LINE-1 Hypomethylation is Associated with Poor Risperidone Response in a First Episode of Psychosis Cohort

Abstract

Aim: We investigated the DNA methylation profile over LINE-1 in antipsychotic-naive, first-episode psychosis-patients (n = 69) before and after 2 months of risperidone treatment and in healthy controls (n = 62). Materials & methods: Patients were evaluated using standardized scales and classified as responders and nonresponders. DNA from blood was bisulfite converted and LINE-1 fragments were amplified and pyrosequencing was performed. Results: Lower LINE-1 methylation was observed in antipsychotic-naive first-episode psychosis patients than in healthy controls. Lower DNA methylation levels before treatment were associated with poor risperidone responses. A positive correlation was observed between LINE-1 methylation levels and positive symptoms response. Conclusion: Our study brings new insight regarding how epigenomic studies and clinical correlation studies can supplement psychosis treatment.

Keywords::

• DNA methylation
• LINE-1
• psychosis
• risperidone
• schizophrenia
• treatment response

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-2019-0350

Acknowledgments

The authors would like to thank the patients, their families, the psychiatrists and nurses for their participation in this study.

Financial & competing interests disclosure

This study was supported by Fundação de Amparo à Pesquisado Estado de São Paulo (FAPESP 2010/08968-6; 2011/50740-5; 2014/07280-1; 2016/04983-7; 2017/25016-8), Brazil. RA Bressan reports grants and nonfinancial support from Fundação de Amparo a Pesquisa de São Paulo (FAPESP/2016/02246-5), Brasil; grants and nonfinancial support from Conselho Nacional de Desenvolvimento Científico e Tecnologia (CNPq), Brasil, personal fees and nonfinancial support from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Brasil, during the conduct of the study; grants, personal fees and nonfinancial support from Janssen, personal fees from Ache Laboratórios Farmacêuticos, grants and personal fees from Roche, outside the submitted work. SDJ funding: SDJ was part supported by NARSAD Young Investigator Grant (YI 60373) and European Union’s Horizon 2020 research and innovation programme (Marie Sklodowska-Curie grant agreement 658195). 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

The Research Ethics Committee of Universidade Federal de São Paulo (UNIFESP) approved the research protocol, and all participants gave informed consent (CAAE no. 48242015.9.0000.5505).

Additional information

Funding

This study was supported by Fundação de Amparo à Pesquisado Estado de São Paulo (FAPESP 2010/08968-6; 2011/50740-5; 2014/07280-1; 2016/04983-7; 2017/25016-8), Brazil. RA Bressan reports grants and nonfinancial support from Fundação de Amparo a Pesquisa de São Paulo (FAPESP/2016/02246-5), Brasil; grants and nonfinancial support from Conselho Nacional de Desenvolvimento Científico e Tecnologia (CNPq), Brasil, personal fees and nonfinancial support from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Brasil, during the conduct of the study; grants, personal fees and nonfinancial support from Janssen, personal fees from Ache Laboratórios Farmacêuticos, grants and personal fees from Roche, outside the submitted work. SDJ funding: SDJ was part supported by NARSAD Young Investigator Grant (YI 60373) and European Union’s Horizon 2020 research and innovation programme (Marie Sklodowska-Curie grant agreement 658195). 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.