Desorganização como preditor de resistência ao tratamento e desfechos desfavoráveis na esquizofrenia
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=7780818 https://repositorio.unifesp.br/handle/11600/59570 |
Resumo: | The heterogeneous outcomes and symptoms in schizophrenia hinder the development of more effective diagnostic methods and treatments. Patients with greater severity of disorganized symptoms appear to be a distinct group, with poor response to conventional antipsychotics and poor outcome. Disorganized syndrome then applies to be a valid marker to identify a more homogeneous subgroup of disease. General objective: To validate disorganization as a predictor of unfavorable outcomes. The following outcomes were investigated in 5 studies: treatment resistance, global severity, functional impairment and symptom progression. Methods: Three samples were included in the analyzes: 1- Longitudinal sample (n = 203), with patients evaluated at admission and discharged during hospitalization in the psychiatry ward of Hospital Luzia de Pinho Melo - included in the five studies. 2- Cross-sectional sample (n = 207) of patients with multiple episodes from the schizophrenia outpatient clinic (Schizophrenia Program- Proesq, UNIFESP) - included in three studies. 3- A cohort (N = 55) of first-episode from Santa Casa de Misericórdia of São Paulo - included in one study. In all samples, the diagnosis of schizophrenia was confirmed by the SCID-I and symptom intensity was assessed using the Positive and Negative Symptoms Syndrome Scale (PANSS), Calgary Depression Scale for Schizophrenia (Calgary), Clinical Global Impression (CGI) and the Global Assessment of Functioning Scale (GAF). Results: Study 1: Eighty-five patients classified 13 according to traditional subtypes were compared for symptom severity and prevalence of treatment resistant schizophrenia (TRS). Patients with disorganized schizophrenia had a higher prevalence of ERT (60%) than paranoid schizophrenia (20%) (Chi-square = X value, p = 0.001). Study 2: The positive, disorganized and negative PANSS dimensions were compared for overall severity with CGI in the acute and stable phase in patients from 3 different centers (n = 298). The disorganized dimension presented the highest correlation with the CGI (0.86). Study 3: In patients from 2 different centers (n = 247), the dimensions of PANSS were compared with functioning in the acute, stable and remission phase. Increased disorganization at baseline predicted non-remission after treatment (p = 0.007; OR = 1.18). It was the dimension that most impaired functioning of patients in the acute phase (p <0.001). Study 4: Patients from 2 different centers (n = 203) were separated into 3 groups (first episode, with up to 5 years of disease and with more than 5 years of disease) and the intensity of each dimension were compared. The disorganized dimension presented the largest progressive increase in intensity among the first episode groups, up to 5 years of disease and more than 5 years of disease. Study 5: In a discovery sample (n = 164), a predictive model of TRS was built based on PANSS items, which were tested in a replication sample (n = 207). The accuracy of the model was tested on a ROC curve in the exploration and replication samples. The sensitivity and specificity of the exploration sample and the replication sample were, respectively, 77.8% and 83.3%, 72.3% and 74.4%. Conclusion: Integrating dimensional and categorical aspects into the psychopathology of schizophrenia has the potential to generate empirical validated data for both clinical practice and research. Dimensions and categories are still the most accessible diagnostic tools for the clinician. New syndrome models associated with clinical outcomes will be instrumental in progressively progressing to precision medicine in psychiatry. |
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Desorganização como preditor de resistência ao tratamento e desfechos desfavoráveis na esquizofreniaDisorganized SchizophreniaTreatment Resistant SchizophreniaClozapineDisorganized DimensionFormal Change Of ThoughtEsquizofrenia DesorganizadaEsquizofrenia Resistente Ao TratamentoClozapinaDimensão DesorganizadaAlteração Formal Do PensamentoThe heterogeneous outcomes and symptoms in schizophrenia hinder the development of more effective diagnostic methods and treatments. Patients with greater severity of disorganized symptoms appear to be a distinct group, with poor response to conventional antipsychotics and poor outcome. Disorganized syndrome then applies to be a valid marker to identify a more homogeneous subgroup of disease. General objective: To validate disorganization as a predictor of unfavorable outcomes. The following outcomes were investigated in 5 studies: treatment resistance, global severity, functional impairment and symptom progression. Methods: Three samples were included in the analyzes: 1- Longitudinal sample (n = 203), with patients evaluated at admission and discharged during hospitalization in the psychiatry ward of Hospital Luzia de Pinho Melo - included in the five studies. 