Mitochondrial Related Gene Expression In Affective Disorders In Postmortem Brain

Marquis P. Vawter; Hiro Tomita; Mary Atz; Jun Li; Fan Meng; Kevin Overman; Ling Shao; Ben Bolstad; Terry Speed; John Stead; Prabhakara Choudary; Charles Neal Jr; Simon Evans; David Walsh; Rick Myers; Stanley J. Watson; E.G. Jones; Huda Akil; William E. Bunney; Jr.
Society for Neuroscience 34th Annual Meeting. 2004.


Recent reports of mitochondrial gene expression in bipolar disorder and schizophrenia has increased interest in whether the observed mitochondrial gene expression differences are related to agonal and diagnostic group differences. The broad effects of pH and agonal factors on microarray analysis of gene expression were found in pathways related to stress and oxidative phosphorylation (Li et al., 2004; Tomita et al., 2004). We have analyzed molecular profiles in multiple brain regions of mood disorder subjects and controls for mitochondrial related gene expression and now report data from additional samples run on U133A Affymetrix chips. Comparison within control subjects only that are stratified by either pH or agonal factors results in gene differences related to mitochondrial pathways such as oxidative phosphorylation. The direction of gene expression differences is such that lower pH will result 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 outlier pH and agonal factor cases, bipolar disorder and major depression subjects were compared to control subjects. Although a 'mitochondrial effect' remains in affective disorder comparisons to controls, the effect is reduced in amplitude. Mitochondrial encoded genes were not measured on the Affymetrix microarray, therefore specific mitochondrial encoded gene expression and the copy number of mtDNA were measured by Q-PCR. Alterations in mitochondrial gene expression and copy number by Q-PCR were found suggesting dysregulation at the mitochondrial level in affective disorders independent of agonal factor and pH.