Evidence for fractional anisotropy and mean diffusivity white matter abnormalities in the internal capsule and cingulum in patients with obsessive–compulsive disorder

Evidence for fractional anisotropy and mean diffusivity white matter abnormalities in the internal capsule and cingulum in patients with obsessive–compulsive disorder

PDF

J Psychiatry Neurosci 2012;37(3):193-9

Christine Lochner, PhD; Jean-Paul Fouché, MSc; Stefan du Plessis, MBChB; Bruce Spottiswoode, PhD; Soraya Seedat, MBChB, MMed (Psych), PhD; Naomi Fineberg, MBBS; Samuel R. Chamberlain, MB/BChir, PhD; Dan J. Stein, PhD, DPhil

Lochner, Seedat, Stein — MRC Unit on Anxiety and Stress Disorders, Department of Psychiatry, University of Stellenbosch; Fouché, du Plessis — Department of Psychiatry, University of Stellenbosch; Spottiswoode — MRC/UCT Medical Imaging Research Unit, Department of Human Biology, University of Cape Town, and the Division of Radiology, University of Stellenbosch, South Africa; Fineberg, Chamberlain — Department of Psychiatry, University of Cambridge School of Clinical Medicine, Addenbrooke’s Hospital, Cambridge, UK; Fineberg — National Obsessive Compulsive Disorders Service, Queen Elizabeth II Hospital, Welwyn Garden City, UK; Stein — Department of Psychiatry, University of Cape Town, South Africa

Abstract

Background: There is evidence to suggest that obsessive–compulsive disorder (OCD) is associated with structural abnormalities in cortico–striato–thalamic circuits, yet the extent of white matter abnormalities is not well established. In this study, we used diffusion tensor imaging (DTI) to examine white matter integrity in specific regions of interest (ROIs) in patients with OCD.
Methods: Patients with OCD and sex-, age- and IQ-matched healthy controls underwent DTI. The primary objective was to explore whether patients with OCD had white matter abnormalities in the anterior limb of the internal capsule (ALIC), the uncinate fasciculus, the genu of the corpus callosum and the cingulum. The secondary objective was to evaluate the relation between fractional anisotropy and mean diffusivity in these ROIs and other clinical variables (including age at onset of OCD, OCD severity and levels of depressive and anxiety symptomatology) in patients with OCD.
Results: There were 15 patients and 17 controls enrolled in our study. Compared with healthy controls, patients with OCD showed increased fractional anisotropy in bilateral regions of the ALIC adjacent to the body of the caudate, as well as decreased fractional anisotropy in the right anterior limb near the head of the caudate. Patients also had decreased mean diffusivity in the body of the right cingulum and the left anterior cingulum compared with controls. Correlational analyses revealed significant associations of fractional anisotropy and mean diffusivity in select circuits with OCD, depression and anxiety severity scores.
Limitations: Inclusion of patients with OCD receiving pharmacotherapy may have been a limitation. In addition, the patients were heterogeneous in terms of their obsessive–compulsive symptom profiles; we did not distinguish between different obsessive–compulsive symptom dimensions.
Conclusion: The study results provide further evidence for OCD-related white matter abnormalities in the ALIC and cingulum, consistent with a cortico striatal model of OCD.


Submitted June 29, 2011; Revised Oct. 17, 2011; Accepted Oct. 21, 2011.

Acknowledgements: We are grateful to Lundbeck Pharmaceuticals and Siemens Medical Solutions South Africa for their support.

Competing interests: C. Lochner declares that her work has received institutional grant support from the National Research Council (competitive funding for rated researchers) and the Harry and Doris Crossley Foundation. J.P. Fouché declares having received grant support from the Departments of Psychiatry, Universities of Stellenbosch and Cape Town, and travel support from the European and South African Research Network in Anxiety Disorders. None declared for S. du Plessis. None declared for B. Spottiswoode. S. Seedat declares having received institutional grant support from the National Research Foundation and the National Institutes of Health, as well as lecture fees from Servier, Astra Zeneca, Lundbeck and Dr. Reddy’s. N. Fineberg declares having consulted for Servier, Lundbeck, GlaxoSmithKline and Bristol Myers Squibb; and having received grant support from Lundbeck, GlaxoSmithKline and Servier; lecture fees from Lundbeck, Bristol Myers Squibb and Servier; royalties from Oxford University Press; payment for educational presentations from Lundbeck and travel support from Wyeth and Cephalon. S. Chamberlain declares having consulted for Cambridge Cognition, P1Vital, Lucinda Ellery and Shire, and having received lecture fees from Lilly. D. Stein declares membership of the advisory boards of Eli Lilly, Lundbeck and Pfizer, membership of the speakers’ bureaus of GlaxoSmithKline, Lundbeck, Pfizer, Solvay and Servier, and having received consultant fees from Servier, Wyeth and Biocodex.

Contributors: C. Lochner, N. Fineberg and D. Stein designed the study. C. Lochner acquired the data, which all authors analyzed. C. Lochner wrote the article, which J.-P. Fouché, S. du Plessis, B. Spottiswoode, S. Seedat, N. Fineberg, S. Chamberlain and D. Stein reviewed. All authors approved its publication.

DOI: 10.1503/jpn.110059

Correspondence to: C. Lochner, PO Box 19063, Tygerberg, 7505, South Africa; cl2@sun.ac.za