Abstract
Major Depressive Disorder (MDD) has been associated with telomere dysfunction and alterations in mitochondrial activity, which seem to be co-regulated in human cells. To investigate this co-regulation in MDD, we assessed telomere length (TL) in peripheral blood mononuclear cells (PBMC) and selected immune cell subsets by quantitative fluorescence in situ hybridization and mitochondrial respiratory activity in PBMC by high-resolution respirometry in a study cohort of 18 MDD patients and 21 non-depressed controls. We provide initial evidence for a differential vulnerability to telomere attrition in selected adaptive immune cell populations. Here we found the highest difference in TL between depressed and control subjects for memory cytotoxic T cells. Depression was associated with reduced mitochondrial activity (mitochondrial bioenergetics), but increased mitochondrial density (mitochondrial biogenesis) in PBMC. Exploratory post-hoc analyses indicated that the changes in TL and immune cell bioenergetics were most pronounced in MDD patients who reported experiences of childhood sexual abuse. Among MDD patients, PBMC TL was as a trend positively associated with mitochondrial density and negatively associated with mitochondrial leak respiration, but not with mitochondrial activity related to biological energy production. These initial findings support the hypothesis of a co-regulation between telomeres and mitochondrial biogenesis but not mitochondrial bioenergetics among MDD patients.
Highlights
With a lifetime prevalence of 5–12% in men and 10–25% in women[1], depression is one of the most prevalent mental health disorders and has recently been ranked as the leading cause for mental and physical disability worldwide by the World Health Organization[2]
In line with this hypothesis, we showed previously that specific measures of mitochondrial activity, in particular basal oxygen consumption, maximal capacity of the electron transfer system (ETS), respiration related to adenosine triphosphate (ATP) production, spare respiratory capacity, and mitochondrial coupling efficiency were reduced in immune cells of Major Depressive Disorder (MDD) patients in dependence on the depressive symptom severity[9]
A three-group-comparison taking the self-reported history of childhood sexual abuse (CSA) among depressed individuals into account revealed significant main effects of group on immuno-cellular bioenergetics (Fig. 2): regarding the ATP-turnover-related respiration (F[2,31] = 7.82, p = 0.002) and the coupling efficiency (F[2,31] = 10.92, p < 0.001), the analyses showed a stepwise decrease with the highest levels in control subjects with and without CSA, decreased levels in MDD patients without CSA and the strongest decrease in MDD patients with CSA
Summary
With a lifetime prevalence of 5–12% in men and 10–25% in women[1], depression is one of the most prevalent mental health disorders and has recently been ranked as the leading cause for mental and physical disability worldwide by the World Health Organization[2]. Telomerase may constitute another link, as it was shown that under conditions of oxidative stress, ROS production, mtDNA damage, apoptosis and respiratory chain functions are modulated by TERT, the catalytic subunit of the telomere-elongating enzyme[29,30] In line with these co-regulatory mechanisms, there is a growing body of evidence showing a significant positive association between TL and mitochondrial DNA (mtDNA) copy number in whole blood, both in healthy individuals[31,32,33] and individuals with axis I psychopathologies (depression or anxiety disorder) and/or a history of childhood adversity[34]. The whole blood mtDNA copy number was thereby adapted as a measure for cellular mitochondrial density and mitochondrial biogenesis, which does, not provide any insights into mitochondrial bioenergetics
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
