Study protocol for a randomized controlled trial with rituximab for psychotic disorder in adults (RCT-Rits).

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. TRIAL REGISTRATION: NCT05622201, EudraCT-nr 2022-000220-37 version 2.1. registered 14th of October 2022.

Peer and sibling substance use: predictors of substance use among adolescents in Mexico.

OBJECTIVE: To examine the extent to which peer drug use and sibling drug use predict alcohol abuse/dependence disorder status and the use of drugs other than alcohol among school-based youth in Mexico. METHODS: Data were collected on 1 203 middle and high school students in northern Mexico in May 1998. Participation was voluntary, and responses were confidential. Logistic regression analyses estimated the association that peer drug use and that sibling drug use had with alcohol abuse/dependence diagnosis and the lifetime use of drugs other than alcohol. RESULTS: Students who had siblings or peers who used alcohol and other drugs were more likely to meet the standard alcohol abuse/dependence criteria defined by the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV), and were more likely to have used drugs other than alcohol. Controlling for potentially important confounders, we found that adolescents with the highest level of peer substance use were eight times as likely to meet alcohol abuse/dependence criteria and four times as likely to use other drugs. Youth who had siblings who used drugs were about twice as likely to meet alcohol abuse/dependence criteria and about 2.5 times as likely to use drugs other than alcohol when compared to youth with no sibling substance use. CONCLUSIONS: Consistent with extant findings among youth in the United States of America, peer and sibling substance use are major risk factors for substance use among school-based youth in Mexico. Students in Mexico may benefit from prevention strategies found to be effective among students in the United States.

Peer and sibling substance use: predictors of substance use among adolescents in Mexico

OBJECTIVO: Examinar en qué medida el uso de drogas por los pares y hermanos es factor pronóstico del abuso o la dependencia del alcohol y del uso de drogas distintas del alcohol en escolares mexicanos. MÉTODOS: Se recolectaron datos acerca de 1 203 estudiantes de los últimos años de primaria y de secundaria en el norte de México en mayo de 1998. La participación en el estudio fue voluntaria, y las respuestas fueron confidenciales. Mediante análisis de regresión logística se estimó la asociación entre el uso de drogas por los pares y hermanos por un lado, y por el otro el diagnóstico de abuso o dependencia del alcohol y el uso de sustancias distintas del alcohol en algún momento de la vida. RESULTADOS: Los estudiantes cuyos hermanos o pares ingerían bebidas alcohólicas y consumían otras drogas mostraron mayores probabilidades de satisfacer los criterios estándares de abuso o dependencia del alcohol, según los define el Manual diagnóstico y estadístico de enfermedades mentales, cuarta edición (MDE-IV), y de haber consumido drogas distintas del alcohol. Después de controlado el efecto de posibles factores de confusión, los adolescentes con los niveles más altos de abuso de sustancias por parte de sus pares se mostraron ocho veces más propensos a satisfacer los criterios de abuso o dependencia del alcohol y cuatro veces más propensos a consumir otros tipos de sustancias. Los adolescentes cuyos hermanos consumían drogas tenían una probabilidad dos veces mayor de satisfacer los criterios de abuso o dependencia del alcohol y una probabilidad 2,5 veces mayor de consumir drogas en comparación con jóvenes cuyos hermanos no consumían ninguna sustancia. CONCLUSIONES: Tal como indican otros resultados obtenidos con adolescentes en Estados Unidos de América, el uso de sustancias por los pares y hermanos es un factor de riesgo de consumo de sustancias en escolares en México. Estos últimos podrían beneficiarse de estrategias preventivas cuya eficacia en jóvenes estadounidenses se haya demostrado.