OC10 - Biology and Suicidal Behaviour
Telomere Length and Mitochondrial DNA Copy Number in Depressed Adolescent Individuals With and Without SuicidalitySuicide is the 3rd leading cause of death among adolescents and young adults. On the other hand, MDD is the most significant biological and psychological risk factor for adolescent suicide. Recent evidence suggests that accelerated cellular aging could be involved in various psychiatric illnesses, including MDD. Telomere length (TL) and mitochondrial DNA copy number (mtDNA-cn) are the two important contributors to cellular aging. Telomeres are the nucleoprotein complexes that preserve chromosomal stability and integrity, and their shortening could influence cellular senescence and DNA damage. On the other hand, mtDNA-cn, an indirect measurement of mitochondrial function, is a marker of cellular aging and can be compensated for DNA damage. It has been proposed that TL and mtDNA-cn are co-regulated. Recently, some but not all studies suggest an association of TL length with MDD in the adult population. In addition, a few studies also suggest changes in mtDNA-cn in these populations. So far, no studies have examined the relationship between TL and mtDNA-cn adolescent depression and suicidality. We assessed a total of 53 adolescents (19 MDD with suicide attempt/suicidal ideation [MDD+SI/SA], 14 MDD without SA/SI [MDD-SI/SA], and 20 healthy controls [HC]). Clinical assessments were made using BDI, CSS-R, HAM-D, and BAI. Early-life adversities were examined using CTQ. Genomic DNA was isolated, and TL was measured as the ratio between the number of telomere repeats and that of a single-copy nuclear-hemoglobin [HGB] gene. mtDNA-cn was calculated based on measuring the amount of mtDNA (NADH dehydrogenase, subunit 1) relative to that of (HGB]). The data were analyzed using ANOVA followed by Tukeys test. Correlations were examined using the Person correlation coefficient. Significance was set at p?0.05. TL was significantly lower (p=.045), and mtDNA-cn was significantly higher in MDD group compared to HC (p = 0.028). TL in the MDD+SA/SI was significantly lower than in the HC (p=0.024), whereas mtDNA-cn in the MDD+SA/SI was significantly higher than in the HC controls (p=0.02). Furthermore, TL was significantly positively correlated with mtDNA-cn in HC (p <0.001) and MDD-SA/SI (p=0.045). On the other hand, although not significant, telomere length was negatively correlated with mtDNAcn in MDD+SA/SI. TL was significantly negatively correlated with HAM-D (p=0.010) and BAI (p=0.03), and mtDNA-cn was significantly positively correlated with diagnosis (p=0.009) and emotional abuse (p=0.035). Our studies suggest that both TL and mtDNA-cn could serve as biomarkers for suicidality in adolescents with MDD and that early-life stress, particularly emotional abuse, could be the mediator of mtDNA-cn abnormality in these patients.