Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Am J Med Genet C Semin Med Genet. 2012 Nov 15;160C(4):295-300. doi: 10.1002/ajmg.c.31342. Epub 2012 Oct 5.
The brain's high concentrations of cholesterol make it especially vulnerable to the cholesterol biosynthetic defect that characterizes Smith-Lemli-Opitz syndrome (SLOS). An attempt to characterize the cognitive and behavioral phenotype of SLOS has identified increased rates of intellectual disability, language and motor developmental delay, repeated self-injury behaviors, sensory hyperreactivity, hyperactivity, affect dysregulation, and sleep disturbances. Some research has suggested that carriers of the gene mutation that results in SLOS display increased risk of suicidal behavior. Cholesterol dysregulation impairs neuroplasticity, which may be a mechanism underlying some of the mentioned abnormalities. Discrete positive effects have been reported with the use of cholesterol supplementation in the treatment of SLOS. Research has been limited by the small number of subjects available, and a limited understanding of lipid metabolism in the brain. Hopefully future research will help clarify the role that cholesterol plays in cognitive and behavioral abnormalities like the ones associated with SLOS. This would accelerate the development of treatments for SLOS, and perhaps also further understanding of non-syndromic psychiatric disorders such as autism and attention deficit hyperactivity disorder.
大脑中胆固醇的高浓度使其特别容易受到 Smith-Lemli-Opitz 综合征（SLOS）特征的胆固醇生物合成缺陷的影响。试图描述 SLOS 的认知和行为表型已经确定了智力残疾、语言和运动发育迟缓、反复自我伤害行为、感觉超敏反应、多动、情绪失调和睡眠障碍的发生率增加。一些研究表明，导致 SLOS 的基因突变携带者表现出自杀行为的风险增加。胆固醇失调会损害神经可塑性，这可能是上述一些异常的机制之一。在 SLOS 的治疗中使用胆固醇补充剂已经报告了明显的积极效果。研究受到可用受试者数量少和对大脑脂质代谢理解有限的限制。希望未来的研究将有助于阐明胆固醇在认知和行为异常中的作用，这些异常与 SLOS 有关。这将加速 SLOS 的治疗方法的发展，并可能进一步了解自闭症和注意力缺陷多动障碍等非综合征性精神障碍。
