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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
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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“one of these SNPs (−50 T to C) is linked to a later age of onset of BPD and a greater response to total sleep deprivation (TSD) and long-term lithium treatment (Benedetti et al., 2004; Benedetti et al., 2005).”
From Circadian genes, rhythms and the biology of mood disorders (2007) · cites this paper as Benedetti et al., 2005
In the citing paper
“other studies failed to show a general association between these SNPs and BPD”
From Circadian genes, rhythms and the biology of mood disorders (2007) · cites this paper as Benedetti et al., 2005
In the citing paper
“one of these SNPs (−50 T to C) is linked to a later age of onset of BPD and a greater response to total sleep deprivation (TSD) and long-term lithium treatment (Benedetti et al., 2004; Benedetti et al., 2005).”
From Circadian genes, rhythms and the biology of mood disorders (2007) · cites this paper as Benedetti et al., 2005
In the citing paper
“one of these SNPs (−50 T to C) is linked to a later age of onset of BPD and a greater response to total sleep deprivation (TSD) and long-term lithium treatment (Benedetti et al., 2004; Benedetti et al., 2005).”
From Circadian genes, rhythms and the biology of mood disorders (2007) · cites this paper as Benedetti et al., 2005
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Self-citation
Metadata
- 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
- Venue
- Neuroscience Letters
- Publisher
- Elsevier BV
- Published
- 2005-03
- Volume
- 376
- Issue
- 1
- Pages
- 51-55
- ISSN
- 0304-3940 (ISSN-L)
- 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
- 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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