March 18, 2009

mtDNA and mental illness

PLoS ONE doi:10.1371/journal.pone.0004913

Mitochondrial Variants in Schizophrenia, Bipolar Disorder, and Major Depressive Disorder

Brandi Rollins et al.



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.


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.


1 comment:

AK said...

The best "innovative treatment to improve mitochondrial health and brain function", IMO, will be in vivo mtDNA correction. This may sound science-fictional, but consider how many things we take for granted today would have been science-fictional 30 years ago.

One possibility would be a viroid that enters the cell, looks for the specific DNA error to be fixed, and self-destructs if it doesn't find it. It would then release (into the mitochondrion) a complete copy of the corrected mtChromosome, along with some sort of directed intra-cellular, mitochondrially-targeted destructor for the incorrect mtChromosome. Ideally, such a viroid would have no reproductive capabilities, but instead would be created in vitro and released into the body in massive quantities.