Medicina de precisión en Psiquiatría: enfoque integral para las enfermedades mentales severas
La convergencia entre la psiquiatría y la medicina de precisión como un enfoque innovador, surge como una perspectiva prometedora que busca transformar la atención al utilizar características únicas del paciente (datos clínicos, genéticos y ambientales), para abordar las limitaciones actuales en el...
- Autores:
-
Taimal, Darío
Sierra, Nicolás
Orozco Betancourt, Laura Valentina
Hernández Cuellar, Camilo Eduardo
Valencia Echeverry, Johanna
Palacio Ortiz, Juan David
López Jaramillo, Carlos Alberto
- Tipo de recurso:
- Fecha de publicación:
- 2024
- Institución:
- Universidad de Antioquia
- Repositorio:
- Repositorio UdeA
- Idioma:
- spa
- OAI Identifier:
- oai:bibliotecadigital.udea.edu.co:10495/48074
- Acceso en línea:
- https://hdl.handle.net/10495/48074
- Palabra clave:
- Variación Genética
Genetic Variation
Enfermedades Mentales Severas
Mental Disorders
Polimorfismos de un Solo Nucleótido
Polymorphism Single Nucleotide
Trastorno Bipolar
Bipolar Disorder
Trastorno Depresivo Mayor
Depressive Disorder, Major
Esquizofrenia
Schizophrenia
https://id.nlm.nih.gov/mesh/D014644
https://id.nlm.nih.gov/mesh/D001523
https://id.nlm.nih.gov/mesh/D001714
https://id.nlm.nih.gov/mesh/D003865
https://id.nlm.nih.gov/mesh/D012559
ODS 3: Salud y bienestar. Garantizar una vida sana y promover el bienestar de todos a todas las edades
- Rights
- openAccess
- License
- http://creativecommons.org/licenses/by-nc-sa/4.0/
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Medicina de precisión en Psiquiatría: enfoque integral para las enfermedades mentales severas |
| dc.title.translated.none.fl_str_mv |
Precision Medicine in Psychiatry: Comprehensive Approach to Severe Mental Illnesses |
| title |
Medicina de precisión en Psiquiatría: enfoque integral para las enfermedades mentales severas |
| spellingShingle |
Medicina de precisión en Psiquiatría: enfoque integral para las enfermedades mentales severas Variación Genética Genetic Variation Enfermedades Mentales Severas Mental Disorders Polimorfismos de un Solo Nucleótido Polymorphism Single Nucleotide Trastorno Bipolar Bipolar Disorder Trastorno Depresivo Mayor Depressive Disorder, Major Esquizofrenia Schizophrenia https://id.nlm.nih.gov/mesh/D014644 https://id.nlm.nih.gov/mesh/D001523 https://id.nlm.nih.gov/mesh/D001714 https://id.nlm.nih.gov/mesh/D003865 https://id.nlm.nih.gov/mesh/D012559 ODS 3: Salud y bienestar. Garantizar una vida sana y promover el bienestar de todos a todas las edades |
| title_short |
Medicina de precisión en Psiquiatría: enfoque integral para las enfermedades mentales severas |
| title_full |
Medicina de precisión en Psiquiatría: enfoque integral para las enfermedades mentales severas |
| title_fullStr |
Medicina de precisión en Psiquiatría: enfoque integral para las enfermedades mentales severas |
| title_full_unstemmed |
Medicina de precisión en Psiquiatría: enfoque integral para las enfermedades mentales severas |
| title_sort |
Medicina de precisión en Psiquiatría: enfoque integral para las enfermedades mentales severas |
| dc.creator.fl_str_mv |
Taimal, Darío Sierra, Nicolás Orozco Betancourt, Laura Valentina Hernández Cuellar, Camilo Eduardo Valencia Echeverry, Johanna Palacio Ortiz, Juan David López Jaramillo, Carlos Alberto |
| dc.contributor.author.none.fl_str_mv |
Taimal, Darío Sierra, Nicolás Orozco Betancourt, Laura Valentina Hernández Cuellar, Camilo Eduardo Valencia Echeverry, Johanna Palacio Ortiz, Juan David López Jaramillo, Carlos Alberto |
| dc.contributor.researchgroup.none.fl_str_mv |
