Cited by 184Bipolar Disorder and TreatmentSchizophrenia research and treatmentTreatment of Major Depression

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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·2005·Neuroscience Letters

DOI 10.1016/j.neulet.2004.11.022

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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-beta (GSK3-beta) has been linked with different age at onset of bipolar illness and with different antidepressant effects of total sleep deprivation. GSK3-beta 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-beta*C/C genotype in the studied populations.

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Authors: Benedetti, F., Serretti, A., Pontiggia, A., Bernasconi, A., Lorenzi, C., Colombo, C., & Smeraldi, E.
Affiliations: Vita-Salute San Raffaele University (IT)
IRCCS Ospedale San Raffaele (IT)
Corresponding author: Benedetti, Francesco
ORCID: Benedetti, Francesco
Serretti, Alessandro
Lorenzi, Cristina
Colombo, Cristina
Venue: Neuroscience Letters
Publisher: Elsevier BV
Published: 2005-03
Volume: 376
Issue: 1
Pages: 51-55
ISSN: 0304-3940 (ISSN-L)
DOI: 10.1016/j.neulet.2004.11.022
OpenAlex: W2078634434
Cited by: 184
References: 30
Citations by year: 2026: 3 · 2025: 3 · 2023: 3 · 2022: 7 · 2020: 8 · 2019: 9 · 2018: 7 · 2017: 3 · 2016: 7 · 2015: 8 · 2014: 15 · 2013: 16 · 2012: 13
FWCI: 4.81
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Neuroscience Letters (publishedVersion)
PubMed (publishedVersion)
Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
Keywords: lithium response, bipolar I disorder, glycogen synthase kinase-3β, promoter polymorphism, genetic susceptibility, mood episode recurrence, molecular clock, endophenotypes, valproic acid, age of onset
MeSH terms: Glycogen Synthase Kinase 3 beta, Adult, Analysis of Variance, Bipolar Disorder, DNA Mutational Analysis, Female, Humans, Lithium, Male, Middle Aged, Pharmacogenetics, Promoter Regions, Genetic, RNA, Messenger, Time, Time Factors, Reverse Transcriptase Polymerase Chain Reaction, Polymorphism, Single Nucleotide, Glycogen Synthase Kinase 3

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

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