Behavioral Studies of Carriers for Cholesterol Biosynthesis Disorders

项目5--几项研究表明，低胆固醇与暴力死亡(包括自杀)以及反社会障碍、情感障碍、人格障碍和品行障碍等精神障碍之间存在关联。基于这一观察，我们假设与胆固醇合成相关的突变携带者也可能有更高的行为问题风险。本研究的目的是研究与低胆固醇相关的激素代谢紊乱携带者的行为表型，包括Smith-Lemli Opitz综合征、CK综合征、SC4MOL缺乏症、Child综合征和点状软骨发育不良2。共有144名个体(75名受试者和69名对照)将从5个地点(UBC、OHSU、UNMC、CCHMC和UPMC)招募作为STAIR联盟的一部分。 我们的研究将分两部分进行。首先，将对所有受试者和30名对照组进行有效的人格障碍问卷(人格病理学维度评估-基本问卷[DAPP-BQ]，非适应性和适应性人格量表-2[SNAP-2])，以识别异常行为特征。其次，为了阐明与这些行为相关的大脑功能变化，我们将使用fMRI来检测工作记忆任务的血流动力学反应。51名受试者(从上述75名受试者中随机选择)和39名对照组将接受这部分研究。行为和功能磁共振数据将在UBC的楼梯统计核心的帮助下进行分析。基于我们的初步数据，我们预计会发现与对照组相比，类固醇生物合成障碍携带者的行为发生了显著的变化。此外，我们预测，在类固醇代谢紊乱携带者中看到的神经元激活将显著低于对照组。这项研究的长期目标是通过使用所提出的工具，找到新的标记物，不仅可以改善胆固醇合成障碍的行为疗法，还可以改善普通人群中患有类似行为的个人的行为疗法。

Project 5 - Several studies have demonstrated an association between low cholesterol and both violent death (including suicide) and psychiatric disorders such as antisocial disorder, affective disorders, personality disorders and conduct disorder. Based on this observation, we hypothesized that carriers of mutations associated with cholesterol synthesis might also have a higher risk for behavioral problems. The aim of this study is to characterize the behavioral phenotype in carriers of disorders of sterol metabolism associated with low cholesterol, including Smith-Lemli Opitz syndrome, CK syndrome, SC4MOL deficiency, CHILD syndrome and chondrodysplasia punctata 2. A total of 144 individuals (75 subjects and 69 controls) will be recruited from the 5 sites (UBC, OHSU, UNMC, CCHMC, and UPMC) as part of the STAIR consortium. Our study will be done in 2 parts. Firstly, well validated personality disorder questionnaires (Dimensional Assessment of Personality Pathology-Basic Questionnaire [DAPP-BQ], the Schedule for Nonadaptive and Adaptive Personality-2 [SNAP-2]) will be administered to all subjects and 30 controls to identify aberrant behavioral traits. Secondly, to clarify the functional brain changes associated with these behaviors, the hemodynamic responses to working memory tasks will be examined using fMRI. Fifty one subjects (chosen randomly from the above stated 75 subjects) and 39 controls will undergo this part of the study. Behavioral and fMRI Data will be analyzed at UBC with the help of the the STAIR statistical core. Based on our preliminary data, we anticipate finding significant changes in behavior amonst carriers of sterol biosynthesis disorders compared to controls. In addition, we predict that the neuron activation seen in carriers of sterol metabolism disorders will be significantly lower then controls. The long term goal of this study is through the use of the proposed tools, find new markers that could potentially lead to improved behavioral therapies not only for disorders of cholesterol synthesis but also for individuals in the general population that suffer from similar behaviors.