A glycogen synthase kinase 3-β promoter gene single nucleotide polymorphism is associated with age at onset and response to total sleep deprivation in bipolar depression

Francesco Benedetti, Alessandro Serretti, Cristina Colombo, Cristina Lorenzi, Viviana Tubazio, Enrico Smeraldi

Research output: Contribution to journalArticlepeer-review

Abstract

The molecular mechanisms driving the biological clock in the suprachiasmatic nucleus of the hypothalamus may play a role in mood disorders. A single nucleotide polymorphism (SNP) (-50 T/C) falling into the effective promoter region (nt -171 to +29) of the gene coding for glycogen synthase kinase 3-β (GSK3-β) has been linked with different age at onset of bipolar illness. GSK3-β codes for an enzyme which is a target for the action of lithium and valproic acid, and the inhibition of which causes antidepressant-like behaviors in a preclinical model.We studied the effect of this polymorphism on the acute response to total sleep deprivation of 60 depressed bipolar type I inpatients. Homozygotes for the mutant allele of GSK3-β promoter (-50 T/C) SNP showed a later onset of bipolar illness, and better acute effects of TSD treatment on perceived mood (as rated on VAS). Overall, these observations suggest a protective role for this genotype in respect to bipolar illness.Results warrant interest for the variants of genes pertaining to the molecular clock as possible endophenotypes of bipolar disorder, and for GSK3-β as a target of a new class of antidepressant drugs, but caution ought to be taken in interpreting these preliminary results and future replication studies must be awaited because of the low frequency of the GSK3-β*C/C genotype in the studied populations.

Original languageEnglish
Pages (from-to)123-126
Number of pages4
JournalNeuroscience Letters
Volume368
Issue number2
DOIs
Publication statusPublished - Sep 23 2004

Keywords

  • Age at onset
  • Bipolar disorder
  • Endophenotype
  • Glycogen synthase kinase 3-β
  • Sleep deprivation

ASJC Scopus subject areas

  • Neuroscience(all)

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