Endophenotypes of obsessive–compulsive disorder: rationale, evidence and future potential

Abstract

Obsessive–compulsive disorder (OCD) is a heritable and debilitating neuropsychiatric condition. Attempts to delineate genetic contributions have met with limited success, and there is an ongoing search for intermediate trait or vulnerability markers rooted in the neurosciences. Such markers would be valuable for detecting people at risk of developing the condition, clarifying etiological factors and targeting novel treatments. This review begins with brief coverage of the epidemiology of OCD, and presents a hierarchical model of the condition. The advantages of neuropsychological assessment and neuroimaging as objective measures of brain integrity and function are discussed. We describe the concept of endophenotypes and examples of their successful use in medicine and psychiatry. Key areas of focus in the search for OCD endophenotypes are identified, such as measures of inhibitory control and probes of the integrity of orbitofrontal and posterior parietal cortices. Finally, we discuss exciting findings in unaffected first-degree relatives of patients with OCD that have led to the identification of several candidate endophenotypes of the disorder, with important implications for neurobiological understanding and treatment of this and related conditions.

Keywords::

• endophenotype
• functional
• human
• imaging
• inhibition
• intermediate
• MRI
• neuroimaging
• obsessive–compulsive disorder
• OCD
• phenotype
• structural

Financial & competing interests disclosure

Samuel Chamberlain consults for Cambridge Cognition. Lara Menzies reports no potential conflicts of interest. The authors’ research work was funded by grants from NARSAD (Distinguished Investigator Award to Prof Ed Bullmore at the Brain Mapping Unit, University of Cambridge), the Medical Research Council and Wellcome Trust. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.