Immuno-Génétique, Inflammation, Retro-Virus, Environnement

The investigators and others have been able to demonstrate that HERV-W envelope gene (Env) encodes a pro-inflammatory and neurotoxic protein after reactivation by environmental factors. In this context, the investigators have reported preliminary data showing an association between Human Endogenous Retroviruses type "W" family (HERV-W) and major psychotic disorder, bipolar disorder (BD) and schizophrenia (SZ) : In 2008, the investigators reported for the first time, the presence of ENV protein in the serum of 50 % of SZ patients associated with a chronic inflammatory status reflected by elevated serum level of C-Reactive Protein (CRP). The investigators have been able to confirm this finding and extend it to BD and showed an elevation of HERV-W RNA transcripts both in BD and SZ as compared to healthy controls. Furthermore, the investigators also observed for the first time that toxoplasma Gondii, known to be able to induce reactivation of HERV-W, is associated with an increased risk to develop BD (OR: 2.3) close to the one previously observed in SZ (OR= 2.17)

The present project I-GIVE aims to extend and refine such findings and to obtain a proof of concept of the involvement of Human Endogenous Retrovirus elements in bipolar disorder and schizophrenia. I-GIVE is divided into four complementary scientific tasks:

1. assessing the systemic HERV-W (ENV and GAG) antigen serum levels and the RNA and DNA copy number variants of stabilized and acutely ill patients,
2. measuring the systemic associated immuno-inflammatory cascade in BD patients at different stages of the disorder and occurrence of medical comorbidities,
3. identifying the clinical characteristics of patients according to HERV-W expression and immuno-inflammatory profiles,
4. exploring the gene (immuno-genetic) x environment interactions that may modulate the immuno-inflammatory response

Clinical and biological data from acute BP and SZ patients will be compared first with themselves at two different times. They will be compared also to healthy control's data, and third to stabilised BP and SZ patients.