Mitochondrial variants in schizophrenia, bipolar disorder, and major depressive disorder.
BACKGROUND
Mitochondria provide most of the energy for brain cells by the process of oxidative phosphorylation. Mitochondrial abnormalities and deficiencies in oxidative phosphorylation have been reported in individuals with schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD) in transcriptomic, proteomic, and metabolomic studies. Several mutations in mitochondrial DNA (mtDNA) sequence have been reported in SZ and BD patients.


RESULTS
Dorsolateral prefrontal cortex (DLPFC) from a cohort of 77 SZ, BD, and MDD subjects and age-matched controls (C) was studied for mtDNA sequence variations and heteroplasmy levels using Affymetrix mtDNA resequencing arrays. Heteroplasmy levels by microarray were compared to levels obtained with SNaPshot and allele specific real-time PCR. This study examined the association between brain pH and mtDNA alleles. The microarray resequencing of mtDNA was 100% concordant with conventional sequencing results for 103 mtDNA variants. The rate of synonymous base pair substitutions in the coding regions of the mtDNA genome was 22% higher (p = 0.0017) in DLPFC of individuals with SZ compared to controls. The association of brain pH and super haplogroup (U, K, UK) was significant (p = 0.004) and independent of postmortem interval time.


CONCLUSIONS
Focusing on haplogroup and individual susceptibility factors in psychiatric disorders by considering mtDNA variants may lead to innovative treatments to improve mitochondrial health and brain function.
Rollins
Brandi
B
Department of Psychiatry & Human Behavior, University of California Irvine, Irvine, California, United States of America.
Martin
Maureen V
MV
Sequeira
P Adolfo
PA
Moon
Emily A
EA
Morgan
Ling Z
LZ
Watson
Stanley J
SJ
Schatzberg
Alan
A
Akil
Huda
H
Myers
Richard M
RM
Jones
Edward G
EG
Wallace
Douglas C
DC
Bunney
William E
WE
Vawter
Marquis P
MP
D001714:Bipolar Disorder / Q000235:genetics*; D016022:Case-Control Studies; D004272:DNA, Mitochondrial / Q000235:genetics*; D003865:Major Depressive Disorder / Q000235:genetics*; D019075:Electrophoresis, Capillary; D006239:Haplotypes; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D010085:Oxidative Phosphorylation; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000235:genetics*
D004272:DNA, Mitochondrial