title: Brain white matter integrity and association with age at onset in pediatric obsessive-compulsive disorder.
abstract: BACKGROUND
  Obsessive-compulsive disorder (OCD) is a common and debilitating neuropsychiatric illness thought to involve abnormal connectivity of widespread brain networks, including frontal-striatal-thalamic circuits. At least half of OCD cases arise in childhood and their underlying neuropathology may differ at least in part from that of adult-onset OCD. Yet, only a few studies have examined brain white matter (WM) integrity in childhood-onset OCD using diffusion tensor imaging (DTI), and none have examined potential associations with age at onset.
  
  
  RESULTS
  In this study, 17 youth with OCD and 19 healthy control subjects, ages 10 to 19 years, underwent DTI on a 3T Siemens scanner. DSM-IV diagnoses were established with standardized interviews, and OCD symptom severity was evaluated using the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS). Voxel-wise analyses were conducted on data processed with tract-based spatial statistics (TBSS) to derive measures of fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD). OCD patients had significantly lower FA in seven WM clusters, with over 80% of significant voxels in bilateral frontal cortex and corpus callosum (CC). There were no regions of significantly higher FA in patients compared with controls. Patients also had significantly higher RD in right frontal cortex and right body of the CC. Earlier age at onset of OCD correlated significantly with lower FA in the right thalamus and with higher RD in the right CC. FA and RD were not significantly associated with symptom severity.
  
  
  CONCLUSIONS
  These findings point to compromised WM integrity and reduced myelination in some brain regions of children with OCD, particularly the CC and fiber tracts that connect the frontal lobes to widespread cortical and subcortical targets. They also suggest that age at onset may be a moderator of some of the WM changes in pediatric OCD.
authors.affiliation: Center for Depression, Anxiety and Stress Research, McLean Hospital, 115 Mill Street, mailstop 334, Belmont, MA 02478 USA ; Department of Psychiatry, Harvard Medical School, Boston, MA USA.
authors.forename: Isabelle M
authors.initials: IM
authors.lastname: Rosso
authors.affiliation: Center for Depression, Anxiety and Stress Research, McLean Hospital, 115 Mill Street, mailstop 334, Belmont, MA 02478 USA ; Department of Psychiatry, Harvard Medical School, Boston, MA USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Olson
authors.affiliation: Department of Psychology, University of Miami, 5665 Ponce de Leon Blvd, Flipse Building, Coral Gables, Miami, FL 33146 USA.
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Britton
authors.affiliation: British Columbia Mental Health and Addictions Research Institute, University of British Columbia, Vancouver, BC Canada ; UBC Psychiatry A3-118, 938 West 28th Ave, Vancouver, BC V5Z 4H4 Canada.
authors.forename: S Evelyn
authors.initials: SE
authors.lastname: Stewart
authors.affiliation: Center for Morphometric Analysis, Massachusetts General Hospital, Bldg 149, 13th Street, Charlestown, MA 02129 USA ; Department of Neurology, Harvard Medical School, Boston, MA USA ; Department of Radiology, Harvard Medical School, Boston, MA USA.
authors.forename: George
authors.initials: G
authors.lastname: Papadimitriou
authors.affiliation: Center for Depression, Anxiety and Stress Research, McLean Hospital, 115 Mill Street, mailstop 334, Belmont, MA 02478 USA ; Department of Psychiatry, Harvard Medical School, Boston, MA USA.
authors.forename: William Ds
authors.initials: WD
authors.lastname: Killgore
authors.affiliation: Center for Morphometric Analysis, Massachusetts General Hospital, Bldg 149, 13th Street, Charlestown, MA 02129 USA ; Department of Neurology, Harvard Medical School, Boston, MA USA ; Department of Radiology, Harvard Medical School, Boston, MA USA.
authors.forename: Nikos
authors.initials: N
authors.lastname: Makris
authors.affiliation: Department of Psychiatry, Harvard Medical School, Boston, MA USA ; Department of Psychiatry, Massachusetts General Hospital, Simches Research Building, 185 Cambridge Street, Suite 2282, Boston, MA 02114 USA.
authors.forename: Sabine
authors.initials: S
authors.lastname: Wilhelm
authors.affiliation: Department of Psychiatry, Harvard Medical School, Boston, MA USA ; Department of Psychiatry, Massachusetts General Hospital, Simches Research Building, 185 Cambridge Street, Suite 2282, Boston, MA 02114 USA ; Department of Psychiatry, University of Arizona, Tucson, AZ USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Jenike
authors.affiliation: Center for Depression, Anxiety and Stress Research, McLean Hospital, 115 Mill Street, mailstop 334, Belmont, MA 02478 USA ; Department of Psychiatry, Harvard Medical School, Boston, MA USA.
authors.forename: Scott L
authors.initials: SL
authors.lastname: Rauch
keywords: Age at onset; Childhood; Corpus callosum; Diffusion tensor imaging; Obsessive-compulsive disorder; Thalamus