Lithium and GSK3-β Promoter Gene Variants Influence White Matter Microstructure in Bipolar Disorder View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2013-01

AUTHORS

Francesco Benedetti, Irene Bollettini, Ignazio Barberi, Daniele Radaelli, Sara Poletti, Clara Locatelli, Adele Pirovano, Cristina Lorenzi, Andrea Falini, Cristina Colombo, Enrico Smeraldi

ABSTRACT

Lithium is the mainstay for the treatment of bipolar disorder (BD) and inhibits glycogen synthase kinase 3-β (GSK3-β). The less active GSK3-β promoter gene variants have been associated with less detrimental clinical features of BD. GSK3-β gene variants and lithium can influence brain gray matter structure in psychiatric conditions. Diffusion tensor imaging (DTI) measures of white matter (WM) integrity showed widespred disruption of WM structure in BD. In a sample of 70 patients affected by a major depressive episode in course of BD, we investigated the effect of ongoing long-term lithium treatment and GSK3-β promoter rs334558 polymorphism on WM microstructure, using DTI and tract-based spatial statistics with threshold-free cluster enhancement. We report that the less active GSK3-β rs334558*C gene-promoter variants, and the long-term administration of the GSK3-β inhibitor lithium, were associated with increases of DTI measures of axial diffusivity (AD) in several WM fiber tracts, including corpus callosum, forceps major, anterior and posterior cingulum bundle (bilaterally including its hippocampal part), left superior and inferior longitudinal fasciculus, left inferior fronto-occipital fasciculus, left posterior thalamic radiation, bilateral superior and posterior corona radiata, and bilateral corticospinal tract. AD reflects the integrity of axons and myelin sheaths. We suggest that GSK3-β inhibition and lithium could counteract the detrimental influences of BD on WM structure, with specific benefits resulting from effects on specific WM tracts contributing to the functional integrity of the brain and involving interhemispheric, limbic, and large frontal, parietal, and fronto-occipital connections. More... »

PAGES

313

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/npp.2012.172

DOI

http://dx.doi.org/10.1038/npp.2012.172

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1008800971

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/22990942


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