Long-term response to lithium salts in bipolar illness is influenced by the glycogen synthase kinase 3-β -50 T/C SNP

Francesco Benedetti, Alessandro Serretti, Adriana Pontiggia, Alessandro Bernasconi, Cristina Lorenzi, Cristina Colombo, Enrico Smeraldi

Research output: Contribution to journalArticle

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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 and with different antidepressant effects of total sleep deprivation. GSK3-β codes for an enzyme which is a target for the action of lithium and possibly of valproic acid. We studied the effect of this polymorphism on the therapeutic response to lithium salts of 88 bipolar type I patients. Data about recurrence rate of mood episodes were collected for at least 2 years before lithium and 2 years on lithium. Results showed that homozygotes for the wild variant did not change their recurrence index while carriers of the mutant allele improved, thus supporting the hypothesis that GSK is a target for the therapeutic action of lithium. Results warrant interest for the variants of genes pertaining to the molecular clock as possible endophenotypes of bipolar disorder, 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)51-55
Number of pages5
JournalNeuroscience Letters
Volume376
Issue number1
DOIs
Publication statusPublished - Mar 7 2005

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Glycogen Synthase Kinase 3
Lithium
Single Nucleotide Polymorphism
Salts
Biological Clocks
Endophenotypes
Recurrence
Suprachiasmatic Nucleus
Sleep Deprivation
Homozygote
Valproic Acid
Mood Disorders
Bipolar Disorder
Age of Onset
Genetic Promoter Regions
Antidepressive Agents
Genes
Hypothalamus
Alleles
Genotype

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Long-term response to lithium salts in bipolar illness is influenced by the glycogen synthase kinase 3-β -50 T/C SNP. / Benedetti, Francesco; Serretti, Alessandro; Pontiggia, Adriana; Bernasconi, Alessandro; Lorenzi, Cristina; Colombo, Cristina; Smeraldi, Enrico.

In: Neuroscience Letters, Vol. 376, No. 1, 07.03.2005, p. 51-55.

Research output: Contribution to journalArticle

Benedetti, Francesco ; Serretti, Alessandro ; Pontiggia, Adriana ; Bernasconi, Alessandro ; Lorenzi, Cristina ; Colombo, Cristina ; Smeraldi, Enrico. / Long-term response to lithium salts in bipolar illness is influenced by the glycogen synthase kinase 3-β -50 T/C SNP. In: Neuroscience Letters. 2005 ; Vol. 376, No. 1. pp. 51-55.
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