Strong associations of telomere length and mitochondrial copy number with suicidality and abuse history in adolescent depressed individuals

Abstract

Major depressive disorder (MDD) is highly prevalent in adolescents and is a major risk factor for suicidality. Recent evidence shows that accelerated cellular senescence/aging is associated with psychiatric illness, including depression, in adults. The present study examined if the relationships of telomere length (TL) and mitochondrial DNA copy number (mtDNAcn), two critical indicators of cellular senescence/aging, are altered in depressed adolescents and whether these alterations are associated with suicidality, early-life adversities, and other co-occuring factors. In genomic DNA isolated from 53 adolescents (ages 16–19, 19 MDD with suicide attempt/suicidal ideation [MDD + SI/SA], 14 MDD without SA/SI [MDD-SI/SA], and 20 healthy controls [HC]), TL and mtDNAcn were measured as the ratio between the number of telomere repeats and that of a single-copy nuclear-hemoglobin [HBG] gene or the amount of mtDNA (NADH dehydrogenase, subunit 1) relative to HBG. Our data show that TL was significantly lower, and mtDNAcn was significantly higher in the total MDD group than HC. TL was significantly lower and mtDNAcn was significantly higher in the MDD + SA/SI group than in the HC, whereas there were no differences in the MDD-SI/SA group. TL was positively correlated with mtDNAcn in both HC and MDD-SA/SI groups; however, TL was negatively correlated with mtDNAcn in MDD + SA/SI. Furthermore, TL was negatively correlated with the severity of both depression and anxiety, while mtDNAcn was positively correlated with the severity of prior emotional abuse. Our study indicates that cellular senescence is more advanced in depressed adolescents with suicidal ideation and that childhood emotional abuse may participate in such a process.

Examining the biological impacts of parent–child relationship dynamics on preschool‐aged children who have experienced adversity

“…While substantial evidence has linked shorter telomere length with depression in adults (Tyrka et al., 2016), there is relatively limited evidence demonstrating associations of telomere length and behavioral health outcomes in early childhood. Some work has indicated associations of depression with telomere length in middle childhood and adolescence (Humphreys et al., 2020; Ochi et al., 2023; Wade et al., 2020), and one recent study found no association between depression and telomere length in children and adolescents (Heleniak et al., 2023). In one study of children ages 5–6 years, shorter telomeres were associated with greater stress reactivity (Kroenke et al., 2011).…”

“…In one study of children ages 5–6 years, shorter telomeres were associated with greater stress reactivity (Kroenke et al., 2011). While there is no previous work in mtDNAcn in early childhood and behavioral health outcomes, two studies in adolescents have suggested associations with depression (Humphreys et al., 2020; Ochi et al., 2023).…”