Erick Jorge Canales-Rodríguez1, Edith Pomarol-Clotet2, Joaquim Radua3, Salvador Sarró2, Silvia Alonso-Lana2, Caterina Del Mar Bonnín4, José Manuel Goikolea4, Teresa Maristany5, Roberto García-Álvarez6, Eduard Vieta4, Peter McKenna2, Raymond Salvador2. 1. Fundación para la Investigación y Docencia Maria Angustias Giménez (FIDMAG) Germanes Hospitalàries, Barcelona; Centro de Investigación Biomédica en Red de Salud Mental, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain. Electronic address: ejcanalesr@gmail.com. 2. Fundación para la Investigación y Docencia Maria Angustias Giménez (FIDMAG) Germanes Hospitalàries, Barcelona; Centro de Investigación Biomédica en Red de Salud Mental, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain. 3. Fundación para la Investigación y Docencia Maria Angustias Giménez (FIDMAG) Germanes Hospitalàries, Barcelona; Centro de Investigación Biomédica en Red de Salud Mental, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain; Institute of Psychiatry, King's College London, London, United Kingdom. 4. Centro de Investigación Biomédica en Red de Salud Mental, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain; Bipolar Disorders Program, Institute of Neuroscience, Hospital Clinic Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS). 5. Centro de Investigación Biomédica en Red de Salud Mental, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain; Bipolar Disorders Program, Institute of Neuroscience, Hospital Clinic Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS); Servicio de Diagnostico por la Imagen, Hospital Sant Joan de Déu, Esplugues de Llobregrat, Barcelona, Spain. 6. Research and Collaborations, General Electric Healthcare, Buc, France.
Abstract
BACKGROUND: Evidence from decades of magnetic resonance imaging (MRI) research in bipolar disorder has been summarized in meta-analyses of various MRI modalities. Notably, although structural MRI studies suggest gray matter reductions are restricted to specific cortical regions, functional MRI has also shown involvement of subcortical dysfunction. Such disparity in results is open to discussion and requires further exploration with additional MRI modalities. METHODS: We applied whole-brain high angular resolution molecular diffusion imaging to compare different properties of the water diffusion process in brain tissues, using different contrasts. Specifically, we looked at fractional anisotropy, mean diffusivity, probability of return to the origin, and generalized fractional anisotropy in a sample of 40 euthymic patients with bipolar disorder and 40 well-matched healthy control subjects. RESULTS: Convergent abnormalities were detected by contrasts in various tissue types. Apart from alterations in white matter (in corpus callosum, cingulum bundle, corona radiata, and superior fronto-occipital fasciculus) and cortical gray matter (in medial frontal cortex, left insula, Heschl's gyrus, and cerebellum), three of the contrasts (fractional anisotropy, mean diffusivity, and generalized fractional anisotropy) revealed abnormalities in subcortical structures, including the hippocampus, the thalamus and the caudate nucleus. CONCLUSIONS: Our findings point to a wider pattern of axonal pathology in bipolar disorder than previously thought. Although findings related to cortical gray matter are consistent with structural meta-analyses, subcortical abnormalities suggest a cytoarchitectonic basis for previously reported subcortical dysfunction. Diffusion results could be interpreted in terms of loss of tissue volume and/or altered membrane permeability, agreeing with both hypotheses of mitochondrial malfunction and neuroinflammation.
BACKGROUND: Evidence from decades of magnetic resonance imaging (MRI) research in bipolar disorder has been summarized in meta-analyses of various MRI modalities. Notably, although structural MRI studies suggest gray matter reductions are restricted to specific cortical regions, functional MRI has also shown involvement of subcortical dysfunction. Such disparity in results is open to discussion and requires further exploration with additional MRI modalities. METHODS: We applied whole-brain high angular resolution molecular diffusion imaging to compare different properties of the water diffusion process in brain tissues, using different contrasts. Specifically, we looked at fractional anisotropy, mean diffusivity, probability of return to the origin, and generalized fractional anisotropy in a sample of 40 euthymic patients with bipolar disorder and 40 well-matched healthy control subjects. RESULTS: Convergent abnormalities were detected by contrasts in various tissue types. Apart from alterations in white matter (in corpus callosum, cingulum bundle, corona radiata, and superior fronto-occipital fasciculus) and cortical gray matter (in medial frontal cortex, left insula, Heschl's gyrus, and cerebellum), three of the contrasts (fractional anisotropy, mean diffusivity, and generalized fractional anisotropy) revealed abnormalities in subcortical structures, including the hippocampus, the thalamus and the caudate nucleus. CONCLUSIONS: Our findings point to a wider pattern of axonal pathology in bipolar disorder than previously thought. Although findings related to cortical gray matter are consistent with structural meta-analyses, subcortical abnormalities suggest a cytoarchitectonic basis for previously reported subcortical dysfunction. Diffusion results could be interpreted in terms of loss of tissue volume and/or altered membrane permeability, agreeing with both hypotheses of mitochondrial malfunction and neuroinflammation.
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