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Abstract(s)
A esquizofrenia é uma síndrome complexa de etiologia desconhecida e difícil manejo. O tratamento atualmente disponível está aquém do ideal, e o diagnóstico é muitas vezes complicado. A bilirrubina não-conjugada tem sido pesquisada como um potencial marcador biológico para a doença, de forma a facilitar o diagnóstico, seleção de tratamento e seguimento. Este artigo de revisão tem como objetivo reunir os estudos publicados até o momento sobre a relação entre esta molécula e a esquizofrenia. Foram utilizados critérios amplos para serem incluídos o máximo de estudos relevantes. Catorze estudos foram selecionados: três estudaram os efeitos da hiperbilirrubinemia não-conjugada em modelos animais, seis demonstraram um aumento da incidência de esquizofrenia em pacientes com bilirrubina não-conjugada aumentada, dois relataram um aumento da incidência da doença em pacientes com bilirrubina não-conjugada diminuída, e três ligaram uma maior incidência de esquizofrenia em pacientes com uma maior excreção do produto oxidativo da molécula, as chamadas biopirrinas. Devido a estudos com resultados aparentemente contraditórios, foi levantada a hipótese de que a relação entre a esquizofrenia e a bilirrubina não-conjugada não fosse linear, e que existisse uma disfunção de base nos mecanismos inflamatórios. Descreveram-se os dois modelos mais aceites para a patofisiologia da esquizofrenia, e elucidou-se o possível papel da molécula em ambos. Explicou-se o sistema tampão da bilirrubina e o seu papel na defesa antioxidante do organismo. Comparou-se, por último, os níveis médios de bilirrubina não-conjugada de pacientes esquizofrénicos, esquizoafetivos e bipolares, levantando-se a hipótese de serem diferentes pontos num mesmo espectro patológico. Finalmente, conclui-se que a bilirrubina não-conjugada é uma molécula promissora como um eventual marcador biológico para a doença, e comentou-se a necessidade de esforços subsequentes na pesquisa desta proteína.
Schizophrenia is a complex syndrome of unknown etiology and difficult management. The currently available treatment is far from ideal, and the diagnosis is often complicated. Unconjugated bilirubin has been researched as a potential biological marker of the disease, as a way to facilitate the diagnosis, treatment selection and follow-up. The objective of this review article is to gather the studies published to date about the relationship between this molecule and schizophrenia. Broad inclusion criteria have been used as to include as many relevant studies as possible. Fourteen studies were selected: three analyzed the effects of unconjugated hyperbilirubinemia in animal models, six demonstrated an increased incidence of schizophrenia in patients with increased unconjugated bilirubin, two reported an increased incidence of the disease in patients with decreased unconjugated bilirubin, and three linked an increased incidence of schizophrenia with an increased excretion of bilirubin’s oxidative product, the so-called biopyrrins. Because of apparently contradictory reported results, the hypothesis that the relationship between schizophrenia and unconjugated bilirubin wasn’t linear, and that there was an inflammatory disfunction explaining this, was considered. The two most accepted models for the pathophysiology of schizophrenia were described, and the possible role of the molecule in each was clarified. The bilirubin buffer system and its role in the body’s antioxidant defense was explained. The average levels of unconjugated bilirubin of schizophrenic, schizoaffective and bipolar patients were also compared, having been hypothesized that these diseases could be different points of a same pathological spectrum. Finally, it was concluded that unconjugated bilirubin is a promising molecule that could be used as a possible biological marker for schizophrenia, and the necessity of subsequent efforts for its research was considered.
Schizophrenia is a complex syndrome of unknown etiology and difficult management. The currently available treatment is far from ideal, and the diagnosis is often complicated. Unconjugated bilirubin has been researched as a potential biological marker of the disease, as a way to facilitate the diagnosis, treatment selection and follow-up. The objective of this review article is to gather the studies published to date about the relationship between this molecule and schizophrenia. Broad inclusion criteria have been used as to include as many relevant studies as possible. Fourteen studies were selected: three analyzed the effects of unconjugated hyperbilirubinemia in animal models, six demonstrated an increased incidence of schizophrenia in patients with increased unconjugated bilirubin, two reported an increased incidence of the disease in patients with decreased unconjugated bilirubin, and three linked an increased incidence of schizophrenia with an increased excretion of bilirubin’s oxidative product, the so-called biopyrrins. Because of apparently contradictory reported results, the hypothesis that the relationship between schizophrenia and unconjugated bilirubin wasn’t linear, and that there was an inflammatory disfunction explaining this, was considered. The two most accepted models for the pathophysiology of schizophrenia were described, and the possible role of the molecule in each was clarified. The bilirubin buffer system and its role in the body’s antioxidant defense was explained. The average levels of unconjugated bilirubin of schizophrenic, schizoaffective and bipolar patients were also compared, having been hypothesized that these diseases could be different points of a same pathological spectrum. Finally, it was concluded that unconjugated bilirubin is a promising molecule that could be used as a possible biological marker for schizophrenia, and the necessity of subsequent efforts for its research was considered.
Description
Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2018
Keywords
Esquizofrenia Bilirrubina não-conjugada Biopirrinas Doença bipolar Psiquiatria