Tract-specific white matter structural disruption in patients with bipolar disorder

Authors

  • Francesco Benedetti,

    1. Department of Clinical Neurosciences, Scientific Institute and University Vita-Salute San Raffaele
    2. C.E.R.M.A.C. (Centro di Eccellenza Risonanza Magnetica ad Alto Campo), University Vita-Salute San Raffaele
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  • Martina Absinta,

    1. C.E.R.M.A.C. (Centro di Eccellenza Risonanza Magnetica ad Alto Campo), University Vita-Salute San Raffaele
    2. Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, Scientific Institute and University Vita-Salute San Raffaele, Milan
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  • Maria A Rocca,

    1. C.E.R.M.A.C. (Centro di Eccellenza Risonanza Magnetica ad Alto Campo), University Vita-Salute San Raffaele
    2. Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, Scientific Institute and University Vita-Salute San Raffaele, Milan
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  • Daniele Radaelli,

    1. Department of Clinical Neurosciences, Scientific Institute and University Vita-Salute San Raffaele
    2. C.E.R.M.A.C. (Centro di Eccellenza Risonanza Magnetica ad Alto Campo), University Vita-Salute San Raffaele
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  • Sara Poletti,

    1. Department of Clinical Neurosciences, Scientific Institute and University Vita-Salute San Raffaele
    2. C.E.R.M.A.C. (Centro di Eccellenza Risonanza Magnetica ad Alto Campo), University Vita-Salute San Raffaele
    3. Dipartimento di Scienze Farmacologiche, Università degli Studi di Palermo, Palermo
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  • Alessandro Bernasconi,

    1. Department of Clinical Neurosciences, Scientific Institute and University Vita-Salute San Raffaele
    2. C.E.R.M.A.C. (Centro di Eccellenza Risonanza Magnetica ad Alto Campo), University Vita-Salute San Raffaele
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  • Sara Dallaspezia,

    1. Department of Clinical Neurosciences, Scientific Institute and University Vita-Salute San Raffaele
    2. C.E.R.M.A.C. (Centro di Eccellenza Risonanza Magnetica ad Alto Campo), University Vita-Salute San Raffaele
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  • Elisabetta Pagani,

    1. C.E.R.M.A.C. (Centro di Eccellenza Risonanza Magnetica ad Alto Campo), University Vita-Salute San Raffaele
    2. Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, Scientific Institute and University Vita-Salute San Raffaele, Milan
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  • Andrea Falini,

    1. C.E.R.M.A.C. (Centro di Eccellenza Risonanza Magnetica ad Alto Campo), University Vita-Salute San Raffaele
    2. Department of Neuroradiology, Scientific Institute and University Vita-Salute San Raffaele, Milan
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  • Massimiliano Copetti,

    1. Biostatistics Unit, IRCCS-Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy
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  • Cristina Colombo,

    1. Department of Clinical Neurosciences, Scientific Institute and University Vita-Salute San Raffaele
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  • Giancarlo Comi,

    1. C.E.R.M.A.C. (Centro di Eccellenza Risonanza Magnetica ad Alto Campo), University Vita-Salute San Raffaele
    2. Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, Scientific Institute and University Vita-Salute San Raffaele, Milan
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  • Enrico Smeraldi,

    1. Department of Clinical Neurosciences, Scientific Institute and University Vita-Salute San Raffaele
    2. C.E.R.M.A.C. (Centro di Eccellenza Risonanza Magnetica ad Alto Campo), University Vita-Salute San Raffaele
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  • Massimo Filippi

    1. C.E.R.M.A.C. (Centro di Eccellenza Risonanza Magnetica ad Alto Campo), University Vita-Salute San Raffaele
    2. Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, Scientific Institute and University Vita-Salute San Raffaele, Milan
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  • The authors of this paper do not have any commercial associations that might pose a conflict of interest in connection with this manuscript.

Corresponding author:
Dr. Francesco Benedetti
Istituto Scientifico Ospedale San Raffaele
Department of Clinical Neurosciences
San Raffaele Turro
Via Stamira d’Ancona 20
20125, Milano, Italy
Fax: +39-02-26433265
E-mail: benedetti.francesco@hsr.it

Abstract

Benedetti F, Absinta M, Rocca MA, Radaelli D, Poletti S, Bernasconi A, Dallaspezia S, Pagani E, Falini A, Copetti M, Colombo C, Comi G, Smeraldi E, Filippi M. Tract-specific white matter structural disruption in patients with bipolar disorder. Bipolar Disord 2011: 13: 414–424. © 2011 The Authors. Journal compilation © 2011 John Wiley & Sons A/S.

Objectives:  A growing body of evidence suggests that, independent of localized brain lesions, mood disorders can be associated with dysfunction of brain networks involved in the modulation of emotional and cognitive behavior. We used diffusion tensor (DT) tractography to quantify the presence and extent of structural injury to the connections between the amygdala and other brain regions, which included the subgenual, the supragenual and posterior cingulate, the parahippocampal, the orbitofrontal and dorsolateral prefrontal cortices, as well as the insula.

Methods:  Using a 3.0 Tesla scanner, conventional and DT magnetic resonance imaging sequences of the brain were acquired from 15 adult patients with major depressive disorder (MDD), 15 with bipolar disorder (BD), and 21 age-matched healthy controls. Using FSL software, diffusivity changes of the white matter (WM) fiber bundles belonging to the emotional network were measured.

Results:  Compared to controls and MDD patients, BD patients had significantly decreased average fractional anisotropy, increased average mean diffusivity, and increased average axial and radial diffusivity values in the majority of the WM fiber bundles connecting structures of the anterior limbic network (p-values ranging from 0.002 to 0.040). Medication load did not influence the results with the exception of lithium, which was associated with normal diffusivity values in tracts connecting the amygdala with the subgenual cingulate cortex.

Conclusions:  We detected specific WM abnormalities, suggestive of disrupted integrity of fiber bundles in the brains of patients with BD. These abnormalities might contribute to understanding both mood dysregulation and cognitive disturbances in BD, and might provide an objective marker to monitor treatment efficacy in this condition.

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