Background: Telomeres cap and protect DNA but shorten with each somatic cell division. Aging and environmental and lifestyle factors contribute to the speed of telomere attrition. Current evidence suggests a link between relative telomere length (RTL) and depression but the directionality of the relationship remains unclear. We prospectively examined associations between RTL and subsequent depressive symptom trajectories.Methods: Among 8,801 women of the Nurses' Health Study, depressive symptoms were measured every 4 years from 1992 to 2012; group-based trajectories of symptoms were identified using latent class growth-curve analysis. Multinomial logistic models were used to relate midlife RTLs to the probabilities of assignment to subsequent depressive symptom trajectory groups.Results: We identified four depressive symptom trajectory groups: minimal depressive symptoms (62%), worsening depressive symptoms (14%), improving depressive symptoms (19%), and persistent-severe depressive symptoms (5%).Longer midlife RTLs were related to significantly lower odds of being in the worsening symptoms trajectory versus minimal trajectory but not to other trajectories. In comparison with being in the minimal symptoms group, the multivariable-adjusted odds ratio of being in the worsening depressive symptoms group was 0.78 (95% confidence interval, 0.62-0.97; p = 0.02), for every standard deviation increase in baseline RTL. Conclusions:In this large prospective study of generally healthy women, longer telomeres at midlife were associated with significantly lower risk of a subsequent trajectory of worsening mood symptoms over 20 years. The results raise the possibility of telomere shortening as a novel contributing factor to late-life depression. K E Y W O R D S depression, depressive symptoms, late-life, telomeres, trajectories Depress Anxiety. 2019;36:565-575. wileyonlinelibrary.com/journal/da

Background Depression frequently co-occurs with cognitive decline, but the nature of this association is unclear. We examined relations of late-life depressive symptom patterns to subsequent domain-specific cognitive changes. Methods Depressive symptoms were measured at up to 3 timepoints among 11,675 Nurses’ Health Study participants prior to cognitive testing. Depressive symptom patterns were categorized as non-depressed, variable, or persistent, based on published severity cutpoints. Outcomes were global, verbal, and executive function-attention composite scores. Results Participants with persistent depressive symptoms had worse executive function-attention decline compared to non-depressed participants (multivariable-adjusted mean difference=-0.03 units/year, 95% CI: −0.05, −0.01; p=0.003); this difference was comparable to 8 years of aging. However, being in the persistent vs. non-depressed group was not significantly related to verbal (p=0.71) or global score (p=0.09) decline. By contrast, compared to the non-depressed group, those with variable depressive symptoms had worse verbal memory decline (multivariable-adjusted mean difference=−0.01 units/year, 95% CI: −0.02, −0.002; p=0.03); this group showed no differences for global or executive function-attention decline. Conclusions A variable pattern of depressive symptom severity related to subsequent decline in verbal memory, while a persistent pattern related to decline in executive function-attention. Findings could signal differences in underlying neuropathologic processes among persons with differing depression patterns and late-life cognitive decline.

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