Differences in Telomere Length Between Patients with Bipolar Disorder and Controls are Influenced by Lithium Treatment

Pisanu, Claudia; Congiu, Donatella; Manchia, Mirko; Caria, Paola; Cocco, Cristina; Dettori, Tinuccia; Frau, Daniela Virginia; Manca, Elias; Meloni, Anna; Nieddu, Mariella; Noli, Barbara; Pinna, Federica; Robledo, Renato; Sogos, Valeria; Ferri, Gian Luca; Carpiniello, Bernardo; Vanni, Roberta; Bocchetta, Alberto; Severino, Giovanni; Ardau, Raffaella; Chillotti, Caterina; Zompo, Maria Del; Squassina, Alessio

doi:10.2217/pgs-2020-0028

Cited by 32 publications

(22 citation statements)

References 56 publications

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“…A recent study found that bipolar disorder patients who had never been treated with lithium had shorter telomeres than healthy controls, while patients treated with lithium had longer telomeres than the never treated patients, although not compared to healthy controls. 17 Our finding that antidepressant medication use was associated with reduced telomere length in individuals with depression confirms a preliminary study showing that antidepressant use (n=40) was associated with shorter telomeres, independent of depression diagnosis and current depression severity. 40 Although previous research suggested that age-related decline in telomere length was greater in individuals with chronic stress or comorbidities, 41 we observed similar association between telomere length and age in individuals with mental disorders and the control group.…”

Section: Discussionsupporting

confidence: 88%

“…16 Bipolar disorder patients not exposed to lithium had shorter telomeres than patients who had been treated with lithium. 17 Most previous studies have had limited sample sizes and few studies have included cross-disorder comparisons within the same database. There has also been little exploration of associations between telomere length and genetic risk for mental disorders.…”

Section: Introductionmentioning

confidence: 99%

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Telomere length and its associations with mental disorders, age and genetic risk for mental disorders

Mutz

Lewis

2022

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Background: Mental disorders are associated with substantially increased morbidity and reduced life expectancy. Accelerated biological ageing might contribute to excess mortality of individuals with mental disorders. The aim of this study was to characterise telomere length, a biological hallmark of ageing, in individuals with mental disorders, and to examine associations between telomere length, age and genetic risk for mental disorders. Methods: The UK Biobank is a multicentre, community-based observational study that recruited >500,000 middle-aged and older adults across England, Scotland and Wales. Average leukocyte telomere length (T/S ratio) was measured using quantitative polymerase chain reaction. Polygenic risk scores (PRS) were calculated for individuals of European ancestry. We estimated differences in T/S ratio and age-related changes in T/S ratio between individuals with anxiety disorder, depression or bipolar disorder and people without mental disorders. We also estimated associations between T/S ratio and PRS for these three disorders. Results: The analyses included up to 308,725 participants. Individuals with depression had shorter telomeres than people without mental disorders (adjusted β = -0.011, 95% CI -0.019 to -0.004, pBonf. = 0.027). There was only limited evidence of case-control differences in telomere length for anxiety disorders or bipolar disorders. Age-related changes in telomere length did not differ between individuals with and without mental disorders. PRS for depression were associated with shorter telomeres (β = -0.006, 95% CI -0.010 to -0.003, pBonf. = 0.001). There was no evidence that PRS for anxiety disorder or bipolar disorder were associated with telomere length. Conclusion: Although telomere length is a biological hallmark of ageing, we observed limited evidence that leukocyte telomere length is a clinically useful marker to quantify accelerated biological ageing in middle-aged and older adults with a lifetime history of anxiety disorder, depression or bipolar disorder.

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Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Telomere length and its associations with mental disorders, age and genetic risk for mental disorders

Mutz

Lewis

2022

Preprint

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“…Several studies investigated TL in patients with MDD and different results have been found, some of which showed that TL is shorter in patients than in non-psychiatric controls [66][67][68][69][70]. Similar findings have been reported in BD [67,[71][72][73][74], and different studies showed that treatment with the mood stabilizer lithium correlated with longer LTL [75][76][77]. Fewer studies investigated differences in TL between responders and non-responders to antidepressant treatment.…”

