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

被引：116

作者：

Benedetti, Francesco ^{[1
,2
,3
]}

Bollettini, Irene ^{[1
,2
,3
]}

Barberi, Ignazio ^{[4
]}

Radaelli, Daniele ^{[1
,2
,3
]}

Poletti, Sara ^{[1
,2
,3
]}

Locatelli, Clara ^{[1
,2
,3
]}

Pirovano, Adele ^{[1
,2
]}

Lorenzi, Cristina ^{[1
,2
]}

Falini, Andrea ^{[3
,5
]}

Colombo, Cristina ^{[1
,2
]}

Smeraldi, Enrico ^{[1
,2
,3
]}

机构：

[1] Osped San Raffaele, Ist Sci, Dept Clin Neurosci, Inst Sci, I-20125 Milan, Italy

[2] Univ Vita Salute, San Raffaele Turro, Milan, Italy

[3] Univ Vita Salute San Raffaele, CERMAC, Milan, Italy

[4] Univ Palermo, Dipartimento Sci Farmacol, Dottorato Neurosci & Disturbi Comportamento, Milan, Italy

[5] Inst Sci, Dept Neuroradiol, Milan, Italy

来源：

NEUROPSYCHOPHARMACOLOGY | 2013年 / 38卷 / 02期

关键词：

GSK3-beta; lithium; bipolar disorder; white matter; cingulum bundle; GLYCOGEN-SYNTHASE KINASE-3; SINGLE NUCLEOTIDE POLYMORPHISM; CORPUS-CALLOSUM; MOOD STABILIZERS; ANTIDEPRESSANT RESPONSE; CHOLESTEROL-METABOLISM; FRACTIONAL ANISOTROPY; SPATIAL STATISTICS; VOXELWISE ANALYSIS; NEURONAL POLARITY;

D O I：

10.1038/npp.2012.172

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Lithium is the mainstay for the treatment of bipolar disorder (BD) and inhibits glycogen synthase kinase 3-beta (GSK3-beta). The less active GSK3-beta promoter gene variants have been associated with less detrimental clinical features of BD. GSK3-beta 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-beta 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-beta rs334558*C gene-promoter variants, and the long-term administration of the GSK3-beta 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-beta 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. Neuropsychopharmacology (2013) 38, 313-327; doi:10.1038/npp.2012.172; published online 19 September 2012

引用

页码：313 / 327

页数：15

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