Chamberlain S R, Blackwell A D, Fineberg N A, Robbins T W, Sahakian B J
Department of Psychiatry, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, P.O. Box 189, Cambridge CB2 2QQ, UK.
Neurosci Biobehav Rev. 2005 May;29(3):399-419. doi: 10.1016/j.neubiorev.2004.11.006.
Obsessive compulsive disorder (OCD) is a highly debilitating neuropsychiatric condition with estimated lifetime prevalence of 2-3%, more than twice that of schizophrenia. However, in contrast to other neuropsychiatric conditions of a comparable or lesser prevalence, relatively little is understood about the aetiology, neural substrates and cognitive profile of OCD. Despite strong evidence for OCD being familial, with risk to first-degree relatives much greater than for the background population, its genetic underpinnings have not yet been adequately delineated. Although cognitive dysfunction is evident in the everyday behaviour of OCD sufferers and is central to contemporary psychological models, theory-based studies of neurocognitive function have yet to reveal a reliable cognitive signature, and interpretation has often been confounded by failures to control for co-morbidities. The neuroimaging findings in OCD are amongst the most robust reported in the psychiatric literature, with structural and functional abnormalities frequently reported in orbitofrontal cortex, anterior cingulate cortex, and caudate nucleus. In spite of this, our relative lack of understanding of OCD neurochemical processes continues to impede progress in the development of novel pharmacological treatment approaches. Integrating the neurobiological, cognitive, and clinical findings, we propose that OCD might usefully be conceptualised in terms of lateral orbitofrontal loop dysfunction, and that failures in cognitive and behavioural inhibitory processes appear to underlie many of the symptoms and neurocognitive findings. We highlight existing limitations in the literature, and the potential utility of endophenotypes in overcoming these limitations. We propose that neurocognitive indices of inhibitory functions may represent a useful heuristic in the search for endophenotypes in OCD. This has direct implications not only for OCD but also for putative obsessive-compulsive spectrum conditions including attention deficit hyperactivity disorder, Tourette's syndrome, and trichotillomania (compulsive hair pulling).
强迫症（OCD）是一种极具致残性的神经精神疾病，估计终生患病率为2%-3%，是精神分裂症患病率的两倍多。然而，与其他患病率相当或较低的神经精神疾病相比，人们对强迫症的病因、神经基质和认知特征了解相对较少。尽管有充分证据表明强迫症具有家族遗传性，一级亲属患病风险远高于普通人群，但其遗传基础尚未得到充分阐明。虽然强迫症患者的日常行为中明显存在认知功能障碍，且这是当代心理学模型的核心，但基于理论的神经认知功能研究尚未揭示出可靠的认知特征，而且由于未能控制共病情况，解释常常受到混淆。强迫症的神经影像学研究结果是精神病学文献中报道最为确凿的之一，眶额皮质、前扣带回皮质和尾状核经常出现结构和功能异常。尽管如此，我们对强迫症神经化学过程相对缺乏了解，这继续阻碍着新型药物治疗方法的开发进展。综合神经生物学、认知和临床研究结果，我们提出，强迫症可能有用地被概念化为外侧眶额环路功能障碍，认知和行为抑制过程的失败似乎是许多症状和神经认知研究结果的基础。我们强调了文献中现有的局限性，以及内表型在克服这些局限性方面的潜在效用。我们提出，抑制功能的神经认知指标可能是寻找强迫症内表型的有用启发式方法。这不仅对强迫症有直接影响，而且对包括注意力缺陷多动障碍、妥瑞氏症和拔毛癖（强迫性拔毛）在内的疑似强迫谱系疾病也有直接影响。
