Objective Leukocyte telomere length (LTL) is a biomarker of cellular aging affected by chronic stress. The relationship of LTL to the stress hormones, cortisol and catecholamines, is unclear, as are possible differences between healthy controls (HC) and individuals with Major Depressive Disorder (MDD). This small pilot study is the first to examine the relationship between cortisol, catecholamines and LTL specifically in un-medicated MDD in comparison with HC. Methods Participants included 16 un-medicated MDD subjects and 15 HC for assay of LTL, 12-hour overnight urinary free cortisol and catecholamine levels. Results LTL, cortisol and catecholamine levels did not significantly differ between groups. In HC, a hierarchical regression analysis indicated that higher levels of cortisol were correlated with shorter LTL (p=.003) above and beyond age and sex. Higher catecholamine levels were nearly-significant with shorter LTL (p=.055). Neither hormone was correlated with shorter LTL in MDD (p’s >.28). To assess a possible cumulative effect of stress hormone activation, a summary score was calculated for each subject based on the number of stress hormone levels above the median for that group (HC or MDD). A significant inverse graded relationship was observed between LTL and the number of activated systems in HC (p=.001), but not in MDD (p=.96). Conclusion This pilot study provides preliminary evidence that stress hormone levels, especially cortisol, are inversely related to LTL in HC, but not in un-medicated MDD. Clarification of these relationships in larger samples could aid in understanding differential mechanisms underlying stress-related cellular aging in healthy and depressed populations.

Objective-Leukocyte telomere length (LTL) is a biomarker of cellular aging affected by chronic stress. The relationship of LTL to the stress hormones, cortisol and catecholamines, is unclear, as are possible differences between healthy controls (HC) and individuals with Major Depressive Disorder (MDD). This small pilot study is the first to examine the relationship between cortisol, catecholamines and LTL specifically in un-medicated MDD in comparison with HC.Methods-Participants included 16 un-medicated MDD subjects and 15 HC for assay of LTL, 12-hour overnight urinary free cortisol and catecholamine levels.Results-LTL, cortisol and catecholamine levels did not significantly differ between groups. In HC, a hierarchical regression analysis indicated that higher levels of cortisol were correlated with shorter LTL (p=.003) above and beyond age and sex. Higher catecholamine levels were nearlysignificant with shorter LTL (p=.055). Neither hormone was correlated with shorter LTL in MDD (p's >.28). To assess a possible cumulative effect of stress hormone activation, a summary score was calculated for each subject based on the number of stress hormone levels above the median for

The risk of Coronary Artery Disease (CAD) has been recognized to be approximately 50% due to genetic predisposition and the remainder due to lifestyle and acquired causes. The first genetic risk variant was discovered in 2007 and since that time over 200 genetic risk variants predisposing to CAD have been discovered. These risk variants have been encrypted on to a microarray in preparation for their evaluation as a means to predict one’s risk for CAD. The Polygenic Risk Score (PRS) derived from these variants provides a single number for the total genetic risk burden. The PRS has been evaluated in several studies, totaling over 1 million individuals. Individuals categorized as high genetic risk for CAD based on PRS stratification show 2-3 fold increase risk for cardiac events. Retrospective analysis of several clinical trials showed lowering plasma LDL cholesterol is associated with decreased genetic risk and the frequency of cardiac events. A prospective study showed a favorable lifestyle to be associated with 47% reduction in the high genetic risk group and a similar reduction of 50% from physical activity in another prospective study. The PRS unlike acquired factors is not age-dependent but determined at conception and does not change throughout one’s lifetime. The several ethical, legal, and social implications associated with the clinical use of a PRS for CAD is fully discussed. The routine clinical application of the PRS for early primary prevention of CAD has the potential to be a paradigm shift in the prevention of this pandemic disease.