Section: Introductionmentioning

confidence: 82%

“…In the analysis of GWAS data, we observed no significant enrichment between genetic variants associated with LTL and variants nominally associated with response to ECT. While LTL is a highly heritable trait, and shorter genetically predicted TL has been associated with increased risk of some disorders, such as coronary artery disease and other cardiovascular disorders [59,85], previous studies aiming to assess the presence of an enrichment between genetic variants associated with LTL and psychiatric phenotypes mostly yielded negative results [77,86,87].…”

Section: Discussionmentioning

confidence: 99%

Investigating the Role of Leukocyte Telomere Length in Treatment-Resistant Depression and in Response to Electroconvulsive Therapy

Pisanu

Vitali

Meloni

et al. 2021

JPM

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Psychiatric disorders seem to be characterized by premature cell senescence. However, controversial results have also been reported. In addition, the relationship between accelerated aging and treatment-resistance has scarcely been investigated. In the current study, we measured leukocyte telomere length (LTL) in 148 patients with treatment-resistant depression (TRD, 125 with major depressive disorder, MDD, and 23 with bipolar disorder, BD) treated with electroconvulsive therapy (ECT) and analyzed whether LTL was associated with different response profiles. We also compared LTL between patients with TRD and 335 non-psychiatric controls. For 107 patients for which genome-wide association data were available, we evaluated whether a significant overlap among genetic variants or genes associated with LTL and with response to ECT could be observed. LTL was negatively correlated with age (Spearman’s correlation coefficient = −0.25, p < 0.0001) and significantly shorter in patients with treatment-resistant MDD (Quade’s F = 35.18, p < 0.0001) or BD (Quade’s F = 20.84, p < 0.0001) compared to controls. Conversely, baseline LTL was not associated with response to ECT or remission. We did not detect any significant overlap between genetic variants or genes associated with LTL and response to ECT. Our results support previous findings suggesting premature cell senescence in patients with severe psychiatric disorders and suggest that LTL could not be a predictive biomarker of response to ECT.

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“…Powell et al ( 122 ) reported longer TL in buccal smears from lithium-treated BD patients compared to patients not on lithium treatment while Coutts et al ( 123 ) found an association between chronic lithium treatment and longer whole blood TL in BD patients ( 122 , 123 ). Most recently, Pisanu et al ( 124 ) reported that BD patients with a history of lithium treatment had longer leukocyte TL compared to those who never had been treated with lithium and similar TL compared to controls ( 124 ). In the only prospective clinical study on lithium’s effect of TL thus far, Köse Çinar ( 125 ) found that manic BD patients had shorter TL than healthy controls and that TL was significantly increased at remission after treatment with lithium and antipsychotics ( 125 ).…”

Section: Telomere Maintenancementioning

confidence: 99%

Lithium and the Interplay Between Telomeres and Mitochondria in Bipolar Disorder

et al. 2020

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Bipolar disorder is a severe psychiatric disorder which affects more than 1% of the world’s population and is a leading cause of disability among young people. For the past 50 years, lithium has been the drug of choice for maintenance treatment of bipolar disorder due to its potent ability to prevent both manic and depressive episodes as well as suicide. However, though lithium has been associated with a multitude of effects within different cellular pathways and biological systems, its specific mechanism of action in stabilizing mood remains largely elusive. Mitochondrial dysfunction and telomere shortening have been implicated in both the pathophysiology of bipolar disorder and as targets of lithium treatment. Interestingly, it has in recent years become clear that these phenomena are intimately linked, partly through reactive oxygen species signaling and the subcellular translocation and non-canonical actions of telomerase reverse transcriptase. In this review, we integrate the current understanding of mitochondrial dysfunction, oxidative stress and telomere shortening in bipolar disorder with documented effects of lithium. Moreover, we propose that lithium’s mechanism of action is intimately connected with the interdependent regulation of mitochondrial bioenergetics and telomere maintenance.

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Differences in Telomere Length Between Patients with Bipolar Disorder and Controls are Influenced by Lithium Treatment

Cited by 32 publications

References 56 publications

Telomere length and its associations with mental disorders, age and genetic risk for mental disorders

Telomere length and its associations with mental disorders, age and genetic risk for mental disorders

Investigating the Role of Leukocyte Telomere Length in Treatment-Resistant Depression and in Response to Electroconvulsive Therapy

Lithium and the Interplay Between Telomeres and Mitochondria in Bipolar Disorder

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