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. 2023 Sep;28(9):3920-3929.
doi: 10.1038/s41380-023-02263-0. Epub 2023 Sep 21.

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

Shinichiro Ochi  1   2 , Bhaskar Roy  1 , Kevin Prall  1 , Richard C Shelton  1 , Yogesh Dwivedi  3
Affiliations

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

Shinichiro Ochi et al. Mol Psychiatry. 2023 Sep.

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.

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Conflict of interest statement

RCS has received grant support from the National Institutes of Health, Patient-Centered Outcomes Research Institute, American Foundation for Suicide Prevention, Acadia Pharmaceuticals, Alkermes, Inc., Allergan, Plc, Alto Pharmaceuticals, Avanir Pharmaceuticals, Inc., Boehringer Ingelheim, Denovo Biopharma, Genomind, InMune Bio, Intra-cellular Therapies, Janssen Pharmaceuticals, LivaNova PLC, Navitor Pharmaceuticals, Neurocrine Biosciences, Neurorx, Novartis Pharmaceuticals, Otsuka Pharmaceutical Company, Sunovion Pharmaceuticals, and Takeda Pharmaceuticals. He has received consulting fees from Acadia Pharmaceuticals, Allergan, Plc, Alphasigma USA, Inc., Boehringer Ingelheim, Cerecor, Inc., Denovo Biopharma, Janssen Pharmaceuticals, Myriad Neuroscience, Neurorx, Novartis AG, Otsuka Pharmaceuticals, Seelos Therapeutics, Inc., Sunovion Pharmaceuticals, and Takeda Pharmaceuticals. Other authors report no conflict of interest.

Figures

Fig. 1
Fig. 1. Telomere length and mtDNA copy number between healthy controls and MDD.
A TL in the total MDD (n = 33) was significantly lower than in the HC (n = 20). B mtDNAcn in the total MDD (n = 33) was significantly higher than HC (n = 20). Error bars show the mean ± SD. Student’s t test was used. *P < 0.05 was defined as significance. MDD Major Depressive Disorder, HC Healthy Controls, mtDNAcn mtDNA copy number.
Fig. 2
Fig. 2. Telomere length and mtDNA copy number between healthy controls, MDD-SA/SI, and MDD + SA/SI.
A TL in the MDD + SA/SI group (n = 19) was significantly lower than the HC group (n = 20). There was no significant difference between the MDD + SA/SI group (n = 19) and MDD-SA/SI (n = 14) groups and between the MDD-SA/SI group and HC group. B mtDNAcn in the MDD + SA/SI group was significantly lower compared to the HC group. There was no significant difference between MDD + SA/SI group and MDD-SA/SI group and between the MDD- SA/SI group and the HC group. Error bars show the mean ± SD. ANOVA adjusted by Bonferroni correction was used. *P < 0.05 was defined as significance. MDD Major Depressive Disorder, SA suicide attempt, SI suicidal ideation, HC Healthy Controls, mtDNAcn mtDNA copy number.
Fig. 3
Fig. 3. Correlation of Telomere length and mtDNA copy number between healthy controls, MDD-SA/SI, and MDD + SA/SI.
TL was significantly positively correlated with mtDNAcn in the HC group (n = 20) and the MDD-SA/SI group (n = 14). Telomere length was negatively correlated with mtDNAcn in MDD + SA/SI group (n = 19), although the data did not reach the significance level. Spearman’s correlation was used. *P < 0.05 was defined as significance. *p < 0.05, **p < 0.01, ***p < 0.001. MDD Major Depressive Disorder, SA suicide attempt, SI suicidal ideation, mtDNAcn mtDNA copy number.
Fig. 4
Fig. 4. Telomere length and mtDNA copy number between healthy controls, MDD-SA/SI, and MDD + SA/SI.
A TL was significantly correlated with CDRS total score. B TL was significantly correlated with BAI total score. C mtDNAcn was significantly correlated with CTQ emotional abuse (EA). *P < 0.05 was defined as significance. *p < 0.05, **p < 0.01. mtDNAcn mtDNA copy number; CDRS Children’s Depression Rating Scale, BAI Beck Anxiety Inventory, CTQ Childhood Trauma Questionnaire.
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