Are the epigenetic changes predictive of therapeutic efficacy for psychiatric disorders? A translational approach towards novel drug targets

Vincenzo Micale; Martina Di Bartolomeo; Serena Di Martino; Tibor Stark; Bernardo Dell'Osso; Filippo Drago; Claudio D'Addario

doi:10.1016/j.pharmthera.2022.108279

Are the epigenetic changes predictive of therapeutic efficacy for psychiatric disorders? A translational approach towards novel drug targets

Pharmacol Ther. 2023 Jan:241:108279. doi: 10.1016/j.pharmthera.2022.108279. Epub 2022 Sep 11.

Authors

Vincenzo Micale¹, Martina Di Bartolomeo², Serena Di Martino³, Tibor Stark⁴, Bernardo Dell'Osso⁵, Filippo Drago⁶, Claudio D'Addario⁷

Affiliations

¹ Department of Biomedical and Biotechnological Sciences, Section of Pharmacology, University of Catania, Catania, Italy. Electronic address: vincenzomicale@unict.it.
² Faculty of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, Teramo, Italy.
³ Department of Biomedical and Biotechnological Sciences, Section of Pharmacology, University of Catania, Catania, Italy.
⁴ Department of Pharmacology, Faculty of Medicine, Masaryk University, Brno, Czech Republic; Scientific Core Unit Neuroimaging, Max Planck Institute of Psychiatry, Munich, Germany.
⁵ Department of Biomedical and Clinical Sciences 'Luigi Sacco', University of Milan, Milan, Italy, Department of Mental Health, ASST Fatebenefratelli-Sacco, Milan, Italy; "Aldo Ravelli" Research Center for Neurotechnology and Experimental Brain Therapeutics, Department of Health Sciences, University of Milan Medical School, Milan, Italy; Department of Psychiatry and Behavioral Sciences, Stanford University, CA, USA.
⁶ Department of Biomedical and Biotechnological Sciences, Section of Pharmacology, University of Catania, Catania, Italy. Electronic address: fdrago@unict.it.
⁷ Faculty of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, Teramo, Italy; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.

PMID: 36103902
DOI: 10.1016/j.pharmthera.2022.108279

Abstract

The etiopathogenesis of mental disorders is not fully understood and accumulating evidence support that clinical symptomatology cannot be assigned to a single gene mutation, but it involves several genetic factors. More specifically, a tight association between genes and environmental risk factors, which could be mediated by epigenetic mechanisms, may play a role in the development of mental disorders. Several data suggest that epigenetic modifications such as DNA methylation, post-translational histone modification and interference of microRNA (miRNA) or long non-coding RNA (lncRNA) may modify the severity of the disease and the outcome of the therapy. Indeed, the study of these mechanisms may help to identify patients particularly vulnerable to mental disorders and may have potential utility as biomarkers to facilitate diagnosis and treatment of psychiatric disorders. This article summarizes the most relevant preclinical and human data showing how epigenetic modifications can be central to the therapeutic efficacy of antidepressant and/or antipsychotic agents, as possible predictor of drugs response.

Keywords: Antidepressants; Antipsychotics; Bipolar disorder; DNA methylation; Depression; Epigenetics; Schizophrenia.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Antipsychotic Agents* / therapeutic use
DNA Methylation
Epigenesis, Genetic
Humans
Mental Disorders* / drug therapy
Mental Disorders* / genetics
MicroRNAs*

Substances

Antipsychotic Agents
MicroRNAs