Biomarkers of treatment-resistant schizophrenia: A systematic review

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  • dc.contributor.author Pisanu, Claudia
  • dc.contributor.author Severino, Giovanni
  • dc.contributor.author Minelli, Alessandra
  • dc.contributor.author Dierssen, Mara
  • dc.contributor.author Potier, Marie-Claude
  • dc.contributor.author Fabbri, Chiara
  • dc.contributor.author Serretti, Alessandro
  • dc.contributor.author Gennarelli, Massimo
  • dc.contributor.author European College of Neuropsychopharmacology (ECNP) Pharmacogenomics & Transcriptomics Network
  • dc.contributor.author Baune, Bernhard T.
  • dc.contributor.author Squassina, Alessio
  • dc.date.accessioned 2025-01-28T08:18:29Z
  • dc.date.available 2025-01-28T08:18:29Z
  • dc.date.issued 2024
  • dc.description.abstract Treatment-resistant schizophrenia (TRS) is associated with great disability, functional impairment, and substantial socioeconomic costs. While clozapine is indicated in patients with TRS, its use is restricted to patients who have not responded to at least 2 other antipsychotics, thus implying a series of empirical trials of different drugs before receiving effective treatment. In this scenario, the identification of reliable biological markers to predict the risk for TRS before starting pharmacological treatments might significantly improve the management of TRS in its early stages. We conducted a systematic review on PubMed, Scopus and Web of Science to identify studies investigating peripheral biological markers of TRS. A total of 75 articles were included. These studies mostly investigated the association between TRS and genetic markers (n = 42, of which 16 with a genome-wide and 25 with a candidate-gene design) and protein/metabolite markers (n = 23), while only a minority of studies investigated RNA markers (n = 5), methylation levels (n = 4), gut microbiota profiles (n = 1), or more than one type of marker (n = 3). The elucidation of peripheral biomarkers of TRS is challenging due to the large heterogeneity across studies in terms of clinical definition of TRS, the relatively small sample size of many studies, as well as the lack of powered studies integrating data at a multi-omic level. Nonetheless, available studies suggest TRS to be a trait with a significant heritability and point to inflammation and cytokine imbalance as the most promising pathways involved in this complex phenotype.
  • dc.description.sponsorship Bernhard T Baune, Claudia Pisanu, Mara Dierssen, Marie-Claude Potier, Chiara Fabbri, Alessandro Serretti, Alessio Squassina and Alessandra Minelli received support from Psych-STRATA, a project funded from the European Union's Horizon Europe research and innovation programme under Grant Agreement No. 101057454. Massimo Gennarelli received support by the Italian Ministry of Health under Grant [Ricerca Corrente 2022].
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Pisanu C, Severino G, Minelli A, Dierssen M, Potier MC, Fabbri C, et al. Biomarkers of treatment-resistant schizophrenia: A systematic review. Neuroscience Applied. 2024;3:104059. DOI: 10.1016/j.nsa.2024.104059
  • dc.identifier.doi http://dx.doi.org/10.1016/j.nsa.2024.104059
  • dc.identifier.issn 2772-4085
  • dc.identifier.uri http://hdl.handle.net/10230/69327
  • dc.language.iso eng
  • dc.publisher Elsevier
  • dc.relation.ispartof Neuroscience Applied. 2024;3:104059
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/HE/101057454
  • dc.rights © 2024 The Authors. Published by Elsevier B.V. on behalf of European College of Neuropsychopharmacology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
  • dc.subject.keyword Biomarkers
  • dc.subject.keyword Precision medicine
  • dc.subject.keyword Personalized medicine
  • dc.subject.keyword Precision psychiatry
  • dc.subject.keyword GWAS
  • dc.subject.keyword Inflammation
  • dc.subject.keyword Interleukin 6
  • dc.subject.keyword IL-6
  • dc.subject.keyword Methylation
  • dc.subject.keyword RNA
  • dc.title Biomarkers of treatment-resistant schizophrenia: A systematic review
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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