title: Neuropsychiatry and White Matter Microstructure in Huntington's Disease.
abstract: BACKGROUND
  Neuropsychiatric symptoms in Huntington's disease (HD) are often evident prior to clinical diagnosis. Apathy is highly correlated with disease progression, while depression and irritability occur at different stages of the disease, both before and after clinical onset. Little is understood about the neural bases of these neuropsychiatric symptoms and to what extent those neural bases are analogous to neuropsychiatric disorders in the general population.
  
  
  OBJECTIVE
  We used Diffusion Tensor Imaging (DTI) to investigate structural connectivity between brain regions and any putative microstructural changes associated with depression, apathy and irritability in HD.
  
  
  METHODS
  DTI data were collected from 39 premanifest and 45 early-HD participants in the Track-HD study and analysed using whole-brain Tract-Based Spatial Statistics. We used regression analyses to identify white matter tracts whose structural integrity (as measured by fractional anisotropy, FA) was correlated with HADS-depression, PBA-apathy or PBA-irritability scores in gene-carriers and related to cumulative probability to onset (CPO).
  
  
  RESULTS
  For those with the highest CPO, we found significant correlations between depression scores and reduced FA in the splenium of the corpus callosum. In contrast, those with lowest CPO demonstrated significant correlations between irritability scores and widespread FA reductions. There was no significant relationship between apathy and FA throughout the whole brain.
  
  
  CONCLUSIONS
  We demonstrate that white matter changes associated with both depression and irritability in HD occur at different stages of disease progression concomitant with their clinical presentation.
authors.affiliation: Wellcome Trust Centre for Neuroimaging, UCL, London, UK.|Institute of Cognitive Neuroscience, University College London, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Gregory
authors.affiliation: Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK.
authors.forename: Rachael I
authors.initials: RI
authors.lastname: Scahill
authors.affiliation: Developmental Imaging and Biophysics Section, UCL Institute of Child Health, London, UK.
authors.forename: Kiran K
authors.initials: KK
authors.lastname: Seunarine
authors.affiliation: Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester and Manchester Academic Health Science Centre, Manchester, UK.|Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Stopford
authors.affiliation: Department of Computer Science and Centre for Medical Image Computing, UCL, London, UK.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Computer Science and Centre for Medical Image Computing, UCL, London, UK.
authors.forename: Jiaying
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Neurology, University of Ulm, Ulm, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Orth
authors.affiliation: APHP Department of Genetics, Groupe Hospitalier Pitié-Salpêtrière, and Institut du Cerveau et de la Moelle, INSERM U1127, CNRS UMR7225, Sorbonne Universités - UPMC Université Paris VI UMR_S1127, Paris, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Durr
authors.affiliation: Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Raymund A C
authors.initials: RA
authors.lastname: Roos
authors.affiliation: Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.|Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, IA, USA.
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Langbehn
authors.affiliation: Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.|Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, IA, USA.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Long
authors.affiliation: Department of Electrical and Computer Engineering, University of Iowa, Iowa City, IA, USA.
authors.forename: Hans
authors.initials: H
authors.lastname: Johnson
authors.affiliation: Wellcome Trust Centre for Neuroimaging, UCL, London, UK.|Institute of Cognitive Neuroscience, University College London, UK.
authors.forename: Geraint
authors.initials: G
authors.lastname: Rees
authors.affiliation: Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK.|National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Tabrizi
authors.affiliation: Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester and Manchester Academic Health Science Centre, Manchester, UK.|Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
authors.forename: David
authors.initials: D
authors.lastname: Craufurd
mesh_terms: D000328:Adult; D016880:Anisotropy; D057565:Apathy / Q000502:physiology*; D000067290:Behavior Rating Scale; D003866:Depressive Disorder / Q000473:pathology*; D056324:Diffusion Tensor Imaging / Q000379:methods; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000473:pathology*; D007508:Irritable Mood / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis; D011795:Surveys and Questionnaires; D066127:White Matter / Q000473:pathology*
keywords: Huntington’s disease; apathy; depression; diffusion tensor imaging; irritability