Peripheral and central glucose utilizations modulated by mitochondrial DNA 10398A in bipolar disorder
Abstract
Bipolar disorder (BD) is highly heritable and associated with dysregulation of brain glucose utilizations (GU). The mitochondrial DNA (mtDNA) 10398A polymorphism, as a reported BD risk factor, leads to deficient glycolytic energy production by affecting mitochondrial matrix pH and intracellular calcium levels. However, whether mtDNA-10398A has functional effects on the brain and how our body responds remain elusive. We compared peripheral and central glucose-utilizing patterns between mtDNA A10398G polymorphisms in BD and their unaffected siblings (BDsib). Since siblings carry identical mtDNA, we hypothesized that certain characteristics co-segregate in BD families. We recruited twenty-seven pairs of non-diabetic BD patients and their BDsib and 30 well-matched healthy control subjects (HC). The following were investigated: mtDNA, fasting plasma glucose/insulin, cognitive functions including Montreal Cognitive Assessment (MoCA), and brain GU at rest. Insulin resistance was rechecked in sixty-one subjects (19-BD, 18-BDsibib, and 24-HC) six months later. We found that BD-pairs (BD+BDsib) carried more mtDNA-10398A and had higher fasting glucose, even after controlling for many covariates. BD-pairs had abnormally lower dorso-prefron...Continue Reading
References
Meta-analyses of cognitive functioning in euthymic bipolar patients and their first-degree relatives
Citations
Valproate inhibits mitochondrial bioenergetics and increases glycolysis in Saccharomyces cerevisiae.
Related Concepts
Related Feeds
Bipolar Disorder
Bipolar disorder is characterized by manic and/or depressive episodes and associated with uncommon shifts in mood, activity levels, and energy. Discover the latest research this illness here.