Treatment-Resistant Schizophrenia: Genetic and Neuroimaging Correlates
Schizophrenia is a severe neuropsychiatric disorder that affects approximately 0.5–1% of the population. Response to antipsychotic therapy is highly variable, and it is not currently possible to predict those patients who will or will not respond to antipsychotic medication. Furthermore, a high perc...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-04-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2019.00402/full |
| _version_ | 1818507771195162624 |
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| author | Antonio Vita Antonio Vita Alessandra Minelli Stefano Barlati Stefano Barlati Giacomo Deste Edoardo Giacopuzzi Paolo Valsecchi Cesare Turrina Cesare Turrina Massimo Gennarelli Massimo Gennarelli |
| author_facet | Antonio Vita Antonio Vita Alessandra Minelli Stefano Barlati Stefano Barlati Giacomo Deste Edoardo Giacopuzzi Paolo Valsecchi Cesare Turrina Cesare Turrina Massimo Gennarelli Massimo Gennarelli |
| author_sort | Antonio Vita |
| collection | DOAJ |
| description | Schizophrenia is a severe neuropsychiatric disorder that affects approximately 0.5–1% of the population. Response to antipsychotic therapy is highly variable, and it is not currently possible to predict those patients who will or will not respond to antipsychotic medication. Furthermore, a high percentage of patients, approximately 30%, are classified as treatment-resistant (treatment-resistant schizophrenia; TRS). TRS is defined as a non-response to at least two trials of antipsychotic medication of adequate dose and duration. These patients are usually treated with clozapine, the only evidence-based pharmacotherapy for TRS. However, clozapine is associated with severe adverse events. For these reasons, there is an increasing interest to identify better targets for drug development of new compounds and to establish better biomarkers for existing medications. The ability of antipsychotics to improve psychotic symptoms is dependent on their antagonist and reverse agonist activities at different neuroreceptors, and some genetic association studies of TRS have focused on different pharmacodynamic factors. Some genetic studies have shown an association between antipsychotic response or TRS and neurodevelopment candidate genes, antipsychotic mechanisms of action (such as dopaminergic, serotonergic, GABAergic, and glutamatergic) or pharmacokinetic factors (i.e., differences in the cytochrome families). Moreover, there is a growing body of literature on the structural and functional neuroimaging research into TRS. Neuroimaging studies can help to uncover the underlying neurobiological reasons for such resistance and identify resistant patients earlier. Studies examining the neuropharmacological mechanisms of antipsychotics, including clozapine, can help to improve our knowledge of their action on the central nervous system, with further implications for the discovery of biomarkers and the development of new treatments. The identification of the underlying mechanisms of TRS is a major challenge for developing personalized medicine in the psychiatric field for schizophrenia treatment. The main goal of precision medicine is to use genetic and brain-imaging information to improve the safety, effectiveness, and health outcomes of patients via more efficiently targeted risk stratification, prevention, and tailored medication and treatment management approaches. The aim of this review is to summarize the state of art of pharmacogenetic, pharmacogenomic and neuroimaging studies in TRS. |
| first_indexed | 2024-12-10T22:22:36Z |
| format | Article |
| id | doaj.art-cb970a7cf23b4d6fac48ff02faa6e098 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-10T22:22:36Z |
| publishDate | 2019-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-cb970a7cf23b4d6fac48ff02faa6e0982022-12-22T01:31:17ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122019-04-011010.3389/fphar.2019.00402434603Treatment-Resistant Schizophrenia: Genetic and Neuroimaging CorrelatesAntonio Vita0Antonio Vita1Alessandra Minelli2Stefano Barlati3Stefano Barlati4Giacomo Deste5Edoardo Giacopuzzi6Paolo Valsecchi7Cesare Turrina8Cesare Turrina9Massimo Gennarelli10Massimo Gennarelli11Department of Mental Health and Addiction Services, ASST Spedali Civili, Brescia, ItalyDepartment of Clinical and Experimental Sciences, University of Brescia, Brescia, ItalyDepartment of Molecular and Translational Medicine, University of Brescia, Brescia, ItalyDepartment of Mental Health and Addiction Services, ASST