Grupo de Investigación en Psiquiatría GIPSI |
| dc.subject.decs.none.fl_str_mv |
Variación Genética Genetic Variation Enfermedades Mentales Severas Mental Disorders Polimorfismos de un Solo Nucleótido Polymorphism Single Nucleotide Trastorno Bipolar Bipolar Disorder Trastorno Depresivo Mayor Depressive Disorder, Major Esquizofrenia Schizophrenia |
| topic |
Variación Genética Genetic Variation Enfermedades Mentales Severas Mental Disorders Polimorfismos de un Solo Nucleótido Polymorphism Single Nucleotide Trastorno Bipolar Bipolar Disorder Trastorno Depresivo Mayor Depressive Disorder, Major Esquizofrenia Schizophrenia https://id.nlm.nih.gov/mesh/D014644 https://id.nlm.nih.gov/mesh/D001523 https://id.nlm.nih.gov/mesh/D001714 https://id.nlm.nih.gov/mesh/D003865 https://id.nlm.nih.gov/mesh/D012559 ODS 3: Salud y bienestar. Garantizar una vida sana y promover el bienestar de todos a todas las edades |
| dc.subject.meshuri.none.fl_str_mv |
https://id.nlm.nih.gov/mesh/D014644 https://id.nlm.nih.gov/mesh/D001523 https://id.nlm.nih.gov/mesh/D001714 https://id.nlm.nih.gov/mesh/D003865 https://id.nlm.nih.gov/mesh/D012559 |
| dc.subject.ods.none.fl_str_mv |
ODS 3: Salud y bienestar. Garantizar una vida sana y promover el bienestar de todos a todas las edades |
| description |
La convergencia entre la psiquiatría y la medicina de precisión como un enfoque innovador, surge como una perspectiva prometedora que busca transformar la atención al utilizar características únicas del paciente (datos clínicos, genéticos y ambientales), para abordar las limitaciones actuales en el diagnóstico, selección de tratamientos y variabilidad de la eficacia terapéutica en la enfermedad mental severa. [Tomado de la introducción] |
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2024 |
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2024 |
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2025-11-03T13:57:03Z |
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Artículo de revista |
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Taimal D, Sierra N, Orozco LV, Hernández-Cuellar CE, Valencia Echeverry J, Palacio-Ortiz JD, López C. Medicina de precisión en Psiquiatría: Enfoque integral para las enfermedades mentales severas. [Internet]. Medellín: Perlas Clínicas, Facultad de Medicina, Universidad de Antioquia; 2024 [Acceso día de mes de año]. DOI: https://doi.org/10.59473/medudea.pc.2024.93 |
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https://hdl.handle.net/10495/48074 |
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10.59473/medudea.pc.2024.93 |
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Taimal D, Sierra N, Orozco LV, Hernández-Cuellar CE, Valencia Echeverry J, Palacio-Ortiz JD, López C. Medicina de precisión en Psiquiatría: Enfoque integral para las enfermedades mentales severas. [Internet]. Medellín: Perlas Clínicas, Facultad de Medicina, Universidad de Antioquia; 2024 [Acceso día de mes de año]. DOI: https://doi.org/10.59473/medudea.pc.2024.93 10.59473/medudea.pc.2024.93 |
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spa |
