Molecular characterization of bipolar disorder by comparing gene expression profiles of postmortem brains of major mental disorders

Mol Psychiatry. 2004 Apr;9(4):406-16. doi: 10.1038/sj.mp.4001437.

Abstract

We performed the oligonucleotide microarray analysis in bipolar disorder, major depression, schizophrenia, and control subjects using postmortem prefrontal cortices provided by the Stanley Foundation Brain Collection. By comparing the gene expression profiles of similar but distinctive mental disorders, we explored the uniqueness of bipolar disorder and its similarity to other mental disorders at the molecular level. Notably, most of the altered gene expressions in each disease were not shared by one another, suggesting the molecular distinctiveness of these mental disorders. We found a tendency of downregulation of the genes encoding receptor, channels or transporters, and upregulation of the genes encoding stress response proteins or molecular chaperons in bipolar disorder. Altered expressions in bipolar disorder shared by other mental disorders mainly consisted of upregulation of the genes encoding proteins for transcription or translation. The genes identified in this study would be useful for the understanding of the pathophysiology of bipolar disorder, as well as the common pathophysiological background in major mental disorders at the molecular level. In addition, we found the altered expression of LIM and HSPF1 both in the brains and lymphoblastoid cells in bipolar disorder. These genes may have pathophysiological importance and would be novel candidate genes for bipolar disorder.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Age Factors
  • Bipolar Disorder / genetics*
  • Bipolar Disorder / metabolism
  • Cluster Analysis
  • Cytoskeletal Proteins
  • Depressive Disorder, Major / genetics*
  • Depressive Disorder, Major / metabolism
  • Female
  • Gene Expression Profiling*
  • Gene Expression Regulation / physiology
  • HSP40 Heat-Shock Proteins
  • Heat-Shock Proteins / genetics*
  • Heat-Shock Proteins / metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • LIM Domain Proteins
  • Lymphocytes / metabolism
  • Male
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Reference Values
  • Schizophrenia / genetics*
  • Schizophrenia / metabolism
  • Sex Factors

Substances

  • Adaptor Proteins, Signal Transducing
  • Cytoskeletal Proteins
  • DNAJB1 protein, human
  • HSP40 Heat-Shock Proteins
  • Heat-Shock Proteins
  • Intracellular Signaling Peptides and Proteins
  • LIM Domain Proteins
  • PDLIM7 protein, human