Abstract Background The role of inflammation in the aetiology of schizophrenia has gained wide attention and research on the association shows an exponential growth in the last 15 years. Autoimmune diseases and severe infections are risk factors for the later development of schizophrenia, elevated inflammatory markers in childhood or adolescence are associated with a greater risk of schizophrenia in adulthood, individuals with schizophrenia have increased levels of pro-inflammatory cytokines compared to healthy controls, and autoimmune diseases are overrepresented in schizophrenia. However, treatments with anti-inflammatory agents are so far of doubtful clinical relevance. The primary objective of this study is to test whether the monoclonal antibody rituximab, directed against the B-cell antigen CD20 ameliorates psychotic symptoms in adults with schizophrenia or schizoaffective disorder and to examine potential mechanisms. A secondary objective is to examine characteristics of inflammation-associated psychosis and to identify pre-treatment biochemical characteristics of rituximab responders. A third objective is to interview a subset of patients and informants on their experiences of the trial to obtain insights that rating scales may not capture. Methods A proof-of-concept study employing a randomised, parallel-group, double-blind, placebo-controlled design testing the effect of B-cell depletion in patients with psychosis. 120 participants with a diagnosis of schizophrenia spectrum disorders (SSD) (ICD-10 codes F20, F25) will receive either one intravenous infusion of rituximab (1000 mg) or saline. Psychiatric measures and blood samples will be collected at baseline, week 12, and week 24 post-infusion. Brief assessments will also be made in weeks 2 and 7. Neuroimaging and lumbar puncture, both optional, will be performed at baseline and endpoints. Approximately 40 of the patients and their informants will be interviewed for qualitative analyses on the perceived changes in well-being and emotional qualities, in addition to their views on the research. Discussion This is the first RCT investigating add-on treatment with rituximab in unselected SSD patients. If the treatment is helpful, it may transform the treatment of patients with psychotic disorders. It may also heighten the awareness of immune-psychiatric disorders and reduce stigma. https://bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-023-05250-5
Interesting snippet. It isn't very well structured logically but the bits of data are interesting. The MHC includes complement genes and complement is involved in innate responses that have nothing to do with B cells. It has been shown to be involved in brain neuron plasticity, as they say, which may have nothing to do with immunity. So that bit of evidence is compatible with schizophrenia involving complement but not B cells. The mores interesting fact is that a transplant of bone marrow from someone with schizophrenia induced psychosis in the recipient. That suggest that whether the MHC link is to complement or B cells it might involve haemopoietic cells - either B cells or macrophages. I might see if I can find out more about ref 19. The rationale for using rituximab looks a bit thin to me but good enough to try, when dealing with an awful illness like schizophrenia (as it was for ME).
The bone marrow transplant case is somewhat problematic because the donor with schizophrenia was his brother. Having a first-degree relative with scz is a strong risk factor for developing this heritable condition. However, first onset in 60s is unusual, though not unheard of. I’d be more convinced if the donor was unrelated. It looks like the recipient developed psychotic symptoms about 4 months after the transplant. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4287892/
Rituximab as an adjunctive treatment for schizophrenia spectrum disorder or obsessive-compulsive disorder: Two open-label pilot studies on treatment-resistant patients https://www.sciencedirect.com/science/article/pii/S0022395622006719 Abstract In this explorative study, we investigated if an adjunctive treatment with one single dose of the monoclonal antibodyrituximab would improve symptoms and function in treatment-resistant patients with schizophrenia spectrum disorder (SSD, n = 9) or obsessive-compulsive disorder (OCD, n = 10), based on the inflammatory hypothesis for mental disorders. Patients were followed for one year. Disability was measured with the Personal and Social Performance score (PSP). At baseline, the mean PANSSscore in the SSD group was 99 ± 32 and the mean Y-BOCS score in the OCD group was 27.5 ± 7. Mean PSP scores were 32 ± 10.2 and 42.5 ± 9.9 in the SSD and OCD groups, respectively. Seven had Paediatric Acute-Onset Neuropsychiatric Syndrome (PANS) in retrospect, and 3 SSD patients had schizo-obsessive subtype. 4/8 SSD patients showed a ≥40% reduction in PANSS at endpoint I week 20, however, 7/9 were similarly improved already at week 12. Among the OCD patients, 2/10 showed a ≥35% reduction in Y-BOCS at week 20. Disability was significantly improved only in the SSD group. The percentual decrease of PANSS scores in SSD patients was associated with the increase in immunoglobulinlevels week 20 (n = 8: IgG r = 0.85, p = .007; IgA r = 0.79, p = .019; IgM r = 0.73, p = .038).
Certainly complicated. But 4 months is a good time for maximal graft versus host disease. Yes, you would've thought they would have got some simple practical advice from people with experience with the approach. It should be 5-6months and needs to be interpreted in the context of B cell return.
