Document Detail


Mitochondrial variants in schizophrenia, bipolar disorder, and major depressive disorder.
MedLine Citation:
PMID:  19290059     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
METHODOLOGY/PRINCIPAL FINDINGS: 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.
Authors:
Brandi Rollins; Maureen V Martin; P Adolfo Sequeira; Emily A Moon; Ling Z Morgan; Stanley J Watson; Alan Schatzberg; Huda Akil; Richard M Myers; Edward G Jones; Douglas C Wallace; William E Bunney; Marquis P Vawter
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-03-17
Journal Detail:
Title:  PloS one     Volume:  4     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2009  
Date Detail:
Created Date:  2009-03-17     Completed Date:  2009-05-28     Revised Date:  2013-06-02    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e4913     Citation Subset:  IM    
Affiliation:
Department of Psychiatry & Human Behavior, University of California Irvine, Irvine, California, United States of America.
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MeSH Terms
Descriptor/Qualifier:
Bipolar Disorder / genetics*
Case-Control Studies
DNA, Mitochondrial / genetics*
Depressive Disorder, Major / genetics*
Electrophoresis, Capillary
Haplotypes
Humans
Mitochondria / metabolism
Mutation*
Oligonucleotide Array Sequence Analysis
Oxidative Phosphorylation
Polymorphism, Single Nucleotide
Schizophrenia / genetics*
Grant Support
ID/Acronym/Agency:
#MH54844/MH/NIMH NIH HHS; MH42251/MH/NIMH NIH HHS; P50 MH60398/MH/NIMH NIH HHS
Chemical
Reg. No./Substance:
0/DNA, Mitochondrial
Comments/Corrections

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