https://orcid.org/0000-0003-4579-6607
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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.
Plain language summary
The most common way to treat schizophrenia is antipsychotic medication. However, not all antipsychotics work for all patients. The only way to find a suitable antipsychotic is to prescribe one and wait, sometimes for months, to see if it works. Finding an alternative to this trial-and-error method would help reduce patient suffering and costs for healthcare systems. The idea is to look in the DNA of our blood cells for specific marks that can change in response to our lifestyle or health condition. These marks could help us predict how patients will react to the drug. In other words, they can serve as biomarkers of antipsychotic response. The current work examined the blood of schizophrenia patients before and 4 weeks after starting medication. The patients who did not respond well to the drug had different marks on the genes involved in immune defense and nervous system functioning. Some of these genes also play roles in the development of schizophrenia, whereas others can directly affect what happens to the drug in the patient’s body. Although marks that predict how patients will react were not identified with certainty, valuable targets for future research were identified.
Tweetable abstract
Blood methylomes of schizophrenia patients suggest the role of immune and neuronal systems in antipsychotic treatment response and reveal potential targets for antipsychotic response biomarker research.
Supplementary data
To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2023-0017
Author Contributions
A Lokmer and CG Alladi made equal contributions. A Lokmer: analysis and interpretation of data, drafting the work, critical revision and final version approval. Cg Alladi: design, data acquisition, critical revision and final version approval. R Troudet: analysis, critical revision and final version approval. D Bacq-Daian: data acquisition, critical revision and final version approval. A Boland-Auge: data acquisition, critical revision and final version approval. V Latapie: data acquisition, critical revision and final version approval. JF Deleuze: data acquisition, critical revision and final version approval. RP RajKumar: design, critical revision and final version approval. DG Shewade: design, critical revision and final version approval. F Bélivier: concept and design, critical revision and final version approval. C Marie-Claire: design, critical revision and final version approval. S Jamain: concept and design, data interpretation, critical revision and final version approval. All authors agree to be accountable for all aspects of the work.
Declaration of interest
The authors declare they have no competing financial interests or personal relationships that could influence the reported work.
Financial & competing interests disclosure
This study was supported by the Investissements d’Avenir program managed by the Agence Nationale pour la Recherche (ANR) under reference ANR-11-IDEX-0004-02 (Labex BioPsy), ANR-10-COHO-10-01 (Cohorte PSY-COH) and Indo-French Centre for the Promotion of Advanced Research (IFCPAR/CEFIPRA) for promoting the collaboration (grant no. IFC/4098/RCF2016/853) between Jawaharlal Institute of Post-graduate Medical Education and Research (JIPMER) and University of Sorbonne, Paris, France. This work also received financial support from the Institut National pour la Santé et la Recherche Médicale (Inserm), the Fondation FondaMental, the International Foundation (IF) and the Commissariat à l’énergie atomique et aux énergies alternatives (CEA). S Jamain’s team is affiliated with the Paris School of Neuroscience (ENP) and the Bio-Psy Laboratory of Excellence. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.
Ethical conduct of research
Informed consent was obtained from each study participant and the patient’s legally acceptable representative (LAR) or a family member. The Institutional Ethics Committee approved the study protocol before the commencement of the study (IEC project no. JIP/IEC/4/2013/189).
Data sharing statement
All data including R objects and figures that are not included as supplementary material are available on Figshare. Raw methylation intensity data are deposited in the ArrayExpress repository under the accession number E-MTAB-11921. All scripts necessary to reproduce the presented analysis are available upon request from the authors.