Long-term lithium treatment in bipolar disorder is associated with longer leukocyte telomeres

Martinsson, Lina; Wei, Yunbing; Xu, Dawei; Melas, Philippe A.; Mathé, Aleksander A.; Schalling, Martin; Lavebratt, Catharina; Backlund, Lena

doi:10.1038/tp.2013.37

Cited by 141 publications

(129 citation statements)

References 42 publications

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“…There may be gender differences, and as we only included males in our study, we cannot be sure that our findings can be extrapolated to women. Interestingly, there are also several environmental factors that may impact on telomere length such as the use of Lithium that increases telomere length (Martinsson et al 2013) and vigorous physical activity that protects against telomere shortening by traumatic stress .…”

Section: Discussionmentioning

confidence: 99%

Longitudinal changes of telomere length and epigenetic age related to traumatic stress and post-traumatic stress disorder

Boks

Mierlo

Rutten

et al. 2015

Psychoneuroendocrinology

192

182

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Several studies have reported an association between traumatic stress and telomere length suggesting that traumatic stress has an impact on aging at the cellular level. A newly derived tool provides an additional means to investigate cellular aging by estimating epigenetic age based on DNA methylation profiles. We therefore hypothesise that in a longitudinal study of traumatic stress both indicators of cellular aging will show increased aging. We expect that particularly in individuals that developed symptoms of post--traumatic stress disorder (PTSD) increases in these aging parameters would stand out.From an existing longitudinal cohort study, ninety--six male soldiers were selected based on trauma exposure and the presence of symptoms of PTSD. All military personnel were deployed in a combat zone in Afghanistan and assessed before and 6 months after deployment. The Self--Rating Inventory for PTSD was used to measure the presence of PTSD symptoms, while exposure to combat trauma during deployment was measured with a 19--item deployment experiences checklist. These groups did not differ for age, gender, alcohol consumption, cigarette smoking, military rank, length, weight, or medication use. In DNA from whole blood telomere length was measured and DNA methylation levels were assessed using the Illumina 450K DNA methylation arrays. Epigenetic aging was estimated using the DNAm age estimator procedure.The association of trauma with telomere length was in the expected direction but not significant (B=--10.2, p=0.52). However, contrary to our expectations, development of PTSD symptoms was associated with the reverse process, telomere lengthening (B=1.91, p= 0.018). In concordance, trauma significantly accelerated epigenetic aging (B=1.97, p=0.032) and similar to the findings in telomeres, development of PTSD symptoms was inversely associated with epigenetic aging (B=--0.10, p= 0.044). Blood cell count, medication and premorbid early life trauma exposure did not confound the results.Overall, in this longitudinal study of military personnel deployed to Afghanistan we show an acceleration of ageing by trauma. However, development of PTSD symptoms was associated with telomere lengthening and reversed epigenetic aging. These findings warrant further study of a perhaps dysfunctional compensatory cellular aging reversal in PTSD.3

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Section: Discussionmentioning

confidence: 99%

Longitudinal changes of telomere length and epigenetic age related to traumatic stress and post-traumatic stress disorder

Boks

Mierlo

Rutten

et al. 2015

Psychoneuroendocrinology

192

182

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“…Recent evidence from a BD cohort further demonstrated that patients on long-term lithium therapy had longer telomeres (about 10%) than those not responding well to lithium or healthy controls. 19 A recent study reported immunosenescent cells and shortened telomeres in female patients with BD. 20 A 2015 multicenter study and meta-analysis addressing whether BD can be considered an accelerated aging (AA) disease included seven cohorts with 1,115 patients.…”

Section: Introductionmentioning

confidence: 99%

Shortened telomere length in bipolar disorder: a comparison of the early and late stages of disease

Barbé-Tuana

Parisi

Panizzutti

et al. 2016

Rev. Bras. Psiquiatr.

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Objective: Bipolar disorder (BD) has been associated with increased rates of age-related diseases, such as type II diabetes, metabolic syndrome, osteoporosis, and cardiovascular disorders. Several biological findings have been associated with age-related disorders, including increased oxidative stress, inflammation, and telomere shortening. The objective of this study was to compare telomere length among participants with BD at early and late stages and age-and gender-matched healthy controls. Methods: Twenty-six euthymic subjects with BD and 34 healthy controls were recruited. Genomic DNA was extracted from peripheral blood and mean telomere length was measured using real-time quantitative polymerase chain reaction. Results: Telomere length was significantly shorter in both the early and late subgroups of BD subjects when compared to the respective controls (p = 0.002 and p = 0.005, respectively). The sample size prevented additional subgroup analyses, including potential effects of medication, smoking status, and lifestyle. Conclusion: This study is concordant with previous evidence of telomere shortening in BD, in both early and late stages of the disorder, and supports the notion of accelerated aging in BD.

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“…DNA from peripheral blood samples was extracted using a sodium dodecylsulfate-urea and phenol/chloroform/isoamylalcohol procedure, as previously described [19]. Global DNA methylation levels were measured with the 5-mC DNA ELISA Kit (Zymo Research Corporation, Irvine, Calif., USA), a method used for the quantification of global DNA methylation which utilizes 5-mC antibodies that bind specifically to methylated sites of the genome.…”

Section: Methodsmentioning

confidence: 99%

Mood Stabilizers and the Influence on Global Leukocyte DNA Methylation in Bipolar Disorder

Backlund

Wei

Martinsson³

et al. 2015

Complex Psychiatry

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Little is known about the relationship between treatments for bipolar disorder (BD), their therapeutic responses and the DNA methylation status. We investigated whether global DNA methylation levels differ between healthy controls and bipolar patients under different treatments. Global DNA methylation was measured in leukocyte DNA from bipolar patients under lithium monotherapy (n = 29) or combination therapy (n = 32) and from healthy controls (n = 26). Lithium response was assessed using the Alda scale. Lithium in monotherapy was associated with hypomethylation (F = 4.63, p = 0.036). Lithium + valproate showed a hypermethylated pattern compared to lithium alone (F = 7.27, p = 0.011). Lithium response was not associated with DNA methylation levels. These data suggest that the choice of treatment in BD may lead to different levels of global DNA methylation. However, further research is needed to understand its clinical significance.

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Long-term lithium treatment in bipolar disorder is associated with longer leukocyte telomeres

Cited by 141 publications

References 42 publications

Longitudinal changes of telomere length and epigenetic age related to traumatic stress and post-traumatic stress disorder

Longitudinal changes of telomere length and epigenetic age related to traumatic stress and post-traumatic stress disorder

Shortened telomere length in bipolar disorder: a comparison of the early and late stages of disease

Mood Stabilizers and the Influence on Global Leukocyte DNA Methylation in Bipolar Disorder

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