Gray matter structural alterations in obsessive-compulsive disorder: relationship to neuropsychological functions

Numerous magnetic resonance (MR) studies have examined gray matter structural alterations in patients with obsessive-compulsive disorder (OCD). Few, however, have used automated, highly reliable techniques such as voxel-based morphometry (VBM) to examine the entire brain in contrast to selected regions of interest. Moreover, few studies have examined the functional correlates of gray matter abnormalities in OCD. We used VBM to evaluate regional gray matter differences between 21 OCD patients and 21 age- and sex-matched healthy volunteers. All patients had comprehensive neuropsychological assessments. MR images were normalized to a customized template and segmented using optimized VBM. OCD patients had significantly more gray matter in the left thalamus compared with healthy volunteers. OCD patients without major depression had significantly more gray matter in the thalamus (bilaterally) and left orbitofrontal cortex as well as an unpredicted region of more right dorsolateral prefrontal gray matter, which remained significant after correction for multiple comparisons, compared with healthy volunteers. In the subgroup of patients without depression, greater right hemisphere thalamic and dorsolateral prefrontal gray matter correlated significantly with worse motor functioning and processing speed, respectively. In this subgroup there was also a tendency for more gray matter in the left orbitofrontal cortex and right dorsolateral prefrontal cortex to be associated with greater symptom severity. Our findings provide additional support for the involvement of cortical-striatal-thalamic circuits in the pathophysiology of OCD and preliminary evidence that a defect involving the dorsolateral prefrontal cortex may also be implicated. Moreover, our data suggest that gray matter structural alterations in OCD have neuropsychological correlates, which may be useful in further characterizing structure-function relations in this disorder.