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White Matter Abnormalities in Obsessive-compulsive Disorder
A Diffusion Tensor Imaging Study
Philip R. Szeszko, PhD;
Babak A. Ardekani, PhD;
Manzar Ashtari, PhD;
Anil K. Malhotra, MD;
Delbert G. Robinson, MD;
Robert M. Bilder, PhD;
Kelvin O. Lim, MD
Arch Gen Psychiatry. 2005;62:782-790.
Context Several neurobiological models of obsessive-compulsive disorder (OCD) posit a primary role for dysfunction 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 investigation 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 anterior cingulate gyrus compared with healthy volunteers as inferred from diffusion tensor imaging. Additional analyses examined group differences in white matter integrity across the entire brain.
Design, Setting, and Participants Fifteen patients with a DSM-IV diagnosis of OCD and 15 healthy volunteers matched for age, sex, and handedness underwent diffusion tensor imaging and structural magnetic resonance 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 standardization in Talairach space.
Main Outcome Measures Clinical ratings of symptom 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 matter revealed lower FA bilaterally in the parietal region (supramarginal gyri), right posterior cingulate gyrus, and left occipital lobe (lingual gyrus). No areas of significantly higher FA were observed in patients compared with healthy volunteers. Lower FA in the parietal region correlated significantly with higher Yale-Brown Obsessive-Compulsive Scale scores.
Conclusions These preliminary findings provide evidence of an abnormality that involves the anterior cingulate white matter in the pathogenesis of OCD and are consistent with neurobiological models that posit a defect in connectivity in the anterior cingulate basal ganglia–thalamocortical circuit. White matter abnormalities in other brain regions may also be implicated in the neurobiology of OCD.
Author Affiliations: Department of Psychiatry Research, The Zucker Hillside Hospital, North Shore–Long Island Jewish Health System, Glen Oaks, NY (Drs Szeszko, Malhotra, and Robinson); Department of Psychiatry, Albert Einstein College of Medicine, Bronx, NY (Drs Szeszko, Malhotra, and Robinson); Nathan S. Kline Institute for Psychiatric Research, Center for Advanced Brain Imaging, Orangeburg, NY (Dr Ardekani); Department of Radiology, North Shore–Long Island Jewish Health System, New Hyde Park, NY (Dr Ashtari); UCLA Neuropsychiatric Institute and Geffen School of Medicine, Los Angeles, Calif (Dr Bilder); and Department of Psychiatry and Center for Magnetic Resonance Research, University of Minnesota, Minneapolis (Dr Lim).
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