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Related Experiment Videos

Molecular evidence for mitochondrial dysfunction in bipolar disorder.

Christine Konradi1, Molly Eaton, Matthew L MacDonald

  • 1Department of Psychiatry, Harvard Medical School, Boston, Massachusetts, USA. konradi@mclean.harvard.edu

Archives of General Psychiatry
|March 3, 2004
PubMed
Summary

Bipolar disorder is linked to decreased expression of mitochondrial genes in the brain. This suggests impaired energy metabolism and cellular processes in individuals with bipolar disorder.

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • The underlying mechanisms of bipolar disorder are not fully understood.
  • Emerging evidence suggests altered gene expression plays a role in bipolar disorder.

Purpose of the Study:

  • To investigate the expression levels of 12,558 nuclear genes in the human hippocampus.
  • To compare gene expression between healthy controls, individuals with bipolar disorder, and individuals with schizophrenia.

Main Methods:

  • Utilized gene arrays to analyze messenger RNA (mRNA) expression.
  • Verified findings using real-time quantitative polymerase chain reaction (RT-qPCR).
  • Studied three groups: 10 healthy controls, 9 with bipolar disorder, and 8 with schizophrenia.

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Main Results:

  • Significantly decreased expression of nuclear mRNA for mitochondrial proteins was observed in the hippocampus of individuals with bipolar disorder.
  • This decrease was not observed in individuals with schizophrenia.
  • Individuals with bipolar disorder showed a substantial reduction in genes involved in oxidative phosphorylation and adenosine triphosphate (ATP)-dependent proteasome degradation.

Conclusions:

  • Findings indicate widespread dysregulation of mitochondrial energy metabolism in bipolar disorder.
  • Suggests downstream deficits in ATP-dependent cellular processes contribute to the pathophysiology of bipolar disorder.