Mitochondrial variants in schizophrenia, bipolar disorder, and major depressive disorder. Export

@article{citeulike:4313449, abstract = {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.}, author = {Rollins, Brandi and Martin, Maureen V. and Sequeira, P. Adolfo and Moon, Emily A. and Morgan, Ling Z. and Watson, Stanley J. and Schatzberg, Alan and Akil, Huda and Myers, Richard M. and Jones, Edward G. and Wallace, Douglas C. and Bunney, William E. and Vawter, Marquis P.}, citeulike-article-id = {4313449}, citeulike-linkout-0 = {http://dx.doi.org/10.1371/journal.pone.0004913}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19290059}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19290059}, doi = {10.1371/journal.pone.0004913}, issn = {1932-6203}, journal = {PloS one}, keywords = {bipolar, depression, mtdna, schizophrenia}, number = {3}, posted-at = {2009-10-21 17:45:14}, priority = {5}, title = {Mitochondrial variants in schizophrenia, bipolar disorder, and major depressive disorder.}, url = {http://dx.doi.org/10.1371/journal.pone.0004913}, volume = {4}, year = {2009} }

TY - JOUR ID - citeulike:4313449 L3 - citeulike-article-id:4313449 N2 - 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. IS - 3 JF - PloS one SN - 1932-6203 TI - Mitochondrial variants in schizophrenia, bipolar disorder, and major depressive disorder. VL - 4 KW - bipolar KW - depression KW - mtdna KW - schizophrenia AU - Rollins, Brandi AU - Martin, Maureen AU - Sequeira, Adolfo AU - Moon, Emily AU - Morgan, Ling AU - Watson, Stanley AU - Schatzberg, Alan AU - Akil, Huda AU - Myers, Richard AU - Jones, Edward AU - Wallace, Douglas AU - Bunney, William AU - Vawter, Marquis PY - 2009/// UR - http://dx.doi.org/10.1371/journal.pone.0004913 ER -