PBMC telomerase activity correlates with hippocampal volume in major depression

Abstract

The cellular enzyme elomerase replenishes telomeric DNA, which can be lost during repeated mitoses or during exposure to inflammation and oxidation. However, telomerase may have other, non-canonical functions, including (in animal models) antidepressant and neurogenesis-enhancing effects. In this study, we determined the relationship between telomerase activity [(measured in peripheral blood mononuclear cells (PBMCs)] and hippocampal (HC) volume in depressed individuals (MDDs) and matched controls.Nineteen medication-free subjects with MDD and 17 matched healthy controls underwent 4T MRI scanning and fasting morning venipuncture for assessment of unstimulated PBMC telomerase activity. Due to the exploratory nature of the study, corrections for multiple comparisons were not applied.Hippocampal volume was smaller, but not significantly so, in the MDDs than the controls. As reported previously, MDD subjects had significantly higher PBMC telomerase activity than the controls (p=0.007). Within the MDD group (but not in the control group or in the combined sample), PBMC telomerase activity was positively correlated with HC volume (r=0.49, p<0.04).The relationship between telomerase activity in PBMCs and telomerase activity in the HC is unknown. Nonetheless, these results are consistent with emerging preclinical data that telomerase may have neurotrophic and antidepressant effects, may facilitate the neurotrophic effects of brain derived neruotrophic factor (BDNF) and may reverse certain signs of aging, and with clinical data that telomerase may be associated with favorable antidepressant responses. Our finding of significant telomerase/HC correlations only in the MDD subjects raises the possibility that telomerase may play a compensatory or reparative role in this disease.

Keywords

• telomerase
• depression
• hippocampal volume
• antidepressant effects