Leukocyte Telomere Length in Major Depression: Correlations with Chronicity, Inflammation and Oxidative Stress - Preliminary Findings

Depression is associated with an unusually high rate of aging-related illnesses and early mortality. One aspect of “accelerated aging” in depression may be shortened leukocyte telomeres. When telomeres critically shorten, as often occurs with repeated mitoses or in response to oxidation and inflammation, cells may die. Indeed, leukocyte telomere shortening predicts early mortality and medical illnesses in non-depressed populations. We sought to determine if leukocyte telomeres are shortened in Major Depressive Disorder (MDD), whether this is a function of lifetime depression exposure and whether this is related to putative mediators, oxidation and inflammation.Leukocyte telomere length was compared between 18 unmedicated MDD subjects and 17 controls and was correlated with lifetime depression chronicity and peripheral markers of oxidation (F2-isoprostane/Vitamin C ratio) and inflammation (IL-6). Analyses were controlled for age and sex.The depressed group, as a whole, did not differ from the controls in telomere length. However, telomere length was significantly inversely correlated with lifetime depression exposure, even after controlling for age (p<0.05). Average telomere length in the depressed subjects who were above the median of lifetime depression exposure (≥9.2 years' cumulative duration) was 281 base pairs shorter than that in controls (p<0.05), corresponding to approximately seven years of “accelerated cell aging.” Telomere length was inversely correlated with oxidative stress in the depressed subjects (p<0.01) and in the controls (p<0.05) and with inflammation in the depressed subjects (p<0.05).These preliminary data indicate that accelerated aging at the level of leukocyte telomeres is proportional to lifetime exposure to MDD. This might be related to cumulative exposure to oxidative stress and inflammation in MDD. This suggest that telomere shortening does not antedate depression and is not an intrinsic feature. Rather, telomere shortening may progress in proportion to lifetime depression exposure

Leukocyte telomere length in major depression: correlations with chronicity, inflammation and oxidative stress--preliminary findings.

BackgroundDepression is associated with an unusually high rate of aging-related illnesses and early mortality. One aspect of "accelerated aging" in depression may be shortened leukocyte telomeres. When telomeres critically shorten, as often occurs with repeated mitoses or in response to oxidation and inflammation, cells may die. Indeed, leukocyte telomere shortening predicts early mortality and medical illnesses in non-depressed populations. We sought to determine if leukocyte telomeres are shortened in Major Depressive Disorder (MDD), whether this is a function of lifetime depression exposure and whether this is related to putative mediators, oxidation and inflammation.MethodologyLeukocyte telomere length was compared between 18 unmedicated MDD subjects and 17 controls and was correlated with lifetime depression chronicity and peripheral markers of oxidation (F2-isoprostane/Vitamin C ratio) and inflammation (IL-6). Analyses were controlled for age and sex.Principal findingsThe depressed group, as a whole, did not differ from the controls in telomere length. However, telomere length was significantly inversely correlated with lifetime depression exposure, even after controlling for age (p&lt;0.05). Average telomere length in the depressed subjects who were above the median of lifetime depression exposure (≥9.2 years' cumulative duration) was 281 base pairs shorter than that in controls (p&lt;0.05), corresponding to approximately seven years of "accelerated cell aging." Telomere length was inversely correlated with oxidative stress in the depressed subjects (p&lt;0.01) and in the controls (p&lt;0.05) and with inflammation in the depressed subjects (p&lt;0.05).ConclusionsThese preliminary data indicate that accelerated aging at the level of leukocyte telomeres is proportional to lifetime exposure to MDD. This might be related to cumulative exposure to oxidative stress and inflammation in MDD. This suggest that telomere shortening does not antedate depression and is not an intrinsic feature. Rather, telomere shortening may progress in proportion to lifetime depression exposure

Characteristics of Depressed and Control Subjects.

1<p>Subjective socioeconomic status was measured using a 10-rung ladder version of the MacArthur Scale of Subjective Social Status <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0017837#pone.0017837-Adler1" target="_blank">[100]</a>, with higher numbers equaling higher perceived socioeconomic status.</p>2<p>Physical Activity Level was measured with the Yale Physical Activity Survey (YPAS) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0017837#pone.0017837-Dipietro1" target="_blank">[101]</a>. On this scale, 1 =  “not very active;” 2 =  “weekend/vacations only;” 3 =  “more than 1–2 times per week;” 4 =  “more than 3 times per week.” Other measures on the YPAS, such as “Vigorous Activity” and “Duration of Vigorous Activity” yielded similar differences between groups.</p

Relationship between cumulative lifetime duration of depression and leukocyte telomere length (in base pairs, bp).

<p>(F =  4.70, p<0.05, controlling for age and sex by hierarchical linear regression).</p

Relationship between serum IL-6 concentrations (pg/ml) and leukocyte telomere length (in base pairs, bp) in depressed subjects.

<p>(F =  3.29, p<0.05, controlling for age, sex and BMI). The relationship missed significance in the combined sample (depressed plus controls) (F =  2.45, p = 0.07, controlling for age, sex and BMI) and was not significant in the controls alone (not plotted) (F =  2.28, p =  0.13, controlling for age, sex and BMI).</p

Relationship between the oxidative stress ratio (F-2 isoprostanes/Vitamin C concentrations, Ln transformed) and leukocyte telomere length (in base pairs, bp).

<p>Filled circles represent depressed subjects (“MDD”) (F =  6.04, p<0.01, controlling for age and sex), and open squares represent controls (“Cont”) (F =  4.38, p<0.05, controlling for age and sex). In the combined sample (depressed plus controls), the relationship was also statistically significant (F =  8.21, p<0.001, controlling for age and sex).</p