Spedali Civili, Brescia, ItalyDepartment of Clinical and Experimental Sciences, University of Brescia, Brescia, ItalyDepartment of Mental Health and Addiction Services, ASST Spedali Civili, Brescia, ItalyGenetic Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, ItalyDepartment of Clinical and Experimental Sciences, University of Brescia, Brescia, ItalyDepartment of Mental Health and Addiction Services, ASST Spedali Civili, Brescia, ItalyDepartment of Clinical and Experimental Sciences, University of Brescia, Brescia, ItalyDepartment of Molecular and Translational Medicine, University of Brescia, Brescia, ItalyGenetic Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, ItalySchizophrenia is a severe neuropsychiatric disorder that affects approximately 0.5–1% of the population. Response to antipsychotic therapy is highly variable, and it is not currently possible to predict those patients who will or will not respond to antipsychotic medication. Furthermore, a high percentage of patients, approximately 30%, are classified as treatment-resistant (treatment-resistant schizophrenia; TRS). TRS is defined as a non-response to at least two trials of antipsychotic medication of adequate dose and duration. These patients are usually treated with clozapine, the only evidence-based pharmacotherapy for TRS. However, clozapine is associated with severe adverse events. For these reasons, there is an increasing interest to identify better targets for drug development of new compounds and to establish better biomarkers for existing medications. The ability of antipsychotics to improve psychotic symptoms is dependent on their antagonist and reverse agonist activities at different neuroreceptors, and some genetic association studies of TRS have focused on different pharmacodynamic factors. Some genetic studies have shown an association between antipsychotic response or TRS and neurodevelopment candidate genes, antipsychotic mechanisms of action (such as dopaminergic, serotonergic, GABAergic, and glutamatergic) or pharmacokinetic factors (i.e., differences in the cytochrome families). Moreover, there is a growing body of literature on the structural and functional neuroimaging research into TRS. Neuroimaging studies can help to uncover the underlying neurobiological reasons for such resistance and identify resistant patients earlier. Studies examining the neuropharmacological mechanisms of antipsychotics, including clozapine, can help to improve our knowledge of their action on the central nervous system, with further implications for the discovery of biomarkers and the development of new treatments. The identification of the underlying mechanisms of TRS is a major challenge for developing personalized medicine in the psychiatric field for schizophrenia treatment. The main goal of precision medicine is to use genetic and brain-imaging information to improve the safety, effectiveness, and health outcomes of patients via more efficiently targeted risk stratification, prevention, and tailored medication and treatment management approaches. The aim of this review is to summarize the state of art of pharmacogenetic, pharmacogenomic and neuroimaging studies in TRS.https://www.frontiersin.org/article/10.3389/fphar.2019.00402/fulltreatment resistant schizophrenia (TRS)geneticpharmacogeneticpharmacogenomicneuroimagingprecision medicine |
| spellingShingle | Antonio Vita Antonio Vita Alessandra Minelli Stefano Barlati Stefano Barlati Giacomo Deste Edoardo Giacopuzzi Paolo Valsecchi Cesare Turrina Cesare Turrina Massimo Gennarelli Massimo Gennarelli Treatment-Resistant Schizophrenia: Genetic and Neuroimaging Correlates Frontiers in Pharmacology treatment resistant schizophrenia (TRS) genetic pharmacogenetic pharmacogenomic neuroimaging precision medicine |
| title | Treatment-Resistant Schizophrenia: Genetic and Neuroimaging Correlates |
| title_full | Treatment-Resistant Schizophrenia: Genetic and Neuroimaging Correlates |
| title_fullStr | Treatment-Resistant Schizophrenia: Genetic and Neuroimaging Correlates |
| title_full_unstemmed | Treatment-Resistant Schizophrenia: Genetic and Neuroimaging Correlates |
| title_short | Treatment-Resistant Schizophrenia: Genetic and Neuroimaging Correlates |
| title_sort | treatment resistant schizophrenia genetic and neuroimaging correlates |
| topic | treatment resistant schizophrenia (TRS) genetic pharmacogenetic pharmacogenomic neuroimaging precision medicine |
| url | https://www.frontiersin.org/article/10.3389/fphar.2019.00402/full |
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