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Treatment-Resistant Schizophrenia: Insights From Genetic Studies and Machine Learning Approaches
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. Univ Cagliari, Sect Neurosci & Clin Pharmacol, Dept Biomed Sci, Cagliari, Italy.ORCID iD: 0000-0002-9151-4319
Univ Cagliari, Sect Neurosci & Clin Pharmacol, Dept Biomed Sci, Cagliari, Italy;Dalhousie Univ, Dept Psychiat, Halifax, NS, Canada.
2019 (English)In: Frontiers in Pharmacology, ISSN 1663-9812, E-ISSN 1663-9812, Vol. 10, article id 617Article, review/survey (Refereed) Published
Abstract [en]

Schizophrenia (SCZ) is a severe psychiatric disorder affecting approximately 23 million people worldwide. It is considered the eighth leading cause of disability according to the Wood Health Organization and is associated with a significant reduction in life expectancy. Antipsychotics represent the first-choice treatment in SCZ, but approximately 30% of patients fail to respond to acute treatment. These patients are generally defined as treatment-resistant and are eligible for clozapine treatment. Treatment-resistant patients show a more severe course of the disease, but it has been suggested that treatment-resistant schizophrenia (TRS) may constitute a distinct phenotype that is more than just a more severe form of SCZ. TRS is heritable, and genetics has been shown to play an important role in modulating response to antipsychotics. Important efforts have been put into place in order to better understand the genetic architecture of TRS, with the main goal of identifying reliable predictive markers that might improve the management and quality of life of TRS patients. However, the number of candidate gene and genome-wide association studies specifically focused on TRS is limited, and to date, findings do not allow the disentanglement of its polygenic nature. More recent studies implemented polygenic risk score, gene-based and machine learning methods to explore the genetics of TRS, reporting promising findings. In this review, we present an overview on the genetics of TRS, particularly focusing our discussion on studies implementing polygenic approaches.

Place, publisher, year, edition, pages
2019. Vol. 10, article id 617
Keywords [en]
schizophrenia, antipsychotics, response, clozapine, pharmacogenetics, polygenic risk score
National Category
Psychiatry
Identifiers
URN: urn:nbn:se:uu:diva-387531DOI: 10.3389/fphar.2019.00617ISI: 000469474900001PubMedID: 31191325OAI: oai:DiVA.org:uu-387531DiVA, id: diva2:1329397
Available from: 2019-06-24 Created: 2019-06-24 Last updated: 2019-06-24Bibliographically approved

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