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Epigenetics processes involved in schizophrenia and antipsychotic treatment

AI Summary
  • Epigenetic mechanisms, notably DNA methylation and histone modifications, mediate gene-environment interactions and account for schizophrenia risk beyond genetic variants.
  • Epigenetic alterations and accelerated biological ageing are investigated as biomarkers for psychosis risk stratification and predicting poor antipsychotic treatment response.
  • Therapeutic strategies targeting epigenetic processes are being explored to modify disease expression and improve outcomes in psychotic disorders.
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Handb Clin Neurol. 2026;219:205-221. doi: 10.1016/B978-0-443-19043-8.00024-4.

ABSTRACT

Schizophrenia is a severe psychiatric disorder characterized by abnormalities of thought, behavior, cognition, and affect. Risk factors for schizophrenia include a family history of psychosis, obstetric complications, childhood trauma, urban living, illicit substance use, and social isolation. It has long been concluded that there is a genetic component contributing to the development of schizophrenia; however, research studies in the pregenomic, postgenomic, and multiomics eras failed to illustrate the mechanisms underlying the genetic basis for this complex disease. According to these studies, the genetic variants explain only a portion of the risk, and epigenetic mechanisms may explain the remaining part. Epigenetic processes are changes in how genes function and are expressed without altering the corresponding genetic code. The two most studied epigenetic modifications are DNA methylation and posttranslational histone modifications. These changes may mediate the gene-environment interactions at the molecular level and determine the expression of schizophrenia. Recent studies diverted their attention to examining epigenetic changes and biologic aging as potential biomarkers for identifying individuals at risk for psychosis and poor response to treatment. The main purpose of this chapter is to review the current knowledge of epigenetics in schizophrenia and explore the possibilities of targeting epigenetic mechanisms for treatment in psychotic disorders.

PMID:42880837 | DOI:10.1016/B978-0-443-19043-8.00024-4

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