Depressive Symptoms and Short Telomere Length Are Associated with Increased Mortality in Bladder Cancer Patients

Abstract

Background Depression is associated with an increased risk of mortality in cancer patients; it has been hypothesized that depression-associated alterations in cell aging mechanisms in particular, the telomere/telomerase maintenance system, may underlie this increased risk. We evaluated the association of depressive symptoms and telomere length to mortality and recurrence/progression in 464 bladder cancer patients. Methods We used the CES-D and SCID to assess current depressive symptoms and lifetime MDD, respectively, and telomere length was assessed from peripheral blood lymphocytes. Multivariate Cox regression was used to assess the association of depression, and telomere length to outcomes and the joint effect of both. Kaplan-Meier plots and log rank tests were used to compare survival time of subgroups by depression variables and telomere length. Results Patients with depressive symptoms (CES-D ≥16) had a 1.83-fold (95%CI= 1.08 to 3.08, P=0.024) increased risk of mortality compared to patients without depressive symptoms (CES-D < 16) and shorter disease-free survival time (P=0.004). Patients with both depressive symptoms and lifetime history of MDD were at 4.88-fold (95%CI=1.40 to 16.99; P=0.013) increased risk compared to patients with neither condition. Compared to patients without depressive symptoms and long telomere length, patients with depressive symptoms and short telomeres exhibited a 4-fold increased risk of mortality (HR=3.96, 95% CI=1.86 to 8.41, P=0.0003) and significantly shorter disease-free survival time (P<0.001). Conclusion Short telomere length and depressive symptoms are associated with bladder cancer mortality individually and jointly. Impact Further investigation of interventions that impact depression and telomere length may be warranted in cancer patients.

Psychiatric disorders and leukocyte telomere length: Underlying mechanisms linking mental illness with cellular aging

“…It is not yet known whether combining LTL measures with psychiatric disorder status may inform clinical practices. For example, a recent study found that the combination of short telomere length with depression was (compared with either measure alone) a strong prospective predictor of both cancer disease progression and mortality in a cohort of bladder cancer patients (Lin et al, 2015). Further study of cell aging in psychiatric illnesses and of its moderators and mediators may even help define more homogenous diagnoses based on underlying biological aspects of pathophysiology.…”

“…Hassett et al (2012) found significant correlations between LTL and depression ratings but not an overall between-group difference in LTL. Twelve studies did not report significant results (Canela et al, 2007; Epel et al, 2013; Georgin-Lavialle et al, 2013; Huzen et al, 2010; Ladwig et al, 2013; Lin et al, 2015; Parks et al, 2009; Phillips et al, 2013; Rius-Ottenheim et al, 2012; Shaffer et al, 2012; Surtees et al, 2011; Yen and Lung, 2013). The reasons for overall difference between the studies using categorical diagnostic inclusion criteria versus those using dimensional symptom ratings are not known, but could be due to the use of only short-term symptom rating scales (generally 1–2 weeks), lack of illness duration or severity requirements, lack of functional impairment requirements and generally including subjects with milder symptomatology in the dimensional depression studies.…”

Psychological Profiles in the Prediction of Leukocyte Telomere Length in Healthy Individuals

“…While some studies have found self-reported symptoms of depression to predict shorter telomere length [29, 86], results have been less consistent than with diagnosed mood disorders (see recent meta-analysis [87]). A novel finding in this study is that comorbid psychological states may influence the association of depression with TL.…”

Leukocyte Telomere Length Predicts SSRI Response in Major Depressive Disorder: A Preliminary Report

“…Shortened LTL in MDD and other psychiatric disorders could have pathophysiological significance by indicating accelerated aging at the cellular level and by synergizing with depression diagnosis in predicting mortality in certain populations [17]. However, few studies have investigated the association between LTL and psychopharmacological outcomes.…”