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Lithium and GSK-3β promoter gene variants influence cortical gray matter volumes in bipolar disorder
- Source :
- Psychopharmacology. 232:1325-1336
- Publication Year :
- 2014
- Publisher :
- Springer Science and Business Media LLC, 2014.
-
Abstract
- RATIONALE:Lithium is the mainstay for the treatment of bipolar disorder (BD) and inhibits glycogen synthase kinase-3β (GSK-3β). The less active GSK-3β promoter gene variants have been associated with less detrimental clinical features of BD. GSK-3β gene variants and lithium can influence brain gray and white matter structure in psychiatric conditions, so we studied their combined effect in BD.OBJECTIVES:The aim of this study is to investigate the effects of ongoing long-term lithium treatment and GSK-3β promoter rs334558 polymorphism on regional gray matter (GM) volumes of patients with BD.MATERIALS AND METHODS:GM volumes were estimated with 3.0 Tesla MRI in 150 patients affected by a major depressive episode in course of BD. Duration of lifetime lithium treatment was retrospectively assessed. Analyses were performed by searching for significant effects of lithium and rs334558 in the whole brain.RESULTS:The less active GSK-3β rs334558*G gene promoter variant and the long-term administration of lithium were synergistically associated with increased GM volumes in the right frontal lobe, in a large cluster encompassing the boundaries of subgenual and orbitofrontal cortex (including Brodmann areas 25, 11, and 47). Effects of lithium on GM revealed in rs334558*G carriers only, consistent with previously reported clinical effects in these genotype groups, and were proportional to the duration of treatment.CONCLUSIONS:Lithium and rs334558 influenced GM volumes in areas critical for the generation and control of affect, which have been widely implicated in the process of BD pathophysiology. In the light of the protective effects of lithium on white matter integrity, our results suggest that the clinical effects of lithium associate with a neurotrophic effect on the whole brain, probably mediated by GSK-3β inhibition.
- Subjects :
- Adult
Male
medicine.medical_specialty
Bipolar Disorder
Lithium
Treatment of bipolar disorder
White matter
Glycogen Synthase Kinase 3
Internal medicine
Neuroplasticity
medicine
Humans
Bipolar disorder
Gray Matter
Major depressive episode
Glycogen synthase
GSK3B
Retrospective Studies
Cerebral Cortex
Pharmacology
Glycogen Synthase Kinase 3 beta
Polymorphism, Genetic
biology
business.industry
Genetic Variation
Organ Size
Middle Aged
medicine.disease
Magnetic Resonance Imaging
Endocrinology
medicine.anatomical_structure
biology.protein
GSK3-beta, lithium, bipolar disorder, white matter, cingulum bundle
Female
Orbitofrontal cortex
medicine.symptom
business
Neuroscience
Antipsychotic Agents
Subjects
Details
- ISSN :
- 14322072 and 00333158
- Volume :
- 232
- Database :
- OpenAIRE
- Journal :
- Psychopharmacology
- Accession number :
- edsair.doi.dedup.....2860152823815ce3c34c851741ec5959