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Science 18 July 2008:
Vol. 321. no. 5887, pp. 421 - 422
DOI: 10.1126/science.1154433
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Reports

Orbitofrontal Dysfunction in Patients with Obsessive-Compulsive Disorder and Their Unaffected Relatives

Samuel R. Chamberlain,1,2,3* Lara Menzies,1,2,3 Adam Hampshire,4 John Suckling,1,2 Naomi A. Fineberg,1,3 Natalia del Campo,1,2 Mike Aitken,2,5 Kevin Craig,1,2,3 Adrian M. Owen,4 Edward T. Bullmore,1,2,6 Trevor W. Robbins,2,5 Barbara J. Sahakian1,2

Obsessive-compulsive disorder (OCD) is characterized by repetitive thoughts and behaviors associated with underlying dysregulation of frontostriatal circuitry. Central to neurobiological models of OCD is the orbitofrontal cortex, a neural region that facilitates behavioral flexibility after negative feedback (reversal learning). We identified abnormally reduced activation of several cortical regions, including the lateral orbitofrontal cortex, during reversal learning in OCD patients and their clinically unaffected close relatives, supporting the existence of an underlying previously undiscovered endophenotype for this disorder.

1 Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Box 189, Cambridge CB2 0QQ, UK.
2 Behavioral and Clinical Neuroscience Institute (BCNI), University of Cambridge, Cambridge CB2 3EB, UK.
3 National OCD Treatment Service, Queen Elizabeth II Hospital, Welwyn Garden City AL7 4HQ, UK.
4 Medical Research Council (MRC) Cognition and Brain Sciences Unit, Cambridge CB2 7EF, UK.
5 Department of Experimental Psychology, University of Cambridge, Cambridge CB2 3EB, UK.
6 Clinical Unit Cambridge, GlaxoSmithKline, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.

* To whom correspondence should be addressed. E-mail: srchamb{at}gmail.com

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Science. ISSN 0036-8075 (print), 1095-9203 (online)