polack et al, 2020) and described their pathogenic effect at the synaptic cleft in psychosis, (Johansson et al, 2020).
Finally, thanks to clinically and biologically/immunologically multi-assessed cohorts of patients, we recently identified immuno-clinical signature of resistance to treatment and metabolic syndrome in schizophrenia as well that of psychotic patients having both inflammation and HERV-W antigenemia).
The development of the field of “Immuno-Psychiatry” was made possible thanks multiple projects funded by Agence Nationale de la Recherche, H2020 and IMI European programs, foundation de France, fondation de la recherche médicale and fondation Fondamental and to a vast network of multidisciplinary national and international collaborations.
M BERK, M LEBOYER, I SOMMERS eds, Immuno-psychiatry: facts and prospects » 2021, Springer Nature Publications2021, Springer Nature Publications
PAPE K, TAMOUZA R, ZIPP F, LEBOYER M. Immunoneuropsychiatry - novel perspectives on brain disordersNature Reviews Neurology, 2019 Jun;15(6):317-328. doi: 10.1038/s41582-019-0174-4. Review. PMID: 30988501
OLIVEIRA J, OLIVEIRA-MAIA AJ, TAMOUZA R, BROWN AS, LEBOYER M. Infectious and immunogenetic factors in bipolar disorder.Acta Psychiatr Scand. 2017 Oct;136(4):409-423. doi: 10.1111/acps.12791.
TAMOUZA R, KRISHNAMOORTHY R, LEBOYER M. Understanding the genetic contribution of the human leukocyte antigen system to common major psychiatric disorders in a world pandemic context.Brain Behav Immun. 2021 Jan;91:731-739. doi: 10.1016/j.bbi.2020.09.033. Epub 2020 Oct 5.PMID: 33031918
TAMOUZA R, MEYER U, FOISELLE M, RICHARD JR, WU CL, BOUKOUACI W, LE CORVOISIER P, BARRAU C, LUCAS A, PERRON H, LEBOYER M. Identification of inflammatory subgroups of schizophrenia and bipolar disorder patients with HERV-W ENV antigenemia by unsupervised cluster analysis.Transl Psychiatry. 2021 Jul 6;11(1):377. doi: 10.1038/s41398-021-01499-0.PMID: 34230451
Johansson Em, Bouchet D, Tamouza R, Ellul P, Morr As, Avignone E, Germi R, Leboyer M, Perron H, Groc L. Human endogenous retroviral protein triggers deficit in glutamate synapse maturation and behaviors associated with psychosis.Science Adv. 2020 Jul 17;6(29):eabc0708. doi: 10.1126/sciadv.abc0708.
Jezequel J, Johansson EM, Dupuis JP, Rogemond V, Gréa H, Kellermayer B, Hamdani N, LeGuen E, Rabu C, Lepleux M, Spatola M, Mathias E, Bouchet D, Ramsey AJ, Yolken RH, Tamouza R, Dalmau J, Honnorat J, Leboyer M, Groc L. Dynamic desorganization of synaptic NMDA receptors trigerred by autoantibodies from psychotic patientsNat Commun, 2017 Nov 27, 8 (1) : 1791
Leboyer M, Godin O, ….. Tamouza R. Immune Signatures of Treatment-Resistant Schizophrenia: A FondaMental Academic Centers of Expertise for Schizophrenia (FACE-SZ) StudySchizophrenia Bulletin Open, Volume 2, Issue 1, Jan 2021. sgab012
Mariaselvam CM, Ching-Lien Wu CL … Leboyer M, Tamouza R. The Complement C4 Genetic Diversity in First Episode Psychosis of the OPTiMiSE CohortSchizophrenia Bulletin Open, Volume 2, Issue 1, January 2021, sgab003