title: Structural abnormalities in bipolar euthymia: a multicontrast molecular diffusion imaging study.
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.
authors.affiliation: 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.
authors.forename: Erick Jorge
authors.initials: EJ
authors.lastname: Canales-Rodríguez
authors.affiliation: 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.
authors.forename: Edith
authors.initials: E
authors.lastname: Pomarol-Clotet
authors.affiliation: 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.
authors.forename: Joaquim
authors.initials: J
authors.lastname: Radua
authors.affiliation: 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.
authors.forename: Salvador
authors.initials: S
authors.lastname: Sarró
authors.affiliation: 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.
authors.forename: Silvia
authors.initials: S
authors.lastname: Alonso-Lana
authors.affiliation: 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).
authors.forename: Caterina
authors.initials: C
authors.lastname: Del Mar Bonnín
authors.affiliation: 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).
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Goikolea
authors.affiliation: 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.
authors.forename: Teresa
authors.initials: T
authors.lastname: Maristany
authors.affiliation: Research and Collaborations, General Electric Healthcare, Buc, France.
authors.forename: Roberto
authors.initials: R
authors.lastname: García-Álvarez
authors.affiliation: 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).
authors.forename: Eduard
authors.initials: E
authors.lastname: Vieta
authors.affiliation: 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.
authors.forename: Peter
authors.initials: P
authors.lastname: McKenna
authors.affiliation: 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.
authors.forename: Raymond
authors.initials: R
authors.lastname: Salvador
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D006801:Humans; D008297:Male; D066127:White Matter / Q000473:pathology*
keywords: Bipolar disorder; diffusion tensor imaging (DTI); euthymia; high angular resolution diffusion imaging (HARDI); magnetic resonance imaging (MRI); whole-brain statistical analysis