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Wium-Andersen I, Kim M, Vinberg LV, Kessing RS. Personalized Medicine in Psychiatry. Nordic Journal of Psychiatry. 2017;71(1):12–9. Manchia M, Pisanu C, Squassina A, Carpiniello B. Challenges and Future Prospects of Precision Medicine in Psychiatry. Pharmacogenomics and Personalized Medicine. 2020;13:127–40. Spatz MA. Genetics Home Reference. J Med Libr Assoc. 2004;92(2):282–3. Perugi G, Rossi PD, Fagiolini A, Girardi P, Maina G, Sani G, et al. Personalized and Precision Medicine as Informants for Treatment Management of Bipolar Disorder. International Clinical Psychopharmacology. 2019;34(4):189–205. Haggarty SJ, Rakesh Karmacharya RH. Advances toward Precision Medicine for Bipolar Disorder: Mechanisms & Molecules. Molecular Psychiatry. 2021;26(1):168–85. Roche D, Russell V. Can Precision Medicine Advance Psychiatry? Irish Journal of Psychological Medicine. 2021;38(3):163–8. Hasler G, Wolf A. Toward Stratified Treatments for Bipolar Disorders. European Neuropsychopharmacology: The Journal of the European College of Neuropsychopharmacology. 2015;25(3):283–94. Budde M, Forstner AJ, Adorjan K, Schaupp SK, Nöthen MM, Schulze TG. Genetische Grundlagen der bipolaren Störung. Nervenarzt. 2017 Jul;88(7):755–9. Sagar R, Pattanayak RD. Potential Biomarkers for Bipolar Disorder: Where Do We Stand? The Indian Journal of Medical Research. 2017;145(1):7–16. Alda M, Manchia M. Personalized Management of Bipolar Disorder. Neuroscience Letters. 2018;669:3–9. Fabbri C, Serretti A. How to Utilize Clinical and Genetic Information for Personalized Treatment of Major Depressive Disorder: Step by Step Strategic Approach. Clinical Psychopharmacology and Neuroscience: The Official Scientific Journal of the Korean College of Neuropsychopharmacology. 2020;18(4):484–92. Oslin DW, Kevin G, Lynch M-C, Shih EP, Ingram LO, Wray SR, et al. Effect of Pharmacogenomic Testing for Drug-Gene Interactions on Medication Selection and Remission of Symptoms in Major Depressive Disorder: The PRIME Care Randomized Clinical Trial. JAMA: The Journal of the American Medical Association. 2022;328(2):151–61. Hark T, Cornelis SE, Vos F, Aarnoutse RE, Schene AH, Marieke JH, et al. Biomarkers as Predictors of Treatment Response to Tricyclic Antidepressants in Major Depressive Disorder: A Systematic Review. Journal of Psychiatric Research. 2022;150:202–13. Lisoway AJ, Cheng C, Chen CC, Zai AK, Tiwari JL. Toward Personalized Medicine in Schizophrenia: Genetics and Epigenetics of Antipsychotic Treatment. Schizophrenia Research. 2021;232:112–24. Liang-Kun Y, Su Y-Y-N, Zhang H, Yu Z, Lu W-Q, Li Y-F. Prediction of Treatment Response to Antipsychotic Drugs for Precision Medicine Approach to Schizophrenia: Randomized Trials and Multiomics Analysis. Military Medical Research. 2023;10(1). Leon J. Personalizing Dosing of Risperidone, Paliperidone and Clozapine Using Therapeutic Drug Monitoring and Pharmacogenetics. Neuropharmacology. 2020;168. Wada M, Noda Y, Iwata Y, Tsugawa S, Yoshida K, Tani H, et al. Dopaminergic Dysfunction and Excitatory/inhibitory Imbalance in Treatment-Resistant Schizophrenia and Novel Neuromodulatory Treatment. Molecular Psychiatry. 2022;27(7):2950–67. Pruebas De ADN [Internet]. Genetrack Biolabs. [cited 2024 Nov 14]. Available from: https://www.genetrack.com.co/tests/ Molecular G. Genética Molecular de Colombia – Estudios en el ADN [Internet]. Genética Molecular de Colombia. 2021 [cited 2024 Nov 14]. Available from: https://geneticamolecular.co/ Henderson K, Keeling C. Cost-effectiveness of molecular biomarker testing in lung cancer: Enhancing survival and resource optimization. Journal of Precision Oncology. 2021;12(4):463–78. Plan de Beneficios en Salud con Cargo a la UPC. Ministerio de Salud y Protección Social; 2015. Samani N, Watson J, Dean B. Precision medicine in mental health: Implementation challenges in low- and middle-income countries. Global Health Journal. 2022;8(3):115–25. Oslin DW, Lynch KG, Shih M-C, Ingram EP, Wray LO, Chapman SR, et al. Effect of pharmacogenomic testing for drug-gene interactions on medication selection and remission of symptoms in major depressive disorder. JAMA. 2022 Jul 12;328(2):151. Stevens AD, Yu Q. Pharmacogenomics and predictive biomarkers in schizophrenia treatment optimization. Psychiatric Genomics. 2023;34(2):99–112. Wium-Andersen I, Kim M. Integrating blood and genetic biomarkers in psychiatry: A review of cost and practical implications. Nordic Journal of Psychiatry. 2023;77(1):14–22. |
