Lithium and GSK3-β promoter gene variants influence white matter microstructure in bipolar disorder

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

    Risultato della ricerca: Article

    85 Citazioni (Scopus)

    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.
    Lingua originaleEnglish
    pagine (da-a)313-327
    Numero di pagine15
    RivistaNeuropsychopharmacology
    Volume38
    Stato di pubblicazionePublished - 2013

    Fingerprint

    Bipolar Disorder
    Lithium
    Diffusion Tensor Imaging
    Genes
    Pyramidal Tracts
    Corpus Callosum
    Brain
    Myelin Sheath
    White Matter
    Glycogen Synthase Kinase 3 beta
    Surgical Instruments
    Psychiatry
    Axons
    Radiation
    Therapeutics

    All Science Journal Classification (ASJC) codes

    • Pharmacology
    • Psychiatry and Mental health

    Cita questo

    Barberi, I., Falini, A., Lorenzi, C., Smeraldi, E., Colombo, C., Benedetti, F., ... Bollettini, I. (2013). Lithium and GSK3-β promoter gene variants influence white matter microstructure in bipolar disorder. Neuropsychopharmacology, 38, 313-327.

    Lithium and GSK3-β promoter gene variants influence white matter microstructure in bipolar disorder. / Barberi, Ignazio; Falini, Andrea; Lorenzi, Cristina; Smeraldi, Enrico; Colombo, Cristina; Benedetti, Francesco; Pirovano, Adele; Poletti, Sara; Radaelli, Daniele; Locatelli, Clara; Bollettini, Irene.

    In: Neuropsychopharmacology, Vol. 38, 2013, pag. 313-327.

    Risultato della ricerca: Article

    Barberi, I, Falini, A, Lorenzi, C, Smeraldi, E, Colombo, C, Benedetti, F, Pirovano, A, Poletti, S, Radaelli, D, Locatelli, C & Bollettini, I 2013, 'Lithium and GSK3-β promoter gene variants influence white matter microstructure in bipolar disorder', Neuropsychopharmacology, vol. 38, pagg. 313-327.
    Barberi, Ignazio ; Falini, Andrea ; Lorenzi, Cristina ; Smeraldi, Enrico ; Colombo, Cristina ; Benedetti, Francesco ; Pirovano, Adele ; Poletti, Sara ; Radaelli, Daniele ; Locatelli, Clara ; Bollettini, Irene. / Lithium and GSK3-β promoter gene variants influence white matter microstructure in bipolar disorder. In: Neuropsychopharmacology. 2013 ; Vol. 38. pagg. 313-327.
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    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.",
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    AU - Colombo, Cristina

    AU - Benedetti, Francesco

    AU - Pirovano, Adele

    AU - Poletti, Sara

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    AU - Locatelli, Clara

    AU - Bollettini, Irene

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    AB - 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.

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