Evaluation of the Efficacy of Immunomodulatory Therapy in Case of Psychiatric Disorders With Proven Dysimmunity.

This is an open phase III randomized clinical trial studying the superiority of management by immunomodulator treatment of psychiatric disorders (psychosis and bipolar disorders) for patients previously identified as carriers of autoimmunity such as as the presence of a pathogenic anti-glutamatergic NMDA receptor antibody (NMDAr-Ac).

This is an open phase III randomized clinical trial studying the superiority of management by immunomodulator treatment of psychiatric disorders (psychosis and bipolar disorders) for patients previously identified as carriers of autoimmunity such as as the presence of a pathogenic anti-glutamatergic NMDA receptor antibody (NMDAr-Ac). The aim is to assess the clinical efficacy of this treatment associated with the usual recommended psychotropic treatment. To meet this objective, we will use, via a National Center for Scientific Research (CNRS) Research laboratory in Bordeaux, a very sensitive diagnostic platform to detect and demonstrate the pathogenesis of antibodies in patient serum. This platform is operational only within the framework of validation of the results by the reference center for neurological autoimmune diseases in Lyon

Eligibility Criteria:
Inclusion Criteria:

* For Adult: First acute or relapse of psychotic disorders defined by the BPRS-E scale with or without standard pharmacological treatment.
* For Children: Child over 6 years old with a first acute or relapse of psychotic disorders defined by the Kiddie sads-PL scale with or without standard pharmacological treatment.
* Biological diagnosis of pathogenic CNS autoantibodies in the blood.
* MDC scale score \>3 is required for inclusion in step 2.
* Normal ECG in case of previous heart disease.
* Informed consent of the patient or his legal representatives.
* Effective contraception for women of childbearing potential during the study and for at least 12 months after the last rituximab administration.

Exclusion Criteria:

* Developmental disorder related to a genetic disease.
* Co-existing disorder of severe neurological disease.
* Chronic psychotic disorders receiving ongoing neuroleptic treatment with efficacy.
* Hypersensitivity to the active substance (rituximab) or to murine proteins, or to any of the other excipients
* Blood platelets \< 75x109/L
* Neutrophils \< 1.5x109/L
* Neoplastic pathology,
* Hepatitis B or HIV infection,
* Contraindication to immunosuppressant treatment (active severe infection, severely immunocompromised state).
* Severe heart failure (New York Heart Association Class IV) or severe, uncontrolled cardiac disease
* Pregnant or breastfeeding women
* Currently receiving an investigational drug or received an investigational drug or device within 30 days (or 5 half-lives for drugs, whichever is longer) prior to screening.
* Previous treatment with rituximab in the past 12 months.
* Patients with a history of recurring or chronic infections or with underlying conditions which may further predispose them to serious infection (e.g. hypogammaglobulinemia).
* Recent vaccination with live viral vaccine (within 3 months).
* Any other medical illness or disability that, in the opinion of the investigator, would compromise effective trial participation.