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Taimal, DaríoSierra, NicolásOrozco Betancourt, Laura ValentinaHernández Cuellar, Camilo EduardoValencia Echeverry, JohannaPalacio Ortiz, Juan DavidLópez Jaramillo, Carlos AlbertoGrupo de Investigación en Psiquiatría GIPSI2025-11-03T13:57:03Z2024Taimal D, Sierra N, Orozco LV, Hernández-Cuellar CE, Valencia Echeverry J, Palacio-Ortiz JD, López C. Medicina de precisión en Psiquiatría: Enfoque integral para las enfermedades mentales severas. [Internet]. Medellín: Perlas Clínicas, Facultad de Medicina, Universidad de Antioquia; 2024 [Acceso día de mes de año]. DOI: https://doi.org/10.59473/medudea.pc.2024.93https://hdl.handle.net/10495/4807410.59473/medudea.pc.2024.93La convergencia entre la psiquiatría y la medicina de precisión como un enfoque innovador, surge como una perspectiva prometedora que busca transformar la atención al utilizar características únicas del paciente (datos clínicos, genéticos y ambientales), para abordar las limitaciones actuales en el diagnóstico, selección de tratamientos y variabilidad de la eficacia terapéutica en la enfermedad mental severa. [Tomado de la introducción]COL002914715 páginasapplication/pdfspaUniversidad de Antioquia, Facultad de MedicinaMedellín, Colombiahttp://creativecommons.org/licenses/by-nc-sa/4.0/info:eu-repo/semantics/openAccessAttribution-NonCommercial-ShareAlike 4.0 Internationalhttp://purl.org/coar/access_right/c_abf2Medicina de precisión en Psiquiatría: enfoque integral para las enfermedades mentales severasPrecision Medicine in Psychiatry: Comprehensive Approach to Severe Mental IllnessesArtículo de revistahttp://purl.org/coar/resource_type/c_3e5ahttps://purl.org/redcol/resource_type/GCTexthttp://purl.org/coar/version/c_b1a7d7d4d402bcceinfo:eu-repo/semantics/contributionToPeriodicalinfo:eu-repo/semantics/draftWium-Andersen I, Kim M, Vinberg LV, Kessing RS. Personalized Medicine in Psychiatry. Nordic Journal of Psychiatry. 2017;71(1):12–9.Manchia M, Pisanu C, Squassina A, Carpiniello B. Challenges and Future Prospects of Precision Medicine in Psychiatry. Pharmacogenomics and Personalized Medicine. 2020;13:127–40.Spatz MA. Genetics Home Reference. J Med Libr Assoc. 2004;92(2):282–3.Perugi G, Rossi PD, Fagiolini A, Girardi P, Maina G, Sani G, et al. Personalized and Precision Medicine as Informants for Treatment Management of Bipolar Disorder. International Clinical Psychopharmacology. 2019;34(4):189–205.Haggarty SJ, Rakesh Karmacharya RH. Advances toward Precision Medicine for Bipolar Disorder: Mechanisms & Molecules. Molecular Psychiatry. 2021;26(1):168–85.Roche D, Russell V. Can Precision Medicine Advance Psychiatry? Irish Journal of Psychological Medicine. 2021;38(3):163–8.Hasler G, Wolf A. Toward Stratified Treatments for Bipolar Disorders. European Neuropsychopharmacology: The Journal of the European College of Neuropsychopharmacology. 2015;25(3):283–94.Budde M, Forstner AJ, Adorjan K, Schaupp SK, Nöthen MM, Schulze TG. Genetische Grundlagen der bipolaren Störung. Nervenarzt. 2017 Jul;88(7):755–9.Sagar R, Pattanayak RD. Potential Biomarkers for Bipolar Disorder: Where Do We Stand? The Indian Journal of Medical Research. 