PBMC telomerase activity, but not leukocyte telomere length, correlates with hippocampal volume in major depression

Abstract

Accelerated cell aging, indexed in peripheral leukocytes by telomere length and in peripheral blood mononuclear cells (PBMCs) by telomerase activity, has been reported in several studies of major depressive disorder (MDD). However, the relevance of these peripheral measures for brain indices that are presumably more directly related to MDD pathophysiology is unknown. In this study, we explored the relationship between PBMC telomerase activity and leukocyte telomere length and magnetic resonance imaging-estimated hippocampal volume in un-medicated depressed individuals and healthy controls. We predicted that, to the extent peripheral and central telomerase activity are directly related, PBMC telomerase activity would be positively correlated with hippocampal volume, perhaps due to hippocampal telomerase-associated neurogenesis, neuroprotection or neurotrophic facilitation, and that this effect would be clearer in individuals with increased PBMC telomerase activity, as previously reported in un-medicated MDD. We did not have specific hypotheses regarding the relationship between leukocyte telomere length and hippocampal volume, due to conflicting reports in the published literature. We found, in 25 un-medicated MDD subjects, that PBMC telomerase activity was significantly positively correlated with hippocampal volume; this relationship was not observed in 18 healthy controls. Leukocyte telomere length was not significantly related to hippocampal volume in either group (19 unmedicated MDD subjects and 17 healthy controls). Although the nature of the relationship between peripheral telomerase activity and telomere length and the hippocampus is unclear, these preliminary data are consistent with the possibility that PBMC telomerase activity indexes, and may provide a novel window into, hippocampal neuroprotection and/or neurogenesis in MDD.

Leukocyte telomere length and hippocampus volume: a meta-analysis

“…Several possible sources of heterogeneity were identified in sampling strategies and analysis methods. Grodstein et al 20 included a sub-group of patients with minimal cognitive impairment, and Wolkowitz et al 21 included a cohort with major depressive disorder. All studies determined relative average telomere length by PCR as the ratio of telomeres to single genes (T/S ratio).…”

“…All studies determined relative average telomere length by PCR as the ratio of telomeres to single genes (T/S ratio). Two studies (Grodstein et al 20 and King et al 22 ) used the T/S ratio in statistical analyses, whereas the other three studies (Wikgren et al 12 , Jacobs et al 13 , and Wolkowitz et al 21 ) determined the average telomere base pair length and used that for statistical analyses. One study (King et al 22 ) log-transformed telomere length data prior to analysis in order to better approximate a normal distribution.…”

“…One study (King et al 22 ) log-transformed telomere length data prior to analysis in order to better approximate a normal distribution. Three studies (Grodstein et al 20 , Jacobs et al 13 , and Wikgren et al 12 ) did not use a log-transformation, and one study (Wolkowitz et al 21 ) reported that some variables were log-transformed but did not say whether telomere length was one of them.…”

“…Hippocampus volume was determined using magnetic resonance imaging in all included studies. King et al 22 , Jacobs et al 13 , and Wolkowitz et al 21 used FreeSurfer ( http://freesurfer.net/ ) for automated parcellation. Wikgren et al 12 used manual tracing and did not specify whether the person performing the tracing was blind to other participant outcomes at the time.…”

Psychiatric disorders and leukocyte telomere length: Underlying mechanisms linking mental illness with cellular aging

“…To our knowledge, only one study has assessed the relationship of PBMC basal TA to hippocampal volume in MDD. Wolkowitz et al (In press) reported a significant positive correlation between PBMC basal TA and hippocampal volume in a small group of unmedicated individuals with MDD but not in healthy controls. The authors interpreted these results as being consistent with those of the preclinical study by Zhou et al (2011), reviewed above.…”