2- Cross-sectional sample (n = 207) of patients with multiple episodes from the schizophrenia outpatient clinic (Schizophrenia Program- Proesq, UNIFESP) - included in three studies. 3- A cohort (N = 55) of first-episode from Santa Casa de Misericórdia of São Paulo - included in one study. In all samples, the diagnosis of schizophrenia was confirmed by the SCID-I and symptom intensity was assessed using the Positive and Negative Symptoms Syndrome Scale (PANSS), Calgary Depression Scale for Schizophrenia (Calgary), Clinical Global Impression (CGI) and the Global Assessment of Functioning Scale (GAF). Results: Study 1: Eighty-five patients classified 13 according to traditional subtypes were compared for symptom severity and prevalence of treatment resistant schizophrenia (TRS). Patients with disorganized schizophrenia had a higher prevalence of ERT (60%) than paranoid schizophrenia (20%) (Chi-square = X value, p = 0.001). Study 2: The positive, disorganized and negative PANSS dimensions were compared for overall severity with CGI in the acute and stable phase in patients from 3 different centers (n = 298). The disorganized dimension presented the highest correlation with the CGI (0.86). Study 3: In patients from 2 different centers (n = 247), the dimensions of PANSS were compared with functioning in the acute, stable and remission phase. Increased disorganization at baseline predicted non-remission after treatment (p = 0.007; OR = 1.18). It was the dimension that most impaired functioning of patients in the acute phase (p <0.001). Study 4: Patients from 2 different centers (n = 203) were separated into 3 groups (first episode, with up to 5 years of disease and with more than 5 years of disease) and the intensity of each dimension were compared. The disorganized dimension presented the largest progressive increase in intensity among the first episode groups, up to 5 years of disease and more than 5 years of disease. Study 5: In a discovery sample (n = 164), a predictive model of TRS was built based on PANSS items, which were tested in a replication sample (n = 207). The accuracy of the model was tested on a ROC curve in the exploration and replication samples. The sensitivity and specificity of the exploration sample and the replication sample were, respectively, 77.8% and 83.3%, 72.3% and 74.4%. Conclusion: Integrating dimensional and categorical aspects into the psychopathology of schizophrenia has the potential to generate empirical validated data for both clinical practice and research. Dimensions and categories are still the most accessible diagnostic tools for the clinician. New syndrome models associated with clinical outcomes will be instrumental in progressively progressing to precision medicine in psychiatry.Os desfechos e sintomas heterogêneos na esquizofrenia dificultam o desenvolvimento de métodos diagnósticos e tratamentos mais efetivos. Os pacientes com maior gravidade de sintomas desorganizados parecem um grupo distinto, com baixa resposta aos antipsicóticos convencionais e pior evolução. A síndrome desorganizada se candidata então a ser um marcador válido para identificar um subgrupo mais homogêneo de doença. Objetivo geral: Validar a desorganização como indicador de clínica desfavorável. Foram investigados em 5 artigos os seguintes desfechos: resistência ao tratamento, gravidade global, prejuízo funcional e progressão de sintomas. Métodos: Foram incluídas 3 amostras nas análises: 1- Amostra longitudinal (N= 203 ) , com pacientes avaliados na admissão e alta durante a internação na enfermaria de psiquiatria do Hospital Luzia de Pinho Melo entre - investigada nos cinco estudos . 2- Amostra transversal (N= 207) de pacientes com múltiplos episódios do ambulatório de esquizofrenia do Proesq (Programa de Esquizofrenia, UNIFESP) -– utilizada em 3 estudos. 3- Amostra (N= 55) de uma coorte de primeiro episódio da Santa Casa de Misericórdia de São Paulo - utilizada em 1 estudo. Em todas as amostras, o diagnóstico de esquizofrenia foi confirmado pela SCID-I e a intensidade de sintomas foi avaliada por meio da Escala de Sintomas para as Síndromes Positiva e Negativa (PANSS), Escala Calgary de Depressão para Esquizofrenia (Calgary), Escala de Impressão Clínica CGI e Escala de Avaliação o Funcionamento Global AGF. Resultados: Estudo 1: Oitenta e cinco pacientes classificados quanto aos subtipos tradicionais, foram comparados quanto à gravidade de sintomas e à prevalência de esquizofrenia resistente ao tratamento (ERT). Pacientes com esquizofrenia desorganizada apresentou maior prevalência de ERT (60%) do que esquizofrenia paranóide (20%) (Chi-square= X value, p = 0,001). Estudo 2: As dimensões positiva, desorganizada e negativa da PANSS foram comparadas quanto a gravidade global com a CGI na fase aguda e na fase estável, em pacientes de 3 centros diferentes (n= 298). A dimensão desorganizada apresentou maior correlação com a CGI (0,86). Estudo 3: Em pacientes de 2 centros diferentes (n= 247), as dimensões da PANSS foram comparadas quanto à funcionalidade na fase aguda, estável e