Schizophrenia-Associated Idiopathic Unconjugated Hyperbilirubinemia (Gilbert's Syndrome)

Abstract

As an addendum to our list of 1999 reviewers, 1 I extend special gratitude to the following reviewers whose service rendered on our behalf last year will bear fruit in our Journal this year. The commitment and expertise of these devoted individuals are the foundations upon which our scholarly and scientific excellence rests. Schizophrenia-Associated Idiopathic UnconjugatedHyperbilirubinemia (Gilbert's Syndrome): 3 Case Reports Sir: Idiopathic unconjugated hyperbilirubinemia (Gilbert's syndrome) is a relatively common congenital hyperbilirubinemia occurring in 3% to 7% of the population. [1][2][3] Recently, it was reported that schizophrenic patients showed a significantly higher frequency of hyperbilirubinemia relative to patients with other psychiatric disorders and the general healthy population. 4 However, there has been only one previous case report of Gilbert's syndrome occurring in a schizophrenic patient. 5 We report 3 cases in which patients developed schizophrenia and Gilbert's syndrome and discuss clinical aspects of Gilbert's syndrome in schizophrenic patients and the relationship between hyperbilirubinemia and schizophrenia. Case 1. Mr. A, a 26-year-old single man, was diagnosed with schizophrenia at age 23 and admitted to the Shimane Medical University Hospital (Izumo, Japan). At that time, mild hyperbilirubinemia (total bilirubin level = 2.8 mg/dL, direct bilirubin level = 0.3 mg/dL), predominantly unconjugated, was first diagnosed on a routine laboratory test at admission and led us to suspect Gilbert's syndrome. After admission, Mr. A's psychiatric symptoms were well controlled by neuroleptic treatment. Laboratory tests of blood bilirubin levels showed an improvement 2 weeks after admission (total bilirubin level = 0.5 mg/dL, direct bilirubin level = 0.2 mg/dL). At the age of 26, coincident with discontinuation of antipsychotic medication, Mr. A experienced exacerbation of the psychotic condition and recurrent hyperbilirubinemia (total bilirubin level = 3.4 mg/dL, direct bilirubin level = 0.4 mg/dL) with a diagnosis of Gilbert's syndrome. He was readmitted to the Shimane Medical University Hospital in a severely psychotic state. Mr. A's psychotic condition has improved during the past 6 months with the administration of neuroleptics. Laboratory tests of blood bilirubin levels also showed improvement (total bilirubin level = 0.5 mg/dL, irect bilirubin level = 0.2 mg/dL). Mr. A experienced no relapse of psychotic condition with concomitant re-increase of unconjugated bilirubin levels.Case 2. Mr. B, a 33-year-old single man, was diagnosed with schizophrenia at age 25, at which time treatment with neuroleptics was started. Coincident with the onset of psychosis, hyperbilirubinemia (total bilirubin level = 2.3 mg/dL, direct bilirubin level = 0.3 mg/dL), predominantly unconjugated, was first diagnosed on a routine laboratory test and led us to suspect Gilbert's syndrome. At the age of 30 years, Mr. B experienced exacerbation of the psychotic condition. He was admitted to the Shimane Medical Unive...

Bilirubin as a determinant for altered neurogenesis, neuritogenesis, and synaptogenesis

“…Thus, UCB may deleteriously influence several aspects of brain development and function. It is noteworthy that these effects are consistent with the cortical neuropathology observed in schizophrenia, a mental illness that was already suggested to be related with hyperbilirubinemia (Miyaoka et al, 2000). Hence, our study is the first to provide a basis for altered neural development by UCB and its association with long-term changes, leading to uncertain and understudied outcome later in life.…”

“…Jaundice, the clinical manifestation of increased levels of unconjugated bilirubin (UCB) in circulation, is correlated with an augmented risk for the emergence of long-term neurodevelopment disabilities (Dalman and Cullberg, 1999; Miyaoka et al, 2000). UCB interacts with cellular membranes (Rodrigues et al, 2002a,b), activates glia with consequent inflammatory response (Fernandes et al, 2004; Falcão et al, 2005; Fernandes et al, 2006; Gordo et al, 2006; Brites et al, 2008), and induces oxidative and nitrosative stress (Brito et al, 2008a,b).…”

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“…The relevance of bilirubin in these cases of psychotic mania cannot be established, but it may be of interest to mention that bilirubin has been suggested to play a role in hepatic encephalopathy presenting as delirium and mania [23]. Moreover, an excess of idiopathic hyperbilirubinemia has recently been reported in patients hospitalized for schizophrenic psychosis [24,25], as the possible consequence of increased vulnerability of red cell membranes and/or the common polymorphism of the glucuronyl tranferase gene (Gilbert's syndrome).…”

Gilbert's syndrome in a patient with predominantly negative symptoms of schizophrenia

“…It is an unconjugated hyperbilirubinemia, without liver disease or hemolysis, characterised by intermittent jaundice usually associated with fasting or intercurrent illness [4]. Several previous case reports show an association between the improvements in total bilirubin and mental state [5,6]. We report the case of a young man with mainly negative symptoms of schizophrenia in whom there has been little improvement in mental state despite an improvement in total bilirubin.…”

“…To date there have been two case series [5,6] of Gilbert's syndrome associated with schizophrenia. All the patients were overtly psychotic on admission and their mental state improved with the administration of antipsychotic medication.…”