Glycogen synthase kinase-3β genetic polymorphisms and insomnia in depressed patients: A prospective study

J Affect Disord. 2018 Nov:240:230-236. doi: 10.1016/j.jad.2018.07.062. Epub 2018 Jul 24.

Abstract

Background: 80-90% of patients with Major Depressive Episode (MDE) experience insomnia and up-to 50% severe insomnia. Glycogen Synthase Kinase-3β (GSK3B) is involved both in mood regulation and circadian rhythm. Since GSK3B polymorphisms could affect protein levels or functionality, we investigated the association of GSK3B polymorphisms with insomnia in a sample of depressed patients treated with antidepressants.

Methods: In this 6-month prospective real-world treatment study in psychiatric settings (METADAP), 492 Caucasian patients requiring a new antidepressant treatment were included and genotyped for five GSK3B Single Nucleotide Polymorphisms (SNPs) (rs6808874, rs6782799, rs2319398, rs13321783, rs334558). Insomnia and MDE severity were rated using the Hamilton Depression Rating Scale (HDRS). Bi- and multivariate analyses were performed to assess the association between GSK3B SNPs and insomnia (main objective). We also assessed their association with MDE severity and HDRS response/remission after antidepressant treatment.

Results: At baseline severe insomnia was associated with the GSK3B rs334558 minor allele (C+) [OR=1.81, CI95%(1.17-2.80), p=0.008]. GSK3B rs334558 C+ had greater insomnia improvement after 6 months of antidepressant treatment (p=0.007, β=0.17, t=2.736). No association was found between GSK3B SNPs and MDE baseline severity or 6-month response/remission.

Conclusion: GSK3B rs334558 was associated with insomnia but not with MDE severity in depressed patients. Targeting GSK3B in patients with MDE and a severe insomnia could be a way to improve their symptoms with greater efficiency. And it should be further studied whether the GSK3B-insomnia association may fit into the larger picture of mood disorders.

Keywords: Antidepressants response; GSK3B; Insomnia; MDD; MDE; Single nucleotide polymorphism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Alleles
  • Antidepressive Agents / therapeutic use
  • Depressive Disorder / drug therapy
  • Depressive Disorder / genetics*
  • Female
  • Genotyping Techniques
  • Glycogen Synthase Kinase 3 beta / genetics*
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Prospective Studies
  • Sleep Initiation and Maintenance Disorders / genetics*
  • Young Adult

Substances

  • Antidepressive Agents
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta