title: 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 shortness 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.
authors.affiliation: Department of Psychiatry, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, USA. Electronic address: Owen.Wolkowitz@ucsf.edu.
authors.forename: Owen M
authors.initials: OM
authors.lastname: Wolkowitz
authors.affiliation: Department of OBGYN and Reproductive Endocrinology, UCSF School of Medicine, San Francisco, CA, USA.
authors.forename: Synthia H
authors.initials: SH
authors.lastname: Mellon
authors.affiliation: Department of Clinical Sciences, Section for Psychiatry, Lund University, Lund, Sweden.
authors.forename: Daniel
authors.initials: D
authors.lastname: Lindqvist
authors.affiliation: Department of Psychiatry, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, USA.
authors.forename: Elissa S
authors.initials: ES
authors.lastname: Epel
authors.affiliation: Department of Biochemistry and Biophysics, UCSF School of Medicine, San Francisco, CA, USA.
authors.forename: Elizabeth H
authors.initials: EH
authors.lastname: Blackburn
authors.affiliation: Department of Biochemistry and Biophysics, UCSF School of Medicine, San Francisco, CA, USA.
authors.forename: Jue
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of Psychiatry, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, USA.
authors.forename: Victor I
authors.initials: VI
authors.lastname: Reus
authors.affiliation: Department of Psychiatry, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: Burke
authors.affiliation: Department of Psychiatry, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Rosser
authors.affiliation: Department of Psychiatry, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Mahan
authors.affiliation: Department of Psychiatry, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Mackin
authors.affiliation: Department of Psychiatry, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, USA.
authors.forename: Tony
authors.initials: T
authors.lastname: Yang
authors.affiliation: Department of Radiology, UCSF School of Medicine, San Francisco, CA, USA; San Francisco Veterans Administration Medical Center, San Francisco, CA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Weiner
authors.affiliation: Department of Radiology, UCSF School of Medicine, San Francisco, CA, USA; San Francisco Veterans Administration Medical Center, San Francisco, CA, USA.
authors.forename: Susanne
authors.initials: S
authors.lastname: Mueller
mesh_terms: D000328:Adult; D016922:Cellular Senescence / Q000502:physiology; D003865:Major Depressive Disorder / Q000201:enzymology / Q000473:pathology*; D005260:Female; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D009929:Organ Size / Q000502:physiology; D019098:Telomerase / Q000378:metabolism*; D016615:Telomere
chemical_list: D019098:Telomerase
keywords: Brain; Depression; Hippocampus; Leukocytes; Telomerase; Telomeres