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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

Prior studies of Hypothalamic-Pituatary-Adrenal (HPA) associations with hippocampal (HC) volume have yielded inconsistent results. This might be due to the use of basal cortisol rather than cortisol reactivity measures and to the use of cortisol in isolation from related steroids. Therefore, in this study, we assessed the relationship of HC volume to cortisol awakening responses (CARs) and to the ratio of cortisol/DHEA in depressed (MDD) subjects and healthy controls. We additionally assessed cortisol correlations with individual HC subfield volumes.A 4 Tesla T1 MR imaging was conducted for HC volume for 19 MDD subjects and 19 matched controls. Fasting morning serum was assayed for cortisol and DHEA. In addition, salivary samples were assayed for cortisol for 17 MDDs and 15 controls across 3 days: at Waking (Sample 1) and at +30 minutes after waking (Sample 2). The CAR is the difference between daily Sample 1 and Sample 2 salivary concentrations. The slope of the CARincrease was obtained by dividing the CAR by the actual length of time between the two sample collections. Serum cortisol was not significantly correlated with HC volume. However, in the MDD group, serum DHEA, a putative anti-glucocorticoid, was positively correlated with HC volume (p