Molecular evidence for mitochondrial dysfunction in bipolar disorder.
ABSTRACT 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.
Full-textDOI: · Available from: Christine Konradi, Mar 31, 2014
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ABSTRACT: Different lines of evidence suggest that mitochondrial dysfunction may be implicated in bipolar disorder (BD) pathophysiology. Mitochondrial electron transport chain (ETC) is a key target to evaluate mitochondrial function, but its activity has never been assessed in unmedicated BD or during mood episodes. Also, lithium has been shown to increase ETC gene expression/activity in preclinical models and in postmortem brains of BD subjects, but to date, no study has evaluated lithium's direct effects on ETC activity in vivo.Psychopharmacology 06/2014; DOI:10.1007/s00213-014-3655-6 · 3.99 Impact Factor
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ABSTRACT: Bipolar disorder (BD) is a severe brain disease that is associated with a significant risk for suicide. Recent studies indicate that altitude of residence significantly affects overall rate of completed suicide, and is associated with a higher incidence of depressive symptoms. Bipolar disorder has shown to be linked to mitochondrial dysfunction that may increase the severity of episodes. The present study used existing data sets to explore the hypothesis that altitude has a greater effect of suicide in BD, compared with other mental illnesses. The study utilized data extracted from the National Violent Death Reporting System (NVDRS), a surveillance system designed by the Centers for Disease Control and Prevention (CDC) National Center for Injury Prevention and Control (NCIPC). Data were available for 16 states for the years 2005-2008, representing a total of 35,725 completed suicides in 922 U.S. counties. Random coefficient and logistic regression models in the SAS PROC MIXED procedure were used to estimate the effect of altitude on decedent's mental health diagnosis. Altitude was a significant, independent predictor of the altitude at which suicides occurred (F=8.28, p=0.004 and Wald chi-square=21.67, p<0.0001). Least squares means of altitude, independent of other variables, indicated that individuals with BD committed suicide at the greatest mean altitude. Moreover, the mean altitude at which suicides occurred in BD was significantly higher than in decedents whose mental health diagnosis was major depressive disorder (MDD), schizophrenia, or anxiety disorder. Identifying diagnosis-specific risk factors such as altitude may aid suicide prevention efforts, and provide important information for improving the clinical management of BD.Medical Hypotheses 01/2014; 82(3). DOI:10.1016/j.mehy.2014.01.006 · 1.15 Impact Factor