White Matter Abnormalities in Obsessive-compulsive Disorder

Context: Several neurobiological models of obsessive- compulsive disorder (OCD) posit a primary role for dys- function of the anterior cingulate gyrus. Both functional and structural neuroimaging studies have implicated anterior cingulate gray matter abnormalities in the pathophysiology of OCD, but there has been little in- vestigation of the anterior cingulate white matter in this disorder. Objective: To test the hypothesis that patients with OCD have abnormal white matter microstructure in the ante- rior cingulate gyrus compared with healthy volunteers as inferred from diffusion tensor imaging. Additional analyses examined group differences in white matter in- tegrity across the entire brain. Design, Setting, and Participants: Fifteen patients with a DSM-IV diagnosis of OCD and 15 healthy volun- teers matched for age, sex, and handedness underwent diffusion tensor imaging and structural magnetic reso- nance imaging examinations. Fractional anisotropy (FA), a robust intravoxel measure of water self-diffusion, was compared between groups on a voxel-by-voxel basis in the anterior cingulate white matter after standardiza- tion in Talairach space. Main Outcome Measures: Clinical ratings of symp- tom severity (ie, Yale-Brown Obsessive-Compulsive Scale) and FA. Results: Compared with healthy volunteers, patients demonstrated significantly lower FA bilaterally in 3 areas of the anterior cingulate gyrus white matter. Additional analyses conducted across the rest of the brain white mat- ter revealed lower FA bilaterally in the parietal region (su- pramarginal gyri), right posterior cingulate gyrus, and left occipital lobe (lingual gyrus). No areas of signifi- cantly higher FA were observed in patients compared with healthy volunteers. Lower FA in the parietal region cor- related significantly with higher Yale-Brown Obsessive- Compulsive Scale scores. Conclusions: These preliminary findings provide evi- dence of an abnormality that involves the anterior cin- gulate white matter in the pathogenesis of OCD and are consistent with neurobiological models that posit a de- fect in connectivity in the anterior cingulate basal ganglia- thalamocortical circuit. White matter abnormalities in other brain regions may also be implicated in the neu- robiology of OCD. Arch Gen Psychiatry. 2005;62:782-790