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<p>Gene expression profiling studies could be a valuable tool in identifying the specific genes and pathways involved in the mechanism of action of clozapine, leading to a better understanding of the molecular biology underlying treatment-resistant schizophrenia (TRS). We aimed to identify the co-expressed modules that reflect the genetic differences between clozapine-treated and non-clozapine-treated patients with schizophrenia as a proxy of TRS. Gene expression of DLPFC samples from 26 subjects with schizophrenia (13 clozapine treated and 13 non-clozapine treated) were analyzed using Clariom S Human Array. Weighted gene co-expression network analysis (WGCNA) was applied to identify modules of co-expressed genes and to test its association with clozapine treatment. As a result of our analysis of the gene co-expression architecture in the DLPFC, among the 13 modules identified, one module (green) was significantly associated with clozapine treatment (p = 3.7 × 10<sup>−2</sup>). This module was significantly enriched in astrocyte markers (5.7 × 10<sup>−29</sup>) and genes involved in the polygenic architecture of TRS (1.6 × 10<sup>−2</sup>). This finding provides cell type-specific associations that could help in the interpretation of the neurobiological basis of TRS. A better understanding of the specific DLPFC cell types involved in clozapine treatment will contribute to the study of potential pathways and ultimately help improve psychiatric classification tools in personalized medicine.</p>

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Association of astrocyte-specific gene expression in the dorsolateral prefrontal cortex with clozapine treatment in schizophrenia

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月31日

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  • Llucia Prohens,
  • Natalia Rodríguez,
  • Àlex-Gonzàlez Segura,
  • Albert Martínez-Pinteño,
  • David Olivares-Berjaga,
  • Irene Martínez,
  • Gisela Mezquida,
  • Jon A. Santas-Martín,
  • Benito Morentin,
  • Jose-Javier Meana,
  • Luis F. Callado,
  • Patricia Gassó,
  • Guadalupe Rivero,
  • Sergi Mas

摘要

Gene expression profiling studies could be a valuable tool in identifying the specific genes and pathways involved in the mechanism of action of clozapine, leading to a better understanding of the molecular biology underlying treatment-resistant schizophrenia (TRS). We aimed to identify the co-expressed modules that reflect the genetic differences between clozapine-treated and non-clozapine-treated patients with schizophrenia as a proxy of TRS. Gene expression of DLPFC samples from 26 subjects with schizophrenia (13 clozapine treated and 13 non-clozapine treated) were analyzed using Clariom S Human Array. Weighted gene co-expression network analysis (WGCNA) was applied to identify modules of co-expressed genes and to test its association with clozapine treatment. As a result of our analysis of the gene co-expression architecture in the DLPFC, among the 13 modules identified, one module (green) was significantly associated with clozapine treatment (p = 3.7 × 10−2). This module was significantly enriched in astrocyte markers (5.7 × 10−29) and genes involved in the polygenic architecture of TRS (1.6 × 10−2). This finding provides cell type-specific associations that could help in the interpretation of the neurobiological basis of TRS. A better understanding of the specific DLPFC cell types involved in clozapine treatment will contribute to the study of potential pathways and ultimately help improve psychiatric classification tools in personalized medicine.