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Creutzfeldt-Jakob disease and mental illness
Mutations in the prion gene are not associated with schizophrenia in Taiwanese population
Edward R. Winstead

Creutzfeldt-Jakob disease, a human variant of Mad-cow disease, belongs to a family of disorders called human prion diseases. Misshapen prion proteins characterize these disorders, which can be caused by inherited defects in the prion gene. Patients with a form of Creutzfeldt-Jakob disease tend to have psychiatric symptoms, such as depression and hallucinations, and there is some evidence linking the prion gene to schizophrenia. But the data are inconclusive. A new study by researchers at Tzu-Chi General Hospital in Hualien, Taiwan, reports a negative result: The prion gene was not associated with an increased risk for psychiatric disease in a sample of schizophrenics.

"Our data suggest that the human prion gene may not be a susceptibility gene for schizophrenia," the researches write in Molecular Psychiatry. Chia-Hsiang Chen and colleagues sequenced regions of the prion gene in a sample of schizophrenic patients and identified two polymorphisms, but none of the variants was associated with schizophrenia.

"Human prion disease is a unique entity of neurodegenerative disease," Chen and colleagues write in their paper. Although prion diseases mainly involve neurological deficits and demented symptoms, "psychiatric symptoms are not uncommon among patients with human prion-associated disease." According to one estimate, about ten percent of patients with Creutzfeldt-Jakob disease are misdiagnosed and first admitted to psychiatric hospitals.

Chen's research follows (and was inspired by) a 1997 study led by Helena B. Samaia, of the Federal University of São Paulo, Brazil. Samaia's group identified a new mutation in the prion gene in a three-generation family. The 'N171S' mutation was not present in the Taiwanese population.

In the Brazilian study, several members of the family had psychiatric symptoms such as auditory hallucinations, severe depression and delusions. None of the individuals could easily be classified within well-defined clinical categories. The N171S mutation occurred in five out of six family members with the mutation; only one of six unaffected family members had the mutation.

The findings, Samaia and colleagues wrote in Nature, suggest that "inherited prion diseases might include serious atypical psychiatric disorders, in addition to the well-defined strictly neurological pathologies and personality changes." A 1999 study by researchers at the University of Pennsylvania, on the other hand, argues against a role for abnormal prion proteins in the pathogenesis of schizophrenia.

The current study involved two stages. In the first stage, Chen's group analyzed the prion gene in 62 patients with a family history of schizophrenia, yielding the two polymorphisms. In the second stage, the researchers analyzed the prion gene in 172 schizophrenia patients and 100 controls. A statistical analysis revealed no significant differences in the distribution of polymorphisms and combinations of variants among the affected individuals and controls.

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Tsai, M-T. et al. Lack of evidence to support the association of the human prion gene with schizophrenia. Mol Psychiatry 6, 74-78 (January 2001).
Samaia, H.B. et al. A prion-linked psychiatric disorder. Nature 390, 241 (November, 20 1997).

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