Long-term lithium treatment in bipolar disorder is associated with longer leukocyte telomeres
Open accessAbstract
Telomere shortening is a hallmark of aging and has been associated with oxidative stress, inflammation and chronic somatic, as well as psychiatric disorders, including schizophrenia and depression. Additionally, antidepressants have been found to protect against telomere shortening. However, pharmacological telomere studies are lacking in bipolar disorder (BD). Therefore, the objective of this study was to explore telomere length (TL) in patients with BD in the context of lithium treatment. We determined TL by quantitative real-time PCR using peripheral blood leukocytes. Participants were outpatients diagnosed with BD type 1 or 2 (n=256) and healthy controls (n=139). Retrospective case-control and case-case study designs were applied. Lithium response (LiR) was scored using the Alda-Scale. Lithium-treated BD patients overall, as well as those on lithium monotherapy, had 35% longer telomeres compared with controls (P<0.0005, partial η(2)=0.13). TL correlated positively with lithium treatment duration of >30 months (P=0.031, R(2)=0.13) and was negatively associated with increasing number of depressive episodes (P<0.007). BD patients responding well to lithium treatment had longer telomeres than those not responding well. This is the first study to report a positive effect of long-term lithium treatment on TL. Importantly, longer TL was also associated with a better LiR in BD patients. These data suggest that lithium exerts a protective effect against telomere shortening especially when therapeutically efficacious. We hypothesize that induction of telomerase activity may be involved in LiR in BD.
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Martinsson et al. (2013) reported significantly increased LTL in lithium-treated BD subjects compared to controls.
“Martinsson et al. (2013) reported significantly increased LTL in lithium-treated BD subjects compared to controls.”
From Psychiatric disorders and leukocyte telomere length: Underlying mechanisms linking mental illness with cellular aging (2015) · cites this paper as Martinsson et al. (2013)
Martinsson et al. suggested that lithium may exert a protective effect against telomere shortening, especially when therapeutically efficacious, and that lithium-induced telomerase activation might be involved, although TA was not measured.
“The authors suggested that lithium may exert a protective effect against telomere shortening, especially when therapeutically efficacious, and that lithium-induced telomerase activation might be involved, although TA was not measured (Martinsson et al., 2013).”
From Psychiatric disorders and leukocyte telomere length: Underlying mechanisms linking mental illness with cellular aging (2015) · cites this paper as Martinsson et al., 2013
In Martinsson et al., the cumulative amount of time receiving lithium over the preceding 30 months was associated with increased LTL, and lithium responders had longer LTL than lithium non-responders.
“The cumulative amount of time receiving lithium over the preceding 30 months was associated with increased LTL, and lithium responders had longer LTL than lithium non-responders.”
From Psychiatric disorders and leukocyte telomere length: Underlying mechanisms linking mental illness with cellular aging (2015) · cites this paper as Martinsson et al., 2013
The different results in the Elvsåshagen et al. (2011) and Martinsson et al. (2013) studies might be explained by lithium treatment.
“The different results in the Elvsåshagen et al. (2011) and Martinsson et al. (2013) studies might, therefore, be explained by lithium treatment.”
From Psychiatric disorders and leukocyte telomere length: Underlying mechanisms linking mental illness with cellular aging (2015) · cites this paper as Martinsson et al. (2013)
No clinical studies have yet directly assessed the effect of psychotropic medications on LTL.
“This explanation is similar to the finding with lithium treatment reviewed above (Martinsson et al., 2013), although no clinical studies have yet directly assessed the effect of psychotropic medications on LTL.”
From Psychiatric disorders and leukocyte telomere length: Underlying mechanisms linking mental illness with cellular aging (2015) · cites this paper as Martinsson et al., 2013
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- Authors
- Martinsson, L., Wei, Y., Xu, D., Melas, P. A., Mathé, A. A., Schalling, M., Lavebratt, C., & Backlund, L.
- Affiliations
- Karolinska University Hospital (SE)
- Corresponding author
- Martinsson, L
- Venue
- Translational Psychiatry
- Published
- 2013-05-21
- Volume
- 3
- Issue
- 5
- Pages
- e261-e261
- ISSN
- 2158-3188 (ISSN-L)
- PMC
- PMC3669924
- OpenAlex
- W2025700197
- Cited by
- 179
- References
- 46
- Citations by year
- 2026: 7 · 2025: 13 · 2024: 14 · 2023: 8 · 2022: 14 · 2021: 12 · 2020: 17 · 2019: 17 · 2018: 15 · 2017: 10 · 2016: 14 · 2015: 20 · 2014: 16 · 2013: 1
- FWCI
- 12.09
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc-sa
- www.springer.com/tdm (unspecified)
- Locations
- Translational Psychiatry (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- Lundbeckfonden
- Karolinska Institutet
- Stockholms Läns Landsting
- H. Lundbeck A/S
- Medical Research Council
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- bipolar disorder, lithium therapy, telomere length, leukocytes, telomere shortening, lithium response, treatment duration, depressive episodes, telomerase, oxidative stress, inflammation, aging
- MeSH terms
- Adult, Aged, Aged, 80 and over, Bipolar Disorder, Female, Humans, Leukocytes, Male, Middle Aged, Psychiatric Status Rating Scales, Retrospective Studies, Case-Control Studies, Telomere, Lithium Compounds, Young Adult, Telomere Homeostasis, Real-Time Polymerase Chain Reaction
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