The disease mechanism of bipolar disorder remains unknown. Recent studies have provided evidence for abnormal gene expression in bipolar disorder.
To determine the expression of 12558 nuclear genes in the human hippocampus in healthy control subjects and those with bipolar disorder or schizophrenia.
We used gene arrays to study messenger RNA expression. Data were verified with a real-time quantitative polymerase chain reaction assay.
We studied 10 healthy control subjects, 9 subjects with bipolar disorder, and 8 subjects with schizophrenia.
The expression of nuclear messenger RNA coding for mitochondrial proteins was significantly decreased in the hippocampus in subjects with bipolar disorder but not in those with schizophrenia. Subjects with bipolar disorder were characterized by a pronounced and extensive decrease in the expression of genes regulating oxidative phosphorylation and the adenosine triphosphate-dependent process of proteasome degradation.
These findings point toward a widespread dysregulation of mitochondrial energy metabolism and downstream deficits of adenosine triphosphate-dependent processes in bipolar disorder.
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"Mitochondrial complex dysfunctions are thought to be involved in the etiopathogeneses of some psychiatric disorders, particularly schizophrenia (Ben-Shachar and Karry, 2008; Andreazza et al., 2010; Iwamoto et al., 2005; Sun et al., 2006; Konradi et al., 2004; Ben Shachar et al., 1999, 2007, 2009; Washizuka et al., 2009; Dror et al., 2002; Karry et al. 2004; Mehler-Wex et al., 2006; Taurines et al., 2010). Although not as extensive as the investigations in schizophrenia , mitochondrial complex activation has been investigated in the brains and peripheral tissues of BD patients, (Ben-Shachar and Karry, 2008; Andreazza et al., 2010; Iwamoto et al.; 2005; Sun et al.; 2006; Konradi et al., 2004; Ben Shachar et al., 1999; Washizuka et al., 2005, 2009). Whether peripheral tissues actually reflect the situation in the brain should be discussed. "
"Interneuron damage associated with impaired glucose metabolism is possibly mediated by oxidative stress, as increased systemic glucose leads to glycation reactions with plasma proteins resulting in the generation of reactive oxygen species (ROS) (Sato et al., 2010). Another potential source of increased brain ROS is mitochondrial dysfunction (Leadsham et al., 2013), and several mitochondrial proteins were implicated in our findings (Table 1and 4), thus complementing previous evidence for mitochondrial changes in psychiatric disorders (Konradi et al., 2004;Clay et al., 2011). In our analyses, antioxidant enzymes such as superoxide dismutase 1 (SOD1), were found altered in hippocampal tissue (Focking et al., 2011a) (Table 1and 4) and were central to the top IPA protein networks in schizophrenia and bipolar disorder (Fig. 1 and 2), supporting previous findings (Coughlin et al., 2013;Brown et al., 2014;Emiliani et al., 2014). "
"A recent study (Torrell et al., 2013) observed higher levels of CDel in occipital cortex of MDDs and SZ compared to BD and controls, however, their results were not significant and they did not control for age, which is highly correlated with levels of the CDel in many prior studies of brain and other metabolically active tissues. Multiple lines of evidence (transcriptomic, proteomic, neuroimaging, in vitro, peripheral tissue, genetic, and animal studies) implicates mitochondrial dysfunction in mood disorders (Kato and Kato, 2000; Bezchlibnyk et al., 2001; Konradi et al., 2004; Choudary et al., 2005; Iwamoto et al., 2005; Washizuka et al., 2005; Ryan et al., 2006; Sun et al., 2006; Vawter et al., 2006; Kato et al., 2007; Shao et al., 2008; Rao et al., 2010). Recent studies have provided evidence that mtDNA sequence variants, and subsequent mitochondrial dysfunction, are associated with an increased incidence of depression (Gardner et al., 2003; Burnett et al., 2005; Fattal et al., 2006; Vawter et al., 2006; Gardner and Boles, 2008, 2011; Shao et al., 2008; Rollins et al., 2009; Anglin et al., 2012; Inczedy-Farkas et al., 2012), suggesting that Schizophrenia Research 159 (2014) 370–375 ⁎ Corresponding author at: "
[Show abstract][Hide abstract] ABSTRACT: Large deletions in mitochondrial DNA (mtDNA) can occur during or result from oxidative stress leading to a vicious cycle that increases reactive oxygen species (ROS) damage and decreases mitochondrial function, thereby causing further oxidative stress. The objective of this study was to determine if disease specific brain differences of the somatic mtDNA common deletion (4977 bp) could be observed in major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ) compared to a control group.
Full-text · Article · Nov 2014 · Schizophrenia Research