Functional genomics in postmortem human brain: Abnormalities in a DISC1 molecular pathway in schizophrenia

Barbara K. Lipska, Shruti N. Mitkus, Shiny V. Mathew, Robert Fatula, Thomas M. Hyde, Daniel R. Weinberger, Joel E. Kleinman

Research output: Contribution to journalReview article

Abstract

The disrupted in schizophrenia 1 (DlSC1) gene has been identified as a schizophrenia susceptibility gene based on linkage and single nucleotide polymorphism (SNP) association studies and clinical data, suggesting that risk SNPs impact on hippocampal structure and function. We hypothesized that altered expression of DISC1 and/or its molecular partners (nuclear distribution element-like [NUDEL] fasciculation and elongation protein zeta-1 [FEZ1], and lissencephaly 1 [LIS]) may underlie its pathogenic role in schizophrenia and explain its genetic association. We examined the expression of DISC1 and its binding partners in the hippocampus and dorsolateral prefrontal cortex of postmortem human brains of schizophrenic patients and controls. We found no difference in the expression of DISC1 mRNA in schizophrenia, and no association with previously identified risk SNPs. However, the expression of NUDEL, FEZ1, and LIS1 was significantly reduced in tissue from schizophrenic subjects, and the expression of each showed association with high-risk DISC1 polymorphisms. These data suggest involvement of genetically linked abnormalities in the DISC1 molecular pathway in the pathophysiology of schizophrenia.

Original languageEnglish (US)
Pages (from-to)353-357
Number of pages5
JournalDialogues in Clinical Neuroscience
Volume8
Issue number3
StatePublished - Nov 9 2006
Externally publishedYes

Keywords

  • Functional genomics
  • Gene
  • Hippocampus
  • Pathophysiology
  • Postmortem human brain
  • Prefrontal cortex
  • Schizophrenia

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

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