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Retroviral RNA identified in the cerebrospinal fluids and brains of individuals with schizophrenia - PubMed

  • ️Mon Jan 01 2001

Retroviral RNA identified in the cerebrospinal fluids and brains of individuals with schizophrenia

H Karlsson et al. Proc Natl Acad Sci U S A. 2001.

Abstract

Schizophrenia is a serious brain disease of uncertain etiology. A role for retroviruses in the etiopathogenesis of some cases of schizophrenia has been postulated on the basis of clinical and epidemiological observations. We found sequences homologous to retroviral pol genes in the cell-free cerebrospinal fluids (CSFs) of 10 of 35 (29%) individuals with recent-onset schizophrenia or schizoaffective disorder. Retroviral sequences also were identified in the CSFs of 1 of 20 individuals with chronic schizophrenia. However, retroviral sequences were not identified in any of the CSFs obtained from 22 individuals with noninflammatory neurological diseases or from 30 individuals without evidence of neurological or psychiatric diseases (chi(2) = 19.25, P < 0.001). The nucleotide sequences identified in the CSFs of the individuals with schizophrenia or schizoaffective disorder were related to those of the human endogenous retroviral (HERV)-W family of endogenous retroviruses and to other retroviruses in the murine leukemia virus genus. Transcription of RNA homologous to members of the HERV-W family of retroviruses also was found to be up-regulated differentially in the frontal cortex regions of brains obtained postmortem from individuals with schizophrenia, as compared with corresponding tissue from individuals without psychiatric diseases. The transcriptional activation of certain retroviral elements within the central nervous system may be associated with the development of schizophrenia in at least some individuals. The further characterization of retroviral elements within the central nervous system of individuals with schizophrenia might lead to improved methods for the diagnosis and management of this disorder.

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Figures

Figure 1
Figure 1

Agarose gel electrophoresis of PCR products generated by the reactions described in the text. The source of the samples is as follows: lanes a and l, negative controls; lanes b–f, CSFs of five individuals with recent-onset schizophrenia (b, A1; c, A2; d, A3; e, A4; f , A5); lane g, genomic human DNA; lanes h–k, CSFs from four unaffected control individuals; and lane m, 50-bp markers. The nucleotide sequences corresponding to the visualized bands from the CSFs are presented in Fig. 2.

Figure 2
Figure 2

Alignment of nucleotide sequences (A) and predicted amino acids (B) amplified from the CSFs of 10 individuals with acute schizophrenia (A1–10) and one individual with chronic schizophrenia (C1) compared with corresponding sequences from MSRV, ERV9, and FRD retroviruses (GenBank accession nos. AF009668, X57147, and U27240, respectively). The depicted sequences amplified from the CSF samples represent identical sequences obtained from at least seven independent clones. Dashes indicate nucleotides or amino acids that are identical to the reference sequence depicted on the top line. The open circles indicate gaps in sequence. The asterisks indicate the presence of stop codons.

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