Abnormalities of White Matter Microstructure in Unmedicated Obsessive-Compulsive Disorder and Changes after Medication

BACKGROUND: Abnormalities of myelin integrity have been reported in obsessive-compulsive disorder (OCD) using multi-parameter maps of diffusion tensor imaging (DTI). However, it was still unknown to what degree these abnormalities might be affected by pharmacological treatment. OBJECTIVE: To investigate whether the abnormalities of white matter microstructure including myelin integrity exist in OCD and whether they are affected by medication. METHODOLOGY AND PRINCIPAL FINDINGS: Parameter maps of DTI, including fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD), were acquired from 27 unmedicated OCD patients (including 13 drug-naïve individuals) and 23 healthy controls. Voxel-based analysis was then performed to detect regions with significant group difference. We compared the DTI-derived parameters of 15 patients before and after 12-week Selective Serotonin Reuptake Inhibitor (SSRI) therapies. Significant differences of DTI-derived parameters were observed between OCD and healthy groups in multiple structures, mainly within the fronto-striato-thalamo-cortical loop. An increased RD in combination with no change in AD among OCD patients was found in the left medial superior frontal gyrus, temporo-parietal lobe, occipital lobe, striatum, insula and right midbrain. There was no statistical difference in DTI-derived parameters between drug-naive and previously medicated OCD patients. After being medicated, OCD patients showed a reduction in RD of the left striatum and right midbrain, and in MD of the right midbrain. CONCLUSION: Our preliminary findings suggest that abnormalities of white matter microstructure, particularly in terms of myelin integrity, are primarily located within the fronto-striato-thalamo-cortical circuit of individuals with OCD. Some abnormalities may be partly reversed by SSRI treatment

Mean FA, RD, AD and MD values between drug-naive and previously medicated OCD patients.

<p>The units of radial diffusivity (RD), axial diffusivity (AD) and mean diffusivity (MD) is 10⁻³ mm²/s.</p

Areas of abnormal DTI-derived parameters in 27 patients with obsessive-compulsive disorder and 23 healthy controls before medication.

*<p>peak coordinateds represent the location of the maximum pixel values in standard Montreal Neurological Institute (MNI) space.</p><p>df = 48; p<0.001 (uncorrected).</p

The Demographics and Clinical Characteristics of the Baseline Participants.

<p>The Demographics and Clinical Characteristics of the Baseline Participants.</p

Regional radial diffusivity and mean diffusivity in follow-up patients before and after treatment and healthy controls.

<p>Blue bar represents follow-up patients at baseline (N = 15), red bar represents follow-up patients after treatment (N = 15), yellow bar represents healthy controls (N = 23). Error bars is 95% CI (confidence intervals). The units of radial diffusivity (RD) and mean diffusivity (MD) is 10⁻³ mm²/s. ^a Significant difference between obsessive-compulsive disorder patients and healthy controls (p<0.001, ANOVA with least significant difference post hoc test). ^b Significant difference between follow-up patients with obsessive-compulsive disorder before and after treatment (p<0.05, ANOVA with least significant difference post hoc test).</p

Voxel-based analysis between 27 patients with obsessive-compulsive disorder and 23 healthy controls before medication.

<p>The results were overlaid on mean images of corresponding diffusion tensor imaging (DTI) parameters. A. Fractional Anisotropy (FA) decrease; B. Mean Diffusion (MD) increase; C. Axial diffusion (AD) increase; D. Radial diffusion (RD) increase; p<0.001 uncorrected and cluster size>10 voxels. No increased FA and decreased diffusion coefficients (AD, RD and MD) were found.</p