Telomere biology and its maintenance in schizophrenia spectrum disorders: Exploring links to cognition

Schizophr Res. 2024 Oct:272:89-95. doi: 10.1016/j.schres.2024.08.011. Epub 2024 Aug 28.

Abstract

Objective: Contemporary research suggests reduced telomere length in schizophrenia spectrum disorders (SZ) compared to age-adjusted non-affected individuals. However, the role of telomere maintenance and telomere repair in SZ is poorly understood as well as the involvement of telomere biology in cognitive abnormalities in SZ.

Methods: The study consisted of 758 participants (SZ [n = 357] and healthy controls, HC [n = 401]) collected as part of the Norwegian TOP study. Participants were assessed with standardized neuropsychological tests measuring five cognitive domains. Leucocyte telomere length (TL) was measured via blood and determined by quantitative real-time Polymerase Chain Reaction (qPCR) providing a telomere to single copy ratio (T/S ratio), used to estimate the mean telomere length. Telomerase activity was assessed by the expression levels of the Telomerase Reverse Transcriptase (TERT) and Telomerase RNA Component (TERC) genes. To assess telomere maintenance and telomere repair we calculated the telomerase expression to TL ratio (TERT/TL and TERC/TL respectively).

Results: Patients had reduced TERT (F = 5.03, p = 0.03), but not TERC expression (F = 1.04, p = 0.31), and higher TERT/TL (F = 6.68, p = 0.01) and TERC/TL (F = 6.71, p = 0.01), adjusted for age, sex, and ethnicity. No statistically significant association was observed between any of the telomere biology markers and the cognitive domains (p > 0.05).

Conclusion: Our study shows changes in TERT expression and telomere maintenance and telomere repair in SZ compared HC. However, the role of telomere biology in the mechanism underlying cognitive impairment in psychosis seems limited.

Keywords: Cognitive impairments; Schizophrenia spectrum disorders; Telomerase expression; Telomeres/telomere length maintenance and repair.

MeSH terms

  • Adult
  • Cognitive Dysfunction / etiology
  • Cognitive Dysfunction / genetics
  • Cognitive Dysfunction / physiopathology
  • Female
  • Humans
  • Leukocytes / metabolism
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Psychotic Disorders / genetics
  • Psychotic Disorders / physiopathology
  • RNA / genetics
  • Schizophrenia* / genetics
  • Schizophrenia* / physiopathology
  • Schizophrenic Psychology
  • Telomerase* / genetics
  • Telomere Homeostasis / physiology
  • Telomere Shortening / physiology
  • Telomere*

Substances

  • Telomerase
  • TERT protein, human
  • telomerase RNA
  • RNA