title: Patterns of microstructural white matter abnormalities and their impact on cognitive dysfunction in the various phases of type I bipolar disorder.
abstract: BACKGROUND
  In recent years, diffusion tensor imaging (DTI) studies have detected subtle microstructural abnormalities of white matter (WM) in type I bipolar disorder (BD). However, WM alterations in the different phases of BD remain to be explored. The aims of this study is to investigate the WM alterations in the various phases of illness and their correlations with clinical and neurocognitive features.
  
  
  METHODS
  We investigated the DTI-derived fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD) in patients with type I BD (n=61) subdivided in manic (n=21), depressive (n=20) and euthymic phases (n=20) vs. healthy controls (n=42), using a tract-based spatial statistics (TBSS) approach. Then, we investigated whether the subgroups of patients in the various phases of illness present different patterns of WM abnormalities. Finally we studied the correlations between WM alterations and clinical-cognitive parameters.
  
  
  RESULTS
  We found a widespread alteration in WM microstructure (decrease in FA and increase in MD and RD) in BD when compared to controls. The various subgroups of BD showed different spatial patterns of WM alterations. A gradient of increasing WM abnormalities from the euthymic (low degree and localized WM alterations mainly in the midline structures) to the manic (more diffuse WM alterations affecting both midline and lateral structures) and, finally, to the depressive phase (high degree and widespread WM alterations), was found. Furthermore, the WM diffuse alterations correlated with cognitive deficits in BD, such as decreased fluency prompted by letter and decreased hits and increased omission errors at the continuous performance test.
  
  
  CONCLUSIONS
  Patients under treatment.
  
  
  CONCLUSIONS
  The WM alterations in type I BD showed different spatial patterns in the various phases of illness, mainly affecting the active phases, and correlated with some cognitive deficits. This suggests a complex trait- and state-dependent pathogenesis of WM abnormalities in BD.
authors.affiliation: Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Health, Section of Psychiatry, University of Genoa, Genoa, Italy. Electronic address: paola.magioncalda@gmail.com.
authors.forename: Paola
authors.initials: P
authors.lastname: Magioncalda
authors.affiliation: Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Health, Section of Psychiatry, University of Genoa, Genoa, Italy. Electronic address: matteomartino9@gmail.com.
authors.forename: Matteo
authors.initials: M
authors.lastname: Martino
authors.affiliation: Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Health, Section of Psychiatry, University of Genoa, Genoa, Italy. Electronic address: benedetta.conio@hotmail.it.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Conio
authors.affiliation: Department of Radiology, Section of Neuroradiology, University of Genoa, Genoa, Italy. Electronic address: aaa_sj86@yahoo.it.
authors.forename: Niccolò
authors.initials: N
authors.lastname: Piaggio
authors.affiliation: Department of Neurology, Radiology and Neuroscience, Mount Sinai School of Medicine, New York, USA. Electronic address: roxana.oana@gmail.com.
authors.forename: Roxana
authors.initials: R
authors.lastname: Teodorescu
authors.affiliation: Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Health, Section of Psychiatry, University of Genoa, Genoa, Italy. Electronic address: andrea.escelsior@live.com.
authors.forename: Andrea
authors.initials: A
authors.lastname: Escelsior
authors.affiliation: Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Health, Section of Psychiatry, University of Genoa, Genoa, Italy. Electronic address: valeviaggia@hotmail.com.
authors.forename: Valentina
authors.initials: V
authors.lastname: Marozzi
authors.affiliation: Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Health, Section of Psychiatry, University of Genoa, Genoa, Italy. Electronic address: giulio.rocchi@hotmail.com.
authors.forename: Giulio
authors.initials: G
authors.lastname: Rocchi
authors.affiliation: Magnetic Resonance Research Center on Nervous System Diseases, University of Genoa, Genoa, Italy. Electronic address: lroccatagliata@neurologia.unige.it.
authors.forename: Luca
authors.initials: L
authors.lastname: Roccatagliata
authors.affiliation: Institute of Mental Health Research, University of Ottawa, Ottawa, Canada; Taipei Medical University, Graduate Institute of Humanities in Medicine, Taipei, Taiwan; Taipei Medical University-Shuang Ho Hospital, Brain and Consciousness Research Center, New Taipei City, Taiwan; National Chengchi University, Research Center for Mind, Brain and Learning, Taipei, Taiwan; Centre for Cognition and Brain Disorders (CCBD), Normal University Hangzhou, Hangzhou, China. Electronic address: georg.northoff@theroyal.ca.
authors.forename: Georg
authors.initials: G
authors.lastname: Northoff
authors.affiliation: Department of Neurology, Radiology and Neuroscience, Mount Sinai School of Medicine, New York, USA; Magnetic Resonance Research Center on Nervous System Diseases, University of Genoa, Genoa, Italy. Electronic address: matilde.inglese@mssm.edu.
authors.forename: Matilde
authors.initials: M
authors.lastname: Inglese
authors.affiliation: Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Health, Section of Psychiatry, University of Genoa, Genoa, Italy. Electronic address: mario.amore@unige.it.
authors.forename: Mario
authors.initials: M
authors.lastname: Amore
mesh_terms: D000328:Adult; D016880:Anisotropy; D001714:Bipolar Disorder / Q000503:physiopathology*; D016022:Case-Control Studies; D003072:Cognition Disorders / Q000503:physiopathology*; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D066127:White Matter / Q000473:pathology*
keywords: Bipolar disorder; Bipolar phases; Cognitive deficit; DTI; TBSS; White matter abnormalities