title: The somatic common deletion in mitochondrial DNA is decreased in schizophrenia.
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. The accumulation of the mtDNA common deletion was measured using a quantitative assay across 10 brain regions (anterior cingulate cortex, amygdala, caudate nucleus, dorsolateral prefrontal cortex, hippocampus, nucleus accumbens, orbitofrontal cortex, putamen, substantia nigra, and thalamus). The correlation with age of the mtDNA deletion was highly significant across brain regions as previously shown. A significant decrease in the global accumulation of common deletion in subjects with SZ compared to MDD, BD, and controls was observed after correcting for age, pH, PMI, and gender. The decreases in SZ were largest in dopaminergic regions. One potential side effect of antipsychotic drugs on mitochondria is the impairment of mitochondria function, which might explain these findings. The decreased global brain mtDNA common deletion levels suggests that mitochondrial function is impaired and might be part of an overall mitochondria dysfunction signature in subjects with schizophrenia.
authors.affiliation: Functional Genomics Laboratory, Department of Psychiatry and Human Behavior, University of California, Irvine, USA.
authors.forename: Firoza
authors.initials: F
authors.lastname: Mamdani
authors.affiliation: Functional Genomics Laboratory, Department of Psychiatry and Human Behavior, University of California, Irvine, USA.
authors.forename: Brandi
authors.initials: B
authors.lastname: Rollins
authors.affiliation: Functional Genomics Laboratory, Department of Psychiatry and Human Behavior, University of California, Irvine, USA.
authors.forename: Ling
authors.initials: L
authors.lastname: Morgan
authors.affiliation: Functional Genomics Laboratory, Department of Psychiatry and Human Behavior, University of California, Irvine, USA.
authors.forename: P Adolfo
authors.initials: PA
authors.lastname: Sequeira
authors.affiliation: Functional Genomics Laboratory, Department of Psychiatry and Human Behavior, University of California, Irvine, USA. Electronic address: mvawter@uci.edu.
authors.forename: Marquis P
authors.initials: MP
authors.lastname: Vawter
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001921:Brain / Q000473:pathology; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D006801:Humans; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000175:diagnosis / Q000235:genetics*; D013223:Statistics as Topic
chemical_list: D004272:DNA, Mitochondrial
keywords: Haloperidol; Mitochondrial bioenergetics; Mitochondrial common deletion; Mood disorders; Schizophrenia