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/agedependent 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.

Alterations of cellular aging markers in obsessive–compulsive disorder: mitochondrial DNA copy number and telomere length

“…Notably, a postmortem study found that people who had died by suicide had a higher mtDNAcn in peripheral blood but a lower mtDNAcn in the prefrontal cortex compared to controls. 62 Shorter telomere length was also identified in both the peripheral blood and prefrontal cortex of the same people, showing an opposite relationship between telomere length and mtDNAcn in postmortem blood and brain tissue. However, whether these peripheral biomarkers accurately reflect neuronal biomarkers remains unclear, and this is a methodological limitation of human research involving clinical populations.…”

Epigenetic Clock Analysis in Children With Fetal Alcohol Spectrum Disorder

“…Therefore, TL largely reflects cellular biological aging (Mather et al, 2011). Similar to DNAm age, TL shortening has been reported in individuals with age-related diseases, including psychiatric disorders, such as MDD (Simon et al, 2006), BD (Rizzo et al, 2013), schizophrenia (Kao et al, 2008), PTSD (O'Donovan et al, 2011), completed suicide (Otsuka et al, 2017), and alcohol dependence (Kang et al, 2017). Recently, Lu and colleagues developed DNAmbased TL (DNAmTL) based on 140 CpG sites from blood samples and showed that DNAmTL of leukocytes is more strongly associated with chronological age than measured leukocyte TL (LTL) and outperforms LTL in predicting mortality and morbidity (Lu et al, 2019b).…”