Risperidone Response in Patients with Schizophrenia Drives DNA Methylation Changes in Immune and Neuronal Systems

Abstract

Background: The choice of efficient antipsychotic therapy for schizophrenia relies on a time-consuming trial-and-error approach, whereas the social and economic burdens of the disease call for faster alternatives. Material & methods: In a search for predictive biomarkers of antipsychotic response, blood methylomes of 28 patients were analyzed before and 4 weeks into risperidone therapy. Results: Several CpGs exhibiting response-specific temporal dynamics were identified in otherwise temporally stable methylomes and noticeable global response-related differences were observed between good and bad responders. These were associated with genes involved in immunity, neurotransmission and neuronal development. Polymorphisms in many of these genes were previously linked with schizophrenia etiology and antipsychotic response. Conclusion: Antipsychotic response seems to be shaped by both stable and medication-induced methylation differences.

Global DNA and RNA Methylation Signature in Response to Antipsychotic Treatment in First-Episode Schizophrenia Patients

“…Blood methylomes in patients prior to treatment and 4-weeks post treatment with risperidone revealed that response to medication is influenced based on the region of methylation marks, and correspondingly, antipsychotics cause dysregulation in the methylome. 37 Similarly, Marques et al 38 evaluated the LINE-1 DNA methylation levels in FEP patients prior to and post treatment with risperidone. It was observed that there was a significant LINE-1 hypomethylation in FEP cases compared to controls, and this influenced the response to risperidone treatment.…”

Identification of immune-related biomarkers in peripheral blood of schizophrenia using bioinformatic methods and machine learning algorithms

“…It is also worth noting that the current study used MK-801 to establish a NMDAR hyperfunction animal model, thus whether abnormal CLIC3 expression is associated with NMDAR dysfunction requires to be verified in future studies. Moreover, risperidone was widely reported to have positive effects on immune dysfunction ( Richtand et al, 2011 ; Casquero-Veiga et al, 2019 ; Lokmer et al, 2023 ). Therefore, whether risperidone regulates the immune system through modulating CLIC3 expression is worth being explored in the future.…”