Agonal Factors, Aging, and Drug Abuse Affect Mitochondrial Gene Expression in Postmortem Brain Implications for Neuropsychiatric Disorders

Marquis Vawter
38th Winter Conference on Brain Research. 2005.


Reports of mitochondrial related gene expression in bipolar disorder and schizophrenia have increased interest as to whether the observed mitochondrial gene expression differences are relevant to agonal and diagnostic group differences. The broad effects of pH and agonal factors on microarray analysis of gene expression were also reported in pathways related to stress and oxidative phosphorylation. We analyzed gene expression from bipolar disorder type I (BPD), recurrent major depression (MDD), and control groups for mitochondrial related gene expression by microarray, Q-PCR, and in situ hybridization. Comparison of microarray results between control subjects stratified by either pH or agonal factors resulted in gene expression differences related to mitochondrial pathways such as oxidative phosphorylation. The direction of gene expression differences is such that lower pH in controls resulted in an apparent down-regulation of gene expression in a large number of genes related to mitochondrial function in cortical and cerebellar cortices. After eliminating low pH cases with agonal factors from all three groups, the BPD and MDD groups were compared to control subjects. The 'mitochondrial effect' is reduced in amplitude in affective disorder group comparisons to controls in cases without agonal factors. Alterations in mitochondrial-encoded transcript levels by Q-PCR were found in mood disorders compared to controls. Taken together, the data suggest dysregulation at the mitochondrial level in affective disorders independent of agonal factors and pH and offers evidence in support of the mitochondrial dysregulation hypothesis of bipolar disorder and extension to major depression.