Mitochondrial DNA (mtDNA) in brain samples from patients with major psychiatric disorders: Gene expression profiles, MtDNA content and presence of the MtDNA common deletion

Abstract

Several lines of evidence support a mitochondrial dysfunction in major psychiatric disorders. The objective of this study was to determine whether mitochondrial DNA (mtDNA) expression or content are implicated in the mitochondrial dysfunction observed in schizophrenia (SCH), bipolar disorder (BD), and major depressive disorder (MDD). MtDNA gene expression and mtDNA content (including the MT-ND4 deletion) were measured by RT-qPCR and qPCR, respectively. Post-mortem brain tissue from 60 subjects, divided evenly into four diagnostic groups (SCH, BD, MDD, and control (C)), was analyzed. MT-ND1 gene expression was significantly increased in the BD group compared with the C group. MDD and SCH patients showed a similar pattern of mtDNA expression, which was different from that in BD patients. Similarly, a larger number of MDD and SCH patients tended to have the MT-ND4 gene deleted compared with BD and C subjects. However, no other significant differences were observed in mtDNA gene expression and mtDNA content. Notably, high variability was observed in the mtDNA gene expression and content in each diagnostic group. Previous studies and the present work provide evidence for a role of mtDNA in SCH, BD and MDD. However, further studies with larger patient and control groups as well as by analyzing distinct brain regions are needed to elucidate the role of mtDNA in major psychiatric disorders.

Leukocyte mitochondrial DNA copy number in bipolar disorder

“…The present results are in accordance with three studies in BD postmortem brains which showed no alteration in mtDNA content Sabunciyan et al, 2007;Torrell et al, 2013). In contrast with our findings, one study found that mtDNA content slightly increased in post-mortem BD subjects (Vawter et al, 2006).…”

“…Although mtDNA encodes ETC proteins which lower its transcription in BD (Konradi et al, 2004;Sun et al, 2006), evidence challenges the association between mtDNA content and mtDNA transcription (Torrell et al, 2013;Vawter et al, 2006). Rather, it is possible that mtDNA sequence plays a more crucial role in mtDNA expression (Reinecke et al, 2009).…”

“…Abnormal mtDNA number content has been associated with disturbed mitochondrial function and increased oxidative stress (Malik and Czajka, 2013). In BD, only one post-mortem study found subtle changes in mtDNA (Vawter et al, 2006), while others found no differences compared to controls Sabunciyan et al, 2007;Torrell et al, 2013). Importantly, a study of elderly patients showed decreased mtDNA content associated with depressive symptoms (Kim et al, 2011).…”

Mitochondrial DNA copy number is reduced in male combat veterans with PTSD

“…The mtDNAcn has been reported to be significantly high in autism (Giulivi et al 2010), significantly reduced in some (but not in all) studies on bipolar disorder (Chang et al 2014, de Sousa et al 2014, Kakiuchi et al 2005, Sabunciyan et al 2007, Torrell et al 2013, Vawter et al 2006) and positively associated with childhood adversity and lifetime psychopathology in healthy people (Tyrka et al 2015). A recent study in community-dwelling women (n=142) found significantly lower mtDNAcn in people with higher depressive symptoms (not necessarily diagnosed with Major Depressive Disorder [MDD]) compared to those with lower depressive symptoms (Kim M. Y. et al 2011).…”

Association between the mitochondrial DNA 4977 common deletion in the hair shaft and hearing loss in presbycusis

“…Numerous studies have reported that deletions of mitochondrial DNA (mtDNA) have a vital role in aging and acquired impairment in various human organs, including the brain, heart, liver, skin, skeletal muscle and cornea (4)(5)(6). Cochlea tissue is rich in mtDNA, which have a high probability of deletion.…”