title: Mild White Matter Changes in Un-medicated Obsessive-Compulsive Disorder Patients and Their Unaffected Siblings.
abstract: OBJECTIVE
  Obsessive-compulsive disorder (OCD) is a common neuropsychiatric disorder with moderate genetic influences and white matter abnormalities in frontal-striatal and limbic regions. Inconsistencies in reported white matter results from diffusion tensor imaging (DTI) studies can be explained, at least partly, by medication use and between-group differences in disease profile and stage. We used a family design aiming to establish whether white matter abnormalities, if present in un-medicated OCD patients, also exist in their unaffected siblings.
  
  
  METHODS
  Forty-four OCD patients, un-medicated for at least the past 4 weeks, 15 of their unaffected siblings, and 37 healthy controls (HC) underwent DTI using a 3-Tesla MRI-scanner. Data analysis was done using tract-based spatial statistics (TBSS). Fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD) values were compared within seven skeletonised regions of interest (ROIs), i.e., corpus callosum, bilateral cingulum bundle, bilateral inferior longitudinal fasciculus/frontal-occipital fasciculus (ILF/FOF) and bilateral superior longitudinal fasciculus (SLF).
  
  
  RESULTS
  Un-medicated OCD patients, compared with HC, had significantly lower FA in the left cingulum bundle. FA was trend-significantly lower in all other ROIs, except for the corpus callosum. Significant three-group differences in FA (and in RD at trend-significant level) were observed in the left cingulum bundle, with the unaffected siblings representing an intermediate group between OCD patients and HC.
  
  
  CONCLUSIONS
  OCD patients showed lower FA in the left cingulum bundle, partly driven by trend-significantly higher values in RD. Since the unaffected siblings were found to be an intermediate group between OCD patients and HC, this white matter alteration may be considered an endophenotype for OCD.
authors.affiliation: Department of Anatomy and Neurosciences, VU University Medical CenterAmsterdam, Netherlands; Department of Psychiatry, VU University Medical CenterAmsterdam, Netherlands; Department of Social and Behavioural Science, Utrecht UniversityUtrecht, Netherlands.
authors.forename: Siyan
authors.initials: S
authors.lastname: Fan
authors.affiliation: Department of Anatomy and Neurosciences, VU University Medical CenterAmsterdam, Netherlands; Department of Psychiatry, VU University Medical CenterAmsterdam, Netherlands; Neuroscience Campus Amsterdam, VU/VU University Medical CenterAmsterdam, Netherlands; The OCD Team, Haukeland University HospitalBergen, Norway.
authors.forename: Odile A
authors.initials: OA
authors.lastname: van den Heuvel
authors.affiliation: Department of Social and Behavioural Science, Utrecht UniversityUtrecht, Netherlands; Academic Anxiety Center AltrechtUtrecht, Netherlands.
authors.forename: Danielle C
authors.initials: DC
authors.lastname: Cath
authors.affiliation: Department of Anatomy and Neurosciences, VU University Medical CenterAmsterdam, Netherlands; Neuroscience Campus Amsterdam, VU/VU University Medical CenterAmsterdam, Netherlands; Netherlands Institute for NeuroscienceAmsterdam, Netherlands.
authors.forename: Ysbrand D
authors.initials: YD
authors.lastname: van der Werf
authors.affiliation: Department of Anatomy and Neurosciences, VU University Medical CenterAmsterdam, Netherlands; Department of Psychiatry, VU University Medical CenterAmsterdam, Netherlands; Neuroscience Campus Amsterdam, VU/VU University Medical CenterAmsterdam, Netherlands; The OCD Team, Haukeland University HospitalBergen, Norway.
authors.forename: Stella J
authors.initials: SJ
authors.lastname: de Wit
authors.affiliation: Department of Anatomy and Neurosciences, VU University Medical CenterAmsterdam, Netherlands; Department of Psychiatry, VU University Medical CenterAmsterdam, Netherlands; Neuroscience Campus Amsterdam, VU/VU University Medical CenterAmsterdam, Netherlands.
authors.forename: Froukje E
authors.initials: FE
authors.lastname: de Vries
authors.affiliation: Department of Psychiatry, VU University Medical CenterAmsterdam, Netherlands; Neuroscience Campus Amsterdam, VU/VU University Medical CenterAmsterdam, Netherlands.
authors.forename: Dick J
authors.initials: DJ
authors.lastname: Veltman
authors.affiliation: Neuroscience Campus Amsterdam, VU/VU University Medical CenterAmsterdam, Netherlands; Department of Physics and Medical Technology, VU University Medical CenterAmsterdam, Netherlands.
authors.forename: Petra J W
authors.initials: PJ
authors.lastname: Pouwels
keywords: diffusion tensor imaging; endophenotype; fractional anisotropy; obsessive-compulsive disorder