Resting leukocyte telomerase activity is elevated in major depression and predicts treatment response

Abstract

Telomeres are DNA-protein complexes that cap linear DNA strands, protecting DNA from damage. When telomeres critically shorten, cells become susceptible to senescence and apoptosis. Telomerase, a cellular ribonucleoprotein enzyme, rebuilds the length of telomeres and promotes cellular viability. Leukocyte telomeres are reportedly shortened in major depression, but telomerase activity in depression has not been previously reported. Further, there are no published reports of the effects of antidepressants on telomerase activity or on the relationship between telomerase activity and antidepressant response. Peripheral blood mononuclear cell (PBMC) telomerase activity was assessed in 20 medication-free depressed individuals and 18 controls. In total, 16 of the depressed individuals were then treated with sertraline in an open-label manner for 8 weeks, and PBMC telomerase activity was reassessed in 15 of these individuals after treatment. Pre- and post-treatment symptom severity was rated with the Hamilton Depression Rating Scale. All analyses were corrected for age and sex. Pretreatment telomerase activity was significantly elevated in the depressed individuals compared with the controls (P = 0.007) and was directly correlated with depression ratings (P< 0.05) across all subjects. In the depressed group, individuals with relatively lower pretreatment telomerase activity and with relatively greater increase in telomerase activity during treatment, showed superior antidepressant responses (P < 0.05 and P < 0.005, respectively). This is the first report characterizing telomerase activity in depressed individuals. PBMC telomerase activity might reflect a novel aspect of depressive pathophysiology and might represent a novel biomarker of antidepressant responsiveness.

The Age-by-Disease Interaction Hypothesis of Late-Life Depression

“…Mechanisms related to oxidative stress, cellular metabolism and genome integrity, either through repair or maintenance of proper telomere length for instance, are current topics of research. 64,82-85 The brain and neuronal systems specificities of these biological processes represent unique areas of investigation for psychiatric and or neurological disorders. Another important topic of further investigation relates to the individual variability in age-related vulnerability to develop functional declines and associated disease symptoms, including LLD.…”

How “Reversible” Is Telomeric Aging?

“…Higher telomerase, while probably always beneficial for telomere protection, might also serve as an indicator of a high level of cellular stress. Telomerase appears to increase during acute stress (43) and certain states of chronic adversity, such as low education, depression, and caregiving (48)(49)(50), presumably to combat oxidative stress and to protect the telomere. In depressed people, although they had elevated telomerase at baseline, treatment with an antidepressant led to further increases in telomerase activity, and this telomerase increase was associated with a greater reduction in depressive symptoms (49).…”

Hjärnan formas av psykologisk behandling

“…For instance, Stein and colleagues (2013) reported that individuals with SAD were at greater risk than healthy individuals to be affected by hypertension. Also, there is evidence linking accelerated cellular aging to stress (Blackburn, Epel, & Lin, 2015;Epel et al, 2004) as well as psychiatric disorders such as MDD (Verhoeven et al, 2014;Wolkowitz et al, 2012) and anxiety disorders (Verhoeven et al, 2015). In a large cohort, Verhoeven et al (2015) found that individuals with anxiety disorders (including SAD) had shorter leukocyte telomeres relative to healthy controls.…”