White matter abnormalities in patients with obsessive-compulsive disorder and their first-degree relatives.
OBJECTIVE
Obsessive-compulsive disorder (OCD) is a common, heritable neuropsychiatric disorder, hypothetically underpinned by dysconnectivity of large-scale brain systems. The extent of white matter abnormalities in OCD is unknown, and the genetic basis of this disorder is poorly understood. The authors used diffusion tensor imaging, a magnetic resonance imaging technique, for examining white matter abnormalities in brain structure through quantification of water diffusion, to confirm whether white matter abnormalities exist in OCD. They also explored whether such abnormalities occur in healthy first-degree relatives of patients, indicating they may be endophenotypes representing increased genetic risk for OCD.


METHODS
The authors used diffusion tensor imaging to measure fractional anisotropy of white matter in 30 patients with OCD, 30 unaffected first-degree relatives, and 30 matched healthy comparison subjects. Regions of significantly abnormal fractional anisotropy in patients in relation to healthy comparison subjects were identified by permutation tests. The authors assessed whether these abnormalities were also evident in the first-degree relatives. A secondary region-of-interest analysis was undertaken to assess the extent of replication between our data and previous relevant literature.


RESULTS
Patients with OCD demonstrated significantly reduced fractional anisotropy in a large region of right inferior parietal white matter and significantly increased fractional anisotropy in a right medial frontal region. Relatives also exhibited significant abnormalities of fractional anisotropy in these regions.


CONCLUSIONS
These findings indicate that OCD is associated with white matter abnormalities in parietal and frontal regions. Similar abnormalities in unaffected first-degree relatives suggest these may be white matter endophenotypes for OCD.
Brain Mapping Unit, Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Cambridge CB22QQ, UK. lacm2@cam.ac.uk
Lara
L
Menzies
Guy B
GB
Williams
Samuel R
SR
Chamberlain
Cinly
C
Ooi
Naomi
N
Fineberg
John
J
Suckling
Barbara J
BJ
Sahakian
Trevor W
TW
Robbins
Ed T
ET
Bullmore
D000328:Adult; D016880:Anisotropy; D001921:Brain / Q000473:pathology*; D001931:Brain Mapping; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D005625:Frontal Lobe / Q000473:pathology; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000473:pathology; D009771:Obsessive-Compulsive Disorder / Q000175:diagnosis* / Q000235:genetics*; D010296:Parietal Lobe / Q000473:pathology; D010641:Phenotype; D015203:Reproducibility of Results