em remissão. A desorganização foi preditora de menor a chance de obter remissão após o tratamento (p = 0,007; OR = 1,18). Foi a dimensão que mais afetou a funcionalidade dos pacientes na fase aguda (p <0,001). Estudo 4: Pacientes de 2 centros diferentes (n = 203) foram separados em 3 grupos (primeiro episódio, com até 5 anos de doença e com 12 mais de 5 anos de doença) que foram comparados quanto à intensidade de cada dimensão. A dimensão desorganizada apresentou o maior aumento progressivo de intensidade entre os grupos de primeiro episódio, até 5 anos de doença e mais de 5 anos de doença Estudo 5: Numa amostra de descoberta (n=164), foi construído um modelo preditivo de ERT baseado nos itens da PANSS, que foi testado em amostra de replicação (n= 207). A acurácia do modelo foi testada em curva ROC nas amostras de exploração e replicação. A sensibilidade e especificidade da amostra de exploração e da amostra de replicação foi, respectivamente, de 77,8% e 83,3%, 72,3% e 74,4%. Conclusão: Integrar aspectos dimensionais e categóricos na psicopatologia da esquizofrenia tem o potencial de gerar dados empiricamente validados tanto para a prática clínica como para pesquisa. Dimensões e categorias ainda são os instrumentos diagnósticos mais acessíveis ao clínico. Novos modelos sindrômicos associados a desfechos clínicos serão fundamentais para avançar progressivamente para a medicina de precisão em psiquiatria.Dados abertos - Sucupira - Teses e dissertações (2019)Universidade Federal de São Paulo (UNIFESP)Araripe Neto, Ary Gadelha De Alencar [UNIFESP]http://lattes.cnpq.br/8107200180236710http://lattes.cnpq.br/3379099368507304Universidade Federal de São Paulo (UNIFESP)Ortiz, Bruno Bertolucci [UNIFESP]2021-01-19T16:33:42Z2021-01-19T16:33:42Z2019-10-25info:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/publishedVersion114f.https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=7780818ORTIZ, Bruno Bertolucci. Desorganização como preditor de resistência ao tratamento e desfechos desfavoráveis na esquizofrenia. 2019. 114 f. Tese (Doutorado em Psiquiatria e Psicologia Médica) – Escola Paulista de Medicina, Universidade Federal de São Paulo. São Paulo, 2019.https://repositorio.unifesp.br/handle/11600/59570porinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP2024-06-17T15:31:03Zoai:repositorio.unifesp.br/:11600/59570Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestbiblioteca.csp@unifesp.bropendoar:34652024-06-17T15:31:03Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.none.fl_str_mv |
Desorganização como preditor de resistência ao tratamento e desfechos desfavoráveis na esquizofrenia |
title |
Desorganização como preditor de resistência ao tratamento e desfechos desfavoráveis na esquizofrenia |
spellingShingle |
Desorganização como preditor de resistência ao tratamento e desfechos desfavoráveis na esquizofrenia Ortiz, Bruno Bertolucci [UNIFESP] Disorganized Schizophrenia Treatment Resistant Schizophrenia Clozapine Disorganized Dimension Formal Change Of Thought Esquizofrenia Desorganizada Esquizofrenia Resistente Ao Tratamento Clozapina Dimensão Desorganizada Alteração Formal Do Pensamento |
title_short |
Desorganização como preditor de resistência ao tratamento e desfechos desfavoráveis na esquizofrenia |
title_full |
Desorganização como preditor de resistência ao tratamento e desfechos desfavoráveis na esquizofrenia |
title_fullStr |
Desorganização como preditor de resistência ao tratamento e desfechos desfavoráveis na esquizofrenia |
title_full_unstemmed |
Desorganização como preditor de resistência ao tratamento e desfechos desfavoráveis na esquizofrenia |
title_sort |
Desorganização como preditor de resistência ao tratamento e desfechos desfavoráveis na esquizofrenia |
author |
Ortiz, Bruno Bertolucci [UNIFESP] |
author_facet |
Ortiz, Bruno Bertolucci [UNIFESP] |
author_role |
author |
dc.contributor.none.fl_str_mv |
Araripe Neto, Ary Gadelha De Alencar [UNIFESP] http://lattes.cnpq.br/8107200180236710 http://lattes.cnpq.br/3379099368507304 Universidade Federal de São Paulo (UNIFESP) |
dc.contributor.author.fl_str_mv |
Ortiz, Bruno Bertolucci [UNIFESP] |
dc.subject.por.fl_str_mv |
Disorganized Schizophrenia Treatment Resistant Schizophrenia Clozapine Disorganized Dimension Formal Change Of Thought Esquizofrenia Desorganizada Esquizofrenia Resistente Ao Tratamento Clozapina Dimensão Desorganizada Alteração Formal Do Pensamento |
topic |
Disorganized Schizophrenia Treatment Resistant Schizophrenia Clozapine Disorganized Dimension Formal Change Of Thought Esquizofrenia Desorganizada Esquizofrenia Resistente Ao Tratamento Clozapina Dimensão Desorganizada Alteração Formal Do Pensamento |
description |
