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Unconjugated bilirubin and schizophrenia: a systematic review

Published online by Cambridge University Press:  27 March 2019

Erik Pommerening Dornelles ,
João Gama Marques Open the ORCID record for João Gama Marques [Opens in a new window]  and
Sílvia Ouakinin
Erik Pommerening Dornelles
Affiliation:
Clínica Universitária de Psiquiatria e Psicologia Médica, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal
João Gama Marques*
Affiliation:
Clínica Universitária de Psiquiatria e Psicologia Médica, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal Consulta de Esquizofrenia Resistente, Hospital Júlio de Matos, Centro Hospitalar Psiquiátrico de Lisboa, Lisboa, Portugal
Sílvia Ouakinin
Affiliation:
Clínica Universitária de Psiquiatria e Psicologia Médica, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal
*
*Address for correspondence: João Gama Marques, Hospital Júlio de Matos, Avenida do Brasil, 53, 1749-002 Lisboa, Portugal, Europe. (Email: joaogamamarques@gmail.com)
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Abstract

Schizophrenia is a complex syndrome of unknown etiology and difficult to manage. Unconjugated bilirubin has been researched as a potential biological marker of this syndrome. The objective of this review article was to gather the studies published to date on the relationship between this molecule and schizophrenia. Broad inclusion criteria have been used (PRISMA) to include as many relevant studies as possible. Fourteen studies were selected: 3 analyzed the effects of unconjugated hyperbilirubinemia in animal models; 6 demonstrated an increased incidence of schizophrenia in patients with increased unconjugated bilirubin; 2 reported an increased incidence of the disease in patients with decreased unconjugated bilirubin; and 3 linked an increased incidence of schizophrenia with an increased excretion of the oxidative product of bilirubin, the so-called biopyrrins. Because of apparently contradictory reported results, the hypothesis that the relationship between schizophrenia and unconjugated bilirubin was not linear and that there was an inflammatory dysfunction explaining this was considered. The 2 most accepted models for the pathophysiology of schizophrenia are described, and the possible role of the molecule in each is clarified. The bilirubin buffer system and its role in antioxidant defense was explored. The average levels of unconjugated bilirubin in patients with schizophrenia, schizoaffective disorder, and bipolar disorder 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.

Keywords

biomarkerpsychosisschizophreniaunconjugated bilirubin
Type
Review
Information
CNS Spectrums , Volume 24 , Issue 6 , December 2019 , pp. 577 - 588
Copyright
© Cambridge University Press 2019 

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