Aberrant telomere length and mitochondrial DNA copy number in suicide completers

Abstract

Short telomere length (TL) occurs in individuals under psychological stress, and with various psychiatric diseases. Recent studies have also reported mitochondrial DNA copy number (mtDNAcn) alterations under several neuropsychiatric conditions. However, no study has examined whether aberrant TL or mtDNAcn occur in completed suicide, one of the most serious outcomes of mental illnesses. TL and mtDNAcn in post-mortem samples from 528 suicide completers without severe physical illness (508 peripheral bloods; 20 brains) and 560 samples from control subjects (peripheral bloods from 535 healthy individuals; 25 post-mortem brains) were analysed by quantitative polymerase chain reaction. Suicide completers had significantly shorter TL and higher mtDNAcn of peripheral bloods with sex/age-dependent differences (shorter TL was more remarkably in female/young suicides; higher mtDNAcn more so in male/elderly suicides). The normal age-related decline of TL and mtDNAcn were significantly altered in suicide completers. Furthermore, shorter TL and lower mtDNAcn of post-mortem prefrontal cortex were seen in suicide completers compared to controls. This study shows the first association of aberrant telomeres and mtDNA content with suicide completion. Our results indicate that further research on telomere shortening and mitochondrial dysfunction may help elucidate the molecular underpinnings of suicide-related pathophysiology.

Loss of chromosome Y in blood, but not in brain, of suicide completers

“…This study was approved by the Ethical Committee for Genetic Studies of the Kobe University Graduate School of Medicine. Subject selection and sample preparation were performed as previously described [ 2 ].…”

“…Suicide is a significant public health problem worldwide with approximately 1 million suicides each year. Emerging evidence from genetic studies suggests an underlying genetic pathophysiology in suicidal behavior in people with severe stress or mental disorders [ 1 , 2 ]. In most countries, men have a much higher rate of completed suicide compared to women as well as greater lethality of the suicide method [ 3 – 5 ], although the pathophysiology of this sex difference remains unclear.…”

No Evidence of Persistence or Inheritance of Mitochondrial DNA Copy Number in Holocaust Survivors and Their Descendants

“…Fourth, we may not be observing the right tissue for lasting molecular changes in Holocaust survivors. While an increase of mtDNA due to chronic stress was shown in multiple tissues including saliva, blood and liver in animal models (Cai et al, 2015b), a post-mortem study on suicide completers showed opposite changes in mtDNA levels in blood and dorso-lateral prefrontal cortex (Otsuka et al, 2017). As such, a lack mtDNA copy number difference between Holocaust survivors and controls in blood cells with rapid turnovers does not exclude lasting changes in mtDNA copy number in other tissues that may have important consequences on health and disease.…”

Associations of blood mitochondrial DNA copy number with social-demographics and cancer risk: results from the Mano-A-Mano Mexican American Cohort

“…For example, in a recent study, early-life experiences of adversity and lifetime psychopathology were found to be associated with higher mtDNA copy number ( P < 0.001) [ 41 ]. Similarly, Otsuka et al [ 42 ] reported that mtDNA copy number was significantly higher among individuals who committed suicide than in controls.…”