The somatic common deletion in mitochondrial DNA is decreased in schizophrenia

Area of Science:

• Neuroscience
• Genetics
• Cell Biology

Background:

• Oxidative stress can cause large deletions in mitochondrial DNA (mtDNA), leading to a cycle of increased damage and decreased mitochondrial function.
• The accumulation of the mtDNA common deletion (4977 bp) is linked to cellular dysfunction and aging.

Purpose of the Study:

• To investigate disease-specific brain differences in the somatic mtDNA common deletion (4977 bp) in major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ) compared to controls.
• To explore the relationship between mtDNA deletions and potential underlying mechanisms in these psychiatric disorders.

Main Methods:

• A quantitative assay was used to measure the accumulation of the mtDNA common deletion across 10 specific brain regions.
• Statistical analyses were performed to compare deletion levels between patient groups and controls, correcting for age, pH, postmortem interval (PMI), and gender.

Main Results:

• A significant correlation between age and mtDNA deletion accumulation was observed across all brain regions.
• Subjects with schizophrenia (SZ) showed a significant decrease in global brain mtDNA common deletion accumulation compared to MDD, BD, and control groups.
• These decreases were most pronounced in dopaminergic regions in SZ subjects.

Conclusions:

• The reduced global brain mtDNA common deletion levels in schizophrenia suggest impaired mitochondrial function.
• This impairment may represent a component of a broader mitochondrial dysfunction signature in schizophrenia.
• Potential side effects of antipsychotic medications on mitochondrial function could contribute to these observed differences.