The heterogeneous outcomes and symptoms in schizophrenia hinder the development of more effective diagnostic methods and treatments. Patients with greater severity of disorganized symptoms appear to be a distinct group, with poor response to conventional antipsychotics and poor outcome. Disorganized syndrome then applies to be a valid marker to identify a more homogeneous subgroup of disease. General objective: To validate disorganization as a predictor of unfavorable outcomes. The following outcomes were investigated in 5 studies: treatment resistance, global severity, functional impairment and symptom progression. Methods: Three samples were included in the analyzes: 1- Longitudinal sample (n = 203), with patients evaluated at admission and discharged during hospitalization in the psychiatry ward of Hospital Luzia de Pinho Melo - included in the five studies. 2- Cross-sectional sample (n = 207) of patients with multiple episodes from the schizophrenia outpatient clinic (Schizophrenia Program- Proesq, UNIFESP) - included in three studies. 3- A cohort (N = 55) of first-episode from Santa Casa de Misericórdia of São Paulo - included in one study. In all samples, the diagnosis of schizophrenia was confirmed by the SCID-I and symptom intensity was assessed using the Positive and Negative Symptoms Syndrome Scale (PANSS), Calgary Depression Scale for Schizophrenia (Calgary), Clinical Global Impression (CGI) and the Global Assessment of Functioning Scale (GAF). Results: Study 1: Eighty-five patients classified 13 according to traditional subtypes were compared for symptom severity and prevalence of treatment resistant schizophrenia (TRS). Patients with disorganized schizophrenia had a higher prevalence of ERT (60%) than paranoid schizophrenia (20%) (Chi-square = X value, p = 0.001). Study 2: The positive, disorganized and negative PANSS dimensions were compared for overall severity with CGI in the acute and stable phase in patients from 3 different centers (n = 298). The disorganized dimension presented the highest correlation with the CGI (0.86). Study 3: In patients from 2 different centers (n = 247), the dimensions of PANSS were compared with functioning in the acute, stable and remission phase. Increased disorganization at baseline predicted non-remission after treatment (p = 0.007; OR = 1.18). It was the dimension that most impaired functioning of patients in the acute phase (p <0.001). Study 4: Patients from 2 different centers (n = 203) were separated into 3 groups (first episode, with up to 5 years of disease and with more than 5 years of disease) and the intensity of each dimension were compared. The disorganized dimension presented the largest progressive increase in intensity among the first episode groups, up to 5 years of disease and more than 5 years of disease. Study 5: In a discovery sample (n = 164), a predictive model of TRS was built based on PANSS items, which were tested in a replication sample (n = 207). The accuracy of the model was tested on a ROC curve in the exploration and replication samples. The sensitivity and specificity of the exploration sample and the replication sample were, respectively, 77.8% and 83.3%, 72.3% and 74.4%. Conclusion: Integrating dimensional and categorical aspects into the psychopathology of schizophrenia has the potential to generate empirical validated data for both clinical practice and research. Dimensions and categories are still the most accessible diagnostic tools for the clinician. New syndrome models associated with clinical outcomes will be instrumental in progressively progressing to precision medicine in psychiatry. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-10-25 2021-01-19T16:33:42Z 2021-01-19T16:33:42Z |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=7780818 ORTIZ, Bruno Bertolucci. Desorganização como preditor de resistência ao tratamento e desfechos desfavoráveis na esquizofrenia. 2019. 114 f. Tese (Doutorado em Psiquiatria e Psicologia Médica) – Escola Paulista de Medicina, Universidade Federal de São Paulo. São Paulo, 2019. https://repositorio.unifesp.br/handle/11600/59570 |
url |
https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=7780818 https://repositorio.unifesp.br/handle/11600/59570 |
identifier_str_mv |
ORTIZ, Bruno Bertolucci. Desorganização como preditor de resistência ao tratamento e desfechos desfavoráveis na esquizofrenia. 2019. 114 f. Tese (Doutorado em Psiquiatria e Psicologia Médica) – Escola Paulista de Medicina, Universidade Federal de São Paulo. São Paulo, 2019. |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
114f. |
dc.publisher.none.fl_str_mv |
Universidade Federal de São Paulo (UNIFESP) |
publisher.none.fl_str_mv |
Universidade Federal de São Paulo (UNIFESP) |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UNIFESP instname:Universidade Federal de São Paulo (UNIFESP) instacron:UNIFESP |
instname_str |
Universidade Federal de São Paulo (UNIFESP) |
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UNIFESP |
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UNIFESP |
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Repositório Institucional da UNIFESP |
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Repositório Institucional da UNIFESP |
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Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP) |
repository.mail.fl_str_mv |
biblioteca.csp@unifesp.br |
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1814268355507388416 |