Genetic variants associated with the development and treatment response of refractory schizophrenia: a systematic review and meta-analysis

• Grant number: 24/07352-4
• Support Opportunities: Scholarships in Brazil - Master
• Start date: April 01, 2025
• End date: April 30, 2026
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Marcela Forgerini
• Grantee: Marília Aparecida Batista dos Santos
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Introduction: Schizophrenia is a serious psychiatric disorder, and it is estimated that 30% of patients are unresponsive to treatment (treatment-resistant schizophrenia (TRS)). Although genetic susceptibility appears to be associated with the development of treatment resistance and treatment response, little is known about the variants involved in this risk. Objective: To identify the genetic variants associated with the development of TRS as well as the response to treatment. Methodology: A systematic review will be conducted in the PubMed, Embase, Lilacs and Cochrane Database based on the guiding questions: (i) "What are the genetic variants associated with the development of refractory schizophrenia?" (ii) "What are the genetic variants associated with treatment response in refractory schizophrenia?" and (iii) "How is polygenic risk scoring used to estimate the risk of developing refractory schizophrenia and predict treatment response?". Studies on candidate genes, genome-wide association studies, and those applying polygenic risk scores will be included. Experimental and observational studies will be included. Studies published in non-Roman alphabet languages (e.g., Arabic), in vivo and in vitro studies, reviews, commentaries, editorials, news articles, conference abstracts, theses, and dissertations will be excluded. There will be no limitations regarding publication date, country, level of care, or type of healthcare service. Screening (reading of title and abstract), eligibility (reading of full text), data extraction, and analysis of the methodological quality of the studies will be conducted in duplicate. Expected outcomes: To identify genetic variants associated with the development of TRS and treatment response to provide evidence to promote the effectiveness of pharmacotherapy and support protocol development and health decision-making.