Chamberlain Samuel R, Menzies Lara
Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Cambridge, CB2 2QQ, UK.
Expert Rev Neurother. 2009 Aug;9(8):1133-46. doi: 10.1586/ern.09.36.
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.
强迫症（OCD）是一种具有遗传性且使人衰弱的神经精神疾病。确定其遗传因素的努力成效有限，目前正在寻找基于神经科学的中间性状或易感性标记。此类标记对于检测有患该疾病风险的人群、阐明病因以及靶向新的治疗方法具有重要价值。本综述首先简要介绍强迫症的流行病学情况，并提出该疾病的分层模型。讨论了神经心理学评估和神经成像作为大脑完整性和功能客观测量方法的优势。我们描述了内表型的概念及其在医学和精神病学中成功应用的实例。确定了寻找强迫症内表型的关键重点领域，如抑制控制的测量以及眶额皮质和顶叶后部皮质完整性的探测。最后，我们讨论了强迫症患者未受影响的一级亲属中的一些令人兴奋的发现，这些发现已导致确定了该疾病的几种候选内表型，对理解该疾病及相关疾病的神经生物学机制和治疗具有重要意义。
