Lithium-induced Clock Gene Expression in Lymphoblastoid Cells of Bipolar Affective Patients

Pharmacopsychiatry. 2015 Jul;48(4-5):145-9. doi: 10.1055/s-0035-1549946. Epub 2015 May 26.

Abstract

Introduction: Disturbances of circadian rhythms occur in all episodes of bipolar disorder (BD). Lithium, as gold-standard in the maintenance treatment of BD, is known to influence circadian processes.

Methods: In a pilot study lymphoblastoid cell lines (LCLs) were generated from 8 BD patients and 6 healthy controls. The LCLs were treated with lithiumchloride (LiCl) for 3 weeks. Cell cycles were then synchronized and expressional analysis by quantitative Real Time PCR was done.

Results: BD and controls differed in the period length regarding DBP (albumin D-box binding protein) expression and DBP expression was also influenced by lithium treatment. Furthermore, baseline DBP expression was significantly different between non-treated BD and healthy controls. None of the other analyzed circadian genes showed to be influenced by chronic lithium treatment or to be differentially regulated due to the diagnosis.

Discussion: We here show that chronic lithium treatment of LCLs leads to decreased expression of the clock gene DBP, rendering DBP a lithium-regulated gene. We could confirm the role of the circadian clock as well in lithium mode of action as in the pathomechanisms of BD although future studies with a greater number of participants and cell lines are needed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimanic Agents / pharmacology*
  • Bipolar Disorder / drug therapy*
  • Cell Line
  • Circadian Clocks*
  • DNA-Binding Proteins / biosynthesis*
  • Female
  • Gene Expression / drug effects*
  • Humans
  • Lithium Chloride / pharmacology*
  • Male
  • Pilot Projects
  • Transcription Factors / biosynthesis*

Substances

  • Antimanic Agents
  • DBP protein, human
  • DNA-Binding Proteins
  • Transcription Factors
  • Lithium Chloride