Quantification of total mitochondrial DNA and mitochondrial common deletion in the frontal cortex of patients with schizophrenia and bipolar disorder.
Data published during the last decade are suggestive of a role for mitochondrial dysfunction in the pathogenesis of schizophrenia, bipolar disorder and other psychiatric diseases. In order to determine if the mitochondrial deficits reported in the literature are caused by abnormalities in the mitochondrial DNA of psychiatric patients, we quantified mitochondrial DNA (mtDNA) levels and the 5 kb common mitochondrial deletion (CD) in postmortem frontal cortex tissue. The mitochondrial CD and mtDNA levels were measured in tissue obtained from the frontal cortex (Brodmann Area 46) of 144 individuals (45 patients with schizophrenia, 40 patients with bipolar disorder, 44 controls, and 15 patients with major depression). These variables were measured using newly developed SYBR green and TaqMan real time PCR assays. Both the TaqMan and the SYBR green assays gave similar results. There was no statistically significant difference for the quantity of the common mitochondrial deletion between controls and patients. We also did not detect a difference in the mtDNA levels amongst the diagnosis groups. There were statistically significant differences for the evaluated parameters for smokers, schizophrenic patients on antipsychotic drugs at time of death, and bipolar patients with antidepressant use and alcohol abuse. Based on this study and other reports, we conclude that neither the common mitochondrial deletion nor changes in mitochondrial DNA levels are likely to account for the mitochondrial changes associated with bipolar disorder or schizophrenia. The effect of premortem agonal factors and medication on mitochondrial dysfunction still needs further elucidation.
Sabunciyan
S
S
Department of Pediatrics, Stanley Division of Developmental Neurovirology, Johns Hopkins University, Baltimore, MD, USA.
Kirches
E
E
Krause
G
G
Bogerts
B
B
Mawrin
C
C
Llenos
I C
IC
Weis
S
S
D000328:Adult; D000368:Aged; D001714:Bipolar Disorder / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000032:analysis / Q000235:genetics*; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism* / Q000503:physiopathology; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D028361:Mitochondrial Diseases / Q000150:complications / Q000235:genetics / Q000503:physiopathology; D009154:Mutation; D012559:Schizophrenia / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology
D004272:DNA, Mitochondrial