Expression of telomerase reverse transcriptase positively correlates with duration of lithium treatment in bipolar disorder

Psychiatry Res. 2020 Apr:286:112865. doi: 10.1016/j.psychres.2020.112865. Epub 2020 Feb 11.

Abstract

Bipolar disorder (BD) may be associated with accelerated cellular aging. However, previous studies on telomere length (TL), an important biomarker of cellular aging, have yielded mixed results in BD. We aimed to evaluate the hypothesis that BD is associated with telomere shortening and whether this is counteracted by long-term lithium treatment. We also sought to determine whether long-term lithium treatment is associated with increased expression of telomerase reverse transcriptase (TERT), the catalytic subunit of telomerase. We determined TL and TERT expression in 100 BD I patients and 100 healthy controls. We also genotyped three single nucleotide polymorphisms associated with TL. TERT expression was significantly increased in BD I patients currently on lithium treatment. TERT expression was also significantly positively correlated with duration of lithium treatment in patients treated for 24 months or more. However, we did not find any significant effect of lithium treatment on TL. Neither did we find significant differences in TL between BD patients and controls. We suggest that long-term lithium treatment is associated with an increase in the expression of TERT. We hypothesize that an increase in TERT expression may contribute to lithium's mood stabilizing and neuroprotective properties by improving mitochondrial function and decreasing oxidative stress.

Keywords: Affective disorder; Aging; Mitochondria; Oxidative stress; TERT; Telomere.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aging / genetics
  • Aging / metabolism*
  • Antimanic Agents / therapeutic use*
  • Bipolar Disorder / blood
  • Bipolar Disorder / drug therapy*
  • Bipolar Disorder / genetics*
  • Cellular Senescence / drug effects
  • Cellular Senescence / genetics*
  • Female
  • Humans
  • Lithium / therapeutic use*
  • Lithium Compounds / pharmacology
  • Lithium Compounds / therapeutic use*
  • Male
  • Middle Aged
  • Mitochondria / metabolism
  • Oxidative Stress / drug effects
  • Polymorphism, Single Nucleotide / genetics
  • Real-Time Polymerase Chain Reaction
  • Telomerase / drug effects
  • Telomerase / genetics
  • Telomerase / metabolism*
  • Telomere / drug effects
  • Telomere / genetics
  • Telomere / metabolism
  • Telomere Homeostasis / genetics
  • Telomere Shortening / drug effects
  • Telomere Shortening / genetics

Substances

  • Antimanic Agents
  • Lithium Compounds
  • Lithium
  • TERT protein, human
  • Telomerase