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.
CNS Spectr. 2019 Dec;24(6):577-588. doi: 10.1017/S109285291800161X.
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.
精神分裂症是一种病因不明且难以治疗的复杂综合征。未结合胆红素已被研究为该综合征的潜在生物学标志物。本文综述的目的是收集迄今为止关于该分子与精神分裂症之间关系的研究。采用广泛的纳入标准（PRISMA）尽可能纳入更多相关研究。共选择了 14 项研究：3 项分析了未结合高胆红素血症在动物模型中的作用；6 项表明未结合胆红素升高的患者精神分裂症发病率增加；2 项报告未结合胆红素降低的患者疾病发病率增加；3 项将精神分裂症发病率增加与胆红素氧化产物（所谓的生物吡咯）的排泄增加联系起来。由于报告的结果明显相互矛盾，因此考虑了这样一种假设，即精神分裂症与未结合胆红素之间的关系不是线性的，并且存在一种炎症功能障碍可以解释这种关系。描述了精神分裂症病理生理学的 2 个最被接受的模型，并阐明了该分子在每个模型中的可能作用。还探讨了胆红素缓冲系统及其在抗氧化防御中的作用。比较了精神分裂症、分裂情感障碍和双相情感障碍患者的未结合胆红素平均水平，假设这些疾病可能是同一病理谱的不同点。最后得出结论，未结合胆红素是一种很有前途的分子，可作为精神分裂症的潜在生物学标志物，有必要对其进行进一步研究。
