Altered expression of mitochondria-related genes in postmortem brains of patients with bipolar disorder or schizophrenia, as revealed by large-scale DNA microarray analysis

Hum Mol Genet. 2005 Jan 15;14(2):241-53. doi: 10.1093/hmg/ddi022. Epub 2004 Nov 24.

Abstract

Accumulating evidence suggests that mitochondrial dysfunction underlies the pathophysiology of bipolar disorder (BD) and schizophrenia (SZ). We performed large-scale DNA microarray analysis of postmortem brains of patients with BD or SZ, and examined expression patterns of mitochondria-related genes. We found a global down-regulation of mitochondrial genes, such as those encoding respiratory chain components, in BD and SZ samples, even after the effect of sample pH was controlled. However, this was likely due to the effects of medication. Medication-free patients with BD showed tendency of up-regulation of subset of mitochondrial genes. Our findings support the mitochondrial dysfunction hypothesis of BD and SZ pathologies. However, it may be the expression changes of a small fraction of mitochondrial genes rather than the global down-regulation of mitochondrial genes. Our findings warrant further study of the molecular mechanisms underlying mitochondrial dysfunction in BD and SZ.

MeSH terms

  • Bipolar Disorder / drug therapy
  • Bipolar Disorder / genetics*
  • Bipolar Disorder / metabolism
  • Brain / drug effects
  • Brain / metabolism
  • Gene Expression / physiology*
  • Gene Expression Profiling
  • Humans
  • Hydrogen-Ion Concentration
  • Mitochondria / drug effects
  • Mitochondria / genetics*
  • Mitochondria / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Schizophrenia / drug therapy
  • Schizophrenia / genetics*
  • Schizophrenia / metabolism