Abstract
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 η2=0.13). TL correlated positively with lithium treatment duration of >30 months (P=0.031, R2=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.
Highlights
Bipolar disorder (BD) is a severe and chronic disorder affecting about 1–2% of the population causing immense suffering and excessive costs.[1,2] BD type 1 is characterized by alternating episodes of depression and mania, whereas BD type 2 is characterized by depressions and hypomanias.[3]
Lithium response (LiR) was measured according to the yearly reduction of numbers and/or severity of episodes after the beginning of lithium treatment, controlled for the duration of lithium treatment, the age of onset of BD, the number of years with BD before treatment, the duration of lithium treatment before DNA sampling and the presence of other mood stabilizers, antidepressants, neuroleptics or sleep medication according to the Alda-Scale.[7,22]
As lithium has a neuroprotective effect,[8] we tested whether lithium exposure influenced LTL. This was assessed in Set I comprising of ageand sex-matched LiR and non-LiR BD patients with a duration of lithium treatment that was for LiR: 52 (21,172), 3–468 months, and for non-LiR: 46 (21,113), 3–360 months (numbers indicate: median (25th,75th percentile) range)
Summary
Bipolar disorder (BD) is a severe and chronic disorder affecting about 1–2% of the population causing immense suffering and excessive costs.[1,2] BD type 1 is characterized by alternating episodes of depression and mania, whereas BD type 2 is characterized by depressions and hypomanias.[3]. Lithium has probably several additional modes of action that are important for its therapeutic effects, but these mechanisms remain poorly understood
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