Bloch Michael H, Pittenger Christopher
Yale Child Study Center, Yale University School of Medicine, New Haven, Connecticut ; Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut.
Curr Psychiatry Rev. 2010 May 1;6(2):91-103. doi: 10.2174/157340010791196439.
OCD is a psychiatric disorder with a lifetime prevalence of 1-3% and is a significant cause of disability worldwide. Family studies indicate that OCD has a significant hereditable component, with relatives of OCD cases being 4 times more likely to develop the disorder than the general population. Linkage studies in OCD have generally been underpowered and have failed to reach the statistical threshold for genome-wide significance, but they have nevertheless been useful for revealing potential regions of interest for future candidate gene studies. Candidate gene studies in OCD have thus far focused on genes involved in the serotonergic, dopaminergic, and glutamatergic pathways. These studies have been for the most part inconclusive, and failures to replicate have been the norm until very recently. The only genetic association replicated by multiple groups was with a glutamate transporter gene (). Genome-wide association studies in OCD are in progress, but final results have not yet been reported. As with the study of many other psychiatric disorders, an improved understanding of OCD will only be achieved (1) with larger collaborative efforts involving more probands, (2) the use of probands and controls drawn from epidemiologically-based populations rather than clinical samples, (3) developing a more precise phenotypic description of OCD and (4) measuring important environmental influences that affect OCD pathogenesis and severity.
强迫症是一种终生患病率为1%-3%的精神疾病,是全球致残的一个重要原因。家族研究表明,强迫症有显著的遗传成分,强迫症患者的亲属患该疾病的可能性是普通人群的4倍。强迫症的连锁研究通常样本量不足,未能达到全基因组显著性的统计阈值,但它们对于揭示未来候选基因研究的潜在感兴趣区域仍然是有用的。迄今为止,强迫症的候选基因研究主要集中在涉及血清素能、多巴胺能和谷氨酸能通路的基因上。这些研究大多没有定论,直到最近,无法重复研究结果一直是常态。多个研究小组唯一重复的基因关联是与一种谷氨酸转运体基因有关。强迫症的全基因组关联研究正在进行中,但最终结果尚未公布。与许多其他精神疾病的研究一样,只有通过以下方式才能更好地理解强迫症:(1)开展涉及更多先证者的更大规模合作研究;(2)使用来自基于流行病学的人群而非临床样本的先证者和对照;(3)对强迫症进行更精确的表型描述;(4)衡量影响强迫症发病机制和严重程度的重要环境因素。