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Longitudinal DNA methylation and cell-type proportions alterations in risperidone treatment response in first-episode psychosis
VK. Ota, LM. Spindola, AK. Stavrum, GO. Costa, AVG. Bugiga, MN. Noto, CM. Carvalho, SH. Lee, A. Lokmer, CG. Alladi, DG. Shewade, RP. Rajkumar, F. Bellivier, RA. Bressan, A. Gadelha, S. Jamain, C. Marie-Claire, C. Noto, G. Breen, ML. Santoro, S....
Jazyk angličtina Země Anglie, Velká Británie
Typ dokumentu časopisecké články
- MeSH
- antipsychotika * terapeutické užití MeSH
- dospělí MeSH
- lidé MeSH
- longitudinální studie MeSH
- metylace DNA * účinky léků MeSH
- mladiství MeSH
- mladý dospělý MeSH
- psychotické poruchy * farmakoterapie genetika krev MeSH
- risperidon * terapeutické užití farmakologie MeSH
- schizofrenie * farmakoterapie MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Identifying biological markers to guide treatment decisions in first-episode psychosis (FEP) is essential for improving patient outcomes. This longitudinal study investigated DNA methylation (DNAm) patterns and DNAm-derived cell-type proportions (CTP) in blood and associated them with response to risperidone treatment, a second-generation antipsychotic drug, in antipsychotic-naïve FEP patients. We also explored longitudinal changes in DNAm associated with risperidone treatment. We profiled DNAm in 114 individuals before (anFEP) and after two months of risperidone treatment using microarrays. The main results were compared with 115 healthy controls and validated in an independent cohort of subjects with schizophrenia (n = 26) with one-month follow-up data. We identified 302 differentially methylated positions (DMPs) associated with treatment response, measured by changes in the Positive and Negative Syndrome Scale score, of which 16 were validated in the independent cohort. Sixteen differentially methylated regions (DMRs) were associated with response, with one (in SIPA1L3) being validated. A decrease in B-cell proportions was correlated with symptom improvement in both cohorts. Additionally, four DMPs associated with risperidone treatment were identified: two related to the psychotic state and two specifically to risperidone treatment. DNAm-derived CTP showed alterations in anFEP compared with controls, particularly in the neutrophil-to-lymphocyte ratio, which normalized after treatment. These findings suggest that DNAm, particularly in B-cells, may be a promising marker for monitoring response to risperidone treatment in schizophrenia. Our longitudinal study revealed novel and known genes that may be regulated by risperidone and could be used as response markers to improve prognosis in schizophrenia and FEP.
Bergen Center for Brain Plasticity Haukeland University Hospital Bergen Norway
Departamento de Morfologia e Genética Universidade Federal de São Paulo Sao Paulo Brazil
Departamento de Psiquiatria Universidade Federal de São Paulo Sao Paulo SP Brazil
Department of Clinical Science University of Bergen Bergen Norway
Laboratory of Integrative Neuroscience Universidade Federal de São Paulo Sao Paulo Brazil
Citace poskytuje Crossref.org
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- $a Ota, Vanessa Kiyomi $u Laboratory of Integrative Neuroscience, Universidade Federal de São Paulo (UNIFESP), Sao Paulo, Brazil; Departamento de Morfologia e Genética, Universidade Federal de São Paulo (UNIFESP), Sao Paulo, Brazil
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