2017;145(1):7–16.Alda M, Manchia M. Personalized Management of Bipolar Disorder. Neuroscience Letters. 2018;669:3–9.Fabbri C, Serretti A. How to Utilize Clinical and Genetic Information for Personalized Treatment of Major Depressive Disorder: Step by Step Strategic Approach. Clinical Psychopharmacology and Neuroscience: The Official Scientific Journal of the Korean College of Neuropsychopharmacology. 2020;18(4):484–92.Oslin DW, Kevin G, Lynch M-C, Shih EP, Ingram LO, Wray SR, et al. Effect of Pharmacogenomic Testing for Drug-Gene Interactions on Medication Selection and Remission of Symptoms in Major Depressive Disorder: The PRIME Care Randomized Clinical Trial. JAMA: The Journal of the American Medical Association. 2022;328(2):151–61.Hark T, Cornelis SE, Vos F, Aarnoutse RE, Schene AH, Marieke JH, et al. Biomarkers as Predictors of Treatment Response to Tricyclic Antidepressants in Major Depressive Disorder: A Systematic Review. Journal of Psychiatric Research. 2022;150:202–13.Lisoway AJ, Cheng C, Chen CC, Zai AK, Tiwari JL. Toward Personalized Medicine in Schizophrenia: Genetics and Epigenetics of Antipsychotic Treatment. Schizophrenia Research. 2021;232:112–24.Liang-Kun Y, Su Y-Y-N, Zhang H, Yu Z, Lu W-Q, Li Y-F. Prediction of Treatment Response to Antipsychotic Drugs for Precision Medicine Approach to Schizophrenia: Randomized Trials and Multiomics Analysis. Military Medical Research. 2023;10(1).Leon J. Personalizing Dosing of Risperidone, Paliperidone and Clozapine Using Therapeutic Drug Monitoring and Pharmacogenetics. Neuropharmacology. 2020;168.Wada M, Noda Y, Iwata Y, Tsugawa S, Yoshida K, Tani H, et al. Dopaminergic Dysfunction and Excitatory/inhibitory Imbalance in Treatment-Resistant Schizophrenia and Novel Neuromodulatory Treatment. Molecular Psychiatry. 2022;27(7):2950–67.Pruebas De ADN [Internet]. Genetrack Biolabs. [cited 2024 Nov 14]. Available from: https://www.genetrack.com.co/tests/Molecular G. Genética Molecular de Colombia – Estudios en el ADN [Internet]. Genética Molecular de Colombia. 2021 [cited 2024 Nov 14]. Available from: https://geneticamolecular.co/Henderson K, Keeling C. Cost-effectiveness of molecular biomarker testing in lung cancer: Enhancing survival and resource optimization. Journal of Precision Oncology. 2021;12(4):463–78.Plan de Beneficios en Salud con Cargo a la UPC. Ministerio de Salud y Protección Social; 2015.Samani N, Watson J, Dean B. Precision medicine in mental health: Implementation challenges in low- and middle-income countries. Global Health Journal. 2022;8(3):115–25.Oslin DW, Lynch KG, Shih M-C, Ingram EP, Wray LO, Chapman SR, et al. Effect of pharmacogenomic testing for drug-gene interactions on medication selection and remission of symptoms in major depressive disorder. JAMA. 2022 Jul 12;328(2):151.Stevens AD, Yu Q. Pharmacogenomics and predictive biomarkers in schizophrenia treatment optimization. Psychiatric Genomics. 2023;34(2):99–112.Wium-Andersen I, Kim M. Integrating blood and genetic biomarkers in psychiatry: A review of cost and practical implications. Nordic Journal of Psychiatry. 2023;77(1):14–22.Perlas ClínicasVariación GenéticaGenetic VariationEnfermedades Mentales SeverasMental DisordersPolimorfismos de un Solo NucleótidoPolymorphism Single NucleotideTrastorno BipolarBipolar DisorderTrastorno Depresivo MayorDepressive Disorder, MajorEsquizofreniaSchizophreniahttps://id.nlm.nih.gov/mesh/D014644https://id.nlm.nih.gov/mesh/D001523https://id.nlm.nih.gov/mesh/D001714https://id.nlm.nih.gov/mesh/D003865https://id.nlm.nih.gov/mesh/D012559ODS 3: Salud y bienestar. 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